Neurofeedback, Biofeedback and transcranial Direct Current Stimulation

Neurofeedback, Biofeedback and transcranial Direct Current Stimulation - Abstracts

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Curr Pain Headache Rep. 2009 Feb;13(1):12-7.

Noninvasive transcranial brain stimulation and pain.

Rosen AC, Ramkumar M, Nguyen T, Hoeft F.

Palo Alto Veterans Affairs Health Care System, 3801 Miranda Avenue (151Y), Palo Alto, CA 94304-1207, USA. rosena@psych.stanford.edu

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two noninvasive brain stimulation techniques that can modulate activity in specific regions of the cortex. At this point, their use in brain stimulation is primarily investigational; however, there is clear evidence that these tools can reduce pain and modify neurophysiologic correlates of the pain experience. TMS has also been used to predict response to surgically implanted stimulation for the treatment of chronic pain. Furthermore, TMS and tDCS can be applied with other techniques, such as event-related potentials and pharmacologic manipulation, to illuminate the underlying physiologic mechanisms of normal and pathological pain. This review presents a description and overview of the uses of two major brain stimulation techniques and a listing of useful references for further study.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

PMID: 19126365 [PubMed - in process]

Proc Natl Acad Sci U S A. 2009 Jan 21. [Epub ahead of print]

Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation.

Reis J, Schambra HM, Cohen LG, Buch ER, Fritsch B, Zarahn E, Celnik PA, Krakauer JW.

Human Cortical Physiology Section and Stroke Neurorehabilitation Clinic, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;

Motor skills can take weeks to months to acquire and can diminish over time in the absence of continued practice. Thus, strategies that enhance skill acquisition or retention are of great scientific and practical interest. Here we investigated the effect of noninvasive cortical stimulation on the extended time course of learning a novel and challenging motor skill task. A skill measure was chosen to reflect shifts in the task's speed-accuracy tradeoff function (SAF), which prevented us from falsely interpreting variations in position along an unchanged SAF as a change in skill. Subjects practiced over 5 consecutive days while receiving transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). Using the skill measure, we assessed the impact of anodal (relative to sham) tDCS on both within-day (online) and between-day (offline) effects and on the rate of forgetting during a 3-month follow-up (long-term retention). There was greater total (online plus offline) skill acquisition with anodal tDCS compared to sham, which was mediated through a selective enhancement of offline effects. Anodal tDCS did not change the rate of forgetting relative to sham across the 3-month follow-up period, and consequently the skill measure remained greater with anodal tDCS at 3 months. This prolonged enhancement may hold promise for the rehabilitation of brain injury. Furthermore, these findings support the existence of a consolidation mechanism, susceptible to anodal tDCS, which contributes to offline effects but not to online effects or long-term retention.

PMID: 19164589 [PubMed - as supplied by publisher]

Clin Neurophysiol. 2009 Jan;120(1):80-4. Epub 2008 Nov 21.

Bilateral frontal transcranial direct current stimulation: Failure to replicate classic findings in healthy subjects.

Koenigs M, Ukueberuwa D, Campion P, Grafman J, Wassermann E.

Brain Stimulation Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC 1440, Bethesda, MD 20892-1440, USA.

OBJECTIVE: There has been no modern effort to replicate, further characterize, or quantify the dramatic effects on affect described in controlled studies from the 1960s using bilateral frontal electrodes with an extra-cephalic reference in a mixed group composed primarily of mildly depressed individuals. We performed a comprehensive, quantitative assessment of the effects of bifrontal TDCS on emotion in 21 healthy subjects. METHODS: In a double-blind crossover study, we administered tests of emotional state, affect, emotional decision-making, arousal, and psychomotor functions during sham, anodal, and cathodal TDCS. RESULTS: We found no systematic effects on any measure, despite two subjects who had pronounced mood effects in the predicted direction. There were no adverse events. CONCLUSIONS: In line with some other studies, we found no consistent effects of bifrontal TDCS on measures of emotional function of psychomotor performance. SIGNIFICANCE: These results demonstrate the safety of bilateral anterior frontal TDCS with an extra-cephalic reference, but raise questions about its effectiveness as a modulator of mood and emotional cognition, at least in healthy subjects.

Publication Types: Research Support, N.I.H., Extramural

PMID: 19027357 [PubMed - in process]

Neuropsychologia. 2009 Jan;47(1):212-217. Epub 2008 Aug 3.

Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS).

Boggio PS, Zaghi S, Fregni F.

Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA; Programa de Pós-Graduação em Distúrbios do Desenvolvimento e Núcleo de Neurociências do Comportamento, Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil.

Viewing images of other humans in pain elicits a variety of responses including distress, anxiety, and a sensation that is similar to pain. We aimed to evaluate whether transcranial direct current stimulation (tDCS) could be effective in modulating the emotional aspects of pain as to further explore mechanisms of tDCS in pain relief. Twenty-three healthy subjects rated images with respect to unpleasantness and discomfort/pain (baseline), and then received stimulation with tDCS under four different conditions of stimulation: anodal tDCS of the left primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), occipital cortex (V1); and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. During each stimulation session (after 3min of stimulation), subjects were shown a new set of aversive images and were again asked to rate the images with respect to unpleasantness and discomfort/pain. The results showed that ratings of unpleasantness and discomfort/pain were significantly decreased during DLPFC tDCS only, as compared to baseline and sham tDCS. The other conditions of stimulation (M1 and V1 tDCS) did not result in any significant changes. These results support the notion that DLPFC is a critical area for the emotional processing of pain and also suggests that DLPFC may be a potential target of stimulation for alleviation of pain with a significant emotional-affective component. Our results also suggest that the mechanism of tDCS in modulating emotional pain involve pathways that are independent of those modulating the somatosensory perception of pain.

PMID: 18725237 [PubMed - as supplied by publisher]

J Neurosci. 2008 Dec 24;28(52):14147-55.

Increasing human brain excitability by transcranial high-frequency random noise stimulation.

Terney D, Chaieb L, Moliadze V, Antal A, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, 37075 Göttingen, Germany.

For >20 years, noninvasive transcranial stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS) have been used to induce neuroplastic-like effects in the human cortex, leading to the activity-dependent modification of synaptic transmission. Here, we introduce a novel method of electrical stimulation: transcranial random noise stimulation (tRNS), whereby a random electrical oscillation spectrum is applied over the motor cortex. tRNS induces consistent excitability increases lasting 60 min after stimulation. These effects have been observed in 80 subjects through both physiological measures and behavioral tasks. Higher frequencies (100-640 Hz) appear to be responsible for generating this excitability increase, an effect that may be attributed to the repeated opening of Na(+) channels. In terms of efficacy tRNS appears to possess at least the same therapeutic potential as rTMS/tDCS in diseases such as depression, while furthermore avoiding the constraint of current flow direction sensitivity characteristic of tDCS.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 19109497 [PubMed - in process]

Neurosci Lett. 2008 Dec 12;447(2-3):101-5. Epub 2008 Oct 7.

Differential modulatory effects of transcranial direct current stimulation on a facial expression go-no-go task in males and females.

Boggio PS, Rocha RR, da Silva MT, Fregni F.

Programa de Pós-Graduação em Distúrbios do Desenvolvimento e Núcleo de Neurociências do Comportamento, Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil. boggio@mackenzie.br

The ability to recognize facial expressions has been shown to be different between males and females. Here we aimed to explore further this matter and investigate whether the effects of tDCS applied over the superior temporal cortex differs between males and females during a facial expression go-no-go task. Fourteen healthy subjects were exposed to a facial expression go-no-go task while they received two different conditions of stimulation: anodal tDCS of the left temporal cortex (with cathodal stimulation of the right temporal cortex) and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. During each stimulation session (after 5 min of stimulation), subjects underwent a go-no-go task. The results showed that women had significantly more correct answers when compared to men (p=0.03) that was independent of condition of stimulation and valence of figures. In addition, women made significantly less errors during temporal stimulation when compared to sham stimulation (p=0.009) when responding to sad faces. Similarly, men made significantly more errors during temporal active stimulation as compared with sham stimulation (p=0.004) when responding to sad faces. Our results confirmed the notion that performance to facial expression recognition is increased in females compared with males and that modulation of temporal cortex with tDCS leads to differential effects according to gender.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18926878 [PubMed - in process]

Curr Biol. 2008 Dec 9;18(23):1839-43. Epub 2008 Nov 20.

Frequency-dependent electrical stimulation of the visual cortex.

Kanai R, Chaieb L, Antal A, Walsh V, Paulus W.

Institute of Cognitive Neuroscience & Dept of Psychology, University College London, 17 Queen Square, WC1N 3AR, London, UK. kanair@gmail.com

Noninvasive cortical stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have proved to be powerful tools for establishing causal relationships between brain regions and their functions. In the present study, we demonstrate that a new technique called transcranial alternating current stimulation (tACS) can interact with ongoing rhythmic activities in the visual cortex in a frequency-specific fashion and induce visual experiences (phosphenes). We delivered an oscillatory current over the occipital cortex with tACS. In order to observe interactions with ongoing cortical rhythms, we compared the effects of delivering tACS under conditions of light ("Light" condition) or darkness ("Dark" condition). Stimulation over the occipital cortex induced perception of continuously flickering light most effectively when the beta frequency range was applied in an illuminated room, whereas the most effective stimulation frequency shifted to the alpha frequency range during testing in darkness. Stimulation with theta or gamma frequencies did not produce any visual phenomena. The shift of the effective stimulation frequency indicates that the frequency dependency is caused by interactions with ongoing oscillatory activity in the stimulated cortex. Our results suggest that tACS can be used as a noninvasive tool for establishing a causal link between rhythmic cortical activities and their functions.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 19026538 [PubMed - in process]

Arch Neurol. 2008 Dec;65(12):1571-6.

Transcranial direct current stimulation in stroke recovery.

Schlaug G, Renga V, Nair D.

Neuroimaging and Stroke Recovery Laboratories, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. gschlaug@bidmc.harvard.edu

Transcranial direct current stimulation (TDCS) is an emerging technique of noninvasive brain stimulation that has been found useful in examining cortical function in healthy subjects and in facilitating treatments of various neurologic disorders. A better understanding of adaptive and maladaptive poststroke neuroplasticity and its modulation through noninvasive brain stimulation has opened up experimental treatment options using TDCS for patients recovering from stroke. We review the role of TDCS as a facilitator of stroke recovery, the different modes of TDCS, and the potential mechanisms underlying the neural effects of TDCS.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 19064743 [PubMed - in process]

Expert Rev Med Devices. 2008 Nov;5(6):759-768.

Transcranial direct current stimulation: a noninvasive tool to facilitate stroke recovery.

Schlaug G, Renga V.

Department of Neurology, Neuroimaging and Stroke Recovery Laboratories, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. gschlaug@bidmc.harvard.edu , Department of Neurology, Neuroimaging and Stroke Recovery Laboratories, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Electrical brain stimulation, a technique developed many decades ago and then largely forgotten, has re-emerged recently as a promising tool for experimental neuroscientists, clinical neurologists and psychiatrists in their quest to causally probe cortical representations of sensorimotor and cognitive functions and to facilitate the treatment of various neuropsychiatric disorders. In this regard, a better understanding of adaptive and maladaptive plasticity in natural stroke recovery over the last decade and the idea that brain polarization may modulate neuroplasticity has led to the use of transcranial direct current stimulation (tDCS) as a potential enhancer of natural stroke recovery. We will review tDCS's successful utilization in pilot and proof-of-principle stroke recovery studies, the different modes of tDCS currently in use, and the potential mechanisms underlying the neural effects of tDCS.

PMID: 19025351 [PubMed - as supplied by publisher]

Novel targets for antidepressant therapies.

Holtzheimer PE, Nemeroff CB.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle Northeast, Suite 4000, Atlanta, GA 30322, USA. pholtzh@emory.edu

Most depressed patients fail to achieve remission despite adequate antidepressant monotherapy, and a substantial minority show minimal improvement despite optimal and aggressive therapy. However, major advances have taken place in elucidating the neurobiology of depression, and several novel targets for antidepressant therapy have emerged. Three primary approaches are currently being taken: 1) optimizing the pharmacologic modulation of monoaminergic neurotransmission, 2) developing medications that target neurotransmitter systems other than the monoamines, and 3) directly modulating neuronal activity via focal brain stimulation. We review novel therapeutic targets for developing improved antidepressant therapies, including triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, dopamine receptor agonists, corticotropin-releasing factor-1 receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, N-methyl-D-aspartate receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Developments in therapeutic focal brain stimulation include vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, and deep brain stimulation.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 18980729 [PubMed - in process]

J Neurol Neurosurg Psychiatry. 2008 Oct 31. [Epub ahead of print]

Temporal cortex DC stimulation enhances performance on a visual recognition memory task in Alzheimer's disease.

Boggio PS, Khoury LP, Martins DC, Martins OE, Macedo EC, Fregni F.

Mackenzie Presbyterian University, Brazil.

Several studies have reported that transcranial direct current stimulation (tDCS), a non-invasive method of neuromodulation, enhances some aspects of working memory in healthy and Parkinson's disease subjects. The aim of this study was to investigate the impact of anodal tDCS on recognition memory, working memory and selective attention in Alzheimer's disease (AS). Ten patients with diagnosis of AD received three sessions of anodal tDCS (left dorsolateral prefrontal cortex, left temporal cortex and sham stimulation) with an intensity of 2mA for 30 minutes. Sessions were performed in different days in a randomized order. The following tests were assessed during stimulation: Stroop, Digit Span and a Visual Recognition Memory task (VRM). The results showed a significant effect of stimulation condition on VRM (p=0.0085) and post hoc analysis showed an improvement after temporal (p=0.01) and prefrontal (p=0.01) tDCS as compared with sham stimulation. There were no significant changes in attention as indexed by Stroop task performance. To our knowledge, this is the first trial showing that tDCS can enhance a component of recognition memory. We discuss the potential mechanisms of action and the implications of these results.

PMID: 18977813 [PubMed - as supplied by publisher]

Eur J Neurosci. 2008 Oct;28(8):1667-73.

Modulating activity in the motor cortex affects performance for the two hands differently depending upon which hemisphere is stimulated.

Vines BW, Nair D, Schlaug G.

Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

We modulated neural excitability in the human motor cortex to investigate behavioral effects for both hands. In a previous study, we showed that decreasing excitability in the dominant motor cortex led to a decline in performance for the contralateral hand and an improvement for the ipsilateral hand; increasing excitability produced the opposite effects. Research suggests that the ipsilateral effects were mediated by interhemispheric inhibition. Physiological evidence points to an asymmetry in interhemispheric inhibition between the primary motor cortices, with stronger inhibitory projections coming from the dominant motor cortex. In the present study, we examined whether there is a hemispheric asymmetry in the effects on performance when modulating excitability in the motor cortex. Anodal and cathodal transcranial direct current stimulation were applied to the motor cortex of 17 participants, targeting the non-dominant hemisphere on one day and the dominant hemisphere on another day, along with one sham session. Participants performed a finger-sequence coordination task with each hand before and after stimulation. The dependent variable was calculated as the percentage of change in the number of correct keystrokes. We found that the effects of transcranial direct current stimulation depended upon which hemisphere was stimulated; modulating excitability in the dominant motor cortex significantly affected performance for the contralateral and ipsilateral hands, whereas modulating excitability in the non-dominant motor cortex only had a significant impact for the contralateral hand. These results provide evidence for a hemispheric asymmetry in the ipsilateral effects of modulating excitability in the motor cortex and may be important for clinical research on motor recovery.

PMID: 18973584 [PubMed - in process]

BMC Neurosci. 2008 Oct 28;9:103.

Dual-hemisphere tDCS facilitates greater improvements for healthy subjects' non-dominant hand compared to uni-hemisphere stimulation.

Vines BW, Cerruti C, Schlaug G.

Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. bradley.vines@gmail.com

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive technique that has been found to modulate the excitability of neurons in the brain. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal tDCS increases excitability, whereas cathodal tDCS decreases excitability. Research has shown that applying anodal tDCS to the non-dominant motor cortex can improve motor performance for the non-dominant hand, presumably by means of changes in synaptic plasticity between neurons. Our previous studies also suggest that applying cathodal tDCS over the dominant motor cortex can improve performance for the non-dominant hand; this effect may result from modulating inhibitory projections (interhemispheric inhibition) between the motor cortices of the two hemispheres. We hypothesized that stimultaneously applying cathodal tDCS over the dominant motor cortex and anodal tDCS over the non-dominant motor cortex would have a greater effect on finger sequence performance for the non-dominant hand, compared to stimulating only the non-dominant motor cortex. Sixteen right-handed participants underwent three stimulation conditions: 1) dual-hemisphere - with anodal tDCS over the non-dominant motor cortex, and cathodal tDCS over the dominant motor cortex, 2) uni-hemisphere - with anodal tDCS over the non-dominant motor cortex, and 3) sham tDCS. Participants performed a finger-sequencing task with the non-dominant hand before and after each stimulation. The dependent variable was the percentage of change in performance, comparing pre- and post-tDCS scores. RESULTS: A repeated measures ANOVA yielded a significant effect of tDCS condition (F(2,30) = 4.468, p = .037). Post-hoc analyses revealed that dual-hemisphere stimulation improved performance significantly more than both uni-hemisphere (p = .021) and sham stimulation (p = .041). CONCLUSION: We propose that simultaneously applying cathodal tDCS over the dominant motor cortex and anodal tDCS over the non-dominant motor cortex produced an additive effect, which facilitated motor performance in the non-dominant hand. These findings are relevant to motor skill learning and to research studies of motor recovery after stroke.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 18957075 [PubMed - in process]

Neurosci Lett. 2008 Dec 26;448(2):171-4. Epub 2008 Oct 21.

Improvement of visual scanning after DC brain polarization of parietal cortex in stroke patients with spatial neglect.

Ko MH, Han SH, Park SH, Seo JH, Kim YH.

Department of Physical Medicine and Rehabilitation, Institute for Medical Sciences & Research Institute of Clinical Medicine, Chonbuk National University Medical School, 634-18 Keumam-dong, Dukjin-ku, Jeonju, Jeonbuk 561-712, Republic of Korea.

Previous studies have demonstrated that transcranial direct current (DC) brain polarization can modulate cortical excitability in the human brain. We investigated the effect of anodal DC brain polarization of right parietal cortex on visuospatial scanning in subacute stroke patients with spatial neglect. The patients underwent two neglect tests - figure cancellation and line bisection - before and immediately after anodal DC or sham in a double-blind protocol. Anodal DC was applied to the scalp over the right posterior parietal cortex (PPC) with an intensity of 2.0mA for 20min. Anodal DC brain polarization, but not sham, led to significant improvement in the both neglect tests. These results document a beneficial effect of DC brain polarization on neglect.

PMID: 18952147 [PubMed - in process]

Neurosci Lett. 2008 Dec 12;447(2-3):101-5. Epub 2008 Oct 7.

Differential modulatory effects of transcranial direct current stimulation on a facial expression go-no-go task in males and females.

Boggio PS, Rocha RR, da Silva MT, Fregni F.

The ability to recognize facial expressions has been shown to be different between males and females. Here we aimed to explore further this matter and investigate whether the effects of tDCS applied over the superior temporal cortex differs between males and females during a facial expression go-no-go task. Fourteen healthy subjects were exposed to a facial expression go-no-go task while they received two different conditions of stimulation: anodal tDCS of the left temporal cortex (with cathodal stimulation of the right temporal cortex) and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. During each stimulation session (after 5min of stimulation), subjects underwent a go-no-go task. The results showed that women had significantly more correct answers when compared to men (p=0.03) that was independent of condition of stimulation and valence of figures. In addition, women made significantly less errors during temporal stimulation when compared to sham stimulation (p=0.009) when responding to sad faces. Similarly, men made significantly more errors during temporal active stimulation as compared with sham stimulation (p=0.004) when responding to sad faces. Our results confirmed the notion that performance to facial expression recognition is increased in females compared with males and that modulation of temporal cortex with tDCS leads to differential effects according to gender.

PMID: 18926878 [PubMed - in process]

J Cogn Neurosci. 2008 Oct 14. [Epub ahead of print]

Anodal Transcranial Direct Current Stimulation of the Prefrontal Cortex Enhances Complex Verbal Associative Thought.

Cerruti C, Schlaug G.

1Harvard Graduate School of Education, 2Beth Israel Deaconess Medical Center and Harvard Medical School.

Abstract The remote associates test (RAT) is a complex verbal task with associations to both creative thought and general intelligence. RAT problems require not only lateral associations and the internal production of many words but a convergent focus on a single answer. Complex problem-solving of this sort may thus require both substantial verbal processing and strong executive function capacities. Previous studies have provided evidence that verbal task performance can be enhanced by noninvasive transcranial direct current stimulation (tDCS). tDCS modulates excitability of neural tissue depending on the polarity of the current. The after-effects of this modulation may have effects on task performance if the task examined draws on the modulated region. Studies of verbal cognition have focused largely on the left dorsolateral prefrontal cortex (F3 of the 10-20 EEG system) as a region of interest. We planned to assess whether modulating excitability at F3 could affect complex verbal abilities. In Experiment 1 (anodal, cathodal, or sham stimulation over F3 with the reference electrode over the contralateral supraorbital region), we found a significant overall effect of stimulation condition on RAT performance. Post hoc tests showed an increase in performance after anodal stimulation (1 mA) compared to sham (p = .025) and to cathodal stimulation (p = .038). In Experiment 2 (either anodal stimulation at F3 or separately at its homologue F4), we replicated the anodal effect of the first study, but also showed that anodal stimulation of F4 had no effect on RAT performance. These data provide evidence that anodal stimulation of the left dorsolateral prefrontal cortex can improve performance on a complex verbal problem-solving task believed to require significant executive function capacity.

PMID: 18855556 [PubMed - as supplied by publisher]

J Physiol. 2008 Dec 1;586(Pt 23):5717-25. Epub 2008 Oct 9.

A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS.

Cheeran B, Talelli P, Mori F, Koch G, Suppa A, Edwards M, Houlden H, Bhatia K, Greenwood R, Rothwell JC.

Institute of Neurology, Queen Square, London WC1N 3BG, UK. b.cheeran@ion.ucl.ac.uk.

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation; and homeostatic plasticity in the TDCS/1 Hz rTMS model. The response of Met allele carriers differed significantly in all protocols compared with the response of Val66Val individuals. We suggest that this is due to the effect of BNDF on the susceptibility of synapses to undergo LTP/LTD. The circuits tested here are implicated in the pathophysiology of movement disorders such as dystonia and are being assessed as potential new targets in the treatment of stroke. Thus the polymorphism may be one factor that influences the natural response of the brain to injury and disease.

PMID: 18845611 [PubMed - in process]

Pain Med. 2008 Sep 24. [Epub ahead of print]

Modulatory Effects of Transcranial Direct Current Stimulation on Laser-Evoked Potentials.

Csifcsak G, Antal A, Hillers F, Levold M, Bachmann CG, Happe S, Nitsche MA, Ellrich J, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Robert Koch Strasse 40, 37075 Göttingen, Germany.

ABSTRACT Objective. Invasive stimulation of the motor cortex has been used for years to alleviate chronic intractable pain in humans. In our study, we have investigated the effect of transcranial direct current stimulation (tDCS), a noninvasive stimulation method, for manipulating the excitability of cortical motor areas on laser evoked potentials (LEP) and acute pain perception. Designs and Settings. The amplitude of the N1, N2, and P2 LEP components of 10 healthy volunteers were evaluated prior to and following anodal, cathodal, and sham stimulation of the primary motor cortex. In a separate experiment subjective, pain rating scores of 16 healthy subjects in two perceptual categories (warm sensation, mild pain) were also analyzed. Results. Cathodal tDCS significantly reduced the amplitude of N2 and P2 components compared with anodal or sham stimulation. However, neither of the tDCS types modified significantly the laser energy values necessary to induce moderate pain. In a separate experiment, cathodal stimulation significantly diminished mild pain sensation only when laser-stimulating the hand contralateral to the side of tDCS, while anodal stimulation modified warm sensation. Conclusions. The possible underlying mechanisms of our findings in view of recent neuroimaging studies are discussed. To our knowledge this study is the first to demonstrate the mild antinociceptive effect of tDCS over the primary motor cortex in healthy volunteers.

PMID: 18823388 [PubMed - as supplied by publisher]

Magn Reson Med. 2008 Oct;60(4):782-9.

Myoinositol content in the human brain is modified by transcranial direct current stimulation in a matter of minutes: a 1H-MRS study.

Rango M, Cogiamanian F, Marceglia S, Barberis B, Arighi A, Biondetti P, Priori A.

Department of Neurological Sciences, University of Milan, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy.

Brain content of myoinositol (mI) has been shown to be altered in several neuropsychiatric conditions. Likewise, various forms of electric currents have been applied to the human brain for therapeutic purposes in neuropsychiatric diseases. In this study we aimed to depict the effects of low-power transcranial direct current stimulation (tDCS) on brain mI by proton magnetic resonance spectroscopy ((1)H-MRS). We studied two groups of five healthy subjects by (1)H-MRS: the first group was studied before and after both anodal and sham (placebo) tDCS over the right frontal lobe, and the second group was studied at the same intervals without undergoing either sham or anodal tDCS. Anodal tDCS induced a significant increase of mI content at 30 min after stimulation offset (141.5 +/- 16.7%, P < 0.001) below the stimulating electrode but not in distant regions, such as the visual cortex, whereas sham tDCS failed to induce changes in mI. Neither N-acetyl-aspartate (NAA) nor the other metabolite contents changed after anodal or sham stimulation. (1)H-MRS represents a powerful tool to follow the regional effects of tDCS on brain mI and, possibly, on the related phosphoinositide system. (c) 2008 Wiley-Liss, Inc.

PMID: 18816828 [PubMed - in process]

Mov Disord. 2008 Nov 15;23(15):2259-61.

Transcranial direct current stimulation in two patients with Tourette syndrome.

Mrakic-Sposta S, Marceglia S, Mameli F, Dilena R, Tadini L, Priori A.

Clinical Center for Neuronanotechnology, and Neurostimulation, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Department of Neurological Sciences, University of Milan, Italy.

PMID: 18785641 [PubMed - in process]

Curr Treat Options Neurol. 2008 Sep;10(5):377-85.

Transcranial direct current stimulation for major depression: a general system for quantifying transcranial electrotherapy dosage.

Bikson M, Bulow P, Stiller JW, Datta A, Battaglia F, Karnup SV, Postolache TT.

Teodor T. Postolache, MD Mood and Anxiety Program, University of Maryland School of Medicine, 685 West Baltimore, MSTF Suite 930, Baltimore, MD 21201, USA. Tpostola@psych.umaryland.edu.

There has been a recent resurgence of interest in therapeutic modalities using transcranial weak electrical stimulation through scalp electrodes, such as trans-cranial direct current stimulation (tDCS), as a means of experimentally modifying and studying brain function and possibly treating psychiatric conditions. A range of electrotherapy paradigms have been investigated, but no consistent method has been indicated for reporting reproducible stimulation "dosage." Anecdotal reports, case studies, and limited clinical trials with small numbers suggest that tDCS may be effective in treating some patients with depression, but methods for selecting the optimal stimulation parameters ("dosage") are not clear, and there is no conclusive indication that tDCS is an effective treatment for depression. Larger, controlled studies are necessary to determine its safety and efficacy in a clinical setting. If tDCS can be established as an effective treatment for depression, it would represent a particularly attractive electrotherapy option, as it is a relatively benign and affordable treatment modality. An accurate system for describing reproducible treatment parameters is essential so that further studies can yield evidence-based guidelines for the clinical use of transcranial current stimulation. Development of appropriate parameters requires a biophysical understanding of how electrotherapy affects brain function and should include different paradigms for different clinical applications. As with any dosage guidelines, such a system does not supersede physician judgment on safety.

