Tinnitus and Brain Activation: Insights from Transcranial Magnetic Stimulation

Ear, Nose, & Throat Journal. Apr, 2006  |  Pubmed ID: 16696357

The mechanisms underlying tinnitus are still not completely elucidated, but advances in neuroimaging and brain stimulation have provided us with new insights. Evidence suggests that tinnitus might actually be generated by central rather than peripheral structures. To illustrate the importance of brain activity changes in the pathology of tinnitus, we report the cases of 2 patients who experienced a recurrence/worsening of their tinnitus after they had undergone treatment for major depression with repetitive transcranial magnetic stimulation. We suggest that the tinnitus in these 2 patients was induced by changes in brain activity resulting from transcranial magnetic stimulation of the prefrontal cortex. We also review the pathophysiology and other aspects of tinnitus, focusing on associated brain reorganization.

Disruption of Right Prefrontal Cortex by Low-frequency Repetitive Transcranial Magnetic Stimulation Induces Risk-taking Behavior

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jun, 2006  |  Pubmed ID: 16775134

Decisions require careful weighing of the risks and benefits associated with a choice. Some people need to be offered large rewards to balance even minimal risks, whereas others take great risks in the hope for an only minimal benefit. We show here that risk-taking is a modifiable behavior that depends on right hemisphere prefrontal activity. We used low-frequency, repetitive transcranial magnetic stimulation to transiently disrupt left or right dorsolateral prefrontal cortex (DLPFC) function before applying a well known gambling paradigm that provides a measure of decision-making under risk. Individuals displayed significantly riskier decision-making after disruption of the right, but not the left, DLPFC. Our findings suggest that the right DLPFC plays a crucial role in the suppression of superficially seductive options. This confirms the asymmetric role of the prefrontal cortex in decision-making and reveals that this fundamental human capacity can be manipulated in normal subjects through cortical stimulation. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse or pathological gambling.

Electroencephalographic Recording During Transcranial Magnetic Stimulation in Humans and Animals

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Aug, 2006  |  Pubmed ID: 16793336

We report on the development of an EEG recording system, comprised of electrodes and amplifiers that are compatible with TMS (single and rapid-rate) in both human and animal studies.

A Sham-controlled Trial of a 5-day Course of Repetitive Transcranial Magnetic Stimulation of the Unaffected Hemisphere in Stroke Patients

Stroke; a Journal of Cerebral Circulation. Aug, 2006  |  Pubmed ID: 16809569

It has been recently shown that a single session of repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can improve motor function in stroke patients; however, this improvement is short-lasting. We therefore conducted a randomized, sham-controlled, phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe.

Noninvasive Cortical Stimulation with Transcranial Direct Current Stimulation in Parkinson's Disease

Movement Disorders : Official Journal of the Movement Disorder Society. Oct, 2006  |  Pubmed ID: 16817194

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.

Modulation of Steady-state Auditory Evoked Potentials by Cerebellar RTMS

Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale. Nov, 2006  |  Pubmed ID: 16826412

Steady-state auditory evoked responses (SSAER) obtained via electroencephalography (EEG) co-vary in amplitude with blood flow changes in the auditory area of the cerebellum. The aim of the present EEG study was to probe the cerebellar role in the control of such SSAER. For this purpose, we investigated changes in SSAERs due to transient disruption of the cerebellar hemisphere by repetitive transcranial magnetic stimulation (rTMS). SSAERs to click-trains of three different frequencies in the gamma-band (32, 40 and 47 Hz) were recorded from 45 scalp electrodes in six healthy volunteers immediately after 1-Hz rTMS and compared to baseline SSAERs assessed prior to magnetic stimulation. Cerebellar rTMS contralateral to the stimulated ear significantly reduced the amplitude of steady-state responses to 40-Hz click-trains and showed a tendency to reduce the amplitude to 32-Hz click-trains. No effects were observed for 47-Hz click-trains, nor for magnetic stimulation of the cerebellum ipsilateral to auditory stimulation or after sham stimulation. Our results suggest that interference with cerebellar output by rTMS modifies functional activity associated with cortical auditory processing. The finding of maximum effects on 40-Hz SSAERs provides support to the notion that the cerebellum is part of a distributed network involved in the regulation of cortical oscillatory activity and points at some frequency-specificity for the control of auditory-driven neuronal oscillations.