PMID: 18782510 [PubMed - in process]

Clin Neurophysiol. 2008 Oct;119(10):2179-84. Epub 2008 Aug 31.

Principles of therapeutic use of transcranial and epidural cortical stimulation.

Lefaucheur JP.

Department of Physiology, Hôpital Henri Mondor, Assistance Publique - Hôpitaux, de Paris, 94010 Créteil, France. jean-pascal.lefaucheur@hmn.ap-hop-paris.fr

Among the alternatives to drugs in the treatment of neurological and psychiatric disorders, neuromodulation techniques, including brain stimulation, have been used increasingly this past decade. Cortical targets are especially appealing, because they are easily accessible by noninvasive or invasive methods. Applicable techniques include repetitive transcranial magnetic stimulation (rTMS), transcranial electrical stimulation using pulsed or direct current, and epidural cortical stimulation (ECS) with surgically implanted electrodes. In contrast to deep brain stimulation in movement disorders or electroconvulsive therapy in depression, the efficacy of cortical stimulation to treat neurological or psychiatric disorders has not been yet clearly demonstrated. However, encouraging results have been reported in neuropathic pain (for ECS) and depression (for rTMS). In this review, we will consider some principles and mechanisms of action of these methods. First, it must be noted that fibers of intracortical or cortico-subcortical networks are more prone to be activated by the stimulation than cell bodies of local cortical neurons. Hence, the site(s) of action may be distant from the site of stimulation. In addition, various parameters of stimulation (such as stimulation frequency, intensity, or electrode polarity) and the configuration of the induced electrical field greatly influence the nature of the recruited circuits, and therefore, the overall efficacy. Finally, clinical changes may be delayed and prolonged beyond the time of stimulation, complicating programming algorithms in the case of implanted stimulation device. All these features need to be taken into account when considering cortical stimulation as a method of treatment.

PMID: 18762449 [PubMed - in process]

Neuropsychologia. 2008 Aug 3. [Epub ahead of print]

Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS).

Boggio PS, Zaghi S, Fregni F.

PMID: 18725237 [PubMed - as supplied by publisher]

Eur J Neurol. 2008 Oct;15(10):1124-30. Epub 2008 Aug 20.

Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers.

Boggio PS, Zaghi S, Lopes M, Fregni F.

Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

BACKGROUND AND PURPOSE: We aimed to evaluate whether transcranial direct current stimulation (tDCS) is effective in modulating sensory and pain perception thresholds in healthy subjects as to further explore mechanisms of tDCS in pain relief. METHODS: Twenty healthy subjects received stimulation with tDCS under four different conditions of stimulation: anodal tDCS of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), occipital cortex (V1), and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. Perception threshold and pain threshold to peripheral electrical stimulation of the right index finger were evaluated by a blinded rater. RESULTS: The results showed a significant effect of the interaction time versus stimulation condition for perception (P = 0.046) and pain threshold (P = 0.015). Post hoc comparisons revealed that anodal stimulation of M1 increased both perception (P < 0.001, threshold increase of 6.5%) and pain (P = 0.001, threshold increase of 8.3%) thresholds significantly, whilst stimulation of the DLPFC increased pain threshold only (P = 0.046, threshold increase of 10.0%). There were no significant effects for occipital or sham stimulation. CONCLUSIONS: These results show that both M1 and DLFPC anodal tDCS can be used to modulate pain thresholds in healthy subjects; thus, the mechanism of tDCS in modulating pain involves pathways that are independent of abnormal pain-related neural activity.

PMID: 18717717 [PubMed - in process]

Mt Sinai J Med. 2008 May-Jun;75(3):263-75.

Neurostimulatory therapeutics in management of treatment-resistant depression with focus on deep brain stimulation.

Dumitriu D, Collins K, Alterman R, Mathew SJ.

Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA. dani.dumitriu@mssm.edu

Treatment-resistant depression continues to pose a major medical challenge, as up to one-third of patients with major depressive disorder fail to have an adequate response to standard pharmacotherapies. An improved understanding of the complex circuitry underlying depressive disorders has fostered an explosion in the development of new, nonpharmacological approaches. Each of these treatments seeks to restore normal brain activity via electrical or magnetic stimulation. In this article, the authors discuss the ongoing evolution of neurostimulatory treatments for treatment-resistant depression, reviewing the methods, efficacy, and current research on electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, focal electrically administered stimulated seizure therapy, transcranial direct current stimulation, chronic epidural cortical stimulation, and vagus nerve stimulation. Special attention is given to deep brain stimulation, the most focally targeted approach. The history, purported mechanisms of action, and current research are outlined in detail. Although deep brain stimulation is the most invasive of the neurostimulatory treatments developed to date, it may hold significant promise in alleviating symptoms and improving the quality of life for patients with the most severe and disabling mood disorders.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 18704979 [PubMed - in process]

Behav Brain Funct. 2008 Aug 6;4:34.

Brain stimulation modulates driving behavior.

Beeli G, Koeneke S, Gasser K, Jancke L.

University of Zurich, Institute of Psychology, Division Neuropsychology, Switzerland. s.koeneke@psychologie.uzh.ch.

ABSTRACT: BACKGROUND: Driving a car is a complex task requiring coordinated functioning of distributed brain regions. Controlled and safe driving depends on the integrity of the dorsolateral prefrontal cortex (DLPFC), a brain region, which has been shown to mature in late adolescence. METHODS: In this study, driving performance of twenty-four male participants was tested in a high-end driving simulator before and after the application of transcranial direct current stimulation (tDCS) for 15 minutes over the left or right DLPFC. RESULTS: We show that external modulation of both, the left and the right, DLPFC directly influences driving behavior. Excitation of the DLPFC (by applying anodal tDCS) leads to a more careful driving style in virtual scenarios without the participants noticing changes in their behavior. CONCLUSION: This study is one of the first to prove that external stimulation of a specific brain area can influence a multi-part behavior in a very complex and everyday-life situation, therefore breaking new ground for therapy at a neural level.

PMID: 18684333 [PubMed - in process]

Neuropsychologia. 2008 Nov;46(13):3157-61. Epub 2008 Jul 18.

Prior state of cortical activity influences subsequent practicing of a visuomotor coordination task.

Antal A, Begemeier S, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, 37075 Göttingen, Germany. AAntal@gwdg.de

According to the Bienenstock-Cooper-Munro (BCM) rule, a low overall cortical activity level is suggested to enhance synaptic strength of active neuronal connections, while a high level of activity should diminish it. Whereas the relevance of this mechanism for neuroplasticity in humans has been ascertained on the neurophysiological level, its functional relevance remains unclear so far. The aim of this study was to explore the impact of the pre-performance cortical activity and excitability state on subsequent performance practicing a visuomotor paradigm. Excitability of the primary motor cortex (M1) or the visual area MT/V5 was modulated by 10 min of anodal or cathodal transcranial direct current stimulation (tDCS) in healthy subjects before practice of a visuomotor tracking task. The percentage of correct tracking movements increased significantly in the early phase of practice after both anodal and cathodal stimulations over both cortical areas compared to the no-stimulation condition showing a behavioral improvement at the beginning of the practice process. Stimulation of a control cortical area did not result in significant difference with regard to the practice between cathodal, anodal and sham stimulation. However, the steepness of improvement between the different time-points was significantly increased only at the beginning of the task, and was reduced at the 5'-10' (V5) and 10'-15' (M1) time-window with regard to anodal stimulation, compared to the 'no-stimulation' condition. With regard to cathodal stimulation, the steepness of improvement was significantly lower at the 10'-15' time-window (M1) compared to the 'no-stimulation' condition. The results of our study underline the principal functional relevance of the BCM rule for the efficacy of visuomotor practice, but imply that also other mechanisms have to be taken into account.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18680756 [PubMed - in process]

Behav Brain Funct. 2008 Aug 4;4:33.

Modulating presence and impulsiveness by external stimulation of the brain.

Beeli G, Casutt G, Baumgartner T, Jäncke L.

Institute of Psychology, Department of Neuropsychology, University of Zürich, Switzerland. g.beeli@psychologie.uzh.ch.

ABSTRACT: BACKGROUND: "The feeling of being there" is one possible way to describe the phenomenon of feeling present in a virtual environment and to act as if this environment is real. One brain area, which is hypothesized to be critically involved in modulating this feeling (also called presence) is the dorso-lateral prefrontal cortex (dlPFC), an area also associated with the control of impulsive behavior. METHODS: In our experiment we applied transcranial direct current stimulation (tDCS) to the right dlPFC in order to modulate the experience of presence while watching a virtual roller coaster ride. During the ride we also registered electro-dermal activity. Subjects also performed a test measuring impulsiveness and answered a questionnaire about their presence feeling while they were exposed to the virtual roller coaster scenario. RESULTS: Application of cathodal tDCS to the right dlPFC while subjects were exposed to a virtual roller coaster scenario modulates the electrodermal response to the virtual reality stimulus. In addition, measures reflecting impulsiveness were also modulated by application of cathodal tDCS to the right dlPFC. CONCLUSION: Modulating the activation with the right dlPFC results in substantial changes in responses of the vegetative nervous system and changed impulsiveness. The effects can be explained by theories discussing the top-down influence of the right dlPFC on the "impulsive system".

PMID: 18680573 [PubMed - in process]

Neurosci Lett. 2008 Aug 22;441(2):153-7. Epub 2008 Jun 19.

Muscle-specific variations in use-dependent crossed-facilitation of corticospinal pathways mediated by transcranial direct current (DC) stimulation.

Carson RG, Kennedy NC, Linden MA, Britton L.

School of Psychology, Queen's University Belfast, Belfast, Northern Ireland, UK. r.g.carson@qub.ac.uk

The tendency for contractions of muscles in the upper limb to give rise to increases in the excitability of corticospinal projections to the homologous muscles of the opposite limb is well known. Although the suppression of this tendency is integral to tasks of daily living, its exploitation may prove to be critical in the rehabilitation of acquired hemiplegias. Transcranial direct current (DC) stimulation induces changes in cortical excitability that outlast the period of application. We present evidence that changes in the reactivity of the corticospinal pathway induced by DC stimulation of the motor cortex interact systematically with those brought about by contraction of the muscles of the ipsilateral limb. During the application of flexion torques (up to 50% of maximum) applied at the left wrist, motor evoked potentials (MEPs) were evoked in the quiescent muscles of the right arm by magnetic stimulation of the left motor cortex (M1). The MEPs were obtained prior to and following 10 min of anodal, cathodal or sham DC stimulation of left M1. Cathodal stimulation counteracted increases in the crossed-facilitation of projections to the (right) wrist flexors that otherwise occurred as a result of repeated flexion contractions at the left wrist. In addition, cathodal stimulation markedly decreased the excitability of corticospinal projections to the wrist extensors of the right limb. Thus changes in corticospinal excitability induced by DC stimulation can be shaped (i.e. differentiated by muscle group) by focal contractions of muscles in the limb ipsilateral to the site of stimulation.

PMID: 18582535 [PubMed - indexed for MEDLINE]

Neurology. 2008 Aug 12;71(7):493-8. Epub 2008 Jun 4.

Transcranial direct current stimulation improves recognition memory in Alzheimer disease.

Ferrucci R, Mameli F, Guidi I, Mrakic-Sposta S, Vergari M, Marceglia S, Cogiamanian F, Barbieri S, Scarpini E, Priori A.

Department of Neurological Sciences, University of Milan, Ospedale Maggiore Policlinico, Padiglione Ponti, V F Sforza 35, Milan 20122, Italy.

OBJECTIVE: To evaluate the cognitive effect of transcranial direct current stimulation (tDCS) over the temporoparietal areas in patients with Alzheimer disease (AD). METHODS: In 10 patients with probable AD, we delivered anodal tDCS (AtDCS), cathodal tDCS (CtDCS), and sham tDCS (StDCS) over the temporoparietal areas in three sessions. In each session recognition memory and visual attention were tested at baseline (prestimulation) and 30 minutes after tDCS ended (poststimulation). RESULTS: After AtDCS, accuracy of the word recognition memory task increased (prestimulation: 15.5 +/- 0.9, poststimulation: 17.9 +/- 0.8, p = 0.0068) whereas after CtDCS it decreased (15.8 +/- 0.6 vs 13.2 +/- 0.9, p = 0.011) and after StDCS it remained unchanged (16.3 +/- 0.7 vs 16.0 +/- 1.0, p = 0.75). tDCS left the visual attention-reaction times unchanged. CONCLUSION: Transcranial direct current stimulation (tDCS) delivered over the temporoparietal areas can specifically affect a recognition memory performance in patients with Alzheimer disease (AD). Because tDCS is simple, safe and inexpensive, our finding prompts studies using repeated tDCS, in conjunction with other therapeutic interventions for treating patients with AD.

Publication Types: Case Reports

PMID: 18525028 [PubMed - indexed for MEDLINE]

Fortschr Neurol Psychiatr. 2008 Jun;76(6):354-60.

[Modern neurophysiological strategies in the rehabilitation of impaired hand function following stroke]

[Article in German]

Nowak DA, Grefkes C, Fink GR.

Neurologische Klinik und Poliklinik, Klinikum der Universität zu Köln. dennis.nowak@uk-koeln.de

Modern neurophysiological brain stimulation techniques, such as transcranial magnetic stimulation and direct current stimulation, are powerful tools to inhibit or facilitate cortical excitability for several minutes after stimulation depending on the stimulation parameters used. Purposeful modulation of cortical excitability may induce plastic changes within the cortical network of sensorimotor areas, and has the power to improve the function of the affected hand after stroke. The therapeutic use of transcranial brain stimulation techniques is based on the concept of interhemispheric competition. Here we give an overview of the use of repetitive transcranial magnetic stimulation and direct current stimulation in the rehabilitation of impaired hand function after stroke.

Publication Types: English Abstract Review

PMID: 18512186 [PubMed - indexed for MEDLINE]

Perception. 2008;37(3):367-74.

Transcranial direct current stimulation and visual perception.

Antal A, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, Robert Koch Strasse 40, D 37075 Göttingen, Germany. Aantal@gwdg.de

Membrane potentials and spike sequences represent the basic modes of cerebral information processing. Both can be externally modulated in humans by quite specific techniques: transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS). These methods induce reversible circumscribed cortical excitability changes, either excitatory or inhibitory, outlasting stimulation in time. Experimental pharmacological interventions may selectively enhance the duration of the aftereffects. Whereas rTMS induces externally triggered changes in the neuronal spiking pattern and interrupts or excites neuronal firing in a spatially and temporally restricted fashion, tDCS modulates the spontaneous firing rates of neurons by changing resting-membrane potential. The easiest and most common way of evaluating the cortical excitability changes is by applying TMS to the motor cortex, since it allows reproducible quantification through the motor-evoked potential. Threshold determinations at the visual cortex or psychophysical methods usually require repeated and longer measurements and thus more time for each data set. Here, results derived from the use of tDCS in visual perception, including contrast as well as motion detection and visuo-motor coordination and learning, are summarised. It is demonstrated that visual functions can be transiently altered by tDCS, as has been shown for the motor cortex previously. Up- and down-regulation of different cortical areas by tDCS is likely to open a new branch in the field of visual psychophysics.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18491714 [PubMed - indexed for MEDLINE]

Phys Med Biol. 2008 Jun 7;53(11):N219-25. Epub 2008 May 19.

Determination of optimal electrode positions for transcranial direct current stimulation (tDCS).

Im CH, Jung HH, Choi JD, Lee SY, Jung KY.

Department of Biomedical Engineering, Yonsei University, Wonju 220-710, Korea. ich@yonsei.ac.kr

The present study introduces a new approach to determining optimal electrode positions in transcranial direct current stimulation (tDCS). Electric field and 3D conduction current density were analyzed using 3D finite element method (FEM) formulated for a dc conduction problem. The electrode positions for minimal current injection were optimized by changing the Cartesian coordinate system into the spherical coordinate system and applying the (2+6) evolution strategy (ES) algorithm. Preliminary simulation studies applied to a standard three-layer head model demonstrated that the proposed approach is promising in enhancing the performance of tDCS.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18490807 [PubMed - indexed for MEDLINE]

Neuropsychologia. 2008;46(8):2122-8. Epub 2008 Feb 29.

Limited impact of homeostatic plasticity on motor learning in humans.

Kuo MF, Unger M, Liebetanz D, Lang N, Tergau F, Paulus W, Nitsche MA.

Department of Clinical Neurophysiology, University of Goettingen, Robert Koch Str. 40, 37099 Goettingen, Germany.

Neuroplasticity is the adaptive modification of network connectivity in response to environmental demands and has been identified as a major physiological correlate of learning. Since unrestricted neuroplastic modifications of network connectivity will result in a de-stabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e. high previous activity enhances the threshold for synaptic strengthening and vice versa. However, the relevance of metaplasticity for actual learning processes has not been tested so far. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, and a reaction time task (RTT) by transcranial direct current stimulation (tDCS). If homeostatic rules apply, excitability-diminishing cathodal tDCS should improve subsequent motor learning, especially if combined with the partial NMDA receptor-agonist d-cycloserine, which selectively enhances efficacy of active receptors, while excitability-enhancing anodal tDCS should reduce it. Only the results for anodal tDCS, when combined with d-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has a limited influence on implicit sequential motor learning.

Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't

PMID: 18394661 [PubMed - indexed for MEDLINE]

Neurotherapeutics. 2008 Apr;5(2):345-61.

Noninvasive brain stimulation for Parkinson's disease and dystonia.

Wu AD, Fregni F, Simon DK, Deblieck C, Pascual-Leone A.

Department of Neurology, University of California, Los Angeles, California 90095, USA.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising noninvasive cortical stimulation methods for adjunctive treatment of movement disorders. They avoid surgical risks and provide theoretical advantages of specific neural circuit neuromodulation. Neuromodulatory effects depend on extrinsic stimulation factors (cortical target, frequency, intensity, duration, number of sessions), intrinsic patient factors (disease process, individual variability and symptoms, state of medication treatment), and outcome measures. Most studies to date have shown beneficial effects of rTMS or tDCS on clinical symptoms in Parkinson's disease (PD) and support the notion of spatial specificity to the effects on motor and nonmotor symptoms. Stimulation parameters have varied widely, however, and some studies are poorly controlled. Studies of rTMS or tDCS in dystonia have provided abundant data on physiology, but few on clinical effects. Multiple mechanisms likely contribute to the clinical effects of rTMS and tDCS in movement disorders, including normalization of cortical excitability, rebalancing of distributed neural network activity, and induction of dopamine release. It remains unclear how to individually adjust rTMS or tDCS factors for the most beneficial effects on symptoms of PD or dystonia. Nonetheless, the noninvasive nature, minimal side effects, positive effects in preliminary clinical studies, and increasing evidence for rational mechanisms make rTMS and tDCS attractive for ongoing investigation.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

PMID: 18394576 [PubMed - indexed for MEDLINE]

Methods. 2008 Apr;44(4):329-37.

Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction.

Sparing R, Mottaghy FM.

Institute of Neuroscience and Biophysics, Research Centre Juelich, Juelich, Germany. r.sparing@fz-juelich.de

Noninvasive stimulation of the brain by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) has driven important discoveries in the field of human memory functions. Stand-alone or in combination with other brain mapping techniques noninvasive brain stimulation can assess issues such as location and timing of brain activity, connectivity and plasticity of neural circuits and functional relevance of a circumscribed brain area to a given cognitive task. In this emerging field, major advances in technology have been made in a relatively short period. New stimulation protocols and, especially, the progress in the application of tDCS have made it possible to obtain longer and much clearer inhibitory or facilitatory effects even after the stimulation has ceased. In this introductory review, we outline the basic principles, discuss technical limitations and describe how noninvasive brain stimulation can be used to study human memory functions in vivo. Though improvement of cognitive functions through noninvasive brain stimulation is promising, it still remains an exciting challenge to extend the use of TMS and tDCS from research tools in neuroscience to the treatment of neurological and psychiatric patients.

Publication Types: Review

PMID: 18374276 [PubMed - indexed for MEDLINE]

Cereb Cortex. 2008 Nov;18(11):2701-5. Epub 2008 Mar 27.

Homeostatic metaplasticity of the motor cortex is altered during headache-free intervals in migraine with aura.

Antal A, Lang N, Boros K, Nitsche M, Siebner HR, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, 37073 Göttingen, Germany. aantal@gwdg.de

Preconditioning of the human primary motor cortex (M1) with transcranial direct current stimulation (tDCS) can shape the magnitude and direction of excitability changes induced by a subsequent session of repetitive transcranial magnetic stimulation (rTMS). Here, we examined this form of metaplasticity in migraine patients with visual aura and healthy controls. In both groups, facilitatory preconditioning of left M1 with anodal tDCS increased the mean amplitudes of motor-evoked potentials (MEPs) elicited in the contralateral hand, whereas inhibitory preconditioning with cathodal tDCS produced a decrease in amplitude. Following cathodal tDCS, a short train of low-intensity 5-Hz rTMS antagonized the suppression of the mean MEP amplitude in both groups. In contrast, the homeostatic effects of 5-Hz rTMS differed between groups when rTMS was given after anodal tDCS. In controls 5-Hz rTMS induced a marked decrease in MEP amplitudes, whereas in migraineurs rTMS induced only a modest decrease in MEP amplitudes, which were still facilitated after rTMS when compared with baseline amplitudes. These findings indicate that short-term homeostatic plasticity is altered in patients with visual aura between the attacks.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18372292 [PubMed - in process]

J Pain Symptom Manage. 2008 Jul;36(1):79-91. Epub 2008 Mar 20.

Pergolide increases the efficacy of cathodal direct current stimulation to reduce the amplitude of laser-evoked potentials in humans.

Terney D, Bergmann I, Poreisz C, Chaieb L, Boros K, Nitsche MA, Paulus W, Antal A.

Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany. daniellaterney@yahoo.co.uk

Transcranial direct current stimulation (tDCS) was recently reintroduced as a tool for inducing relatively long-lasting changes in cortical excitability in focal brain regions. Anodal stimulation over the primary motor cortex enhances cortical excitability, whereas cathodal stimulation decreases it. Prior studies have shown that enhancement of D2 receptor activity by pergolide consolidates tDCS-generated excitability diminution for up to 24 hours and that cathodal stimulation of the primary motor cortex diminishes experimentally induced pain sensation and reduces the N2-P2 amplitude of laser-evoked potentials immediately poststimulation. In the present study, we investigated the effect of pergolide and cathodal tDCS over the primary motor cortex on laser-evoked potentials and acute pain perception induced with a Tm:YAG laser in a double-blind, randomized, placebo-controlled, crossover study. The amplitude changes of laser-evoked potentials and subjective pain rating scores of 12 healthy subjects were analyzed prior to and following 15 minutes cathodal tDCS combined with pergolide or placebo intake at five different time points. Our results indicate that the amplitude of the N2 component was significantly reduced following cathodal tDCS for up to two hours. Additionally, pergolide prolonged the effect of the cathodal tDCS for up to 24 hours, and a significantly lowered pain sensation was observed for up to 40 minutes. Our study is a further step toward clinical application of cathodal tDCS over the primary motor cortex using pharmacological intervention to prolong the excitability-diminishing effect on pain perception for up to 24 hours poststimulation. Furthermore, it demonstrates the potential for repetitive daily stimulation therapy for pain patients.

Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't

PMID: 18358692 [PubMed - indexed for MEDLINE]

J Cogn Neurosci. 2008 Sep;20(9):1687-97.

Cerebellar transcranial direct current stimulation impairs the practice-dependent proficiency increase in working memory.

Ferrucci R, Marceglia S, Vergari M, Cogiamanian F, Mrakic-Sposta S, Mameli F, Zago S, Barbieri S, Priori A.

University of Milan, and Fondazione IRCCS Ospeda le Maggiore, Polyclinico Mangiagalli e Regina Elena, Milan, Italy.

How the cerebellum is involved in the practice and proficiency of non-motor functions is still unclear. We tested whether transcranial direct current stimulation (tDCS) over the cerebellum (cerebellar tDCS) induces after-effects on the practice-dependent increase in the proficiency of a working memory (WM) task (Sternberg test) in 13 healthy subjects. We also assessed the effects of cerebellar tDCS on visual evoked potentials (VEPs) in four subjects and compared the effects of cerebellar tDCS on the Sternberg test with those elicited by tDCS delivered over the prefrontal cortex in five subjects. Our experiments showed that anodal or cathodal tDCS over the cerebellum impaired the practice-dependent improvement in the reaction times in a WM task. Because tDCS delivered over the prefrontal cortex induced an immediate change in the WM task but left the practice-dependent proficiency unchanged, the effects of cerebellar tDCS are structure-specific. Cerebellar tDCS left VEPs unaffected, its effect on the Sternberg task therefore seems unlikely to arise from visual system involvement. In conclusion, tDCS over the cerebellum specifically impairs the practice-dependent proficiency increase in verbal WM.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18345990 [PubMed - indexed for MEDLINE]

Neurosci Lett. 2008 Apr 11;435(1):56-9. Epub 2008 Feb 12.

Primary motor cortex activation by transcranial direct current stimulation in the human brain.

Kwon YH, Ko MH, Ahn SH, Kim YH, Song JC, Lee CH, Chang MC, Jang SH.

Department of Physical Therapy, Yeungnam College of Science and Technology, Republic of Korea.

Transcranial direct current stimulation (tDCS) can modulate motor cortex excitability in the human brain. We attempted to demonstrate the cortical stimulation effect of tDCS on the primary motor cortex (M1) using functional MRI (fMRI). An fMRI study was performed for 11 right-handed healthy subjects at 1.5 T. Anodal tDCS was applied to the scalp over the central knob of the M1 in the left hemisphere. A constant current with an intensity of 1.0 mA was applied. The total fMRI paradigm consisted of three sessions with a 5-min resting period between each session. Each session consisted of five successive phases (resting-tDCS-tDCS-tDCS-tDCS), and each of the phases was performed for 21s. Our findings revealed that no cortical activation was detected in any of the stimulation phases except the fourth tDCS phase. In the result of group analysis for the fourth tDCS phase, the average map indicated that the central knob of the left primary motor cortex was activated. In addition, there were activations on the left supplementary motor cortex and the right posterior parietal cortex. We demonstrated that tDCS has a direct stimulation effect on the underlying cortex. It seems that tDCS is a useful modality for stimulating a target cortical region.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18325666 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2008 Mar;27(5):1292-300. Epub 2008 Feb 29.

Premotor transcranial direct current stimulation (tDCS) affects primary motor excitability in humans.

Boros K, Poreisz C, Münchau A, Paulus W, Nitsche MA.

Department of Clinical Neurophysiology, Georg-August University, Robert Koch Strasse 40, 37075 Göttingen, Germany. klara.boros@med.uni-goettingen.de

Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex (PM) modifies the excitability of the ipsilateral primary motor cortex (M1). Transcranial direct current stimulation (tDCS) is a new method to induce neuroplasticity in humans non-invasively. tDCS generates neuroplasticity directly in the cortical area under the electrode, but might also induce effects in distant brain areas, caused by activity modulation of interconnected areas. However, this has not yet been tested electrophysiologically. We aimed to study whether premotor tDCS can modify the excitability of the ipsilateral M1 via cortico-cortical connectivity. Sixteen subjects received cathodal and anodal tDCS of the PM and eight subjects of the dorsolateral prefrontal cortex. Premotor anodal, but not premotor cathodal or prefrontal tDCS, modified selectively short intracortical inhibition/intracortical facilitation (SICI/ICF), while motor thresholds, single test-pulse motor-evoked potential and input-output curves were stable throughout the experiments. Specifically, anodal tDCS decreased intracortical inhibition and increased paired-pulse excitability. The selective influence of premotor tDCS on intracortical excitability of the ipsilateral M1 suggests a connectivity-driven effect of tDCS on remote cortical areas. Moreover, this finding indirectly substantiates the efficacy of tDCS to modulate premotor excitability, which might be of interest for applications in diseases accompanied by pathological premotor activity.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 18312584 [PubMed - indexed for MEDLINE]

J Clin Psychiatry. 2008 Jan;69(1):32-40.

Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study.

Fregni F, Liguori P, Fecteau S, Nitsche MA, Pascual-Leone A, Boggio PS.

Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass. 02215, USA. ffregni@bidmc.harvard.edu

OBJECTIVE: Because neuroimaging studies have shown that cue-provoked smoking craving is associated with changes in the activity of the bilateral dorsolateral prefrontal cortex (DLPFC), we aimed to investigate whether a powerful technique of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), reduces cue-provoked smoking craving as indexed by a visual analog scale. METHOD: We performed a randomized, sham-controlled crossover study in which 24 subjects received sham and active tDCS (anodal tDCS of the left and right DLPFC) in a randomized order. Craving was induced by cigarette manipulation and exposure to a smoking video. The study ran from January 2006 to October 2006. RESULTS: Smoking craving was significantly increased after exposure to smoking-craving cues (p < .0001). Stimulation of both left and right DLPFC with active, but not sham, tDCS reduced craving significantly when comparing craving at baseline and after stimulation, without (p = .007) and with (p = .005) smoking-craving cues. There were no significant mood changes in any of the conditions of stimulation. Adverse events were mild and distributed equally across all treatment conditions. CONCLUSIONS: Our findings extend the results of a previous study on the use of brain stimulation to reduce craving, showing that cortical stimulation with tDCS is beneficial for reducing cue-provoked craving, and thus support the further exploration of this technique for smoking cessation.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 18312035 [PubMed - indexed for MEDLINE]

J Cogn Neurosci. 2008 Aug;20(8):1415-22.

Noninvasive brain stimulation improves language learning.

Flöel A, Rösser N, Michka O, Knecht S, Breitenstein C.

Department of Neurology, University of Münster, Münster, Germany. floeel@uni-muenster.de

Anodal transcranial direct current stimulation (tDCS) is a reliable technique to improve motor learning. We here wanted to test its potential to enhance associative verbal learning, a skill crucial for both acquiring new languages in healthy individuals and for language reacquisition after stroke-induced aphasia. We applied tDCS (20 min, 1 mA) over the posterior part of the left peri-sylvian area of 19 young right-handed individuals while subjects acquired a miniature lexicon of 30 novel object names. Every subject participated in one session of anodal tDCS, one session of cathodal tDCS, and one sham session in a randomized and double-blinded design with three parallel versions of the miniature lexicon. Outcome measures were learning speed and learning success at the end of each session, and the transfer to the subjects' native language after the respective stimulation. With anodal stimulation, subjects showed faster and better associative learning as compared to sham stimulation. Mood ratings, reaction times, and response styles were comparable between stimulation conditions. Our results demonstrate that anodal tDCS is a promising technique to enhance language learning in healthy adults and may also have the potential to improve language reacquisition after stroke.

Publication Types: Controlled Clinical Trial Research Support, Non-U.S. Gov't

PMID: 18303984 [PubMed - indexed for MEDLINE]

Vis Neurosci. 2008 Jan-Feb;25(1):77-81.

Gender-specific modulation of short-term neuroplasticity in the visual cortex induced by transcranial direct current stimulation.

Chaieb L, Antal A, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany. leilachaieb@med.uni-goettingen.de

Transcranial direct current stimulation (tDCS) is a non-invasive method of modulating levels of cortical excitability. In this study, data gathered over a number of previously conducted experiments before and after tDCS, has been re-analyzed to investigate correlations between sex differences with respect to neuroplastic effects. Visual evoked potentials (VEPs), phosphene thresholds (PTs), and contrast sensitivity measurements (CSs) are used as indicators of the excitability of the primary visual cortex. The data revealed that cathodally induced excitability effects 10 min post stimulation with tDCS, showed no significant difference between genders. However, stimulation in the anodal direction revealed sex-specific effects: in women, anodal stimulation heightened cortical excitability significantly when compared to the age-matched male subject group. There was no significant difference between male and female subjects immediately after stimulation. These results indicate that sex differences exist within the visual cortex of humans, and may be subject to the influences of modulatory neurotransmitters or gonadal hormones which mirror short-term neuroplastic effects.

PMID: 18282312 [PubMed - indexed for MEDLINE]

Neuroreport. 2008 Jan 8;19(1):43-7.

Time-dependent effect of transcranial direct current stimulation on the enhancement of working memory.

Ohn SH, Park CI, Yoo WK, Ko MH, Choi KP, Kim GM, Lee YT, Kim YH.

Department of Physical Medicine and Rehabilitation, Division for Neurorehabilitation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.

The time-dependent effect of transcranial direct current stimulation (tDCS) on working memory was investigated by applying anodal stimulation over the left prefrontal cortex. This single-blind, sham-controlled crossover study recruited 15 healthy participants. A three-back verbal working-memory task was performed before, during, and 30 min after 1 mA anodal or sham tDCS. Anodal tDCS, compared with sham stimulation, significantly improved working-memory performance. Accuracy of response was significantly increased after 20 min of tDCS application, and was further enhanced after 30 min of stimulation. This effect was maintained for 30 min after the completion of stimulation. These results suggest that tDCS at 1 mA enhances working memory in a time-dependent manner for at least 30 min in healthy participants.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 18281890 [PubMed - indexed for MEDLINE]

Med Hypotheses. 2008;71(1):58-60. Epub 2008 Feb 20.

A novel approach for treating cerebellar ataxias.

Manto M, Ben Taib NO.

FNRS-Neurologie, ULB Erasme, 808 Route de Lennik, 1070 Bruxelles, Belgium. mmanto@ulb.ac.be

The terminology of cerebellar ataxias encompasses a variety of sporadic and inherited debilitating diseases. Patients exhibit disabling deficits such as dysmetria, kinetic tremor and ataxia of stance/gait. We are currently lacking effective treatments in degenerative cerebellar ataxias. Animal models of cerebellar disorders and studies in ataxic patients have demonstrated that the excitability of the sensorimotor cortex is severely depressed in case of cerebellar lesion. These reduced levels of excitability are associated with learning deficits. Recent experimental data show that transcranial direct current stimulation (tDCS) of the premotor cortex and low-frequency repetitive stimulation of the motor cortex (LFRSM1) restore the excitability of the motor cortex in hemicerebellectomized rats, reinstating the ability of the motor cortex to adapt to sustained peripheral stimulation. The hypothesis is based on the possibility that the combination of tDCS and contralateral LFRSM1 can improve human cerebellar ataxias. The proposed treatment consists of delivering trains of tDCS either in conjunction or in alternance with contralateral LFRSM1, in addition to application of peripheral nerve stimulation to sensitize the sensorimotor cortex. This hypothesis is to be tested in a procedure made of 3 steps in patients exhibiting a sporadic or inherited cerebellar disorder. First, patients are assessed clinically using validated scales of cerebellar ataxias and performing accepted quantified tests. Second, trains of tDCS and LFRSM1 are delivered, using a sham procedure in a cross-over design. Trains of peripheral stimulation are applied at peripheral nerves. Third, patients are re-assessed clinically and with quantified tests. Although grafting of stem cells and gene therapy are being developed, they will not be available soon. A successful treatment of combined neurostimulation would lead to a new and readily available approach in the management of cerebellar ataxias. This new therapy is safe, feasible and may bring symptomatic improvement.

PMID: 18281160 [PubMed - indexed for MEDLINE]

Appetite. 2008 Jul;51(1):34-41. Epub 2007 Dec 23.

Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods.

Fregni F, Orsati F, Pedrosa W, Fecteau S, Tome FA, Nitsche MA, Mecca T, Macedo EC, Pascual-Leone A, Boggio PS.

Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue #KS 454, Boston, MA, 02215, USA. ffregni@bidmc.harvard.edu

We aimed to assess whether modulation of the dorsolateral prefrontal cortex (DLFPC) with noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS), modifies food craving in healthy subjects. We performed a randomized sham-controlled cross-over study in which 23 subjects received sham and active tDCS (anode left/cathode right and anode right/cathode left) of the DLPFC. Subjects were exposed to food and also watched a movie of food associated with strong craving. Desire for food consumption was evaluated by visual analogue scales (VAS) and food consumption before and after treatment. In addition we measured visual attention to food using an eye tracking system. Craving for viewed foods as indexed by VAS was reduced by anode right/cathode left tDCS. After sham stimulation, exposure to real food or food-related movie increased craving; whereas after anode left/cathode right tDCS, the food-related stimuli did not increase craving levels, as revealed by the VAS scale. Moreover, compared with sham stimulation, subjects fixated food-related pictures less frequently after anode right/cathode left tDCS and consumed less food after both active stimulation conditions. These changes were not related to mood changes after any type of tDCS treatment. The effects of tDCS on food craving might be related to a modulation of neural circuits associated with reward and decision-making.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 18243412 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2008 Apr;119(4):805-11. Epub 2008 Jan 18.

Improvement of spatial tactile acuity by transcranial direct current stimulation.

Ragert P, Vandermeeren Y, Camus M, Cohen LG.

Human Cortical Physiology Section (HCPS), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20817, USA.

OBJECTIVE: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been successfully used to induce polarity-specific excitability changes in the brain. However, it is still unknown if anodal tDCS (tDCS(anodal)) applied to the primary somatosensory cortex (S1) can lead to behavioral changes in performance of tactile discriminative tasks. METHODS: Using an accurate tactile discrimination task (grating orientation task: GOT) we tested the hypothesis that application of 1mA of tDCS(anodal) (current density at the electrodes of 0.04mA/cm2) over the left S1 can lead to an improved tactile spatial acuity in the contralateral index-finger (IF). RESULTS: Performance in the GOT task with the contralateral IF but not with the ipsilateral IF was enhanced for about 40min after a 20min application of tDCS(anodal) in the absence of changes with sham stimulation. CONCLUSIONS: These results provide the first evidence that tDCS(anodal) over S1 improves performance in a complex somatosensory task beyond the period of stimulation. SIGNIFICANCE: The ability to induce performance improvement in the somatosensory domain with tDCS applied over S1 could be used to promote functional recovery in patients with diminished tactile perception.

Publication Types: Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

PMID: 18203660 [PubMed - indexed for MEDLINE]

Ideggyogy Sz. 2007 Nov 30;60(11-12):474-9.

Erratum in: Ideggyogy Sz. 2008 Jan 30;61(1-2):58.

Cathodal transcranial direct current stimulation over the parietal cortex modifies facial gender adaptation.

Varga ET, Elif K, Antal A, Zimmer M, Harza I, Paulus W, Kovács G.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, Göttingen. drvargaedina@yahoo.com

Previous studies have observed that prolonged adaptation to a face will bias the perception of a subsequent one. This phenomenon is known as figural or face after-effect. Although currently the topic of face adaptation enjoys utmost popularity, we still don't know much about the neural process underlying it. The aim of the present study was to determine, using transcranial direct current stimulation (tDCS), how the retinotopically organised primary visual cortex (V1) and higher-level, non-retinotopic right lateral temporo-parietal areas interact with facial adaptation processing. Seventeen healthy subjects received 10 min anodal, cathodal or sham stimulation over these areas during a facial adaptation task. Cathodal stimulation of the right temporo-parietal cortex reduces the magnitude of facial adaptation while stimulation over the V1 results in no significant effects. These data imply that mainly lateral temporo-parietal cortical areas play role in facial adaptation and in facial gender discrimination, supporting the idea that the observed after-effects are the result of high-level, configurational adaptation mechanisms.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18198794 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2008 Apr;186(3):409-17. Epub 2008 Jan 15.

Cathodal transcranial direct current stimulation on posterior parietal cortex disrupts visuo-spatial processing in the contralateral visual field.

Schweid L, Rushmore RJ, Valero-Cabré A.

Graduate Program in Medical Sciences, Graduate Division of Medical Sciences, Boston University, Boston, MA 02118, USA.

Transcranial direct current stimulation (tDCS) has recently undergone a resurgence in popularity as a powerful tool to non-invasively manipulate brain activity. While tDCS has been used to alter functions tied to primary motor and visual cortices, its impact on extrastriate visual areas involved in visuo-spatial processing has not yet been examined. In the current study, we applied tDCS to the cat visuoparietal (VP) cortex and assayed performance in a paradigm designed to assess the capacity to detect, localize and orient to static targets appearing at different spatial eccentricities within the visual field. Real or sham cathodal tDCS was unilaterally applied to the VP cortex, and orienting performance was assessed during (online), immediately after (offline; Experiments 1 and 2), and 1 or 24 h after the end of the tDCS stimulation (Experiment 2). Performance was compared to baseline data collected immediately prior to stimulation. Real, but not sham, tDCS induced significant decreases in performance for static visual targets presented in the contrastimulated visual hemifield. The behavioral impact of tDCS was most apparent during the online and immediate offline periods. The tDCS effect decayed progressively over time and performance returned to baseline levels approximately 60 min after stimulation. These results are consistent with the effects of both invasive and non-invasive deactivation methods applied to the same brain region, and indicate that tDCS has the potential to modify neuronal activity in extrastriate visual regions and to sculpt brain activity and behavior in normal and neurologically impaired subjects.

Publication Types: Research Support, N.I.H., Extramural

PMID: 18196224 [PubMed - indexed for MEDLINE]

Clin J Pain. 2008 Jan;24(1):56-63.

Transcranial direct current stimulation over somatosensory cortex decreases experimentally induced acute pain perception.

Antal A, Brepohl N, Poreisz C, Boros K, Csifcsak G, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Robert Koch Strasse 40, 37075 Göttingen, Germany. AAntal@gwdg.de

OBJECTIVE: Multiple cortical areas including the primary somatosensory cortex are known to be involved in nociception. The aim of this study was to investigate the effect of transcranial direct current stimulation (tDCS) that modulates the cortical excitability painlessly and noninvasively, over somatosensory cortex on acute pain perception induced with a Tm:YAG laser. METHODS: Subjective pain rating scores and amplitude changes of the N1, N2, and P2 components of laser-evoked potentials of 10 healthy participants were analyzed before and after anodal, cathodal, and sham tDCS. RESULTS: Our results demonstrate that cathodal tDCS significantly diminished pain perception and the amplitude of the N2 component when the contralateral hand to the side of tDCS was laser-stimulated, whereas anodal and sham stimulation conditions had no significant effect. DISCUSSION: Our study highlights the antinociceptive effect of this technique and may contribute to the understanding of the mechanisms underlying pain relief. The pharmacologic prolongation of the excitability-diminishing after-effects would render the method applicable to different patient populations with chronic pain.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18180638 [PubMed - indexed for MEDLINE]

J Neurosci. 2007 Dec 26;27(52):14442-7.

Focusing effect of acetylcholine on neuroplasticity in the human motor cortex.

Kuo MF, Grosch J, Fregni F, Paulus W, Nitsche MA.

Department of Clinical Neurophysiology, Georg-August-University Göttingen, 37075 Göttingen, Germany.

Cholinergic neuromodulation is pivotal for arousal, attention, and cognitive processes. Loss or dysregulation of cholinergic inputs leads to cognitive impairments like those manifested in Alzheimer's disease. Such dysfunction can be at least partially restored by an increase of acetylcholine (ACh). In animal studies, ACh selectively facilitates long-term excitability changes induced by feed-forward afferent input. Consequently, it has been hypothesized that ACh enhances the signal-to-noise ratio of input processing. However, the neurophysiological foundation for its ability to enhance cognition in humans is not well documented. In this study we explore the effects of rivastigmine, a cholinesterase inhibitor, on global and synapse-specific forms of cortical plasticity induced by transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) on 10-12 healthy subjects, respectively. Rivastigmine essentially blocked the induction of the global excitability enhancement elicited by anodal tDCS and revealed a tendency to first reduce and then stabilize cathodal tDCS-induced inhibitory aftereffects. However, ACh enhanced the synapse-specific excitability enhancement produced by facilitatory PAS and consolidated the inhibitory PAS-induced excitability diminution. These findings are in line with a cholinergic focusing effect that optimizes the detection of relevant signals during information processing in humans.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 18160652 [PubMed - indexed for MEDLINE]

Cereb Cortex. 2008 Sep;18(9):1987-90. Epub 2007 Dec 24.

Studying the neurobiology of social interaction with transcranial direct current stimulation--the example of punishing unfairness.

Knoch D, Nitsche MA, Fischbacher U, Eisenegger C, Pascual-Leone A, Fehr E.

Institute for Empirical Research in Economics, University of Zürich, 8006 Zürich, Switzerland. dknoch@iew.uzh.ch

Studying social behavior often requires the simultaneous interaction of many subjects. As yet, however, no painless, noninvasive brain stimulation tool existed that allowed the simultaneous affection of brain processes in many interacting subjects. Here we show that transcranial direct current stimulation (tDCS) can overcome these limits. We apply right prefrontal cathodal tDCS and show that subjects' propensity to punish unfair behavior is reduced significantly.

Publication Types: Clinical Trial

PMID: 18158325 [PubMed - indexed for MEDLINE]

J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):451-3. Epub 2007 Dec 20.

Comment in: J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):364.

Improved naming after transcranial direct current stimulation in aphasia.

Monti A, Cogiamanian F, Marceglia S, Ferrucci R, Mameli F, Mrakic-Sposta S, Vergari M, Zago S, Priori A.

Neurostimulation Unit, Department of Neurological Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.

Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant technique to improve functional recovery after ischaemic stroke. This study evaluated the effect of tDCS over the left frontotemporal areas in eight chronic non-fluent post-stroke aphasic patients. The protocol consisted of the assessment of picture naming (accuracy and response time) before and immediately after anodal or cathodal tDCS (2 mA, 10 minutes) and sham stimulation. Whereas anodal tDCS and sham tDCS failed to induce any changes, cathodal tDCS significantly improved the accuracy of the picture naming task by a mean of 33.6% (SEM 13.8%).

PMID: 18096677 [PubMed - indexed for MEDLINE]

Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5782-7.

Bidirectional modulation of primary visual cortex excitability: a combined tDCS and rTMS study.

Lang N, Siebner HR, Chadaide Z, Boros K, Nitsche MA, Rothwell JC, Paulus W, Antal A.

Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany. n.lang@neurologie.uni-kiel.de

PURPOSE: In the motor cortex (M1), transcranial direct current stimulation (tDCS) can effectively prime excitability changes that are evoked by a subsequent train of repetitive transcranial magnetic stimulation (rTMS). The authors examined whether tDCS can also prime the cortical response to rTMS in the human visual cortex. METHODS: In nine healthy subjects, the authors applied tDCS (10 minutes; +/-1 mA) to the occipital cortex. After tDCS, they applied a 20-second train of 5 Hz rTMS at 90% of phosphene threshold (PT) intensity. A similar rTMS protocol had previously demonstrated a strong priming effect of tDCS on rTMS-induced excitability changes in M1. PTs were determined with single-pulse TMS before and immediately after tDCS and twice after rTMS. RESULTS: Anodal tDCS led to a transient decrease in PT, and subsequent 5 Hz rTMS induced an earlier return of the PT back to baseline. Cathodal tDCS produced a short-lasting increase in PT, but 5 Hz rTMS did not influence the tDCS-induced increase in PT. In a control experiment on four subjects, a 20-second train of occipital 5 Hz rTMS left the PT unchanged, whereas a 60-second train produced a similar decrease in PT as anodal tDCS alone. CONCLUSIONS: Compared with previous work on the M1, tDCS and rTMS of the visual cortex only produce short-lasting changes in cortical excitability. Moreover, the priming effects of tDCS on subsequent rTMS conditioning are relatively modest. These discrepancies point to substantial differences in the modifiability of human motor and visual cortex.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 18055832 [PubMed - indexed for MEDLINE]

Cerebrovasc Dis. 2007;24 Suppl 1:157-66. Epub 2007 Nov 1.

Brain stimulation in poststroke rehabilitation.

Alonso-Alonso M, Fregni F, Pascual-Leone A.

Berenson-Allen Center for Noninvasive Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass., USA.

Brain stimulation techniques provide a powerful means to modulate the function of specific neural structures, and show potential for future applications in the rehabilitation of stroke patients. Recent studies have started to translate to the bedside the body of data gathered over the last few years on mechanisms underlying brain plasticity and stroke recovery. Both noninvasive and invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation and direct cortical stimulation with epidural electrodes, have recently been tested in small studies with stroke patients. The results to date are very promising. Nonetheless, we are still at an early stage in the field and further evidence is needed to assess the clinical impact of this new approach. In this review, we provide readers with a basic introduction to the field, summarize preliminary studies and discuss future directions. Copyright 2007 S. Karger AG, Basel.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

PMID: 17971652 [PubMed - indexed for MEDLINE]

J Neurosci. 2007 Nov 14;27(46):12500-5.

Diminishing risk-taking behavior by modulating activity in the prefrontal cortex: a direct current stimulation study.

Fecteau S, Knoch D, Fregni F, Sultani N, Boggio P, Pascual-Leone A.

Berenson-Allen Center for Noninvasive Brain Stimulation, Harvard Medical School, Boston, Massachusetts 02215, USA.

Studies have shown increased risk taking in healthy individuals after low-frequency repetitive transcranial magnetic stimulation, known to transiently suppress cortical excitability, over the right dorsolateral prefrontal cortex (DLPFC). It appears, therefore, plausible that differential modulation of DLPFC activity, increasing the right while decreasing the left, might lead to decreased risk taking, which could hold clinical relevance as excessively risky decision making is observed in clinical populations leading to deleterious consequences. The goal of the present study was to investigate whether risk-taking behaviors could be decreased using concurrent anodal transcranial direct current stimulation (tDCS) of the right DLPFC, which allows upregulation of brain activity, with cathodal tDCS of the left DLPCF, which downregulates activity. Thirty-six healthy volunteers performed the risk task while they received either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. We hypothesized that right anodal/left cathodal would decrease risk-taking behavior compared with left anodal/right cathodal or sham stimulation. As predicted, during right anodal/left cathodal stimulation over the DLPFC, participants chose more often the safe prospect compared with the other groups. Moreover, these participants appeared to be insensitive to the reward associated with the prospects. These findings support the notion that the interhemispheric balance of activity across the DLPFCs is critical in decision-making behaviors. Most importantly, the observed suppression of risky behaviors suggests that populations with boundless risk-taking behaviors leading to negative real-life consequences, such as individuals with addiction, might benefit from such neuromodulation-based approaches.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 18003828 [PubMed - indexed for MEDLINE]

Pain Pract. 2007 Dec;7(4):297-306. Epub 2007 Nov 6.

Site-specific effects of transcranial direct current stimulation on sleep and pain in fibromyalgia: a randomized, sham-controlled study.

Roizenblatt S, Fregni F, Gimenez R, Wetzel T, Rigonatti SP, Tufik S, Boggio PS, Valle AC.

Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.

OBJECTIVE: To investigate whether active anodal transcranial direct current stimulation (tDCS) (of dorsolateral prefrontal cortex [DLPFC] and primary motor cortex [M1]) as compared to sham treatment is associated with changes in sleep structure in fibromyalgia. METHODS: Thirty-two patients were randomized to receive sham stimulation or active tDCS with the anode centered over M1 or DLPFC (2 mA, 20 minutes for five consecutive days). A blinded evaluator rated the clinical symptoms of fibromyalgia. All-night polysomnography was performed before and after five consecutive sessions of tDCS. RESULTS: Anodal tDCS had an effect on sleep and pain that was specific to the site of stimulation: such as that M1 and DLPFC treatments induced opposite effects on sleep and pain, whereas sham stimulation induced no significant sleep or pain changes. Specifically, whereas M1 treatment increased sleep efficiency (by 11.8%, P = 0.004) and decreased arousals (by 35.0%, P = 0.001), DLPFC stimulation was associated with a decrease in sleep efficiency (by 7.5%, P = 0.02), an increase in rapid eye movement (REM) and sleep latency (by 47.7%, P = 0.0002, and 133.4%, P = 0.02, respectively). In addition, a decrease in REM latency and increase in sleep efficiency were associated with an improvement in fibromyalgia symptoms (as indexed by the Fibromyalgia Impact Questionnaire). Finally, patients with higher body mass index had the worse sleep outcome as indexed by sleep efficiency changes after M1 stimulation. INTERPRETATION: Our findings suggest that one possible mechanism to explain the therapeutic effects of tDCS in fibromyalgia is via sleep modulation that is specific to modulation of primary M1 activity.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 17986164 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2007 Nov;26(9):2687-91. Epub 2007 Oct 26.

Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex.

Antal A, Terney D, Poreisz C, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany. AAntal@gwdg.de

Stimulation with weak electrical direct currents has been shown to be capable of inducing stimulation-polarity-dependent prolonged diminutions or elevations of cortical excitability, most probably elicited by a hyper- or depolarization of resting membrane potentials. The aim of the present study was to test if cognitive task and motor exercise practiced during the stimulation are able to modify transcranial direct current stimulation-induced plasticity in the left primary motor cortex in 12 healthy subjects. Motor evoked potentials were recorded before and after 10 min of anodal and cathodal transcranial direct current stimulation. In Experiment 1, subjects were required to sit passively during the stimulation, in Experiment 2 the subject's attention was directed towards a cognitive test and in Experiment 3 subjects were instructed to push a ball in their right hand. Both the cognitive task and motor exercise modified transcranial direct current stimulation-induced plasticity; when performing the cognitive task during stimulation the motor cortex excitability was lower after anodal stimulation and higher after cathodal stimulation, compared with the passive condition. When performing the motor exercise, the motor cortex excitability was lower after both anodal and cathodal stimulation, compared with the passive condition. Our results show that transcranial direct current stimulation-induced plasticity is highly dependent on the state of the subject during stimulation.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 17970738 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2008 Feb;185(2):279-86. Epub 2007 Oct 17.

Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area.

Furubayashi T, Terao Y, Arai N, Okabe S, Mochizuki H, Hanajima R, Hamada M, Yugeta A, Inomata-Terada S, Ugawa Y.

Department of Neurology, Division of Neuroscience, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. Furubayashi-tky@umin.ac.jp

The aim of the present paper is to study effects of short and long duration transcranial direct current stimulation (tDCS) on the human motor cortex. In eight normal volunteers, motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) were recorded from the right first dorsal interosseous muscle, and tDCS was given with electrodes over the left primary motor cortex (M1) and the contralateral orbit. We performed two experiments: one for short duration tDCS (100 ms, 1, 3 or 5 mA) and the other for long duration tDCS (10 min, 1 mA). The stimulus onset asynchrony (SOA) between the onset of tDCS and TMS were 1-7 and 10-120 ms for the former experiment. In the latter experiment, TMS was given 0-20 min after the end of 10 min tDCS. We evaluated the effect of tDCS on the motor cortex by comparing MEPs conditioned by tDCS with control MEPs. Cathodal short duration tDCS significantly reduced the size of responses to motor cortical stimulation at SOAs of 1-7 ms when the intensity was equal to or greater than 3 mA. Anodal short duration tDCS significantly increased MEPs when the intensity was 3 mA, but the enhancement did not occur when using 5 mA conditioning stimulus. Moreover, both anodal and cathodal short duration tDCS decreased responses to TMS significantly at SOAs of 20-50 ms and enhanced them at an SOA of 90 ms. Long duration cathodal tDCS decreased MEPs at 0 and 5 min after the offset of tDCS and anodal long duration tDCS increased them at 1 and 15 min. We conclude that the effect at SOAs less than 10 ms is mainly caused by acute changes in resting membrane potential induced by tDCS. The effect at SOAs of 20-100 ms is considered to be a nonspecific effect of a startle-like response produced by activation of skin sensation at the scalp. The effect provoked by long duration tDCS may be short-term potentiation or depression like effects.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 17940759 [PubMed - indexed for MEDLINE]

Brain Res Rev. 2007 Dec;56(2):346-61. Epub 2007 Aug 28.