Effects of Transcranial Direct Current Stimulation on Working Memory in Patients with Parkinson's Disease

Journal of the Neurological Sciences. Nov, 2006  |  Pubmed ID: 16843494

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.

Cognitive Effects of Repeated Sessions of Transcranial Direct Current Stimulation in Patients with Depression

Depression and Anxiety. 2006  |  Pubmed ID: 16845648

RTMS Combined with Motor Learning Training in Healthy Subjects

Restorative Neurology and Neuroscience. 2006  |  Pubmed ID: 16873974

This study explored the effects of motor learning training combined with repetitive transcranial magnetic stimulation (rTMS) on motor performance in healthy subjects.

Comparison of Repetitive Transcranial Magnetic Stimulation and Electroconvulsive Therapy in Unipolar Non-psychotic Refractory Depression: a Randomized, Single-blind Study

The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). Dec, 2006  |  Pubmed ID: 16923322

Repetitive transcranial magnetic stimulation (rTMS) can induce significant antidepressant effects and, for some patients, might be an alternative to electroconvulsive therapy (ECT). The results of studies comparing the efficacy of rTMS and ECT are mixed and, therefore, comparison of these two therapies needs to be further explored. Forty-two patients aged between 18 and 65 yr, referred to ECT due to unipolar non-psychotic depression refractoriness entered the trial. They were randomly assigned to receive either rTMS or ECT. Depressive symptom changes were blindly measured by Hamilton Depression Rating Scale, Visual Analogue Scale and Clinical Global Impression at baseline, after 2 wk and after 4 wk of treatment. There was no difference in the antidepressant efficacy of ECT and rTMS. Response rates were relatively low in both groups (40% and 50% respectively), with no significant difference between them (p=0.55). Remission rates were also low for both groups (20% and 10% respectively), also with no significant difference (p=0.631). There was no significant difference in the neuropsychological test performance after either one of these therapies. Both treatments were associated with a degree of improvement in refractory depression and therefore add to the literature that rTMS can be an effective option to ECT as it is a less costly treatment and is not associated with anaesthetic and other ECT risks.

Predictors of Antidepressant Response in Clinical Trials of Transcranial Magnetic Stimulation

The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). Dec, 2006  |  Pubmed ID: 16939662

Although previous clinical trials have suggested that repetitive transcranial magnetic stimulation (rTMS) has a significant antidepressant effect, the results of these trials are heterogeneous. We hypothesized that individual patients' characteristics might contribute to such heterogeneity. Our aim was to identify predictors of antidepressant response to rTMS. We pooled data from six separate clinical trials conducted independently, which evaluated the effects of rapid rTMS of the left dorsolateral prefrontal cortex in patients with major depression. We investigated 195 patients with regard to demographic, depression and treatment characteristics, psychiatric and drug history. Results showed that age and treatment refractoriness were significant negative predictors of depression improvement when adjusting these variables to other significant predictors and confounders. These findings were not confounded by methodological differences from the six studies, as the results were adjusted for the study site. In conclusion TMS antidepressant therapy in younger and less treatment-resistant patients is associated with better outcome.

Diminishing Reciprocal Fairness by Disrupting the Right Prefrontal Cortex

Science (New York, N.Y.). Nov, 2006  |  Pubmed ID: 17023614

Humans restrain self-interest with moral and social values. They are the only species known to exhibit reciprocal fairness, which implies the punishment of other individuals' unfair behaviors, even if it hurts the punisher's economic self-interest. Reciprocal fairness has been demonstrated in the Ultimatum Game, where players often reject their bargaining partner's unfair offers. Despite progress in recent years, however, little is known about how the human brain limits the impact of selfish motives and implements fair behavior. Here we show that disruption of the right, but not the left, dorsolateral prefrontal cortex (DLPFC) by low-frequency repetitive transcranial magnetic stimulation substantially reduces subjects' willingness to reject their partners' intentionally unfair offers, which suggests that subjects are less able to resist the economic temptation to accept these offers. Importantly, however, subjects still judge such offers as very unfair, which indicates that the right DLPFC plays a key role in the implementation of fairness-related behaviors.