The use of tDCS and CVS as methods of non-invasive brain stimulation.

Been G, Ngo TT, Miller SM, Fitzgerald PB.

Alfred Psychiatry Research Centre, The Alfred Hospital and Monash University School of Psychology, Psychiatry and Psychological Medicine, Commercial Rd, Melbourne, VIC 3004, Australia.

Transcranial direct current stimulation (tDCS) and caloric vestibular stimulation (CVS) are safe methods for selectively modulating cortical excitability and activation, respectively, which have recently received increased interest regarding possible clinical applications. tDCS involves the application of low currents to the scalp via cathodal and anodal electrodes and has been shown to affect a range of motor, somatosensory, visual, affective and cognitive functions. Therapeutic effects have been demonstrated in clinical trials of tDCS for a variety of conditions including tinnitus, post-stroke motor deficits, fibromyalgia, depression, epilepsy and Parkinson's disease. Its effects can be modulated by combination with pharmacological treatment and it may influence the efficacy of other neurostimulatory techniques such as transcranial magnetic stimulation. CVS involves irrigating the auditory canal with cold water which induces a temperature gradient across the semicircular canals of the vestibular apparatus. This has been shown in functional brain-imaging studies to result in activation in several contralateral cortical and subcortical brain regions. CVS has also been shown to have effects on a wide range of visual and cognitive phenomena, as well as on post-stroke conditions, mania and chronic pain states. Both these techniques have been shown to modulate a range of brain functions, and display potential as clinical treatments. Importantly, they are both inexpensive relative to other brain stimulation techniques such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS).

Publication Types: Research Support, Non-U.S. Gov't Review

PMID: 17900703 [PubMed - indexed for MEDLINE]

Neuropsychologia. 2008 Jan 15;46(1):261-8. Epub 2007 Jul 24.

Enhancing language performance with non-invasive brain stimulation--a transcranial direct current stimulation study in healthy humans.

Sparing R, Dafotakis M, Meister IG, Thirugnanasambandam N, Fink GR.

Institute of Neurosciences and Biophysics, Department of Medicine, Research Centre Juelich, Germany. r.sparing@fz-juelich.de

In humans, transcranial direct current stimulation (tDCS) can be used to induce, depending on polarity, increases or decreases of cortical excitability by polarization of the underlying brain tissue. Cognitive enhancement as a result of tDCS has been reported. The purpose of this study was to test whether weak tDCS (current density, 57 microA/cm(2)) can be used to modify language processing. Fifteen healthy subjects performed a visual picture naming task before, during and after tDCS applied over the posterior perisylvian region (PPR), i.e. an area which includes Wernicke's area [BA 22]. Four different sessions were carried out: (1) anodal and (2) cathodal stimulation of left PPR and, for control, (3) anodal stimulation of the homologous region of the right hemisphere and (4) sham stimulation. We found that subjects responded significantly faster following anodal tDCS to the left PPR (p<0.01). No decreases in performance were detected. Our finding of a transient improvement in a language task following the application of tDCS together with previous studies which investigated the modulation of picture naming latency by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) suggest that tDCS applied to the left PPR (including Wernicke's area [BA 22]) can be used to enhance language processing in healthy subjects. Whether this safe, low cost, and easy to use brain stimulation technique can be used to ameliorate deficits of picture naming in aphasic patients needs further investigations.

Publication Types: Clinical Trial Controlled Clinical Trial Research Support, Non-U.S. Gov't

PMID: 17804023 [PubMed - indexed for MEDLINE]

Restor Neurol Neurosci. 2007;25(2):123-9.

Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients.

Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F.

Department of Experimental Psychology and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.

PURPOSE: Recent evidence has suggested that a simple technique of noninvasive brain stimulation - transcranial direct current stimulation (tDCS) - is associated with a significant motor function improvement in stroke patients. METHODS: We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. RESULTS: There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (p< 0.0001) that lasted for 2 weeks after treatment. CONCLUSIONS: The findings of our study support previous research showing that tDCS is significantly associated with motor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non-expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke.

Publication Types: Research Support, N.I.H., Extramural

PMID: 17726271 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2007 Sep;182(2):281-7. Epub 2007 Aug 24.

Effects of transcranial direct current stimulation on the excitability of the leg motor cortex.

Jeffery DT, Norton JA, Roy FD, Gorassini MA.

Centre for Neuroscience and Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada.

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA has been shown to be efficacious in increasing (via anodal tDCS) or decreasing (via cathodal tDCS) the excitability of corticospinal projections to muscles of the hand. In this study, we examined whether tDCS at currents of 2 mA could effect similar changes in the excitability of deeper cortical structures that innervate muscles of the lower leg. Similar to the hand area, 10 min of stimulation with the anode over the leg area of the motor cortex increased the excitability of corticospinal tract projections to the tibialis anterior (TA) muscle, as reflected by an increase in the amplitude of the motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation. MEP amplitudes recorded at rest and during a background contraction were increased following anodal tDCS and remained elevated at 60 min compared to baseline values by 59 and 35%, respectively. However, in contrast to the hand, hyperpolarizing cathodal stimulation at equivalent currents had minimal effect on the amplitude of the MEPs recorded at rest or during background contraction of the TA muscle. These results suggest that it is more difficult to suppress the excitability of the leg motor cortex with cathodal tDCS than the hand area of the motor cortex.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 17717651 [PubMed - indexed for MEDLINE]

Acta Neurochir Suppl. 2007;97(Pt 2):261-72.

Brain stimulation for epilepsy.

Theodore WH, Fisher R.

Clinical Epilepsy Section, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. theodorw@ninds.nih.gov

Brain stimulation has been receiving increasing attention as an alternative therapy for epilepsy that cannot be treated by either antiepileptic medication or surgical resection of the epileptogenic focus. The stimulation methods include transcranial magnetic stimulation (TMS) or electrical stimulation by implanted devices of the vagus nerve (VNS), deep brain structures (DBS) (thalamic or hippocampal), cerebellar or cortical areas. TMS is the simplest and least invasive approach. However, the most common epileptogenic areas (mesial temporal structures) probably lie too deep beneath the surface of the skull for effective TMS. The efficacy of VNS in reducing the frequency or severity of seizures is quite variable and depends on many factors which are currently investigated. VNS is well-tolerated and approved in many countries. DBS is much more invasive than either TMS or VNS. Currently, a number of targets for DBS are investigated including caudate, centromedian or anterior thalamic nuclei, and subthalamic nucleus. Direct stimulation of the epileptic cortical focus is another approach to the neuromodulation in epilepsy. Finally, another line of research investigates the usefulness of implantable seizure detection devices. The current chapter presents the most important evidence on the above methods. Furthermore, other important issues are reviewed such as the selection criteria of patients for brain stimulation and the potential role of brain stimulation in the treatment of depression in epileptic patients.

Publication Types: Review

PMID: 17691312 [PubMed - indexed for MEDLINE]

Drug Alcohol Depend. 2008 Jan 1;92(1-3):55-60. Epub 2007 Jul 19.

Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study.

Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A, Basaglia A, Fregni F.

Nucleo de Neurociencias, Mackenzie University, Sao Paulo, SP, Brazil.

BACKGROUND: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. METHODS: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. RESULTS: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p<0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. CONCLUSIONS: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 17640830 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2007 Jul;26(1):242-9.

Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas.

Cogiamanian F, Marceglia S, Ardolino G, Barbieri S, Priori A.

Dipartimento di Scienze Neurologiche, Università di Milano, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, 20122 Italy.

Neuromuscular fatigue is the exercise-dependent decrease in the ability of muscle fibres to generate force. To investigate whether manipulation of brain excitability by transcranial direct current stimulation (tDCS; 1.5 mA, 10 min, 0.026 C/cm(2)) modulates neuromuscular fatigue, we evaluated the effect of brain polarization over the right motor areas of the cerebral cortex of healthy subjects on the endurance time for a submaximal isometric contraction of left elbow flexors. In 24 healthy volunteers the study protocol comprised an assessment of the maximum voluntary contraction (MVC) for the left elbow flexors and a fatiguing isometric contraction (35% of MVC), before and immediately after brain polarization. One hour elapsed between baseline (T0) and postconditioning (T1) evaluation. After tDCS, MVC remained unchanged from baseline (mean +/- SEM; anodal tDCS: T0, 154.4 +/- 18.07; T1, 142.8 +/- 16.62 N; cathodal tDCS: T0, 156 +/- 18.75; T1, 141.86 +/- 17.53 N; controls: T0, 148.8 +/- 6.64; T1, 137.6 +/- 7.36 N; P > 0.1). Conversely, endurance time decreased significantly less after anodal than after cathodal tDCS or no stimulation (-21.1 +/- 5.5%, -35.7 +/- 3.3% and -39.3 +/- 3.3%, respectively; P < 0.05). None of the evaluated electromyographic variables changed after tDCS. Anodal tDCS could improve endurance time by directly modulating motor cortical excitability, modulating premotor areas, decreasing fatigue-related muscle pain, increasing motivation and improving synergist muscle coupling. Our findings, showing that anodal tDCS over the motor areas of the cerebral cortex improves muscle endurance, open the way to increasing muscle endurance and decreasing muscle fatigue in normal (i.e. sports medicine) and pathological conditions.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 17614951 [PubMed - indexed for MEDLINE]

Nat Clin Pract Neurol. 2007 Jul;3(7):383-93.

Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS.

Fregni F, Pascual-Leone A.

Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

In neurology, as in all branches of medicine, symptoms of disease and the resulting burden of illness and disability are not simply the consequence of the injury, inflammation or dysfunction of a given organ; they also reflect the consequences of the nervous system's attempt to adapt to the insult. This plastic response includes compensatory changes that prove adaptive for the individual, as well as changes that contribute to functional disability and are, therefore, maladaptive. In this context, brain stimulation techniques tailored to modulate individual plastic changes associated with neurological diseases might enhance clinical benefits and minimize adverse effects. In this Review, we discuss the use of two noninvasive brain stimulation techniques--repetitive transcranial magnetic stimulation and transcranial direct current stimulation--to modulate activity in the targeted cortex or in a dysfunctional network, to restore an adaptive equilibrium in a disrupted network for best behavioral outcome, and to suppress plastic changes for functional advantage. We review randomized controlled studies, in focal epilepsy, Parkinson's disease, recovery from stroke, and chronic pain, to illustrate these principles, and we present evidence for the clinical effects of these two techniques.

Publication Types: Research Support, N.I.H., Extramural Review

PMID: 17611487 [PubMed - indexed for MEDLINE]

Cereb Cortex. 2008 Mar;18(3):648-51. Epub 2007 Jun 24.

Boosting focally-induced brain plasticity by dopamine.

Kuo MF, Paulus W, Nitsche MA.

Department of Clinical Neurophysiology, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.

Dopamine (DA) simultaneously produces both excitation and inhibition in the human cortex. In order to shed light on the functional significance of these seemingly opposing effects, we administered the DA precursor levodopa (L-dopa) to healthy subjects in conjunction with 2 neuroplasticity-inducing motor cortex stimulation protocols. Transcranial direct current stimulation (tDCS) induces cortical excitability enhancement by anodal and depression by cathodal brain polarization, which is not restricted to specific subgroups of synapses. In contrast, paired associative stimulation (PAS) induces focal excitability enhancements of somatosensory and motor cortical neuronal synaptic connections. Here, we show that administering L-dopa turns the unspecific excitability enhancement caused by anodal tDCS into inhibition and prolongs the cathodal tDCS-induced excitability diminution. Conversely, it stabilizes the PAS-induced synapse-specific excitability increase. Most importantly, it prolongs all of these aftereffects by a factor of about 20. Hereby, DA focuses synapse-specific excitability-enhancing neuroplasticity in human cortical networks.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 17591596 [PubMed - indexed for MEDLINE]

Cereb Cortex. 2008 Feb;18(2):451-5. Epub 2007 Jun 21.

Lie-specific involvement of dorsolateral prefrontal cortex in deception.

Priori A, Mameli F, Cogiamanian F, Marceglia S, Tiriticco M, Mrakic-Sposta S, Ferrucci R, Zago S, Polezzi D, Sartori G.

Department of Neurological Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena 20122, Italy. alberto.priori@unimi.it

Lies are intentional distortions of event knowledge. No experimental data are available on manipulating lying processes. To address this issue, we stimulated the dorsolateral prefrontal cortex (DLPFC) using transcranial direct current stimulation (tDCS). Fifteen healthy volunteers were tested before and after tDCS (anodal, cathodal, and sham). Two types of truthful (truthful selected: TS; truthful unselected: TU) and deceptive (lie selected: LS; lie unselected: LU) responses were evaluated using a computer-controlled task. Reaction times (RTs) and accuracy were collected and used as dependent variables. In the baseline task, the RT was significantly longer for lie responses than for true responses ([mean +/- standard error] 1153.4 +/- 42.0 ms vs. 1039.6 +/- 36.6 ms; F(1,14) = 27.25, P = 0.00013). At baseline, RT for selected pictures was significantly shorter than RT for unselected pictures (1051.26 +/- 39.0 ms vs. 1141.76 +/- 41.1 ms; F(1,14) = 34.85, P = 0.00004). Whereas after cathodal and sham stimulation, lie responses remained unchanged (cathodal 5.26 +/- 2.7%; sham 5.66 +/- 3.6%), after anodal tDCS, RTs significantly increased but did so only for LS responses (16.86 +/- 5.0%; P = 0.002). These findings show that manipulation of brain function with DLPFC tDCS specifically influences experimental deception and that distinctive neural mechanisms underlie different types of lies.

PMID: 17584853 [PubMed - indexed for MEDLINE]

Int J Neuropsychopharmacol. 2008 Mar;11(2):249-54. Epub 2007 Jun 11.

A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression.

Boggio PS, Rigonatti SP, Ribeiro RB, Myczkowski ML, Nitsche MA, Pascual-Leone A, Fregni F.

Núcleo de Neurociências, Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, Sao Paulo, Brazil. boggio@usp.br

Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group - 'DLPFC'); anodal tDCS of the occipital cortex (active control group - 'occipital') and sham tDCS (placebo control group - 'sham'). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4% (+/-25.8%)] compared to occipital [HDRS reduction of 21.3% (+/-12.9%)] and sham tDCS [HDRS reduction of 10.4% (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.

Publication Types: Clinical Trial, Phase II Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 17559710 [PubMed - indexed for MEDLINE]

J Neurosci. 2007 Jun 6;27(23):6212-8.

Activation of prefrontal cortex by transcranial direct current stimulation reduces appetite for risk during ambiguous decision making.

Fecteau S, Pascual-Leone A, Zald DH, Liguori P, Théoret H, Boggio PS, Fregni F.

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

As adult humans, we are continuously faced with decisions in which proper weighing of the risk involved is critical. Excessively risky or overly cautious decision making can both have disastrous real-world consequences. Weighing of risks and benefits toward decision making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but its role remains unclear. Repetitive transcranial magnetic stimulation studies have shown that disruption of the DLPFC increases risk-taking behavior. Transcranial direct current stimulation (tDCS) allows upregulation of activity in the DLPFC, and we predicted that it might promote more cautious decision making. Healthy participants received one of the following treatments while they performed the Balloon Analog Risk Task: (1) right anodal/left cathodal DLPFC tDCS, (2) left anodal/right cathodal DLPFC tDCS, or (3) sham tDCS. This experiment revealed that participants receiving either one of the bilateral DLPFC tDCS strategies adopted a risk-averse response style. In a control experiment, we tested whether unilateral DLPFC stimulation (anodal tDCS over the right or left DLPFC with the cathodal electrode over the contralateral supraorbital area) was sufficient to decrease risk-taking behaviors. This experiment showed no difference in decision-making behaviors between the groups of unilateral DLPFC stimulation and sham stimulation. These findings extend the notion that DLPFC activity is critical for adaptive decision making, possibly by suppressing riskier responses. Anodal tDCS over DLPFC by itself did not significantly change risk-taking behaviors; however, when the contralateral DLPFC was modulated with cathodal tCDS, an important decrease in risk taking was observed. Also, the induced cautious decision-making behavior was observed only when activity of both DLPFCs was modulated. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse, overeating, or pathological gambling.

Publication Types: Comparative Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 17553993 [PubMed - indexed for MEDLINE]

Clin EEG Neurosci. 2007 Apr;38(2):105-15.

Transcranial and deep brain stimulation approaches as treatment for depression.

Rau A, Grossheinrich N, Palm U, Pogarell O, Padberg F.

Dept. of Psychiatry and Psychotherapy, Ludwig-Maximilians University Munich, Munich, Germany.

Given that a considerable portion of depressed patients does not respond to or remit during pharmacotherapy, there is increasing interest in non-pharmacological strategies to treat depressive disorders. Several brain stimulation approaches are currently being investigated as novel therapeutic interventions beside electroconvulsive therapy (ECT), a prototypic method in this field with proven effectiveness. These neurostimulation methods include repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), deep brain stimulation (DBS) and transcranial direct current stimulation (tDCS). It is via different neuroanatomically defined "windows" that the various approaches access the neuronal networks showing an altered function in depression. Also, the methods vary regarding their degree of invasiveness. One or the other method may finally achieve antidepressant effectiveness with minimized side effects and constitute a new effective treatment for major depression.

Publication Types: Review

PMID: 17515176 [PubMed - indexed for MEDLINE]

Cephalalgia. 2007 Jul;27(7):833-9. Epub 2007 May 10.

Transcranial direct current stimulation reveals inhibitory deficiency in migraine.

Chadaide Z, Arlt S, Antal A, Nitsche MA, Lang N, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany.

The issue of interictal excitability of cortical neurons in migraine patients is controversial: some studies have reported hypo-, others hyperexcitability. The aim of the present study was to observe the dynamics of this basic interictal state by further modulating the excitability level of the visual cortex using transcranial direct current stimulation (tDCS) in migraineurs with and without aura. In healthy subjects anodal tDCS decreases, cathodal stimulation increases transcranial magnetic stimulation (TMS)-elicited phosphene thresholds (PT), which is suggested as a representative value of visual cortex excitability. Compared with healthy controls, migraine patients tended to show lower baseline PT values, but this decrease failed to reach statistical significance. Anodal stimulation decreased phosphene threshold in migraineurs similarly to controls, having a larger effect in migraineurs with aura. Cathodal stimulation had no significant effect in the patient groups. This result strengthens the notion of deficient inhibitory processes in the cortex of migraineurs, which is selectively revealed by activity-modulating cortical input.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 17498207 [PubMed - indexed for MEDLINE]

Restor Neurol Neurosci. 2007;25(1):9-15.

Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: a pilot study.

Hesse S, Werner C, Schonhardt EM, Bardeleben A, Jenrich W, Kirker SG.

Klinik Berlin, Department of Neurological Rehabilitation, Charité - University Medicine Berlin, Germany. bhesse@zedat.fu-berlin.de

BACKGROUND AND PURPOSE: Preliminary reports suggest that central stimulation may enhance the effect of conventional physical therapies after stroke. This pilot study examines the safety and methodology of using transcranial direct stimulation (tDCS) with robot-assisted arm training (AT), to inform planning a larger randomised controlled trial. SUBJECTS: Ten patients, after an ischaemic stroke 4-8 weeks before study onset, no history of epilepsy, participated. Eight had a cortical lesion and 2 had subcortical lesions: all had severe arm paresis and, co-incidentally, 5 had severe aphasia. METHODS: Over six weeks, they received thirty 20 min-sessions of AT. During the first 7 minutes, 1.5mA of tDCS was applied, with the anode over the lesioned hemisphere and the cathode above the contralateral orbit. Arm and language impairment were assessed with the Fugl-Meyer motor score (FM, full range 0-66) and the Aachener Aphasie Test. RESULTS: No major side effects occurred. Arm function of three patients (two with a subcortical lesion) improved significantly, with FM scores increasing from 6 to 28, 10 to 49 and 11 to 48. In the remaining seven patients, all with cortical lesions, arm function changed little, FM scores did not increase more than 5 points. Unexpectedly, aphasia improved in 4 patients. CONCLUSIONS: These procedures are safe, and easy to use in a clinical setting. In future studies, patients should be stratified by degree of arm weakness and lesion site, also the unexpected aphasia improvement warrants following-up.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 17473391 [PubMed - indexed for MEDLINE]

Brain Res Bull. 2007 May 30;72(4-6):208-14. Epub 2007 Jan 24.

Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients.

Poreisz C, Boros K, Antal A, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Robert Koch Strasse 40, 37075 Göttingen, Germany. csaba.poreisz@med.ni-goettingen.de

Cortical excitability changes induced by tDCS and revealed by TMS, are increasingly being used as an index of neuronal plasticity in the human cortex. The aim of this paper is to summarize the partially adverse effects of 567 tDCS sessions over motor and non-motor cortical areas (occipital, temporal, parietal) from the last 2 years, on work performed in our laboratories. One-hundred and two of our subjects who participated in our tDCS studies completed a questionnaire. The questionnaire contained rating scales regarding the presence and severity of headache, difficulties in concentrating, acute mood changes, visual perceptual changes and any discomforting sensation like pain, tingling, itching or burning under the electrodes, during and after tDCS. Participants were healthy subjects (75.5%), migraine patients (8.8%), post-stroke patients (5.9%) and tinnitus patients (9.8%). During tDCS a mild tingling sensation was the most common reported adverse effect (70.6%), moderate fatigue was felt by 35.3% of the subjects, whereas a light itching sensation under the stimulation electrodes occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and insomnia (0.98%) were reported, but fairly infrequently. In addition, the incidence of the itching sensation (p=0.02) and the intensity of tingling sensation (p=0.02) were significantly higher during tDCS in the group of the healthy subjects, in comparison to patients; whereas the occurrence of headache was significantly higher in the patient group (p=0.03) after the stimulation. Our results suggest that tDCS applied to motor and non-motor areas according to the present tDCS safety guidelines, is associated with relatively minor adverse effects in healthy humans and patients with varying neurological disorders.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 17452283 [PubMed - indexed for MEDLINE]

Annu Rev Biomed Eng. 2007;9:527-65.

Noninvasive human brain stimulation.

Wagner T, Valero-Cabre A, Pascual-Leone A.

Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02215, USA.

Noninvasive brain stimulation with transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) is valuable in research and has potential therapeutic applications in cognitive neuroscience, neurophysiology, psychiatry, and neurology. TMS allows neurostimulation and neuromodulation, while tDCS is a purely neuromodulatory application. TMS and tDCS allow diagnostic and interventional neurophysiology applications, and focal neuropharmacology delivery. However, the physics and basic mechanisms of action remain incompletely explored. Following an overview of the history and current applications of noninvasive brain stimulation, we review stimulation device design principles, the electromagnetic and physical foundations of the techniques, and the current knowledge about the electrophysiologic basis of the effects. Finally, we discuss potential biomedical and electrical engineering developments that could lead to more effective stimulation devices, better suited for the specific applications.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 17444810 [PubMed - indexed for MEDLINE]

J Neurosci. 2007 Apr 4;27(14):3807-12.

Timing-dependent modulation of associative plasticity by general network excitability in the human motor cortex.

Nitsche MA, Roth A, Kuo MF, Fischer AK, Liebetanz D, Lang N, Tergau F, Paulus W.

Georg-August-University, Department for Clinical Neurophysiology, 37075 Goettingen, Germany. mnitsch1@gwdg.de

Associative neuroplasticity, which encompasses the modification of synaptic strength by coactivation of two synaptic inputs, has been linked to learning processes. Because unlimited plasticity destabilizes neuronal networks, homeostatic rules were proposed and experimentally proven that control for the amount and direction of plasticity dependent on background network activity. Accordingly, low background activity would enhance facilitatory plasticity, whereas high background activity would inhibit it. However, the impact of background excitability on associative plasticity has not been studied so far in humans. Facilitatory associative plasticity was induced by paired associative stimulation (PAS) in the human motor cortex, whereas background activity was enhanced or diminished by transcranial direct current stimulation (tDCS). When applied before PAS, excitability-enhancing tDCS also boosted the efficacy of PAS, whereas excitability-diminishing tDCS turned it into inhibition. Thus, previous background activity does not influence associative plasticity homeostatically. When tDCS and PAS were applied simultaneously, now in accordance with homeostatic rules of neuroplasticity, reduced background activity resulted in a prolonged excitability enhancement by PAS, whereas enhanced background activity turned it into inhibition. We conclude that background network activity can influence associative plasticity homeostatically. However, only simultaneous modulation of both parameters is in accordance with homeostatic concepts. These findings might be of importance for the development of plasticity-inducing stimulation protocols supporting information processing in humans.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 17409245 [PubMed - indexed for MEDLINE]

Neuroimage. 2007 Apr 15;35(3):1113-24. Epub 2007 Feb 4.

Transcranial direct current stimulation: a computer-based human model study.

Wagner T, Fregni F, Fecteau S, Grodzinsky A, Zahn M, Pascual-Leone A.

Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. twagner@mit.edu <twagner@mit.edu>

OBJECTIVES: Interest in transcranial direct current stimulation (tDCS) in clinical practice has been growing, however, the knowledge about its efficacy and mechanisms of action remains limited. This paper presents a realistic magnetic resonance imaging (MRI)-derived finite element model of currents applied to the human brain during tDCS. EXPERIMENTAL DESIGN: Current density distributions were analyzed in a healthy human head model with varied electrode montages. For each configuration, we calculated the cortical current density distributions. Analogous studies were completed for three pathological models of cortical infarcts. PRINCIPAL OBSERVATIONS: The current density magnitude maxima injected in the cortex by 1 mA tDCS ranged from 0.77 to 2.00 mA/cm(2). The pathological models revealed that cortical strokes, relative to the non-pathological solutions, can elevate current density maxima and alter their location. CONCLUSIONS: These results may guide optimized tDCS for application in normal subjects and patients with focal brain lesions.

PMID: 17337213 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2007 May;118(5):1166-70. Epub 2007 Feb 27.

Perception of comfort during transcranial DC stimulation: effect of NaCl solution concentration applied to sponge electrodes.

Dundas JE, Thickbroom GW, Mastaglia FL.

Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australia. dundaj02@student.uwa.edu.au

OBJECTIVE: To investigate the relationship between perception of comfort and electrolyte concentration and applied voltage during transcranial direct current stimulation (tDCS). METHODS: NaCl solutions (15, 140 and 220 mM NaCl) or deionised water were used as electrolytes to dampen tDCS sponge electrodes. Subjects (14, 7 M, 20-60 years of age) rated comfort on an 11-point scale during 2 min of tDCS (1 mA). RESULTS: Overall participants rated tDCS as comfortable. Perception of comfort was negatively correlated with NaCl concentration (Spearman's rho=-0.88; p<0.05), and a logarithmic relationship was found between applied voltage and ionic strength of electrolytes (Pearson's r=-0.635; p<0.01). There was no relationship between applied voltage and perception of comfort. CONCLUSIONS: The application of NaCl solutions between 15 and 140 mM to sponge electrodes is more likely to be perceived as comfortable during tDCS. SIGNIFICANCE: The reporting of solution concentration and ratings of perception would be useful adjuncts to tDCS studies.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 17329167 [PubMed - indexed for MEDLINE]

J Neurophysiol. 2007 Apr;97(4):3109-17. Epub 2007 Jan 24.

Shaping the effects of transcranial direct current stimulation of the human motor cortex.

Nitsche MA, Doemkes S, Karaköse T, Antal A, Liebetanz D, Lang N, Tergau F, Paulus W.

Department for Clinical Neurophysiology, Georg-August-University, Goettingen, Germany. mnitsch1@gwdg.de

Transcranial DC stimulation (tDCS) induces stimulation polarity-dependent neuroplastic excitability shifts in the human brain. Because it accomplishes long-lasting effects and its application is simple, it is used increasingly. However, one drawback is its low focality, caused by 1) the large stimulation electrode and 2) the functionally effective reference electrode, which is also situated on the scalp. We aimed to increase the focality of tDCS, which might improve the interpretation of the functional effects of stimulation because it will restrict its effects to more clearly defined cortical areas. Moreover, it will avoid unwanted reversed effects of tDCS under the reference electrode, which is of special importance in clinical settings, when a homogeneous shift of cortical excitability is needed. Because current density (current strength/electrode size) determines the efficacy of tDCS, increased focality should be accomplished by 1) reducing stimulation electrode size, but keeping current density constant; or 2) increasing reference electrode size under constant current strength. We tested these hypotheses for motor cortex tDCS. The results show that reducing the size of the motor cortex DC-stimulation electrode focalized the respective tDCS-induced excitability changes. Increasing the size of the frontopolar reference electrode rendered stimulation over this cortex functionally inefficient, but did not compromise the tDCS-generated motor cortical excitability shifts. Thus tDCS-generated modulations of cortical excitability can be focused by reducing the size of the stimulation electrode and by increasing the size of the reference electrode. For future applications of tDCS, such paradigms may help to achieve more selective tDCS effects.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 17251360 [PubMed - indexed for MEDLINE]

Lancet Neurol. 2007 Feb;6(2):188-91.

Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques.

Fregni F, Freedman S, Pascual-Leone A.

Center for Non-invasive Brain Stimulation, Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, USA. ffregni@bidmc.harvard.edu

BACKGROUND: Brain stimulation is a technique that can guide brain plasticity and thus be suitable to treat chronic pain-a disorder that is associated with substantial reorganisation of CNS activity. In fact, the idea of using invasive and non-invasive brain stimulation for pain relief is not new. Studies from the 1950s investigated the use of this therapeutic method for the treatment of chronic pain. However, recent advancements in the techniques of non-invasive brain stimulation have enhanced their modulatory effects and thus become a new, attractive alternative for chronic pain treatment. RECENT DEVELOPMENTS: Recent studies with non-invasive brain stimulation--eg, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)--using new parameters of stimulation have shown encouraging results. These studies explored alternative sites of stimulation, such as the secondary somatosensory cortex (rather than primary motor cortex) for the treatment of chronic visceral pain and new parameters of stimulation, such as repeated sessions of tDCS with 2 mA for the treatment of chronic central pain. WHERE NEXT?: The investigation of non-invasive brain stimulation for therapeutic effects is in its at initial stages; but the preliminary data make us optimistic. Several questions still need to be addressed before any firm conclusion about this therapy is made. Other parameters of stimulation need to be further explored such as theta-burst stimulation and the combination of tDCS and rTMS. The duration of the therapeutic effects is another important issue to be considered, especially because the current devices for brain stimulation do not allow patients to receive this therapy in their homes; therefore, maintenance therapy regimens, as well as the development of portable stimulators, need to be investigated. Further trials must determine the optimum parameters of stimulation. After that, confirmatory, larger studies are mandatory.

Publication Types: Review

PMID: 17239806 [PubMed - indexed for MEDLINE]

Muscle Nerve. 2007 May;35(5):620-4.

Motor cortex abnormalities in amyotrophic lateral sclerosis with transcranial direct-current stimulation.

Quartarone A, Lang N, Rizzo V, Bagnato S, Morgante F, Sant'angelo A, Crupi D, Battaglia F, Messina C, Girlanda P.

Department of Neuroscience, Psychiatric and Anaesthesiological Sciences, University of Messina, Messina, Italy. angelo.quartarone@unime.it

The aim of this study was to identify a neurophysiological marker of upper motoneuron involvement in patients with sporadic amyotrophic lateral sclerosis (ALS). For this purpose we evaluated the after-effects of transcranial direct-current stimulation (tDCS) on excitability of the motor cortex of eight ALS patients and eight healthy controls. Healthy controls showed a transient polarity-specific change in corticospinal excitability of about +/-45%, with anodal tDCS inducing facilitation and cathodal tDCS leading to inhibition, whereas no change could be induced in ALS patients after either type of tDCS. It is likely that the lack of tDCS after-effects in ALS is the result of alterations of the motoneuronal membrane or, alternatively, may represent an electrophysiological correlate of disordered glutamate neurotransmission. Further studies are warranted to confirm these results. The present findings may lead to a new, reliable electrophysiological marker of upper motoneuronal involvement in ALS.

PMID: 17221883 [PubMed - indexed for MEDLINE]

J Affect Disord. 2007 Aug;101(1-3):91-8. Epub 2006 Dec 12.

Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression.

Boggio PS, Bermpohl F, Vergara AO, Muniz AL, Nahas FH, Leme PB, Rigonatti SP, Fregni F.

Department of Experimental Psychology, University of Sao Paulo, Sao Paulo, Brazil. Boggio@usp.br

BACKGROUND: We recently showed that repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) can affect the performance in an affective go-no-go (AGN) task. We aimed to extend this previous investigation testing whether one session of anodal transcranial direct current stimulation (tDCS) of the left DLPFC, as compared with anodal occipital and sham tDCS, affects this AGN task performance. METHODS: Twenty-six patients with major depression were randomized to receive anodal tDCS of the left DLPFC, occipital cortex or sham tDCS (the cathode electrode was placed over the frontopolar area for the three conditions). An AGN task was performed immediately before and after treatment. Performance changes (pre and post-treatment) were compared across groups of treatment and correlated with Hamilton Depression Rating Scale (HDRS) score changes. RESULTS: The results show that anodal stimulation of the left DLPFC was the only condition that induced a significant improvement in task performance as shown by the increase in the number of correct responses. In addition, this effect was specific for figures with positive emotional content. This performance enhancement was not correlated with mood changes after 10 days of tDCS treatment. LIMITATIONS: Although the effects of tDCS are less focal than rTMS, it can induce a longer and stronger modulation of cortical excitability. CONCLUSIONS: Our findings suggest that left DLPFC activity is associated with positive emotional processing, confirming and extending results of previous studies that associated right DLPFC and orbito-frontal cortex activity with emotional processing. Furthermore the effects of tDCS on mood and cognition seem to be independent in major depression. These lines of evidence together shed light on the neural circuitry involved with emotional processing in major depression.

Publication Types: Comparative Study Randomized Controlled Trial

PMID: 17166593 [PubMed - indexed for MEDLINE]

Arch Phys Med Rehabil. 2006 Dec;87(12 Suppl 2):S1.

Neuroplasticity and brain imaging research: implications for rehabilitation.

Levin HS.

Cognitive Neuroscience Laboratory, Baylor College of Medicine, Houston, TX 77030, USA. hlevin@bcm.edu

Advanced brain imaging technologies have been used recently to investigate neuroplasticity in relation to recovery and treatment of neurologic injury and disease. The contributors to this supplement present data and synthesize the extant literature on the use of functional magnetic resonance imaging, magnetic resonance spectroscopy, optical imaging, transcranial magnetic stimulation, and transcranial direct current stimulation to study remodeling of cortical representation of motor and cognitive abilities after stroke and other etiologies of neurologic impairment. In general, the collective findings of these studies support use-dependent neuroplasticity as a mechanism of recovery and response to training. Brain imaging findings support the role of training effects on increased activation of brain regions ipsilateral to unilateral vascular lesions in facilitating recovery from stroke. The articles in this supplement also report the potential therapeutic application of stimulation techniques to enhance reorganization of function.

PMID: 17140873 [PubMed - indexed for MEDLINE]

Arthritis Rheum. 2006 Dec;54(12):3988-98.

Comment in: Arthritis Rheum. 2006 Dec;54(12):3725-7.

A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia.

Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS.

Harvard Medical School, Boston, Massachusetts 02215, USA. ffregni@bidmc.harvard.edu

OBJECTIVE: Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity. Because transcranial direct current stimulation (tDCS) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain, we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia. METHODS: Thirty-two patients were randomized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) (2 mA for 20 minutes on 5 consecutive days). A blinded evaluator rated the patient's pain, using the visual analog scale for pain, the clinician's global impression, the patient's global assessment, and the number of tender points. Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form 36 Health Survey. Safety was assessed with a battery of neuropsychological tests. To assess potential confounders, we measured mood and anxiety changes throughout the trial. RESULTS: Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC (P < 0.0001). Although this effect decreased after treatment ended, it was still significant after 3 weeks of followup (P = 0.004). A small positive impact on quality of life was observed among patients who received anodal M1 stimulation. This treatment was associated with a few mild adverse events, but the frequency of these events in the active-treatment groups was similar to that in the sham group. Cognitive changes were similar in all 3 treatment groups. CONCLUSION: Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia, thus encouraging further trials.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural

PMID: 17133529 [PubMed - indexed for MEDLINE]

J Neurosurg. 2006 Nov;105(5):675-81.

Monitoring of muscle motor evoked potentials during cerebral aneurysm surgery: intraoperative changes and postoperative outcome.

Szelényi A, Langer D, Kothbauer K, De Camargo AB, Flamm ES, Deletis V.

Department of Neurosurgery, Klinikum der Johann Wolfgang Goethe Universität, Frankfurt, Germany. A.Szelenyi@em.uni-frankfurt.de

OBJECT: The authors in this study evaluated muscle motor evoked potentials (MMEPs) elicited by transcranial electrical stimulation (TES) and direct cortical stimulation as a means of monitoring during cerebral aneurysm surgery. The analysis focused on the value and frequencies of any intraoperative changes and their correlation to the postoperative motor status. METHODS: One hundred nineteen patients undergoing surgery for 148 cerebral aneurysms were included in the study. Muscle motor evoked potentials were elicited by a train of five constant-current anodal stimuli with an individual pulse duration of 0.5 msec and a stimulation rate of 2 Hz. Stimulation intensity was up to 240 mA for TES and up to 33 mA for direct cortical stimulation. The MMEPs were continuously recorded from the abductor pollicis brevis and tibialis anterior muscles bilaterally and from the biceps brachii and extensor digitorum communis muscles contralateral to the surgical side. The motor status was evaluated immediately after surgery and 7 days later. In 97% of the patients MMEPs were recordable for continuous neurophysiological monitoring of the vascular territory of interest throughout the surgery. In 14 patients significant intraoperative MMEP changes occurred, resulting in a transient motor deficit in one patient and a permanent motor deficit in six. The permanent loss of MMEPs in three patients was followed by a permanent severe motor deficit in one patient and severe clinical deterioration in the other two. CONCLUSIONS: Data in this study demonstrated that MMEPs are a useful means of intraoperative neurophysiological monitoring of motor pathway integrity and predicting postoperative motor status. The intraoperative loss of MMEPs reliably predicts both severe and permanent postoperative motor deficits.

PMID: 17121127 [PubMed - indexed for MEDLINE]

Zh Nevrol Psikhiatr Im S S Korsakova. 2006;106(10):27-37.

[Micropolarization of the brain: a noninvasive method for correction of morphological and functional disturbances in acute focal brain lesions and their consequences]

[Article in Russian]

Sheliakin AM, Preobrazhenskaia IG, Tiul'kin ON.

The paper is devoted to the use of small direct current in correction of morphological and functional disturbances of the human brain. Two hundred and one patients aged from 7 to 82 years have been studied. In patients with focal brain damages at the acute stage (1-2 days after stroke), the anode and cathode were placed in the projection of a damaged center. In patients in "autonomic status" condition, the anode was placed both in frontal and parietal projection of the right hemisphere cortex and the cathode--on a mastoid of the right hemisphere. Strength of the current used was 300-500 mcA, time of one procedure--30-40 min. The whole treatment course involved no more than 15 procedures. Before the treatment, after 3-5 procedures of micropolarization and at the end of the treatment course, patients underwent computer tomography and electroencephalographic study. Transcranial micropolarization exerts a cerebroprotective effect and has a selective-systemic character due to an increase of neuronal structures activity both directly in the area of the impact that manifests with the absence of brain edema and the reduction of the destruction locus by 10-15% just after three procedures and as in the other brain regions that results in the decrease of intensity of general cerebral symptoms. The micropolarization promotes restoration of the broken functional connections in central regulatory systems caused by improvement of interaction between neurons, structures and systems the results finally in restoration of central regulation of body's functions.

Publication Types: English Abstract Multicenter Study

PMID: 17117671 [PubMed - indexed for MEDLINE]

Exp Neurol. 2007 Mar;204(1):462-6. Epub 2006 Nov 17.

Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression.

Fregni F, Liebetanz D, Monte-Silva KK, Oliveira MB, Santos AA, Nitsche MA, Pascual-Leone A, Guedes RC.

Center for Noninvasive Brain Stimulation, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Ave, KS 452, Boston, MA 02215, USA. ffregni@bidmc.harvard.edu

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 17113079 [PubMed - indexed for MEDLINE]

Curr Opin Neurol. 2006 Dec;19(6):543-50.

Does brain stimulation after stroke have a future?

Talelli P, Rothwell J.

Sobell Department, Institute of Neurology, Queen Square, London, UK.

PURPOSE OF REVIEW: Transcranial methods of cortical stimulation can induce long-term changes in excitability of the cerebral cortex in humans and may be useful as therapeutic interventions in stroke rehabilitation. RECENT FINDINGS: Two approaches have been tested: (1) increasing excitability of the cortex in the stroke hemisphere and (2) suppression of the non-stroke hemisphere to reduce potential interference with function of the stroke hemisphere. The interventions have been transcranial direct current stimulation, transcranial magnetic stimulation and implanted epidural stimulation. All have been reported to give 10-20% functional improvement in small numbers of patients in single-session studies as well as in a small number of longer-term therapeutic trials. Preliminary experiments in aphasic patients using transcranial magnetic stimulation in an interference design show, however, that stimulation of the nonstroke hemisphere can in some patients reduce verbal fluency, questioning the general applicability of the second approach. SUMMARY: Cortical stimulation appears to be a safe and promising intervention for stroke patients. More studies are needed to assess its long-term benefits on substantial numbers of patients. We need to know what type of intervention is best, which patients are likely to benefit, the optimum time to intervene and the duration of any benefits.

Publication Types: Review

PMID: 17102691 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2007 Apr;178(2):261-6. Epub 2006 Oct 19.

Visual evoked potentials modulation during direct current cortical polarization.

Accornero N, Li Voti P, La Riccia M, Gregori B.

Department of Neurological Sciences, University of Rome La Sapienza, Viale Regina Elena 336, 00161 Rome, Italy. neri.accornero@uniroma1.it

Transcranial direct current stimulation (tDCS) at low intensity induces changes in cortical excitability that persist after polarization ends. The effects of anodal and cathodal polarization remain controversial. We studied changes in visual evoked potentials (VEPs) during and after anodal and cathodal tDCS by applying, in healthy volunteers, 1 mA polarization through surface electrodes placed over the occipital scalp (polarizing) and over the anterior or posterior neck-base (reference). We compared tDCS applied at two durations, 3 and 10 min and both polarities. We assessed VEP-P100 latencies and amplitudes in response to pattern-reversal checkerboard stimuli before, during, and after polarization. Anodal polarization reduced VEP-P100 amplitude whereas cathodal polarization significantly increased amplitude but both polarities left latency statistically unchanged. These changes persisted for some minutes after polarization ended depending on the duration of tDCS and on the contrast level of visual stimuli. tDCS-induced changes in VEPs seem to depend on the duration of polarization and type of visual stimuli used. The effects induced on visual cortical neurones during polarization are more consistent than the aftereffects. Studying these changes during polarization may therefore improve our understanding of these phenomena.

PMID: 17051377 [PubMed - indexed for MEDLINE]

Neuroreport. 2006 Nov 6;17(16):1703-7.

Sex differences in cortical neuroplasticity in humans.

Kuo MF, Paulus W, Nitsche MA.

Department of Clinical Neurophysiology, Georg-August-University, Goettingen, Germany. i5484133@web.de

In the present study, we explore sex differences of neuroplasticity in humans, as revealed by transcranial direct current stimulation, which induces motor cortical excitability changes both during and after stimulation. We retrospectively re-analyzed data collected from previous transcranial direct current stimulation studies. In women, the excitability-diminishing after-effects of cathodal transcranial direct current stimulation were relevantly prolonged compared with the male group. Similarly, during a short direct current stimulation that elicits no after-effects, the female group showed more inhibition. In contrast, no significant differences between male and female study participants were found for excitability-enhancing anodal transcranial direct current stimulation. These results suggest sex differences, possibly due to the effects of sex hormones, in the modulation of human cortical plasticity.

PMID: 17047457 [PubMed - indexed for MEDLINE]

J Physiol. 2006 Dec 15;577(Pt 3):795-803. Epub 2006 Oct 5.

Erratum in: J Physiol. 2007 Aug 15;583(Pt 1):409.

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence.

Power HA, Norton JA, Porter CL, Doyle Z, Hui I, Chan KM.

513 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada T6G 2S2.

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the beta-frequency band (15-35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non-invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in beta-band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in beta-band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or beta-band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 17023507 [PubMed - indexed for MEDLINE]

Brain Res Rev. 2007 Feb;53(2):250-9. Epub 2006 Oct 4.

Contribution of noninvasive cortical stimulation to the study of memory functions.

Floel A, Cohen LG.

Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. floeel@uni-muenster.de

In the memory domain, a large body of experimental evidence about subsystems of memory has been collected from classic lesion studies and functional brain imaging. Animal studies have provided information on molecular mechanisms of memory formation. Compared to this work, transcranial magnetic stimulation and transcranial direct current stimulation have made their own unique contribution. Here, we describe how noninvasive brain stimulation has been used to study the functional contribution of specific cortical areas during a given memory task, how these techniques can be used to assess LTP- and LTD-like plasticity in the living human brain, and how they can be employed to modulate memory formation in humans, suggesting an adjuvant role in neurorehabilitative treatments following brain injury.

Publication Types: Research Support, Non-U.S. Gov't Review

PMID: 17023050 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2006 Oct;117(10):2221-7. Epub 2006 Aug 23.

Transcranial direct current stimulation applied over the somatosensory cortex - differential effect on low and high frequency SEPs.

Dieckhöfer A, Waberski TD, Nitsche M, Paulus W, Buchner H, Gobbelé R.

Department of Neurology, University Hospital Aachen, Germany.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has an influence on the excitability of the human motor cortex measured by motor evoked potentials (MEPs) after transcranial magnetic stimulation. Low and high frequency (HFOs) components of somatosensory evoked potentials (SEPs) were studied questioning whether a comparable effect can be observed after applying tDCS to the human somatosensory cortex. METHODS: Multichannel median nerve SEPs were recorded before and after applying tDCS of 1mA over a period of 9min with the cathode placed over the somatosensory cortex and the anode over the contralateral forehead and vice versa in a second session. The source activity of the N20, N30 and HFOs was evaluated before and after application of tDCS. RESULTS: After cathodal tDCS to the somatosensory cortex we found a significant reduction of the N20 source amplitude while there was no effect after anodal stimulation. For the N30 component and HFOs no change in source activity was observed. CONCLUSIONS: Corresponding to the results for the motor cortex a sustained reduction of the excitability of the somatosensory cortex after cathodal tDCS was shown. SIGNIFICANCE: We demonstrated differential effects of tDCS on the high and low frequency components of SEPs confirming the hypothesis of locally and functionally distinct generators of these two components.

PMID: 16931142 [PubMed - indexed for MEDLINE]

Eur J Neurol. 2006 Sep;13(9):996-1001.

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation.

Fregni F, Marcondes R, Boggio PS, Marcolin MA, Rigonatti SP, Sanchez TG, Nitsche MA, Pascual-Leone A.

Harvard Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. ffregni@bidmc.harvard.edu

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation (P = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.

Publication Types: Clinical Trial Comparative Study Randomized Controlled Trial Research Support, N.I.H., Extramural

PMID: 16930367 [PubMed - indexed for MEDLINE]

Epilepsia. 2006 Jul;47(7):1216-24.

Anticonvulsant effects of transcranial direct-current stimulation (tDCS) in the rat cortical ramp model of focal epilepsy.

Liebetanz D, Klinker F, Hering D, Koch R, Nitsche MA, Potschka H, Löscher W, Paulus W, Tergau F.

Department of Clinical Neurophysiology, Georg-August-University, Göttingen, Germany. dliebet@gwdg.de

PURPOSE: Weak direct currents induce lasting alterations of cortical excitability in animals and humans, which are controlled by polarity, duration of stimulation, and current strength applied. To evaluate its anticonvulsant potential, transcranial direct current stimulation (tDCS) was tested in a modified cortical ramp-stimulation model of focal epilepsy. METHODS: The threshold for localized seizure activity (TLS) was determined in freely moving rats by applying a single train of rising bipolar pulses through a unilateral epicranial electrode. After tDCS, TLS was determined repeatedly for 120 min at intervals of 15 min. The first group of animals received two sessions of cathodal tDCS at 100 microA, one for 30 and one for 60 min. A third session consisted of 60 min of anodal tDCS. A second group received cathodal tDCS at 200 microA for 15 and for 30 min, as well as anodal tDCS for 30 min. RESULTS: Sixty minutes of cathodal tDCS at 100 microA resulted in a TLS increase lasting for >or=2 h. When the intensity was increased to 200 microA, a similar lasting TLS elevation occurred after a stimulation of just 30-min duration. In contrast, anodal tDCS at identical stimulation durations and current strengths had no significant effect on TLS. CONCLUSIONS: The anticonvulsive effect induced by cathodal tDCS depends on stimulation duration and current strength and may be associated with the induction of alterations of cortical excitability that outlast the actual stimulation. The results lead to the reasonable assumption that cathodal tDCS could evolve as a therapeutic tool in drug-refractory partial epilepsy.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 16886986 [PubMed - indexed for MEDLINE]

Lancet Neurol. 2006 Aug;5(8):708-12.

Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke?

Hummel FC, Cohen LG.

Human Cortical Physiology Section and Stroke Neurorehabilitation Clinic, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda 20817, USA.

BACKGROUND: Motor impairment resulting from chronic stroke can have extensive physical, psychological, financial, and social implications despite available neurorehabilitative treatments. Recent studies in animals showed that direct epidural stimulation of the primary motor cortex surrounding a small infarct in the lesioned hemisphere (M1(lesioned hemisphere)) elicits improvements in motor function. RECENT DEVELOPMENTS: In human beings, proof of principle studies from different laboratories showed that non-invasive transcranial magnetic stimulation and direct current stimulation that upregulate excitability within M1(lesioned hemisphere) or downregulate excitability in the intact hemisphere (M1(intact hemisphere)) results in improvement in motor function in patients with stroke. Possible mechanisms mediating these effects can include the correction of abnormally persistent interhemispheric inhibitory drive from M1(intact hemisphere) to M1(lesioned hemisphere) in the process of generation of voluntary movements by the paretic hand, a disorder correlated with the magnitude of impairment. In this paper we review these mechanistically oriented interventional approaches. WHAT NEXT?: These findings suggest that transcranial magnetic stimulation and transcranial direct current stimulation could develop into useful adjuvant strategies in neurorehabilitation but have to be further assessed in multicentre clinical trials.

Publication Types: Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Review

PMID: 16857577 [PubMed - indexed for MEDLINE]

Depress Anxiety. 2006;23(8):482-4.

Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression.

Fregni F, Boggio PS, Nitsche MA, Rigonatti SP, Pascual-Leone A.

Publication Types: Letter Randomized Controlled Trial Research Support, N.I.H., Extramural

PMID: 16845648 [PubMed - indexed for MEDLINE]

J Neurol Sci. 2006 Nov 1;249(1):31-8. Epub 2006 Jul 14.

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease.

Boggio PS, Ferrucci R, Rigonatti SP, Covre P, Nitsche M, Pascual-Leone A, Fregni F.

Department of Experimental Psychology, University of Sao Paulo, Sao Paulo, Brazil; Núcleo de Neurociências, Mackenzie University, Sao Paulo, Brazil.

OBJECTIVES: Cognitive impairment is a common feature in Parkinson's disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients. METHODS: We studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA. RESULTS: The results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change. CONCLUSION: tDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.

Publication Types: Research Support, N.I.H., Extramural

PMID: 16843494 [PubMed - indexed for MEDLINE]

Mov Disord. 2006 Oct;21(10):1693-702.

Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson's disease.

Fregni F, Boggio PS, Santos MC, Lima M, Vieira AL, Rigonatti SP, Silva MT, Barbosa ER, Nitsche MA, Pascual-Leone A.

Harvard Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ffregni@bidmc.harvard.edu

Electrical stimulation of deep brain structures, such as globus pallidus and subthalamic nucleus, is widely accepted as a therapeutic tool for patients with Parkinson's disease (PD). Cortical stimulation either with epidural implanted electrodes or repetitive transcranial magnetic stimulation can be associated with motor function enhancement in PD. We aimed to study the effects of another noninvasive technique of cortical brain stimulation, transcranial direct current stimulation (tDCS), on motor function and motor-evoked potential (MEP) characteristics of PD patients. We tested tDCS using different electrode montages [anodal stimulation of primary motor cortex (M1), cathodal stimulation of M1, anodal stimulation of dorsolateral prefrontal cortex (DLPFC), and sham-stimulation] and evaluated the effects on motor function--as indexed by Unified Parkinson's Disease Rating Scale (UPDRS), simple reaction time (sRT) and Purdue Pegboard test--and on corticospinal motor excitability (MEP characteristics). All experiments were performed in a double-blinded manner. Anodal stimulation of M1 was associated with a significant improvement of motor function compared to sham-stimulation in the UPDRS (P < 0.001) and sRT (P = 0.019). This effect was not observed for cathodal stimulation of M1 or anodal stimulation of DLPFC. Furthermore, whereas anodal stimulation of M1 significantly increased MEP amplitude and area, cathodal stimulation of M1 significantly decreased them. There was a trend toward a significant correlation between motor function improvement after M1 anodal-tDCS and MEP area increase. These results confirm and extend the notion that cortical brain stimulation might improve motor function in patients with PD.

Publication Types: Research Support, N.I.H., Extramural

PMID: 16817194 [PubMed - indexed for MEDLINE]

Neurosci Lett. 2006 Aug 14;404(1-2):232-6. Epub 2006 Jun 30.

Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation.

Boggio PS, Castro LO, Savagim EA, Braite R, Cruz VC, Rocha RR, Rigonatti SP, Silva MT, Fregni F.