Immediate Placebo Effect in Parkinson's Disease--is the Subjective Relief Accompanied by Objective Improvement?

European Neurology. 2006  |  Pubmed ID: 17057382

A recent well-conducted meta-analysis showed that placebo effect is associated with a possible small benefit for subjective outcomes, but has no significant effects on objective outcomes. Objective: Herein, we aimed to investigate the immediate effects of two different types of placebo [placebo pill and sham transcranial magnetic stimulation (TMS)] in Parkinson's disease (PD) patients and compared them to the standard treatment (levodopa) in a proper randomized, double-blind, crossover clinical trial.

A Randomized Clinical Trial of Repetitive Transcranial Magnetic Stimulation in Patients with Refractory Epilepsy

Annals of Neurology. Oct, 2006  |  Pubmed ID: 17068786

To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double-blind, sham-controlled trial.

Alpha-band Electroencephalographic Activity over Occipital Cortex Indexes Visuospatial Attention Bias and Predicts Visual Target Detection

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Sep, 2006  |  Pubmed ID: 16971533

Covertly directing visual attention toward a spatial location in the absence of visual stimulation enhances future visual processing at the attended position. The neuronal correlates of these attention shifts involve modulation of neuronal "baseline" activity in early visual areas, presumably through top-down control from higher-order attentional systems. We used electroencephalography to study the largely unknown relationship between these neuronal modulations and behavioral outcome in an attention orienting paradigm. Covert visuospatial attention shifts to either a left or right peripheral position in the absence of visual stimulation resulted in differential modulations of oscillatory alpha-band (8-14 Hz) activity over left versus right posterior sites. These changes were driven by varying degrees of alpha-decreases being maximal contralateral to the attended position. When expressed as a lateralization index, these alpha-changes differed significantly between attention conditions, with negative values (alpha_right < alpha_left) indexing leftward and more positive values (alpha_left < or = alpha_right) indexing rightward attention. Moreover, this index appeared deterministic for processing of forthcoming visual targets. Collapsed over trials, there was an advantage for left target processing in accordance with an overall negative bias in alpha-index values. Across trials, left targets were detected most rapidly when preceded by negative index values. Detection of right targets was fastest in trials with most positive values. Our data indicate that collateral modulations of posterior alpha-activity, the momentary bias of visuospatial attention, and imminent visual processing are linked. They suggest that the momentary direction of attention, predicting spatial biases in imminent visual processing, can be estimated from a lateralization index of posterior alpha-activity.

Hand Function Improvement with Low-frequency Repetitive Transcranial Magnetic Stimulation of the Unaffected Hemisphere in a Severe Case of Stroke

American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. Nov, 2006  |  Pubmed ID: 17079967

Previous research has shown that low-frequency rTMS of the unaffected hemisphere can improve motor function in acute and chronic stroke patients. However, these studies only investigated patients with mild or moderate motor deficits. We report a case of a stroke patient with a severe motor impairment who underwent sham and active repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere and had significantly improved motor function after active, but not after sham, stimulation of the unaffected primary motor cortex. In an additional session of active rTMS, this patient maintained and further enhanced the initial motor improvement. This case report shows that inhibitory rTMS of the unaffected hemisphere can also be beneficial for stroke patients with severe motor deficits and suggests that this approach of noninvasive brain stimulation should be further investigated in this population of patients.

Manipulating Brains

Behavioural Neurology. 2006  |  Pubmed ID: 17148832

Paradoxical Facilitation of Attention in Healthy Humans

Behavioural Neurology. 2006  |  Pubmed ID: 17148835

Transcranial magnetic stimulation (TMS)-induced virtual lesions in healthy subjects can be used to test neurofunctional models of disease. The interhemispheric rivalry model of heminglect is well suited for such investigations, as simple predictions derived from clinical data can be tested without the caveats normally associated with lesion studies. One of these predictions is that release from contralateral inhibition should lead to increased parietal responsiveness, which, in turn, would enhance spatial attention. Here, we detail studies showing TMS-induced paradoxical functional facilitation of attention in healthy individuals and highlight their contribution to the understanding and treatment of neglect syndromes.