Department of Experimental Psychology, University of Sao Paulo, Brazil. boggio@usp.br

Transcranial direct current stimulation (tDCS) is a non-invasive powerful method to modulate brain activity. It can enhance motor learning and working memory in healthy subjects. To investigate the effects of anodal tDCS (1 mA, 20 min) of the dominant and non-dominant primary motor cortex (M1) on hand motor performance in healthy right-handed volunteers, healthy subjects underwent one session of both sham and active anodal stimulation of the non-dominant or dominant primary motor cortex. A blinded rater assessed motor function using the Jebsen Taylor Hand Function Test. For the non-dominant hand, active tDCS was able to improve motor function significantly-there was a significant interaction between time and condition of stimulation (p = 0.003). Post hoc tests showed a significant enhancement of JTT performance after 1 mA anodal tDCS of M1 (mean improvement of 9.41%, p = 0.0004), but not after sham tDCS (mean improvement of 1.3%, p = 0.84). For the dominant hand, however, neither active nor sham tDCS resulted in a significant change in motor performance. Our findings show that anodal tDCS of the non-dominant primary motor cortex results in motor function enhancement and thus confirm and extend the notion that tDCS can change behavior. We speculate that the under-use of the non-dominant hand with its associated consequences in cortical plasticity might be one of the reasons to explain motor performance enhancement in the non-dominant hand only.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 16808997 [PubMed - indexed for MEDLINE]

Neuroreport. 2006 Jul 17;17(10):1047-50.

Testing for causality with transcranial direct current stimulation: pitch memory and the left supramarginal gyrus.

Vines BW, Schnider NM, Schlaug G.

Neuroimaging Laboratory, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

Neuroimaging studies have implicated the left supramarginal gyrus in short-term auditory memory processing, including memory for pitch. The present study investigated the causal role of the left supramarginal gyrus in short-term pitch memory by comparing the effects of cathodal transcranial direct current stimulation when applied over the left or right supramarginal gyrus with sham transcranial direct current stimulation. Only cathodal transcranial direct current stimulation over the left supramarginal gyrus had a detrimental effect on short-term pitch-memory performance in 11 adult participants. These results provide support for the important role of the left supramarginal gyrus in short-term memory for pitch information, and they further demonstrate the potential of transcranial direct current stimulation to modulate the functional contribution of a brain area to a particular cognitive process.

Publication Types: Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 16791101 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2006 Jul;117(7):1623-9. Epub 2006 Jun 9.

Modeling the current distribution during transcranial direct current stimulation.

Miranda PC, Lomarev M, Hallett M.

Faculty of Sciences, Institute of Biophysics and Biomedical Engineering, University of Lisbon, Campo Grande, 1749-016 Lisbon, Portugal. pcmiranda@fc.ul.pt

OBJECTIVE: To investigate the spatial distribution of the magnitude and direction of the current density in the human head during transcranial direct current stimulation (tDCS). METHODS: The current density distribution was calculated using a numerical method to implement a standard spherical head model into which current was injected by means of large electrodes. The model was positioned in 'MNI space' to facilitate the interpretation of spatial coordinates. RESULTS: The magnitude and direction of the current density vector are illustrated in selected brain slices for four different electrode montages. Approximately half of the current injected during tDCS is shunted through the scalp, depending on electrode dimension and position. Using stimulating currents of 2.0 mA, the magnitude of the current density in relevant regions of the brain is of the order of 0.1 A/m2, corresponding to an electric field of 0.22 V/m. CONCLUSIONS: Calculations based on a spherical model of the head can provide useful information about the magnitude and direction of the current density vector in the brain during tDCS, taking into account the geometry and position of the electrodes. Despite the inherent limitations of the spherical head model, the calculated values are comparable to those used in the most recent in vitro studies on modulation of neuronal activity. SIGNIFICANCE: The methodology presented in this paper may be used to assess the current distribution during tDCS using new electrode montages, to help optimize montages that target a specific region of the brain or to preliminarily investigate compliance with safety guidelines.

Publication Types: Comparative Study

PMID: 16762592 [PubMed - indexed for MEDLINE]

Neuroreport. 2006 Apr 24;17(6):671-4.

Contralateral and ipsilateral motor effects after transcranial direct current stimulation.

Vines BW, Nair DG, Schlaug G.

Neuroimaging Laboratory, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

Transcranial direct current stimulation over the left motor area influenced both contralateral and ipsilateral finger sequence movements in seven healthy adults. Effects for the two hands were reversed: anodal stimulation improved right-hand performance significantly more than cathodal stimulation, whereas cathodal stimulation improved left-hand performance significantly more than anodal stimulation. The results show that stimulating a motor region directly, or indirectly by modulating activity in the homologous region on the opposite hemisphere, can affect motor skill acquisition, presumably by facilitating effective synaptic connectivity. This outcome provides evidence for the role of interhemispheric inhibition in corticomotor functioning, and also has implications for treatment methods aimed at facilitating motor recovery after stroke.

Publication Types: Clinical Trial Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 16603933 [PubMed - indexed for MEDLINE]

Pain. 2006 May;122(1-2):197-209. Epub 2006 Mar 27.

Comment in: Pain. 2006 May;122(1-2):11-3.

A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.

Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A.

Harvard Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. ffregni@bidmc.harvard.edu

Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.

Publication Types: Clinical Trial, Phase II Randomized Controlled Trial Research Support, N.I.H., Extramural

PMID: 16564618 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2006 Mar;23(6):1651-7.

Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex.

Nitsche MA, Lampe C, Antal A, Liebetanz D, Lang N, Tergau F, Paulus W.

Georg-August-University, Department for Clinical Neurophysiology, Robert-Koch-Str. 40, 37099 Goettingen, Germany. mnitsch1@gwdg.de

Dopaminergic mechanisms participate in N-methyl-D-aspartate (NMDA) receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Changes of excitability were induced by transcranial direct current stimulation (tDCS). D2 receptor blocking by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor blocking induced by co-administration of sulpiride and pergolide did not re-establish the excitability changes induced by tDCS. This suggests that D2 receptors play a major supporting role in inducing neuroplasticity in the human motor cortex. Enhancement of D2 and, to a lesser degree, D1 receptors by pergolide consolidated tDCS-generated excitability diminution until the morning after stimulation. The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the excitability-diminishing effects of cathodal tDCS for up to 24 h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical excitability, e.g. migraine and epilepsy.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 16553629 [PubMed - indexed for MEDLINE]

Bipolar Disord. 2006 Apr;8(2):203-4.

Treatment of major depression with transcranial direct current stimulation.

Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A.

Publication Types: Letter Randomized Controlled Trial Research Support, N.I.H., Extramural

PMID: 16542193 [PubMed - indexed for MEDLINE]

Brain Res Bull. 2006 Feb 15;68(6):459-63. Epub 2005 Nov 2.

Transcranial direct current stimulation and the visual cortex.

Antal A, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, 37075 Göttingen, Germany. Aantal@gwdg.de

Neuroplastic changes are defined as enduring changes in the organization of the central nervous system, such as the strength of connections, representational patterns, or neuronal properties, either morphological or functional. In recent years, new tools have emerged to induce and manipulate ongoing neuroplastic changes by external stimulation, either by modification of synchronized neuronal activity or modulation of the spontaneous firing rate. The first is performed by transcranial magnetic stimulation (TMS), the latter by direct current stimulation (tDCS). tDCS as a tool aims to induce prolonged neuronal excitability and activity alterations in the human brain via alterations of the neuronal membrane potential and results in prolonged synaptic efficacy changes. Apart from its impressive persistent excitability effects, it is a non-invasive method and can be applied painlessly. Most likely that up- or downregulation of different cortical areas by tDCS will open a new branch in the area of visual psychophysics.

Publication Types: Review

PMID: 16459203 [PubMed - indexed for MEDLINE]

Neurosci Lett. 2006 May 1;398(1-2):85-90. Epub 2006 Jan 30.

After-effects of transcranial direct current stimulation (tDCS) on cortical spreading depression.

Liebetanz D, Fregni F, Monte-Silva KK, Oliveira MB, Amâncio-dos-Santos A, Nitsche MA, Guedes RC.

Department of Clinical Neurophysiology, Georg-August-University, Robert-Koch Strasse 40, 37099 Göttingen, Germany. dliebet@gwdg.de

Abnormal cortical excitability influences susceptibility to cortical spreading depression (CSD) in migraine. Because transcranial direct current stimulation (tDCS) is capable of inducing lasting changes of cortical excitability, we investigated the after-effects of tDCS on the propagation velocity of CSD in the rat. Twenty-five anesthetised rats received either anodal, cathodal or sham tDCS. The stimulation was applied for 20 min at a current strength of 200 microA after the recording of three baseline CSD measurements. Starting 5 min after tDCS, a further three CSDs were elicited and CSD velocity recorded at intervals of 20 min. tDCS and CSD recording was performed under anaesthesia with chloralose and urethane. As compared to the baseline velocity of 3.14 mm/min, anodal tDCS induced a significant increase of propagation velocity during the first post-tDCS recording (3.49 mm/min). In contrast to anodal tDCS, neither cathodal tDCS nor sham tDCS, which consisted of an initial ramped DC stimulation lasting only 20 s, showed a significant effect on CSD propagation velocity. As anodal tDCS is known to induce a lasting increase of cortical excitability in the clinical setting, our results support the notion that CSD propagation velocity reflects cortical excitability. Since cortical excitability and susceptibility to CSD is elevated in migraine patients, anodal tDCS - by increasing cortical excitability - might increase the probability of migraine attack in these patients, even beyond the end of its application.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 16448754 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2006 Apr;117(4):845-50. Epub 2006 Jan 19.

Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation.

Gandiga PC, Hummel FC, Cohen LG.

Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

OBJECTIVE: Brain polarization in the form of transcranial direct current stimulation (tDCS), which influences motor function and learning processes, has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation. Proper testing in Neurorehabilitation requires double-blind sham-controlled study designs. Here, we evaluated the effects of tDCS and sham stimulation (SHAM) on healthy subjects and stroke patients' self-report measures of attention, fatigue, duration of elicited sensations and discomfort. METHODS: tDCS or SHAM was in all cases applied over the motor cortex. Attention, fatigue, and discomfort were self rated by study participants using visual analog scales. Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined. Investigators questioning the patients were blind to the intervention type. RESULTS: tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue, and could not be distinguished from SHAM by study participants nor investigators. CONCLUSIONS: Successful blinding of subjects and investigators and ease of application simultaneously with training protocols supports the feasibility of using tDCS in double-blind, sham-controlled randomized trials in clinical Neurorehabilitation. SIGNIFICANCE: tDCS could evolve into a useful tool, in addition to TMS, to modulate cortical activity in Neurorehabilitation.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 16427357 [PubMed - indexed for MEDLINE]

Neurosurgery. 2005 Oct;57(4 Suppl):331-8; discussion 331-8.

Motor evoked potential monitoring during cerebral aneurysm surgery: technical aspects and comparison of transcranial and direct cortical stimulation.

Szelényi A, Kothbauer K, de Camargo AB, Langer D, Flamm ES, Deletis V.

Division of Intraoperative Neurophysiology, Hyman-Newman Institute for Neurology and Neurosurgery, Beth Israel Medical Center, New York, New York, USA. A.Szelenyi@em.uni-frankfurt.de

OBJECTIVE: This study evaluates technical aspects, handling, and safety of intraoperatively applied transcranial electrical stimulation (TES) and direct cortical stimulation (DCS) for eliciting muscle motor evoked potentials (mMEPs) during cerebral aneurysm surgery. METHODS: In 119 patients undergoing cerebral aneurysm surgery, mMEPs were evoked by a train of five stimuli with individual pulse duration of 0.5 milliseconds, a repetition rate of 2 Hz, and constant current anodal stimulation. The maximal stimulation intensity was 240 mA for transcranial and 33 mA for direct stimulation. mMEPs were recorded continuously from the abductor pollicis brevis, from tibial anterior muscles bilaterally, and from the biceps brachii and extensor digitorum communis muscles contralateral to the side operated on. RESULTS: In 118 (99%) of 119 patients, transcranially evoked mMEPs were monitorable for the vascular territory of interest. DCS was performed successfully in 95 (95%) of 100 patients. In 86 (99%) of 87 patients with internal carotid artery, middle cerebral artery, or posterior circulation aneurysms, mMEPs from upper-extremity muscles were obtained with DCS. In 11 (55%) of 20 patients with anterior communicating artery, anterior cerebral artery, or pericallosal aneurysms, mMEPs from the lower-extremity muscles could be recorded. The incidence of seizures was 0.84% for TES and 1% for DCS. Minor and inconsequential subdural bleeding after positioning of the strip electrode occurred in 2%. CONCLUSION: The cogent comprehensive combination of transcranial and direct cortical electrical stimulation allows for the continuous mMEP monitoring of the cerebral vascular territory of interest in 99% of the patients with cerebral aneurysms. Unwarranted effects of electrode placement and stimulation are rare and without clinical consequences.

Publication Types: Clinical Trial Comparative Study

PMID: 16234682 [PubMed - indexed for MEDLINE]

Trends Cogn Sci. 2005 Nov;9(11):503-5. Epub 2005 Sep 21.

Recharging cognition with DC brain polarization.

Wassermann EM, Grafman J.

Brain Stimulation Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. wassermann@ninds.nih.gov

Electrical direct current (DC) has been applied to the human head throughout history for various reasons and with claims of behavioral effects and clinical benefits. This technique has recently been rediscovered and its effects validated with modern quantitative techniques and experimental designs. Despite the very weak current used, DC polarization applied to specific brain areas can alter verbal fluency, motor learning and perceptual thresholds, and can be used in conjunction with transcranial magnetic stimulation. Compact and safe, this old technique seems poised to allow major advances cognitive science and therapy.

Publication Types: Comparative Study

PMID: 16182596 [PubMed - indexed for MEDLINE]

Neuroreport. 2005 Sep 28;16(14):1551-5.

Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.

Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, Rigonatti SP, Marcolin MA, Freedman SD, Nitsche MA, Pascual-Leone A.

Harvard Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ffregni@bidmc.harvard.edu

Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres. Increased activity in the affected hemisphere can promote recovery, while excessive activity in the unaffected hemisphere may represent a maladaptive strategy. We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients. We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation. Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere (but not sham transcranial direct current stimulation) improved motor performance significantly. These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery.

Publication Types: Clinical Trial Comparative Study Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

PMID: 16148743 [PubMed - indexed for MEDLINE]

Br J Psychiatry. 2005 Aug;187:191-2; author reply 192.

Comment on: Br J Psychiatry. 2005 May;186:446-7.

Transcranial direct current stimulation in developing countries.

Sachdev P.

Publication Types: Comment Letter

PMID: 16110592 [PubMed - indexed for MEDLINE]

Suppl Clin Neurophysiol. 2004;57:708-14.

Outlasting excitability shifts induced by direct current stimulation of the human brain.

Paulus W.

Department of Clinical Neurophysiology, University of Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. wpaulus@med.uni-goettingen.de

tDCS appears to be a promising tool in neuroplasticity research with some perspectives in clinical neurophysiology. It is closely related to modulation of cortical excitability and activity which are key mechanisms for modulating neuroplasticity. Long-term potentiation and long-term depression-like effects have been shown to be involved in learning processes in animal studies so far. Stimulation with weak direct currents is capable of inducing stimulation-polarity-dependent, prolonged, diminutions or elevations of cortical activity and excitability, most probably elicited by a hyper- or depolarisation of resting membrane potentials. Moreover, these modulations are functionally important, since they affect learning processes and epileptic activity. Here excitability changes have been accomplished in the human by non-invasive transcranial direct current stimulation (tDCS). They share some important features with these well-known neuroplastic changes: The duration of the effects depends on stimulation duration and intensity, they are of intracortical origin, and the prolonged effects depend on NMDA-receptor activity. Thus, this technique is a promising method in the field of neuroplastic research in animals and humans and could evolve as a therapeutic tool in some neuro-psychiatric disorders which benefit from modulation of cortical excitability.

Publication Types: Review

PMID: 16106673 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2005 Jul;22(2):495-504.

How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

Lang N, Siebner HR, Ward NS, Lee L, Nitsche MA, Paulus W, Rothwell JC, Lemon RN, Frackowiak RS.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom. nlang@gwdg.de

Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

Publication Types: Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

PMID: 16045502 [PubMed - indexed for MEDLINE]

J Physiol. 2005 Oct 15;568(Pt 2):653-63. Epub 2005 Jul 21.

Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain.

Ardolino G, Bossi B, Barbieri S, Priori A.

Department of Neurological Sciences, Milan University Medical School, Fondazione IRCCS Ospedale Maggiore Policlinico, Italy.

Although cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability, the mechanisms underlying DC-induced changes remain largely unclear. In this study we investigated the effect of cathodal DC stimulation on spontaneous neural activity and on motor responses evoked by stimulation of the central and peripheral nervous system. We studied 17 healthy volunteers. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the motor area were used to study the effects of cathodal tDCS (1.5 mA, 10 min) on resting motor threshold and motor evoked potentials (MEPs) recorded from the contralateral first dorsal interosseous muscle (FDI). The electroencephalographic (EEG) activity in response to cathodal tDCS was analysed by power spectral density (PSD). Motor axonal excitability changes in response to transcutaneous DC stimulation of the ulnar nerve (0.3 mA, 10 min) were assessed by testing changes in the size of the compound muscle action potential (CMAP) elicited by submaximal nerve stimulation. Cathodal tDCS over the motor area for 10 min increased the motor threshold and decreased the size of MEPs evoked by TMS for at least 60 min after current offset (t(0) 71.7 +/- 5%, t(20) 50.8 +/- 11%, t(40) 47.7 +/- 7.7%, and t(60) 39.7 +/- 6.4%, P < 0.01). The tDCS also significantly decreased the size of MEPs elicited by TES (t(0) 64 +/- 16.4%, P = 0.09; t(20) 67.6 +/- 10.8%, P = 0.06; and t(40) 58.3 +/- 9.9%, P < 0.05). At the same time in the EEG the power of delta (2-4 Hz) and theta (4-7 Hz) rhythms increased (delta 181.1 +/- 40.2, P < 0.05; and theta 138.7 +/- 27.6, P = 0.07). At the peripheral level cathodal DC stimulation increased the size of the ulnar nerve CMAP (175 +/- 34.3%, P < 0.05). Our findings demonstrate that the after-effects of tDCS have a non-synaptic mechanism of action based upon changes in neural membrane function. These changes apart from reflecting local changes in ionic concentrations, could arise from alterations in transmembrane proteins and from electrolysis-related changes in [H(+)] induced by exposure to constant electric field.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 16037080 [PubMed - indexed for MEDLINE]

J Physiol. 2005 Oct 1;568(Pt 1):291-303. Epub 2005 Jul 7.

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex.

Nitsche MA, Seeber A, Frommann K, Klein CC, Rochford C, Nitsche MS, Fricke K, Liebetanz D, Lang N, Antal A, Paulus W, Tergau F.

Department of Clinical Neurophysiology, University of Göttingen, Robert Koch Str. 40, 37075 Göttingen, Germany. mnitsch1@gwdg.de

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input-output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input-output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 16002441 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2005 Sep;166(1):23-30. Epub 2005 Jul 6.

Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory.

Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, Marcolin MA, Rigonatti SP, Silva MT, Paulus W, Pascual-Leone A.

Harvard Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330, Brookline Avenue, KS 452., Boston, MA 02215, USA. ffregni@bidmc.harvard.edu

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 15999258 [PubMed - indexed for MEDLINE]

Brain. 2005 Aug;128(Pt 8):1943-50. Epub 2005 May 4.

Homeostatic-like plasticity of the primary motor hand area is impaired in focal hand dystonia.

Quartarone A, Rizzo V, Bagnato S, Morgante F, Sant'Angelo A, Romano M, Crupi D, Girlanda P, Rothwell JC, Siebner HR.

Department of Neuroscience, Psychiatric and Anaethesiological Sciences, University of Messina, Italy. angelo.quartarone@unime.it

The excitability of inhibitory circuits in patients with writer's cramp is reduced at multiple levels within the sensorimotor system, including the primary motor hand area (M1). Although this may play a major role in the pathophysiology of writer's cramp, it is still unclear what factors may cause the imbalance between inhibition and excitation to arise. One possibility is that homeostatic mechanisms that keep cortical excitability within a normal physiological range are impaired. In eight patients with writer's cramp and eight healthy age-matched controls, we combined low-frequency repetitive transcranial magnetic stimulation (rTMS) with transcranial direct current stimulation (TDCS) to probe regional homeostatic plasticity of the left M1. Confirming our previous study (Siebner et al., J Neurosci 2004; 24: 3379-85), 'facilitatory' preconditioning of the M1 with anodal TDCS enhanced the inhibitory effect of subsequent 1 Hz rTMS on corticospinal excitability. Conversely, 'inhibitory' preconditioning with cathodal TDCS reversed the after effect of 1 Hz rTMS, producing an increase in corticospinal excitability. The results were quite different in patients with writer's cramp. Following preconditioning with TDCS, 1 Hz rTMS induced no consistent changes in corticospinal excitability, indicating a loss of the normal 'homeostatic' response pattern. In addition, the normal inhibitory effect of preconditioning with cathodal TDCS was absent. The present data suggest that homeostatic mechanisms that stabilize excitability levels within a useful dynamic range are impaired in patients with writer's cramp. We propose that a faulty homeostatic response to acute increases in corticospinal excitability favours maladaptive motor plasticity. The role of homeostatic-like plasticity in the pathophysiology of task-specific dystonias warrants further study.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 15872016 [PubMed - indexed for MEDLINE]

Br J Psychiatry. 2005 May;186:446-7.

Comment in: Br J Psychiatry. 2005 Aug;187:191-2; author reply 192.

Comment on: Br J Psychiatry. 2004 Nov;185:438-9.

Transcranial direct current stimulation.

Fregni F, Boggio PS, Nitsche M, Pascual-Leone A.

Publication Types: Comment Letter

PMID: 15863752 [PubMed - indexed for MEDLINE]

BMC Neurosci. 2005 Apr 8;6:23.

Bifrontal transcranial direct current stimulation slows reaction time in a working memory task.

Marshall L, Mölle M, Siebner HR, Born J.

University of Lübeck, Department of Neuroendocrinology H23a, Ratzeburger Allee 160, 23538 Lübeck, Germany. marshall@kfg.uni-luebeck.de

BACKGROUND: Weak transcortical direct current stimulation (tDCS) applied to the cortex can shift the membrane potential of superficial neurons thereby modulating cortical excitability and activity. Here we test the possibility of modifying ongoing activity associated with working memory by tDCS. The concept of working memory applies to a system that is capable of transiently storing and manipulating information, as an integral part of the human memory system. We applied anodal and cathodal transcranial direct current (tDCS) stimulation (260 microA) bilaterally at fronto-cortical electrode sites on the scalp over 15 min repeatedly (15 sec-on/15 sec-off) as well as sham-tDCS while subjects performed a modified Sternberg task. RESULTS: Reaction time linearly increased with increasing set size. The slope of this increase was closely comparable for real and sham stimulation indicating that our real stimulation did not effect time required for memory scanning. However, reaction time was slowed during both anodal and cathodal stimulation as compared to placebo (p < 0.05) indicating that real stimulation hampered neuronal processing related to response selection and preparation. CONCLUSION: Intermittent tDCS over lateral prefrontal cortex during a working memory task impairs central nervous processing related to response selection and preparation. We conclude that this decrease in performance by our protocol of intermittent stimulation results from an interference mainly with the temporal dynamics of cortical processing as indexed by event-related sustained and oscillatory EEG activity such as theta.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 15819988 [PubMed - indexed for MEDLINE]

Brain. 2005 Mar;128(Pt 3):490-9. Epub 2005 Jan 5.

Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke.

Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG.

Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20817, USA.

Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind, Sham-controlled, crossover study was designed to test the hypothesis that non-invasive stimulation of the motor cortex could improve motor function in the paretic hand of patients with chronic stroke. Hand function was measured using the Jebsen-Taylor Hand Function Test (JTT), a widely used, well validated test for functional motor assessment that reflects activities of daily living. JTT measured in the paretic hand improved significantly with non-invasive transcranial direct current stimulation (tDCS), but not with Sham, an effect that outlasted the stimulation period, was present in every single patient tested and that correlated with an increment in motor cortical excitability within the affected hemisphere, expressed as increased recruitment curves (RC) and reduced short-interval intracortical inhibition. These results document a beneficial effect of non-invasive cortical stimulation on a set of hand functions that mimic activities of daily living in the paretic hand of patients with chronic stroke, and suggest that this interventional strategy in combination with customary rehabilitative treatments may play an adjuvant role in neurorehabilitation.

Publication Types: Clinical Trial Controlled Clinical Trial Research Support, Non-U.S. Gov't

PMID: 15634731 [PubMed - indexed for MEDLINE]

Neuroreport. 2004 Nov 15;15(16):2491-4.

Direct current stimulation over MT+/V5 modulates motion aftereffect in humans.

Antal A, Varga ET, Nitsche MA, Chadaide Z, Paulus W, Kovács G, Vidnyánszky Z.

Department of Clinical Neurophysiology, Georg-August University, 37075 Göttingen, Germany. A.Antal@gwdg.de

While there is strong evidence for the central role of the human MT+/V5 in motion processing, its involvement in motion adaptation is still the subject of debate. We used transcranial direct current stimulation (tDCS) to test whether MT+/V5 is part of the neural network involved in the long-term adaptation-induced motion after-effect in humans. It was found that both cathodal and anodal stimulation over MT+/V5 resulted in a significant reduction of the perceived motion after-effect duration, but had no effect on performance in a luminance-change-detection task used to determine attentional load during adaptation. Our control experiment excluded the possibility that the observed MT+/V5 stimulation effects were due to a diffused modulation of the early cortical areas, i.e. by the stimulation applied over MT+/V5. These results provide evidence that external modulation of neural excitability in human MT+/V5 affects the strength of perceived motion after-effect and support the involvement of MT+/V5 in motion adaptation processes.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 15538181 [PubMed - indexed for MEDLINE]

J Neurosci. 2004 Nov 3;24(44):9985-92.

Erratum in: J Neurosci. 2005 Jan 12;25(2):1 p following 531.

Transcranial direct current stimulation during sleep improves declarative memory.

Marshall L, Mölle M, Hallschmid M, Born J.

Institute of Neuroendocrinology H23a, University of Lübeck, 23538 Lübeck, Germany. marshall@kfg.uni-luebeck.de

In humans, weak transcranial direct current stimulation (tDCS) modulates excitability in the motor, visual, and prefrontal cortex. Periods rich in slow-wave sleep (SWS) not only facilitate the consolidation of declarative memories, but in humans, SWS is also accompanied by a pronounced endogenous transcortical DC potential shift of negative polarity over frontocortical areas. To experimentally induce widespread extracellular negative DC potentials, we applied anodal tDCS (0.26 mA) [correction] repeatedly (over 30 min) bilaterally at frontocortical electrode sites during a retention period rich in SWS. Retention of declarative memories (word pairs) and also nondeclarative memories (mirror tracing skills) learned previously was tested after this period and compared with retention performance after placebo stimulation as well as after retention intervals of wakefulness. Compared with placebo stimulation, anodal tDCS during SWS-rich sleep distinctly increased the retention of word pairs (p < 0.005). When applied during the wake retention interval, tDCS did not affect declarative memory. Procedural memory was also not affected by tDCS. Mood was improved both after tDCS during sleep and during wake intervals. tDCS increased sleep depth toward the end of the stimulation period, whereas the average power in the faster frequency bands (,alpha, and beta) was reduced. Acutely, anodal tDCS increased slow oscillatory activity <3 Hz. We conclude that effects of tDCS involve enhanced generation of slow oscillatory EEG activity considered to facilitate processes of neuronal plasticity. Shifts in extracellular ionic concentration in frontocortical tissue (expressed as negative DC potentials during SWS) may facilitate sleep-dependent consolidation of declarative memories.

Publication Types: Clinical Trial Controlled Clinical Trial Research Support, Non-U.S. Gov't

PMID: 15525784 [PubMed - indexed for MEDLINE]

Biol Psychiatry. 2004 Nov 1;56(9):634-9.