Disrupting the Brain to Guide Plasticity and Improve Behavior

Progress in Brain Research. 2006  |  Pubmed ID: 17167918

Neurones may be highly stable and nonplastic cellular structures, but they are engaged in dynamically changing, intrinsically plastic neural networks that provide a most energy efficient, spatially compact, and precise means to process input signals and generate adaptable responses to a changing environment. Neural plasticity is evolution's invention to enable the nervous system to escape the restrictions of its own genome (and its highly specialized cellular specification) and thus adapt to environmental pressures, physiologic changes, and experiences. At neural system level two steps of plasticity can be identified: unmasking existing connections that may be followed by establishment of new ones possibly even with integration of new neural structures and neurons. In any case, plastic changes may not necessarily represent a behavioral gain for a given subject, as they represent the mechanism for development and learning, as much as a cause of pathology and disease. The challenge is to learn enough about the mechanisms of plasticity to be able to guide them, suppressing changes that may lead to undesirable behaviors while accelerating or enhancing those that result in a behavioral benefit for the subject or patient. Neurostimulation, including noninvasive brain stimulation techniques, provide an opportunity to modulate brain plasticity in a controlled and specific manner. Such interventions to guide behavior or treat pathological symptomatology might be more immediate in their behavioral repercussion and thus more effective than approaches intent on addressing underlying genetic predispositions.

A Randomized, Sham-controlled, Proof of Principle Study of Transcranial Direct Current Stimulation for the Treatment of Pain in Fibromyalgia

Arthritis and Rheumatism. Dec, 2006  |  Pubmed ID: 17133529

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.

Disruption of Primary Motor Cortex Before Learning Impairs Memory of Movement Dynamics

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Nov, 2006  |  Pubmed ID: 17135408

Although multiple lines of evidence implicate the primary motor cortex (M1) in motor learning, the precise role of M1 in the adaptation to novel movement dynamics and in the subsequent consolidation of a memory of those dynamics remains unclear. Here we used repetitive transcranial magnetic stimulation (rTMS) to dissociate the contribution of M1 to these distinct aspects of motor learning. Subjects performed reaching movements in velocity-dependent force fields over three epochs: a null-field baseline epoch, a clockwise-field learning epoch (15 min after the baseline epoch), and a clockwise-field retest epoch (24 h after the learning epoch). Half of the subjects received 15 min of 1 Hz rTMS to M1 between the baseline and learning epochs. Subjects given rTMS performed identically to control subjects during the learning epoch. However, control subjects performed with significantly less error than rTMS subjects in the retest epoch on the following day. These results suggest that M1 is not critical to the network supporting motor adaptation per se but that, within this network, M1 may be important for initiating the development of long-term motor memories.

Combined Activation and Deactivation of Visual Cortex During Tactile Sensory Processing

Journal of Neurophysiology. Feb, 2007  |  Pubmed ID: 17135476

The involvement of occipital cortex in sensory processing is not restricted solely to the visual modality. Tactile processing has been shown to modulate higher-order visual and multisensory integration areas in sighted as well as visually deprived subjects; however, the extent of involvement of early visual cortical areas remains unclear. To investigate this issue, we employed functional magnetic resonance imaging in normally sighted, briefly blindfolded subjects with well-defined visuotopic borders as they tactually explored and rated raised-dot patterns. Tactile task performance resulted in significant activation in primary visual cortex (V1) and deactivation of extrastriate cortical regions V2, V3, V3A, and hV4 with greater deactivation in dorsal subregions and higher visual areas. These results suggest that tactile processing affects occipital cortex via two distinct pathways: a suppressive top-down pathway descending through the visual cortical hierarchy and an excitatory pathway arising from outside the visual cortical hierarchy that drives area V1 directly.

Low and High Frequency Repetitive Transcranial Magnetic Stimulation for the Treatment of Spasticity

Developmental Medicine and Child Neurology. Jul, 2007  |  Pubmed ID: 17593127

The development of non-invasive techniques of cortical stimulation, such as transcranial magnetic stimulation (TMS), has opened new potential avenues for the treatment of neuropsychiatric diseases. We hypothesized that an increase in the activity in the motor cortex by cortical stimulation would increase its inhibitory influence on spinal excitability through the corticospinal tract and, thus, reduce the hyperactivity of the gamma and alpha neurons, improving spasticity. Seventeen participants (eight males, nine females; mean age 9y 1mo [SD 3y 2mo]) with cerebral palsy and spastic quadriplegia were randomized to receive sham, active 1Hz, or active 5Hz repetitive TMS of the primary motor cortex. Stimulation was applied for 5 consecutive days (90% of motor threshold). The results showed that there was a significant reduction of spasticity after 5Hz, but not sham or 1Hz, stimulation as indexed by the degree of passive movement; however this was not evident when using the Ashworth scale, although a trend for improvement was seen for elbow movement. The safety evaluation showed that stimulation with either 1Hz or 5Hz did not result in any adverse events as compared with sham stimulation. Results of this trial provide initial evidence to support further trials exploring the use of cortical stimulation in the treatment of spasticity.

Technology Insight: Noninvasive Brain Stimulation in Neurology-perspectives on the Therapeutic Potential of RTMS and TDCS

Nature Clinical Practice. Neurology. Jul, 2007  |  Pubmed ID: 17611487

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.

Repeated Sessions of Noninvasive Brain DC Stimulation is Associated with Motor Function Improvement in Stroke Patients

Restorative Neurology and Neuroscience. 2007  |  Pubmed ID: 17726271

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.

RTMS over the Intraparietal Sulcus Disrupts Numerosity Processing

Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale. Jun, 2007  |  Pubmed ID: 17216413

It has been widely argued that the intraparietal sulcus (IPS) is involved in tasks that evoke representations of numerical magnitude, among other cognitive functions. However, the causal role of this parietal region in processing symbolic and non-symbolic numerosity has not been established. The current study used repetitive Transcranial Magnetic Stimulation (rTMS) to the left and right IPS to investigate the effects of temporary deactivations of these regions on the capacity to represent symbolic (Arabic numbers) and non-symbolic (arrays of dots) numerosities. We found that comparisons of both symbolic and non-symbolic numerosities were impaired after rTMS to the left IPS but enhanced by rTMS to the right IPS. A signature effect of numerical distance was also found: greater impairment (or lesser facilitation) when comparing numerosities of similar magnitude. The reverse pattern of impairment and enhancement was found in a control task that required judging an analogue stimulus property (ellipse orientation) but no numerosity judgements. No rTMS effects for the numerosity tasks were found when stimulating an area adjacent but distinct from the IPS, the left and right angular gyrus. These data suggest that left IPS is critical for processing symbolic and non-symbolic numerosity; this processing may thus depend on common neural mechanisms, which are distinct from mechanisms supporting the processing of analogue stimulus properties.

Secondary Motor Disturbances in 101 Patients with Musician's Dystonia

Journal of Neurology, Neurosurgery, and Psychiatry. Sep, 2007  |  Pubmed ID: 17237142

Musician's focal dystonia is usually considered to be task specific but secondary motor disturbances have been reported also. We carried out a detailed evaluation of the incidence of these secondary motor problems in 101 patients.

Recent Advances in the Treatment of Chronic Pain with Non-invasive Brain Stimulation Techniques

Lancet Neurology. Feb, 2007  |  Pubmed ID: 17239806

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.

'Who is the Ideal Candidate?': Decisions and Issues Relating to Visual Neuroprosthesis Development, Patient Testing and Neuroplasticity

Journal of Neural Engineering. Mar, 2007  |  Pubmed ID: 17325411

Appropriate delivery of electrical stimulation to intact visual structures can evoke patterned sensations of light in individuals who have been blind for many years. This pivotal finding has lent credibility to the concept of restoring functional vision by artificial means. As numerous groups worldwide pursue human clinical testing with visual prosthetic devices, it is becoming increasingly clear that there remains a considerable gap between the challenges of prosthetic device development and the rehabilitative strategies needed to implement this new technology in patients. An important area of future work will be the development of appropriate pre- and post-implantation measures of performance and establishing candidate selection criteria in order to quantify technical advances, guide future device design and optimize therapeutic success. We propose that the selection of an 'ideal' candidate should also be considered within the context of the variable neuroplastic changes that follow vision loss. Specifically, an understanding of the adaptive and compensatory changes that occur within the brain could assist in guiding the development of post-implantation rehabilitative strategies and optimize behavioral outcomes.