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

Lang N, Siebner HR, Ernst D, Nitsche MA, Paulus W, Lemon RN, Rothwell JC.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, United Kingdom. nlang@gwdg.de

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 15522246 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2004 Oct;115(10):2419-23.

MRI study of human brain exposed to weak direct current stimulation of the frontal cortex.

Nitsche MA, Niehaus L, Hoffmann KT, Hengst S, Liebetanz D, Paulus W, Meyer BU.

Department of Clinical Neurophysiology, Georg-August-University, Robert-Koch-Str. 40, 37075 Goettingen, Germany. mnitsch1@gwdg.de

OBJECTIVE: To determine whether weak transcranial direct current stimulation (tDCS), which is an interesting new tool inducing prolonged cortical excitability shifts in humans, induces brain edema, disturbance of the blood-brain barrier or structural alterations of the brain detectable by magnetic resonance imaging (MRI). METHODS: In 10 healthy individuals, tDCS, which is known to alter cortical excitability for about 1 h, was applied over motor and pre-frontal cortices. contrast-enhanced t1-, t2-, and diffusion-weighted mri was performed immediately before, 30 and 60 min after tdcs. RESULTS: MRI performed 30 and 60 min after tDCS did not show pathological signal alterations in pre- and post-contrast-enhanced T1-weighted and diffusion-weighted MR sequences. CONCLUSIONS: tDCS protocols which are known to result in cortical excitability changes persisting for an hour after stimulation do not induce brain edema or alterations of the blood-brain barrier or cerebral tissue detectable by MRI. SIGNIFICANCE: These results deliver further evidence for the safety of the currently applied tDCS protocols in humans.

Publication Types: Clinical Trial

PMID: 15351385 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2004 Dec;159(4):530-6. Epub 2004 Jul 13.

Different effects of fatiguing exercise on corticospinal and transcallosal excitability in human hand area motor cortex.

Edgley SA, Winter AP.

Department of Anatomy, University of Cambridge, Downing Street, CB2 3DY Cambridge, UK. sae1000@cam.ac.uk

Following forceful exercise that leads to muscle fatigue, the size of muscle evoked responses (MEPs) generated by transcranial magnetic stimulation (TMS) in the exercised muscle is depressed over a prolonged period. Strong evidence implicates intracortical mechanisms in this depression. As well as evoking MEPs in contralateral muscles, TMS also reduces MEPs evoked in ipsilateral muscles through interhemispheric inhibition mediated by a transcallosal pathway. Here we have sought to determine whether this effect is also depressed after exercise. Using two magnetic stimulators, the aftereffects of unilateral hand muscle exercise on the ability of TMS delivered to the hemisphere that generated the exercise were examined to i) generate MEPs in the exercised hand muscles, and ii) depress MEPs evoked by TMS pulses in contralateral (non-exercised) hand muscles. After exercise there was a significant reduction in the amplitudes of MEPs evoked by TMS in the exercised muscles ( p<0.001). However, the same stimuli remained able to depress responses evoked by TMS to the contralateral hemisphere in the non-exercised muscles as effectively as before the exercise. We conclude that unlike the MEPs evoked by corticospinal output, interhemispheric inhibition evoked from the hemisphere that generated the exercise is not depressed after exercise. A similar differential effect on interhemispheric inhibition and corticospinal output has been reported recently for the effects of transcranial direct current (DC) stimulation of the motor cortex. Fatiguing exercise and transcranial DC stimulation may therefore engage similar intracortical mechanisms.

Publication Types: Clinical Trial

PMID: 15249989 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2004 Jul;20(1):313-6.

Transcranial direct current stimulation disrupts tactile perception.

Rogalewski A, Breitenstein C, Nitsche MA, Paulus W, Knecht S.

Department of Neurology, University of Muenster, Albert-Schweitzer-Strasse 33, 48129 Muenster, Germany. rogalewski@uni-muenster.de

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10-20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability.

Publication Types: Comparative Study

PMID: 15245504 [PubMed - indexed for MEDLINE]

Neuropsychopharmacology. 2004 Aug;29(8):1573-8.

Consolidation of human motor cortical neuroplasticity by D-cycloserine.

Nitsche MA, Jaussi W, Liebetanz D, Lang N, Tergau F, Paulus W.

Department Clinical Neurophysiology, Georg-August-University, Goettingen, Germany. mnitsch1@gwdg.de

D-Cycloserine (CYC), a partial N-methyl-D-aspartate (NMDA) agonist, has been shown to improve cognitive functions in humans. However, the neurophysiological basis of this effect is unclear so far. We studied the impact of this drug on long-lasting after-effects of transcranial direct current (tDCS)-generated motor cortical excitability shifts, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials. While anodal tDCS enhances motor cortical excitability, cathodal tDCS diminishes it. Both effects seem to be NMDA receptor dependent. D-CYC selectively potentiated the duration of motor cortical excitability enhancements induced by anodal tDCS. D-CYC alone did not modulate excitability. The potency of this drug to consolidate neuronal excitability enhancements, most probably by stabilizing the strengthening of NMDA receptors, which is a probable neurophysiological derivate of learning processes, makes it an interesting substance to improve cognitive functions.

PMID: 15199378 [PubMed - indexed for MEDLINE]

Neuroreport. 2004 Jun 7;15(8):1307-10.

Oscillatory brain activity and transcranial direct current stimulation in humans.

Antal A, Varga ET, Kincses TZ, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Robert Koch Strasse 40, 37075 Göttingen, Germany. AAntal@gwdg.de

The aim of this study was to induce changes of the oscillatory activity in the visual cortex of healthy human subjects by modulation of neuronal excitability using weak transcranial direct current stimulation (tDCS). tDCS is a non-invasive stimulation method which induces prolonged, polarity-dependent increases or reductions in cortical excitability. An increase in high frequency oscillatory activity in the beta and gamma frequency ranges is closely related in time to the N70 peak of the primary visual evoked potential (VEP), which is an early sensory component of visual activation. Therefore this potential can be used to observe tDCS-induced changes related to oscillatory activity. VEPs were recorded using sinusoidal luminance gratings in an on/off mode before, immediately after and 10, 20, 30 min after the end of 10 min anodal or cathodal stimulation. Cathodal stimulation significantly decreased while anodal stimulation slightly increased the normalized beta and gamma frequency powers. We have shown here that tDCS transiently and reversibly changed the organized cortical activity elicited by visual stimulation. Since gamma activity is also related to a higher level of information processing, tDCS might be a suitable method to affect higher order cognitive processes. Copyright 2004 Lippincott Williams and Wilkins

Publication Types: Research Support, Non-U.S. Gov't

PMID: 15167555 [PubMed - indexed for MEDLINE]

Neuroreport. 2004 Jun 7;15(8):1287-91.

Long lasting effects of transcranial direct current stimulation on motor imagery.

Quartarone A, Morgante F, Bagnato S, Rizzo V, Sant'Angelo A, Aiello E, Reggio E, Battaglia F, Messina C, Girlanda P.

Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, Clinica Neurologica 2, Policlinico Universitario, 98125 Messina, Italy. angelo.quartarone@unime.it

Transcranial magnetic stimulation (TMS) was employed to probe the modulatory effects of transcranial direct current stimulation of motor cortex on motor evoked responses (MEPs) produced during motor imagery. MEP amplitudes at rest and during motor imagery were assessed before and for a period of 60 min after transcranial direct current stimulation (tDCS) applied over the primary motor cortex at 1 mA for 5 min. Cathodal stimulation induced a decrease of about 30% of MEP amplitude at rest and a 50% reduction of MEP size during imagery. Ten minutes after tDCS, MEPs at rest returned to baseline values while MEPs during motor imagery were suppressed for up to 30 min. No changes in MEP amplitude during imagery were found after anodal stimulation. tDCS could represent a powerful tool to modulate the excitability of motor areas involved in mental practice and motor imagery. Copyright 2004 Lippincott Williams and Wilkins

PMID: 15167551 [PubMed - indexed for MEDLINE]

J Cogn Neurosci. 2004 May;16(4):521-7.

Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans.

Antal A, Nitsche MA, Kruse W, Kincses TZ, Hoffmann KP, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, Goettingen, Germany. AAntal@gwdg.de

The primary aim of this study was to determine the extent to which human MT+/V5, an extrastriate visual area known to mediate motion processing, is involved in visuomotor coordination. To pursue this we increased or decreased the excitability of MT+/V5, primary motor, and primary visual cortex by the application of 7 min of anodal and cathodal transcranial direct current stimulation (tDCS) in healthy human subjects while they were performing a visuomotor tracking task involving hand movements. The percentage of correct tracking movements increased specifically during and immediately after cathodal stimulation, which decreases cortical excitability, only when V5 was stimulated. None of the other stimulation conditions affected visuomotor performance. We propose that the improvement in performance caused by cathodal tDCS of V5 is due to a focusing effect on to the complex motion perception conditions involved in this task. This hypothesis was proven by additional experiments: Testing simple and complex motion perception in dot kinetograms, we found that a diminution in excitability induced by cathodal stimulation improved the subject's perception of the direction of the coherent motion only if this was presented among random dots (complex motion perception), and worsened it if only one motion direction was presented (simple movement perception). Our data suggest that area V5 is critically involved in complex motion perception and identification processes important for visuomotor coordination. The results also raise the possibility of the usefulness of tDCS in rehabilitation strategies for neurological patients with visuomotor disorders.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 15165345 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2004 May;19(10):2888-92.

Facilitation of visuo-motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans.

Antal A, Nitsche MA, Kincses TZ, Kruse W, Hoffmann KP, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, 37075 Goettingen, Germany. AAntal@gwdg.de

Performance of visuo-motor tasks requires the transfer of visual data to motor performance and depends highly on visual perception and cognitive processing, mainly during the learning phase. The primary aim of this study was to determine if the human middle temporal (MT)+/V5, an extrastriate visual area that is known to mediate motion processing, and the primary motor cortex are involved in learning of visuo-motor coordination tasks. To pursue this, we increased or decreased MT+/V5, primary contralateral motor (M1) and primary visual cortex excitability by 10 min of anodal or cathodal transcranial direct current stimulation in healthy human subjects during the learning phase of a visually guided tracking task. The percentage of correct tracking movements increased significantly in the early learning phase during anodal stimulation, but only when the left V5 or M1 was stimulated. Cathodal stimulation had no significant effect. Also, stimulation of the primary visual cortex was not effective for this kind of task. Our data suggest that the areas V5 and M1 are involved in the early phase of learning of visuo-motor coordination.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 15147322 [PubMed - indexed for MEDLINE]

Cereb Cortex. 2004 Nov;14(11):1240-5. Epub 2004 May 13.

Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

Nitsche MA, Grundey J, Liebetanz D, Lang N, Tergau F, Paulus W.

Department of Clinical Neurophysiology, Georg-August-University, Robert Koch Str. 40, 37075 Goettingen, Germany. mnitsch1@gwdg.de

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 15142961 [PubMed - indexed for MEDLINE]

J Neurosci. 2004 Mar 31;24(13):3379-85.

Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex.

Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College of London, London WC1N 3BG, United Kingdom.

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 15056717 [PubMed - indexed for MEDLINE]

Anesth Analg. 2004 Mar;98(3):730-7, table of contents.

The antinociceptive effect of transcranial electrostimulation with combined direct and alternating current in freely moving rats.

Nekhendzy V, Fender CP, Davies MF, Lemmens HJ, Kim MS, Bouley DM, Maze M.

Department of Anesthesiology, Stanford University School of Medicine, Stanford, California 94305-5640, USA. nek@stanford.edu

Transcranial electrostimulation (TES) has been reported to elicit significant analgesia, allowing a substantial reduction of intraoperative opioids. Acceptance of TES into clinical practice is hampered by lack of controlled clinical trials and inconclusive animal data regarding the TES antinociceptive action. This inconclusive data may be explained, in part, by failure in rat experiments to simulate the variables used in humans when TES electrodes are positioned on the skin. In this study we validated the TES antinociceptive effect in a novel animal model of cutaneously administered TES, when the stimulating conditions mimic the ones used in clinical practice. The antinociceptive effect was assessed by measuring nociceptive thresholds in the tail-flick and hot-plate latency tests in awake, unrestrained male rats. Data were analyzed by analysis of variance and mixed-effects population modeling. The administration of TES at 2.25 mA produced an almost immediate, sustained, frequency-dependent (40-60 Hz) antinociceptive effect, reaching approximately 50% of the maximal possible value. We conclude that an antinociceptive effect of cutaneously administered TES can be demonstrated in the rat. Some characteristics of the effect suggest an important role of the sensory nerves of the rat's scalp in mediating the TES antinociceptive response. IMPLICATIONS: Transcranial electrostimulation produces a significant, frequency-dependent antinociceptive effect that may be mediated by cutaneous nerves of the scalp.

Publication Types: Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PMID: 14980928 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2004 Jun;156(4):439-43. Epub 2004 Jan 24.

Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability.

Lang N, Nitsche MA, Paulus W, Rothwell JC, Lemon RN.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, WC1N 3BG, UK. nlang@gwdg.de

Weak transcranial direct current stimulation (tDCS) can induce long lasting changes in cortical excitability. In the present study we asked whether tDCS applied to the left primary motor cortex (M1) also produces aftereffects distant from the site of the stimulating electrodes. We therefore tested corticospinal excitability in the left and the right M1 and transcallosal excitability between the two cortices using transcranial magnetic stimulation (TMS) before and after applying tDCS. Eight healthy subjects received 10 min of anodal or cathodal tDCS (1 mA) to the left M1. We examined the amplitude of contralateral motor evoked potentials (MEPs) and the onset latency and duration of transcallosal inhibition with single pulse TMS. MEPs evoked from the tDCS stimulated (left) M1 were increased by 32% after anodal and decreased by 27% after cathodal tDCS, while transcallosal inhibition evoked from the left M1 remained unchanged. The effect on MEPs evoked from the left M1 lasted longer for cathodal than for anodal tDCS. MEPs evoked from the right M1 were unchanged whilst the duration of transcallosal inhibition evoked from the right M1 was shortened after cathodal tDCS and prolonged after anodal tDCS. The duration of transcallosal inhibition returned to control values before the effect on the MEPs from the left M1 had recovered. These findings are compatible with the idea that tDCS-induced aftereffects in the cortical motor system are limited to the stimulated hemisphere, and that tDCS not only affects corticospinal circuits involved in producing MEPs but also inhibitory interneurons mediating transcallosal inhibition from the contralateral hemisphere.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 14745467 [PubMed - indexed for MEDLINE]

Invest Ophthalmol Vis Sci. 2004 Feb;45(2):702-7.

Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence.

Antal A, Kincses TZ, Nitsche MA, Bartfai O, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany. aantal@gwdg.de

PURPOSE: Transcranial direct current stimulation (tDCS) has been shown to modify the perception threshold of phosphenes elicited by transcranial magnetic stimulation (TMS). The current study was undertaken to examine whether tDCS, when applied over the occipital cortex, is also able to affect visual-evoked potentials (VEPs), which characterize occipital activation in response to visual stimulation, in a polarity-specific way. METHOD: For this purpose, VEPs evoked by sinusoidal luminance grating in an on/off mode were recorded before, immediately after, and 10, 20, and 30 minutes after the end of 5, 10, or 15 minutes of anodal or cathodal tDCS of the primary visual cortex. RESULTS: Significant effects were observed only when low-contrast visual stimuli were applied. Cathodal stimulation decreased, whereas anodal stimulation increased the amplitude of the N70 component. The effect of cathodal stimulation was significant immediately after and 10 minutes after the end of stimulation, if the stimulation duration was sufficiently long (i.e., 10-15 minutes). An increase of N70 amplitude by anodal stimulation was significant only 10 minutes after the end of the 15 minutes tDCS. Cathodal stimulation tended also to affect the amplitude of the P100 component; however, the effect of stimulation was inverse. The amplitude increased immediately after the end of cathodal stimulation. In contrast, anodal stimulation did not affect the P100. The latencies of the N70 and the P100 were not affected by tDCS. CONCLUSIONS: tDCS appears to be a suitable method of inducing reversible excitability changes in a polarity-specific way, not only in the motor but also in the primary visual cortex. The duration of the induced aftereffects depends not only on stimulation duration but also on stimulation polarity. Cathodal stimulation seems to be more effective, in line with previous reports on the motor cortex.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 14744917 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2004 Feb;115(2):456-60.

Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.

Matsunaga K, Nitsche MA, Tsuji S, Rothwell JC.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, 8-11 Queen Square, London WC1N 3BG, UK.

OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.

Publication Types: Comparative Study

PMID: 14744588 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2004 Feb;115(2):255-66.

The physiological basis of transcranial motor cortex stimulation in conscious humans.

Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Mazzone P, Insola A, Tonali PA, Rothwell JC.

Institute of Neurology, Università Cattolica, Largo A. Gemelli 8, 00168, Rome, Italy. vdilazzaro@rm.unicatt.it

Transcranial stimulation of the human motor cortex can evoke several different kinds of descending activity depending on the type of stimulation, the intensity of stimulation and the area of the cortex being stimulated. Thus, transcranial magnetic stimulation preferentially activates different structures than transcranial electrical stimulation. In addition, the response to magnetic stimulation depends on the direction of the induced current in the brain, the waveform of the stimulating current, and the shape of the coil. Stimulation of the lower limb area of motor cortex recruits different elements than stimulation of the upper limb area. These differences occur because different structures in the motor cortex have a differential threshold to the different techniques of stimulation. We have had the opportunity to perform a series of direct recordings of the corticospinal volley evoked by the different techniques of transcranial stimulation from the epidural space of conscious patients with chronically implanted spinal electrodes. These recordings provide insights about the physiological basis of the excitatory and inhibitory phenomena produced by transcranial stimulation.

Publication Types: Review

PMID: 14744565 [PubMed - indexed for MEDLINE]

Suppl Clin Neurophysiol. 2003;56:291-304.

Transcranial magnetic and direct current stimulation of the visual cortex.

Antal A, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Robert Koch Strasse 40, D-37075 Göttingen, Germany. Aantal@gwdg.de

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 14677406 [PubMed - indexed for MEDLINE]

Suppl Clin Neurophysiol. 2003;56:282-7.

Pharmacology of transcranial direct current stimulation: missing effect of riluzole.

Liebetanz D, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Robert-Koch Strasse 40, D-37075 Göttingen, Germany. dliebet@gwdg.de

Publication Types: Comparative Study

PMID: 14677405 [PubMed - indexed for MEDLINE]

Suppl Clin Neurophysiol. 2003;56:249-54.

Transcranial direct current stimulation (tDCS).

Paulus W.

Department of Clinical Neurophysiology, University of Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. w.paulus@med.uni-goettingen.de

tDCS appears to be a promising tool in neuroplasticity research with some tentative perspectives in clinical neurophysiology. The next steps to be carried out encompass better histological safety data. In order to preclude the possibility of neuronal damage, extending tDCS duration should be limited until more direct safety criteria are available than those derived from Agnew and McCreery (1987) (cf. Nitsche et al, this volume). Safe stimulation protocols have to be developed which allow an extension of the duration of after-effects towards a somewhat permanent state, supposing a beneficial effect can be found in neurological diseases or in neurorehabilitation.

Publication Types: Comparative Study

PMID: 14677402 [PubMed - indexed for MEDLINE]

Neuropsychologia. 2004;42(1):113-7.

Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human.

Kincses TZ, Antal A, Nitsche MA, Bártfai O, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.

The aim of our study was to test if the electrical stimulation of the prefrontal cortex (PFC) could modify probabilistic classification learning (PCL). Transcranial direct current stimulation (tDCS) was administered to the left prefrontal and to the primary visual cortex of 22 healthy subjects while they performed a PCL task. In this task subjects learned which of two outcomes would occur on each trial after presentation of a particular combination of cues. Ten minutes of anodal, but not cathodal, stimulation improved implicit learning only when the left PFC was stimulated. Our results show that implicit PLC can be modified by weak anodal tDCS, which probably increases neural excitability, as has been shown in the motor and visual cortices previously. Our results suggest that further studies on the facilitation of learning and memory processes by tDCS are warranted.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 14615081 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2003 Nov;114(11):2220-2; author reply 2222-3.

Safety criteria for transcranial direct current stimulation (tDCS) in humans.

Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W.

Publication Types: Letter

PMID: 14580622 [PubMed - indexed for MEDLINE]

Neuropsychologia. 2003;41(13):1802-7.

Modulation of moving phosphene thresholds by transcranial direct current stimulation of V1 in human.

Antal A, Kincses TZ, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, George-August University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany. aantal@gwdg.de

Small moving sensations, so-called moving phosphenes are perceived, when V5, a visual area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if only V5 takes part in movement perception or other visual areas are also involved in this process. In this study we tested the involvement of V1 in the perception of moving phosphenes by applying transcranial direct current stimulation (tDCS) to this area. tDCS is a non-invasive stimulation technique known to modulate cortical excitability in a polarity-specific manner. Moving and stationary phosphene thresholds (PT) were measured by TMS before, immediately after and 10, 20 and 30 min after the end of 10 min cathodal and anodal tDCS in nine healthy subjects. Reduced PTs were detected immediately and 10 min after the end of anodal tDCS while cathodal stimulation resulted in an opposite effect. Our results show that the excitability shifts induced by V1 stimulation can modulate moving phosphene perception. tDCS elicits transient, but yet reversible effects, thus presenting a promising tool for neuroplasticity research.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

PMID: 14527543 [PubMed - indexed for MEDLINE]

J Physiol. 2003 Nov 15;553(Pt 1):293-301. Epub 2003 Aug 29.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

Nitsche MA, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, Henning S, Tergau F, Paulus W.

Department of Clinical Neurophysiology, Georg-August-University, Goettingen, Germany. mnitsch1@gwdg.de

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

Publication Types: Clinical Trial

PMID: 12949224 [PubMed - indexed for MEDLINE]

J Neurosci Methods. 2003 Aug 15;127(2):193-7.

Increased cortical excitability induced by transcranial DC and peripheral nerve stimulation.

Uy J, Ridding MC.

Department of Physiology, University of Adelaide, Adelaide SA 5005, Australia.

This study investigated the effect of short periods of simultaneous weak anodal direct current (DC) stimulation and peripheral ulnar nerve (ES) stimulation on corticospinal excitability. The experiments involved repeated testing of ten normal subjects with four different protocols: (1) No Stimulation; (2) DC only; (3) ES only; (4) DC plus ES. Motor evoked potentials (MEP) were recorded from the First Dorsal Interosseous (FDI); Abductor Digiti Minimi (ADM) and Flexor Carpi Ulnaris (FCU). The baseline MEP amplitude was compared with that obtained immediately after the first set of stimulation, after the second set of stimulation, 15 min post stimulation and 30 min after stimulation. No significant change was seen with the No Stimulation and ES Only protocols. FDI showed a significant change in the DC protocol after the second set of stimulation but the changes were not present 15 or 30 min after. The DC plus ES protocol showed FDI changes that were significant after the second set of stimulation with the elevations persisting when tested 15 and 30 min post intervention. These observations show that a period of anodal DC stimulation preceding a period of ulnar nerve stimulation resulted in significant and persistent elevations in cortical excitability.

Publication Types: Comparative Study

PMID: 12906948 [PubMed - indexed for MEDLINE]

J Cogn Neurosci. 2003 May 15;15(4):619-26.

Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human.

Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, Tergau F.

Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany. mnitsch1@gwdg.de

Transcranially applied weak direct currents are capable of modulating motor cortical excitability in the human. Anodal stimulation enhances excitability, cathodal stimulation diminishes it. Cortical excitability changes accompany motor learning. Here we show that weak direct currents are capable of improving implicit motor learning in the human. During performance of a serial reaction time task, the primary motor cortex, premotor, or prefrontal cortices were stimulated contralaterally to the performing hand. Anodal stimulation of the primary motor cortex resulted in increased performance, whereas stimulation of the remaining cortices had no effect. We conclude that the primary motor cortex is involved in the acquisition and early consolidation phase of implicit motor learning.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 12803972 [PubMed - indexed for MEDLINE]

Exp Brain Res. 2003 Jun;150(3):375-8. Epub 2003 Apr 16.

Manipulation of phosphene thresholds by transcranial direct current stimulation in man.

Antal A, Kincses TZ, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, Robert Koch Strasse 40, 37070 Göttingen, Germany. Aantal@gwdg.de

Transcranial direct current stimulation (tDCS) can modulate the excitability of the human motor cortex, as revealed by the amplitude of the motor-evoked potentials (MEP). The aim of our study has been to produce localized changes of cerebral excitability of the visual cortex in the intact human by weak anodal and cathodal stimulation. For quantification of current-induced excitability changes, we measured phosphene threshold (PT) using short trains of 5-Hz transcranial magnetic stimulation (TMS) pulses in nine healthy subjects before, immediately after, 10 min, and 20 min after the end of tDCS. PTs are suggested as representative values of visual cortex excitability changes. Reduced PT was detected immediately and 10 min after the end of anodal stimulation, while cathodal stimulation resulted in an opposite effect. Our results show that tDCS elicits a transient, reversible excitability alteration of the visual cortex, thus representing a promising tool for neuroplasticity research.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 12698316 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2003 Apr;114(4):600-4.

Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.

Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell JC, Paulus W.

Department of Clinical Neurophysiology, University of Goettingen, Robert Koch Str. 40, 37075, Goettingen, Germany. mnitsch1@gwdg.de <mnitsch1@gwdg.de>

OBJECTIVE: To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. METHODS: Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. RESULTS: Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. CONCLUSIONS: Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 12686268 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2003 Apr;114(4):589-95.

Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability.

Priori A.

Dipartimento di Scienze Neurologiche, IRCCS Ospedale Maggiore, Policlinico di Milano, Università di Milano, Padiglione Ponti, Via F. Sforza 35, 20122, Milan, Italy. alberto.priori@unimi.it <alberto.priori@unimi.it>

Direct current (DC) is very effective in modulating spontaneous neuronal firing. The history of electrophysiology starts with the discovery of the biological effects of DC and as early as two centuries ago scalp DC was used to treat mental disorder. Psychophysiological investigations suggested a possible effect of scalp DC in humans. More recently several studies assessed, with motor potentials evoked by transcranial brain stimulation, the motor-cortical excitability changes induced by scalp DC. Even weak DCs pass through the scalp and influence human brain activity. DCs delivered at relatively strong intensities (1 mA) and for long periods (10 min or so), not only influence (either increase or decrease) brain excitability during their application in normal subjects, but induce persistent changes in excitability after their offset that, at least in the motor cortex, can last for almost 1 h. Scalp DC might represent a non-invasive simple and valuable potential treatment for psychiatric and neurologic diseases with changes in brain excitability or focally abnormal (increased or decreased) function.

Publication Types: Historical Article Research Support, Non-U.S. Gov't

PMID: 12686266 [PubMed - indexed for MEDLINE]

Neurol Res. 2003 Mar;25(2):143-50.

Corticospinal volleys evoked by transcranial stimulation of the brain in conscious humans.

Di Lazzaro V, Oliviero A, Pilato F, Mazzone P, Insola A, Ranieri F, Tonali PA.

Institute of Neurology, Catholic University, L.go A. Gemelli 8, 00168 Rome, Italy. vdilazzaro@rm.unicatt.it

The direct recording in conscious humans of corticospinal volleys evoked by different magnetic and electric techniques of transcranial stimulation demonstrates that it is possible to activate neurones of the motor cortex in several different ways. Lateral electrical stimulation of the motor cortex preferentially activates the axons of corticospinal neurones in the subcortical white matter, and evokes a D-wave in pyramidal tract. The way of activation of corticospinal neurones using magnetic stimulation depends on the direction of the electrical current induced in the brain and on the shape of the coil. Monophasic magnetic stimulation with a focal figure-of-eight coil inducing posterior-anterior current in the brain activates corticospinal neurones trans-synaptically recruiting an 11-wave, with later I-waves appearing in sequence at higher intensities and a D-wave at very high intensities. If the induced current is rotated to the anterior-posterior direction late I-waves are preferentially recruited and when a D-wave is recruited, it has a later onset than the electrical D-wave, suggesting an activation nearer the cell body of the pyramidal neurones. A latero-medial induced current activates both corticospinal axons at the same point as electrical stimulation evoking a D wave and cortico-cortical axons evoking I-waves. A nonfocal large circular coil centered at the vertex is capable of activating pyramidal neurones both at the initial segment and trans-synaptically evoking a D wave with a longer latency than the electrical D-wave and I-waves. Using a biphasic magnetic stimulation, both phases of the biphasic pulse are capable of activating descending motor output and the pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.

Publication Types: Review

PMID: 12635512 [PubMed - indexed for MEDLINE]

Bipolar Disord. 2002;4 Suppl 1:98-9.

Transcranial direct current stimulation: a new treatment for depression?

Nitsche MA.

Department Clin. Neurophysiology, Georg-August-University, Goettingen, Germany.

Publication Types: Comparative Study

PMID: 12479691 [PubMed - indexed for MEDLINE]

Brain. 2002 Oct;125(Pt 10):2238-47.

Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.

Liebetanz D, Nitsche MA, Tergau F, Paulus W.

Department of Clinical Neurophysiology, Georg-August University Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany.

Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.

Publication Types: Clinical Trial Comparative Study Controlled Clinical Trial Research Support, Non-U.S. Gov't

PMID: 12244081 [PubMed - indexed for MEDLINE]

Nervenarzt. 2002 Apr;73(4):332-5.

[Modulation of cortical excitability by transcranial direct current stimulation]

[Article in German]

Nitsche MA, Liebetanz D, Tergau F, Paulus W.

Abteilung Klinische Neurophysiolgie, Georg-August-Universität Göttingen. mnitsch1@gwdg.de

Modulation of cerebral excitability is thought to be one mechanism underlying the pharmacological treatment of neuropsychiatric diseases such as epilepsy, depression, and dystonia. Repetitive transcranial magnetic stimulation (rTMS) has been tested for several years as a nonpharmacological, noninvasive method of directly influencing patients' cortical functions. We present an overview of the more easily performed transcranial direct current stimulation (tDCS) with weak current, which produces distinctly more pronounced changes in excitability than rTMS. The basic underlying mechanism is a shift in the resting membrane potential towards either hyper- or depolarisation, depending on stimulation polarity. This in turn leads to changes in the excitability of cortical neurons. Anodic stimulation increases cortical excitability, while cathodic stimulation decreases it. These changes persist after the end of stimulation if the stimulation lasts long enough, i.e., at least several minutes. The duration of this aftereffect can be controlled through the duration and intensity of the stimulation. Transcranial direct current stimulation essentially allows a focal, selective, reversible, pain-free, and noninvasive induction of changes in cortical excitability, the therapeutic potential of which must be evaluated in clinical studies, once possible risk factors have been assessed.

Publication Types: English Abstract Research Support, Non-U.S. Gov't Review

PMID: 12040980 [PubMed - indexed for MEDLINE]

Neuroreport. 2001 Nov 16;12(16):3553-5.

External modulation of visual perception in humans.

Antal A, Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen, Robert Koch Str. 40, 37070 Göttingen, Germany.

Static and dynamic contrast sensitivities (sCS and dCS) were evaluated before, during, immediately after and 10 min after anodal and cathodal transcranial direct current stimulation (tDCS) applied to the occipital cortex of 15 healthy subjects. Using 4 c/d spatial and 4 Hz temporal frequencies significant sCS and dCS loss was found during and immediately after 7 min cathodal stimulation while anodal stimulation had no effect. Ten minutes after the end of the stimulation the sCS and dCS values had reached the baseline levels. Our results show that primary visual functions, such as contrast detection can be transiently altered by transcranial weak direct current stimulation, most probably modulating neural excitability, as has been shown in the motor cortex previously. The present study also support the view that this method using weak current can be a non-invasive promising tool to induce reversible focal changes in the nervous system.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 11733710 [PubMed - indexed for MEDLINE]

Neurology. 2001 Nov 27;57(10):1899-901.

Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans.

Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, University of Goettingen, Germany.

The authors show that in the human transcranial direct current stimulation is able to induce sustained cortical excitability elevations. As revealed by transcranial magnetic stimulation, motor cortical excitability increased approximately 150% above baseline for up to 90 minutes after the end of stimulation. The feasibility of inducing long-lasting excitability modulations in a noninvasive, painless, and reversible way makes this technique a potentially valuable tool in neuroplasticity modulation.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 11723286 [PubMed - indexed for MEDLINE]

Magn Reson Med. 2001 Feb;45(2):196-201.

Regional modulation of BOLD MRI responses to human sensorimotor activation by transcranial direct current stimulation.

Baudewig J, Nitsche MA, Paulus W, Frahm J.

Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.

Blood oxygenation level dependent (BOLD) MRI was used to monitor modulations of human sensorimotor activity by prior transcranial direct current stimulation (tDCS). Activation maps for a right hand sequential finger opposition task were obtained for six subjects before as well as 0-5 min and 15-20 min after a 5-min period of 1 mA cathodal and, in a separate session, anodal tDCS of the left-hemispheric motor cortex. Cathodal tDCS resulted in a global decrease of the mean number of activated pixels by 38% (P < 0.01) 0-5 min after stimulation, which reduced to 28% (P < 0.05) 15-20 min after stimulation. A region-of-interest analysis revealed a 57% decrease of activated pixels (P < 0.001) in the supplementary motor area, but no change in the hand area of the primary motor cortex. Anodal tDCS yielded a nonsignificant 5% increase of activated pixels with no regional differences. These findings support the view that reduced neuroaxonal excitability after cathodal tDCS causes reduced brain activity. However, rather than affecting the primary sensorimotor input of an active task, the process appears to dampen those responses that rely on cortico-cortical connections and related processing. Magn Reson Med 45:196-201, 2001. Copyright 2001 Wiley-Liss, Inc.

PMID: 11180425 [PubMed - indexed for MEDLINE]

Neurosci Lett. 2000 Dec 15;296(1):61-3.

Diminution of training-induced transient motor cortex plasticity by weak transcranial direct current stimulation in the human.

Rosenkranz K, Nitsche MA, Tergau F, Paulus W.

Department of Clinical Neurophysiology, University of Goettingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany.

Training of a thumb movement in the opposite direction of a twitch in response to transcranial magnetic stimulation (TMS) induces a transient directional change of post-training TMS-evoked movements towards the trained direction. Functional synaptic mechanisms seem to underlie this rapid training-induced plasticity. Transcranial direct current stimulation (tDCS) induces outlasting changes of cerebral excitability, thus presenting as promising tool for neuroplasticity research. We studied the influence of tDCS, applied over the motorcortex during training, on angular deviation of post-training to pre-training TMS-evoked thumb movements. With tDCS of anodal and cathodal polarity the training-induced directional change of thumb movements was significantly reduced during a 10 min post-training interval, indicating an interference of tDCS with mechanisms of rapid training-induced plasticity.

PMID: 11099834 [PubMed - indexed for MEDLINE]

J Physiol. 2000 Sep 15;527 Pt 3:633-9.

Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.

Nitsche MA, Paulus W.

Department of Clinical Neurophysiology, University of Goettingen, Robert Koch Strasse 40, 37075 Goettingen, Germany. mnitsch1@gwdg.de

In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp. Excitability changes of up to 40 %, revealed by transcranial magnetic stimulation, were accomplished and lasted for several minutes after the end of current stimulation. Excitation could be achieved selectively by anodal stimulation, and inhibition by cathodal stimulation. By varying the current intensity and duration, the strength and duration of the after-effects could be controlled. The effects were probably induced by modification of membrane polarisation. Functional alterations related to post-tetanic potentiation, short-term potentiation and processes similar to postexcitatory central inhibition are the likely candidates for the excitability changes after the end of stimulation. Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive, painless, reversible, selective and focal way.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 10990547 [PubMed - indexed for MEDLINE]

Direct and indirect activation of human corticospinal neurons by transcranial magnetic and electrical stimulation.

Nakamura H, Kitagawa H, Kawaguchi Y, Tsuji H.

Department of Orthopedic Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.

Corticospinal volleys and surface electromyographic (EMG) responses evoked by magnetic and electrical transcranial stimulation were recorded simultaneously in three conscious human subjects. For magnetic stimulation, the figure-of-eight coil was held on the hand motor area either with the induced current through the brain flowing in a postero-anterior direction (P-A stimulation) or in a latero-medial direction (L-M stimulation). For electrical stimulation, the anode was placed 7 cm lateral to the vertex and cathode at the vertex (anodal stimulation). The P-A stimulation that was generally used preferentially evoked I waves, whereas the L-M and anodal stimulation preferentially evoked D wave. The results suggested that the mode of activation by transcranial magnetic stimulation altered, depending on its current direction, and the difference between P-M magnetic and electrical stimulation can be explained by the context of the D and I hypothesis.

PMID: 8762188 [PubMed - indexed for MEDLINE]

Electroencephalogr Clin Neurophysiol Suppl. 1991;43:29-35.

Physiological studies of electric and magnetic stimulation of the human brain.

Rothwell JC.

MRC Human Movement and Balance Unit, National Hospital for Nervous Diseases, London, U.K.

It is suggested that transcranial electric stimulation can activate pyramidal tract projections both directly and indirectly in a manner similar to that described after direct stimulation of the exposed cortex in the monkey. This produces both D- and I-waves in the pyramidal tract. At high intensities of stimulation, the stimulus can spread into the brain and activate pyramidal tract axons several centimeters below the cortical surface. Magnetic stimulation at moderate intensities produces electromyographic (EMG) responses with latencies 1-2 msec longer than those after electric stimulation. Two possible explanations have been put forward to account for this effect: (1) because of the difference in the direction of electric current flow induced in the brain by the 2 forms of stimulation, magnetic stimulation preferentially excites pyramidal tract cells indirectly, and hence evokes only I-waves in the pyramidal tract. (2) Electric stimulation (even at threshold) activates pyramidal axons deep in the white matter, whereas magnetic stimulation activates the pyramidal cells in the gray matter, probably at their initial segment. There is one interesting consequence common to both explanations. Whether magnetic stimulation activates the pyramidal neurons transsynaptically or at their initial segment, the size of the descending volley evoked will depend on the level of excitability of the motor cortex. In contrast, the response to electric stimulation will be less affected, since a proportion of the descending volley is initiated directly at the axon of the pyramidal cell. This differential effect of cortical excitability on the responses to electrical and magnetic stimulation can be useful in describing excitatory or inhibitory influences on motor cortex from other structures.

PMID: 1773767 [PubMed - indexed for MEDLINE]

Zh Nevropatol Psikhiatr Im S S Korsakova. 1991;91(7):75-8.

[Transcranial electric stimulation therapy in the treatment of neurocirculatory asthenia]

[Article in Russian]

Akimov GA, Zabolotnykh VA, Lebedev VP, Zabolotnykh II, Chuprasova TV, Afoshin SA, Rozanov SI, Kassin PL, Preobrazhenskaia SL.

Transcranial electric stimulation (TES), a combination of direct and pulse current totally up to 5 mA, rectangular impulses lasting 3-4 ms at a frequency of 75-80 Mz, via frontal and retromastoid electrodes was carried out for 30 minutes every other day. The treatment consisted of 7 to 10 sessions. Overall 189 patients suffering from vegetovascular dystonia were examined. Of these, 114 persons (group I) received pharmacotherapy and TES, 61 TES (group II), and 14 were on placebo. 83% of the group I patients and 80.3% of the group II patients manifested an appreciable improvement of the well-being which was supported by the data of its general estimation. 22 patients were examined for blood beta-endorphin. It has been shown that its concentration increased and returned to normal during TES.

Publication Types: Clinical Trial Controlled Clinical Trial English Abstract

PMID: 1661490 [PubMed - indexed for MEDLINE]

Zh Nevropatol Psikhiatr Im S S Korsakova. 1991;91(4):90-4.

[One of the methods of treatment of affective disorders in patients with alcoholism]

[Article in Russian]

Krupitskiĭ EM, Burakov AM, Karandashova GF, Lebedev VP, Katsnel'son IaS, Nikitina ZS, Grinenko AIa, Borodkin IuS.

It has been demonstrated by a double blind placebo-controlled study that transcranial electric treatment (TET) by means of combination of direct current and pulse current and pulse current at a frequency of 70-80 Hz is an effective method of correcting affective disorders (anxiety, depressions) in patients suffering from alcoholism. The therapeutic effects of TET are coupled with changes in GABA and monoamine metabolism rather than in beta-endorphin as well as with a decrease of the latent period of the occurrence of alpha-rhythm after eyes closing.

Publication Types: Clinical Trial Controlled Clinical Trial English Abstract

PMID: 1650108 [PubMed - indexed for MEDLINE]

Minerva Stomatol. 1990 Mar;39(3):171-4.

[Masseteric responses following electrical stimulation of the scalp]

[Article in Italian]

Macaluso GM, Pavesi G, Bonanini M, Mancia D, Gennari PU.

Istituto di Clinica Odontoiatrica, Università degli Studi di Parma.

Electromyographic responses of the masseter muscles following electric transcranial stimulations by a conventional constant current stimulator were recorded with surface and needle electrodes. Ipsilateral motor evoked responses following both anodic and cathodic bipolar electrical stimulations performed at 7 and 11 cm laterally to the vertex on the biauricular line were recorded, with latencies ranging from 2 to 3.6 ms. Contralateral responses were not elicited. The ipsilateral responses to stimuli were ascribed to direct stimulation of the trigeminal nerve, probably its intracisternal portion.

Publication Types: Comparative Study English Abstract

PMID: 2366724 [PubMed - indexed for MEDLINE]

Fiziol Zh SSSR Im I M Sechenova. 1988 Aug;74(8):1094-101.

[Transcranial electroanalgesia in rats: an optimal regimen of electrical stimuli]

[Article in Russian]

Lebedev VP, Savchenko AB, Fan AB, Zhilev SIu.

According to earlier experimental results in rabbits the maximal analgesic effect in rats as determined by vocalization test was elicited by transcranial application of combination of direct current and rectangular pulses (70 Hz, 3.0-3.5 ms) with optimal ratio of amplitudes of direct and mean pulse currents being about 2:1. In anesthetized rats during the transcranial application of the current with parameters optimal for analgesia the most prominent inhibition of the nociceptive blood pressure reflexes were also shown. The similar results obtained in different species of animals confirmed our earlier conclusion that the most pronounced transcranial analgesia may be elicited by the narrow band current parameters only. Directions of further investigation on the electroanalgesia mechanisms using transcranial current application in rats as an experimental model are discussed.

Publication Types: Comparative Study English Abstract

PMID: 3197851 [PubMed - indexed for MEDLINE]

Neurosurgery. 1984 Sep;15(3):287-302.

Motor evoked potentials from transcranial stimulation of the motor cortex in humans.

Levy WJ, York DH, McCaffrey M, Tanzer F.

Electrical monitoring of the motor system offers the potential for the detection of injury, the diagnosis of disease, the evaluation of treatment, and the prediction of recovery from damage. Existing evoked potentials monitor one or another sensory modality, but no generally usable motor monitor exists. We have reported a motor evoked potential using direct stimulation of the spinal cord over the motor tracts in cats and in humans. To achieve a less invasive monitor, we used transcranial stimulation over the motor cortex in the cat, thus stimulating the motor cortex. We report here the initial application of this method to humans. A plate electrode over the motor cortex on the scalp and a second electrode on the palate direct a mild current through the motor cortex which will activate the motor pathways. This signal can be recorded over the spinal cord. It can elicit contralateral peripheral nerve and electromyographic signals in the limbs or movements when the appropriate stimulation parameters are used. In clinical use to date, this has been more reliable than the somatosensory evoked potential in predicting motor function in patients where the two tests differed. It offers a number of possibilities for the development of valuable brain and spinal cord monitoring techniques, but requires further animal studies and clinical experience. Studies to date have not demonstrated adverse effects, but evaluation is continuing.

Publication Types: Case Reports

PMID: 6090972 [PubMed - indexed for MEDLINE]

Neurosci Lett. 2008 Dec 26;448(2):171-4. Epub 2008 Oct 21.

Improvement of visual scanning after DC brain polarization of parietal cortex in stroke patients with spatial neglect.

Ko MH, Han SH, Park SH, Seo JH, Kim YH.

PMID: 18952147 [PubMed - in process]

Clin Neurophysiol. 2007 Jun;118(6):1417-8. Epub 2007 Apr 23.

No effect of DC brain polarization on verbal fluency in patients with advanced frontotemporal dementia.

Huey ED, Probasco JC, Moll J, Stocking J, Ko MH, Grafman J, Wassermann EM.

Publication Types: Clinical Trial Letter

PMID: 17452012 [PubMed - indexed for MEDLINE]

BMC Neurosci. 2006 Nov 3;7:73.

Effects of brain polarization on reaction times and pinch force in chronic stroke.

Hummel FC, Voller B, Celnik P, Floel A, Giraux P, Gerloff C, Cohen LG.

Human Cortical Physiology Section and Stroke Neurorehabilitation Clinic, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. f.hummel@uke.uni-hamburg.de <f.hummel@uke.uni-hamburg.de>

BACKGROUND: Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1affected hemisphere) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design. RESULTS: Anodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment. CONCLUSION: tDCS of M1affected hemisphere can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels.

Publication Types: Clinical Trial Comparative Study Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

PMID: 17083730 [PubMed - indexed for MEDLINE]

Epilepsia. 2006 Feb;47(2):335-42.

A controlled clinical trial of cathodal DC polarization in patients with refractory epilepsy.

Fregni F, Thome-Souza S, Nitsche MA, Freedman SD, Valente KD, Pascual-Leone A.

Harvard Center for Noninvasive Brain Stimulation and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, KS 452, Boston, MA 02215, U.S.A. ffregni@bidmc.harvard.edu

PURPOSE: To study the effects of cathodal DC polarization in patients with refractory epilepsy and malformations of cortical development (MCDs) as indexed by seizure frequency and epileptiform EEG discharges. METHODS: Nineteen patients with MCDs and refractory epilepsy underwent one session of DC polarization (20 min, 1 mA) targeting the epileptogenic focus. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after, and 15 and 30 days after either sham or active DC polarization. Seizure frequency after the treatment was compared with baseline. RESULTS: Active compared with sham DC polarization was associated with a significant reduction in the number of epileptiform discharges [mean ED reduction of -64.3% (95% CI, -122.5% to -6.0%) for the active treatment group and -5.8% (95% CI, -26.8% to 15.2%) for the sham treatment group]. A trend (p = 0.06) was noted for decrease in seizure frequency after active compared with sham treatment [mean seizure frequency decrease of -44.0% (95% CI, -95.0% to 7.1%) for the active treatment group and -11.1% (95% CI, -22.2% to 44.4%) for the sham treatment group]. CONCLUSIONS: This randomized, controlled study shows that cathodal DC polarization does not induce seizures and is well tolerated in patients with refractory epilepsy and MCDs. Furthermore, the results suggest that this technique might have an antiepileptic effect based on clinical and electrophysiological criteria.

Publication Types: Comparative Study Randomized Controlled Trial Research Support, N.I.H., Extramural

PMID: 16499758 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2006 Apr;117(4):845-50. Epub 2006 Jan 19.

Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation.

Gandiga PC, Hummel FC, Cohen LG.

Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PMID: 16427357 [PubMed - indexed for MEDLINE]

Neurology. 2005 Mar 8;64(5):872-5.

Safety and cognitive effect of frontal DC brain polarization in healthy individuals.

Iyer MB, Mattu U, Grafman J, Lomarev M, Sato S, Wassermann EM.

Brain Stimulation Unit and Cognitive Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

BACKGROUND: Data from the human motor cortex suggest that, depending on polarity, direct current (DC) brain polarization can depress or activate cortical neurons. Activating effects on the frontal lobe might be beneficial for patients with frontal lobe disorders. This phase 1 study tested the safety of frontal DC, including its effects on frontal and other brain functions. METHODS: The authors applied 20 minutes of anodal, cathodal, or sham DC to the left prefrontal cortex in three groups of right-handed subjects and looked for effects on global measures of processing and psychomotor speed, emotion, and verbal fluency, a measure of local cortical function. In one experiment (n = 30), the authors tested before and after 1 mA DC and monitored EEG in 9 subjects. In two other experiments using 1 mA (n = 43) and 2 mA (n = 30), the authors tested before and then starting 5 minutes after the onset of DC. RESULTS: All subjects tolerated DC well. There were no significant effects on performance with 1 mA DC. At 2 mA, verbal fluency improved significantly with anodal and decreased mildly with cathodal DC. There were no clinically significant effects on the other measures. CONCLUSIONS: Limited exposure to direct current polarization of the prefrontal cortex is safe and can enhance verbal fluency selectively in healthy subjects. As such, it deserves consideration as a procedure to improve frontal lobe function in patients.

Publication Types: Clinical Trial, Phase I Randomized Controlled Trial

PMID: 15753425 [PubMed - indexed for MEDLINE]

J Neurosci. 2004 Mar 31;24(13):3379-85.

Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex.

Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College of London, London WC1N 3BG, United Kingdom.

Publication Types: Research Support, Non-U.S. Gov't

PMID: 15056717 [PubMed - indexed for MEDLINE]

J Physiol. 2004 May 15;557(Pt 1):175-90. Epub 2004 Feb 20.

Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro.

Bikson M, Inoue M, Akiyama H, Deans JK, Fox JE, Miyakawa H, Jefferys JG.

Department of Neurophysiology, University of Birmingham, Egbaston, Birmingham, UK.

The effects of uniform steady state (DC) extracellular electric fields on neuronal excitability were characterized in rat hippocampal slices using field, intracellular and voltage-sensitive dye recordings. Small electric fields (</40/ mV mm(-1)), applied parallel to the somato-dendritic axis, induced polarization of CA1 pyramidal cells; the relationship between applied field and induced polarization was linear (0.12 +/- 0.05 mV per mV mm(-1) average sensitivity at the soma). The peak amplitude and time constant (15-70 ms) of membrane polarization varied along the axis of neurons with the maximal polarization observed at the tips of basal and apical dendrites. The polarization was biphasic in the mid-apical dendrites; there was a time-dependent shift in the polarity reversal site. DC fields altered the thresholds of action potentials evoked by orthodromic stimulation, and shifted their initiation site along the apical dendrites. Large electric fields could trigger neuronal firing and epileptiform activity, and induce long-term (>1 s) changes in neuronal excitability. Electric fields perpendicular to the apical-dendritic axis did not induce somatic polarization, but did modulate orthodromic responses, indicating an effect on afferents. These results demonstrate that DC fields can modulate neuronal excitability in a time-dependent manner, with no clear threshold, as a result of interactions between neuronal compartments, the non-linear properties of the cell membrane, and effects on afferents.

Publication Types: In Vitro Research Support, Non-U.S. Gov't

PMID: 14978199 [PubMed - indexed for MEDLINE]

Clin Neurophysiol. 2003 Apr;114(4):589-95.

Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability.

Priori A.

Publication Types: Historical Article Research Support, Non-U.S. Gov't

PMID: 12686266 [PubMed - indexed for MEDLINE]

Int J Neurosci. 2002 Sep;112(9):1059-72.

Approach to the study of neurophysiological mechanism of food motivation.

Murik SE.

Department of Physiology, Irkutsk State University, Sukhe-Baton St. 5, Irkutsk, 664003, Russia.

The present article estimates depolarization-polarization processes in the nerve tissue of afferent systems, including visceral ones, according to the changes of the direct current (DC) potential level. Food motivation is formed and satisfied concurrently with changes in the neocortex direct current potential level and a number of cerebral brain limbic structures in rats. Lateral hypothalamic nucleus, basolateral amygdala area, and auditory cortex in hungry rats have a more negative DC potential shift than in satisfied animals, while a reverse relation is observed in the ventromedial hypothalamic nucleus. The results obtained are considered an indication of polarization shifts in the mechanism of motivated and emotional behavior. An idea of the determining role of polarization processes in the mechanism of motivated and emotional behavior is developed.

Publication Types: Comparative Study

PMID: 12487095 [PubMed - indexed for MEDLINE]

Zh Vyssh Nerv Deiat Im I P Pavlova. 1998 Jul-Aug;48(4):607-15.

[The interaction in the motor cortex of 2 foci of a "polarization" dominant]

[Article in Russian]

Kiazimova KM.

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow.

The effect of sequential applications of the weak anode DC (0.5-3 mcA) to the areas of fore- and hindlimb representation in the motor cortex was studied in waking unrestrained rabbits. This procedure formed two excitation foci with the dominant properties, i.e., different afferent stimuli (sound, light) produced the dominant behavioral reaction (limb movement). The cooperative inhibition of the dominant foci was observed in the process of formation of the second focus in different time intervals. The second focus inhibited the primary focus for a rather long-term period, and then the mutual inhibition of the foci acquired the reciprocal character. The obtained results testify to excitation redistribution in the motor cortex during the action of weak anode DC on the motor cortex.

Publication Types: English Abstract

PMID: 9778804 [PubMed - indexed for MEDLINE]

Zh Vyssh Nerv Deiat Im I P Pavlova. 1998 Jul-Aug;48(4):591-9.

[The structure of the cortical-subcortical relationships of the cerebral electrical processes during a motor polarization dominant]

[Article in Russian]

Rusinova EV.

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow.

Under conditions of rabbit chronic experiments, it was shown by means of the spectral-coherence analysis that the motor polarization dominant formed by the application of DC anode to the sensorimotor cortex produced a novel structure of the intercentral relations between electrical processes not only in the ipsi-, but in the contralateral brain hemisphere. A certain "isolation" of the primary focus was observed in the cortex of the "dominant" hemisphere, which was manifested in a decrease in its delta-range coherent relations with the other cortical areas. At the dominant optimum (in interstimulus intervals), an interhemispheric asymmetry in the EEG coherence spectra was observed in the delta band between the sensorimotor cortical areas, ventroposterolateral thalamic nuclei, and CA3 fields of the dorsal hippocampi. The asymmetry increased during the testing auditory stimulation. Development of the alpha- and beta-band interhemispheric asymmetry in the structures in question coincided with realization of the motor "dominant" reaction and was suggested to be associated with movement organization.

Publication Types: English Abstract

PMID: 9778802 [PubMed - indexed for MEDLINE]

Neuroreport. 1998 Jul 13;9(10):2257-60.

Polarization of the human motor cortex through the scalp.

Priori A, Berardelli A, Rona S, Accornero N, Manfredi M.

Dipartimento di Scienze Neurologiche, Università degli Studi di Roma La Sapienza, Italy.

Direct currents (DC) applied directly to central nervous system structures produce substantial and long-lasting effects in animal experiments. We tested the functional effects of very weak scalp DC (< 0.5 mA, 7 s) on the human motor cortex by assessing the changes in motor potentials evoked by transcranial magnetic brain stimulation. We performed four different experiments in 15 healthy volunteers. Our findings led to the conclusion that such weak (< 0.5 mA) anodal scalp DC, alternated with a cathodal DC, significantly depresses the excitability of the human motor cortex, providing evidence that a small electric field crosses the skull and influences the brain. A possible mechanism of action of scalp DC is the hyperpolarization of the superficial excitatory interneurones in the human motor cortex.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

PMID: 9694210 [PubMed - indexed for MEDLINE]

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