Transcranial Direct Current Stimulation: a Computer-based Human Model Study

NeuroImage. Apr, 2007  |  Pubmed ID: 17337213

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.

The 'when' Pathway of the Right Parietal Lobe

Trends in Cognitive Sciences. May, 2007  |  Pubmed ID: 17379569

The order of events, whether two events are seen as simultaneous or successive, sets the stage for the moment-to-moment interpretation of the visual world. Evidence from patients who have lesions to the parietal lobes and transcranial magnetic stimulation studies in normal subjects suggest that the right inferior parietal lobe underlies this analysis of event timing. Judgment of temporal order, simultaneity and high-level motion are all compromised following right parietal lesions and degraded after transcranial magnetic stimulation over the right parietal but not elsewhere. The results suggest that the right parietal lobe serves as part of a when pathway for both visual fields. We propose that the disruption of this mechanism is the underlying cause of a wide range of seemingly unrelated tasks being impaired in right parietal patients.

Visual Phosphene Perception Modulated by Subthreshold Crossmodal Sensory Stimulation

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Apr, 2007  |  Pubmed ID: 17428995

Crossmodal sensory interactions serve to integrate behaviorally relevant sensory stimuli. In this study, we investigated the effect of modulating crossmodal interactions between visual and somatosensory stimuli that in isolation do not reach perceptual awareness. When a subthreshold somatosensory stimulus was delivered within close spatiotemporal congruency to the expected site of perception of a phosphene, a subthreshold transcranial magnetic stimulation pulse delivered to the occipital cortex evoked a visual percept. The results suggest that under subthreshold conditions of visual and somatosensory stimulation, crossmodal interactions presented in a spatially and temporally specific manner can sum up to become behaviorally significant. These interactions may reflect an underlying anatomical connectivity and become further enhanced by attention modulation mechanisms.

Antidepressant Effects of High and Low Frequency Repetitive Transcranial Magnetic Stimulation to the Dorsolateral Prefrontal Cortex: a Double-blind, Randomized, Placebo-controlled Trial

The Journal of Neuropsychiatry and Clinical Neurosciences. 2007  |  Pubmed ID: 17431065

Repetitive transcranial magnetic stimulation (rTMS) has antidepressant effects in patients with major depressive disorder. The mechanisms of action and optimal stimulation parameters remain unclear. To test the hypothesis that rTMS exerts antidepressant effects either by enhancing left dorsolateral prefrontal cortex (DLPFC) excitability or by decreasing right DLPFC excitability, the authors studied 45 patients with unipolar recurrent major depressive disorder in a double-blind, randomized, parallel group, sham-controlled trial. Patients were randomized to receive 1 Hz or 10 Hz rTMS to the left DLPFC, 1 Hz to the right DLPFC or sham TMS. Left 10 Hz and right 1 Hz rTMS showed similar significant antidepressant effects. Other parameters led to no significant antidepressant effects.

Noninvasive Human Brain Stimulation

Annual Review of Biomedical Engineering. 2007  |  Pubmed ID: 17444810

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.

The Right Brain Hypothesis for Obesity

JAMA : the Journal of the American Medical Association. Apr, 2007  |  Pubmed ID: 17456824

Safety and Tolerability of Repetitive Transcranial Magnetic Stimulation in Patients with Epilepsy: a Review of the Literature

Epilepsy & Behavior : E&B. Jun, 2007  |  Pubmed ID: 17493877

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a new therapeutic tool in epilepsy, where it can be used to suppress seizures or treat comorbid conditions such as mood disorder. However, as rTMS carries a risk of inducing seizures among other adverse events, its safety and tolerability in the population with epilepsy warrant distinct consideration, as this group is especially seizure-prone. Accordingly, we performed a review of the literature to estimate the risk of seizures and other adverse events associated with rTMS in patients with epilepsy. We performed an English-language literature search, and reviewed all studies published from January 1990 to February 2007 in which patients with epilepsy were treated with rTMS, and complemented the literature search with personal correspondence with authors when necessary. We identified 30 publications that described patients with epilepsy who underwent rTMS, and noted total number of relevant subjects, medication usage, incidence of adverse events, and rTMS parameters including stimulus frequency, number of stimuli, train duration, intertrain interval, coil type, and stimulation sites. The data were analyzed for adverse events related to rTMS. Crude per-subject risk, as well as per-subject mean risk weighted by sample size and risk per 1000 stimuli weighted by number of stimuli in each study, were computed for seizures and for other adverse events. Adverse events or lack thereof was reported in 26 studies (n=280 subjects). Adverse events attributed to rTMS were generally mild and occurred in 17.1% of subjects. Headache was most common, occurring in 9.6%. The most serious adverse event was seizure during treatment, which occurred in four patients (1.4% crude per-subject risk). All but one case were the patients' typical seizures with respect to duration and semiology, and were associated with low-frequency rTMS. A single case of an atypical seizure appearing to arise from the region of stimulation during high-frequency rTMS is reported. No rTMS-related episodes of status epilepticus were reported. We cautiously conclude that the risk of seizure in patients with epilepsy undergoing rTMS is small, and the risk of other mild adverse events is comparable to that seen when rTMS is used to treat other diseases. Status epilepticus or life-threatening seizures have not been reported in patients undergoing rTMS treatment. rTMS thus appears to be nearly as safe in patients with epilepsy as in nonepileptic individuals, and warrants further investigation as a therapy in this population.

Neuroethics and National Security

The American Journal of Bioethics : AJOB. May, 2007  |  Pubmed ID: 17497494

Shape Conveyed by Visual-to-auditory Sensory Substitution Activates the Lateral Occipital Complex

Nature Neuroscience. Jun, 2007  |  Pubmed ID: 17515898

The lateral-occipital tactile-visual area (LOtv) is activated when objects are recognized by vision or touch. We report here that the LOtv is also activated in sighted and blind humans who recognize objects by extracting shape information from visual-to-auditory sensory substitution soundscapes. Recognizing objects by their typical sounds or learning to associate specific soundscapes with specific objects do not activate this region. This suggests that LOtv is driven by the presence of shape information.

Activation of Prefrontal Cortex by Transcranial Direct Current Stimulation Reduces Appetite for Risk During Ambiguous Decision Making

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jun, 2007  |  Pubmed ID: 17553993

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.

Effects of Transcranial Direct Current Stimulation Coupled with Repetitive Electrical Stimulation on Cortical Spreading Depression

Experimental Neurology. Mar, 2007  |  Pubmed ID: 17113079

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.

Opposite Impact on 14C-2-deoxyglucose Brain Metabolism Following Patterns of High and Low Frequency Repetitive Transcranial Magnetic Stimulation in the Posterior Parietal Cortex

Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale. Feb, 2007  |  Pubmed ID: 16972076

Repetitive transcranial magnetic stimulation (rTMS) appears capable of modulating human cortical excitability beyond the duration of the stimulation train. However, the basis and extent of this "off-line" modulation remains unknown. In a group of anesthetized cats, we applied patterns of real or sham focal rTMS to the visuo-parietal cortex (VP) at high (HF) or low (LF) frequency and recorded brain glucose uptake during (on-line), immediately after (off-line), or 1 h after (late) stimulation. During the on-line period LF and HF rTMS induced a significant relative reduction of (14)C-2DG uptake in the stimulated VP cortex and tightly linked cortical and subcortical structures (e.g. the superficial superior colliculus, the pulvinar, and the LPl nucleus) with respect to homologue areas in the unstimulated hemisphere. During the off-line period HF rTMS induced a significant relative increase in (14)C-2DG uptake in the targeted VP cortex, whereas LF rTMS generated the opposite effect, with only mild network impact. Moderate distributed effects were only recorded after LF rTMS in the posterior thalamic structures. No long lasting cortical or subcortical effects were detected during the late period. Our findings demonstrate opposite modulation of rTMS on local and distant effects along a specific network, depending on the pattern of stimulation. Such effects are demonstrated in the anesthetized animal, ruling out behavioral and non-specific reasons for the differential impact of the stimulation. The findings are consistent with previous differential electrophysiological and behavioral effects of low and high frequency rTMS patterns and provide support to uses of rTMS in neuromodulation.

Imaging Correlates of Motor Recovery from Cerebral Infarction and Their Physiological Significance in Well-recovered Patients

NeuroImage. Jan, 2007  |  Pubmed ID: 17070707

We studied motor representation in well-recovered stroke patients. Eighteen right-handed stroke patients and eleven age-matched control subjects underwent functional Magnetic Resonance Imaging (fMRI) while performing unimanual index finger (abduction-adduction) and wrist movements (flexion-extension) using their recovered and non-affected hand. A subset of these patients underwent Transcranial Magnetic Stimulation (TMS) to elicit motor evoked potentials (MEP) in the first dorsal interosseous muscle of both hands. Imaging results suggest that good recovery utilizes both ipsi- and contralesional resources, although results differ for wrist and index finger movements. Wrist movements of the recovered arm resulted in significantly greater activation of the contralateral (lesional) and ipsilateral (contralesional) primary sensorimotor cortex (SM1), while comparing patients to control subjects performing the same task. In contrast, recovered index finger movements recruited a larger motor network, including the contralateral SM1, Supplementary Motor Area (SMA) and cerebellum when patients were compared to control subjects. TMS of the lesional hemisphere but not of the contralesional hemisphere induced MEPs in the recovered hand. TMS parameters also revealed greater transcallosal inhibition, from the contralesional to the lesional hemisphere than in the reverse direction. Disinhibition of the contralesional hemisphere observed in a subgroup of our patients suggests persistent alterations in intracortical and transcallosal (interhemispheric) interactions, despite complete functional recovery.

One Session of High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) to the Right Prefrontal Cortex Transiently Reduces Cocaine Craving

Drug and Alcohol Dependence. Jan, 2007  |  Pubmed ID: 16971058

Cocaine dependence is a public health problem affecting 2 million individuals in USA. Craving is a predictor of subsequent cocaine use and is related to changes in brain activity in networks involving the prefrontal cortex.

Minimal Heating of Titanium Skull Plates During 1Hz Repetitive Transcranial Magnetic Stimulation

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Nov, 2007  |  Pubmed ID: 17890148

Pain in Chronic Pancreatitis: a Salutogenic Mechanism or a Maladaptive Brain Response?

Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]. 2007  |  Pubmed ID: 17898531

Pain in chronic pancreatitis is frequently refractory to medical and even surgical treatment. This refractoriness leads us to believe that a pancreas-independent, brain-mediated mechanism must be responsible. If so, several scenarios are worth considering. First, chronic pain could be the consequence of undesirable neuroplastic changes, by which pathology becomes established and causes disability. Alternatively, pain may be linked to the salutogenic (from salutogenesis, the Latin word for health and well-being) central nervous system response (we defined 'salutogenic response' as the specific modulation of the immune system induced by brain activity changes) to promote healing of the injured viscera. If so, chronic pain could index the ongoing nervous system attempt to promote healing. In this review, we discuss (1) the mechanisms of pain in chronic pancreatitis; (2) potential brain-related salutogenic mechanisms, and (3) the potential relationship of these two factors to the disease status. Furthermore, we consider these aspects in light of a new approach to treat visceral pain: transcranial magnetic stimulation, a noninvasive method of brain stimulation.

Treatment of Cancer Pain with Noninvasive Brain Stimulation

Journal of Pain and Symptom Management. Oct, 2007  |  Pubmed ID: 17903664

Time-dependent Changes in Cortical Excitability After Prolonged Visual Deprivation

Neuroreport. Oct, 2007  |  Pubmed ID: 17921872

Transcranial magnetic stimulation applied to the occipital cortex can elicit phosphenes. Changes in the phosphene threshold provide a measure of visual cortex excitability. Phosphene threshold was measured in participants blindfolded for five consecutive days to assess the effects of prolonged visual deprivation on visual cortical excitability. After 48 h of blindfolding, an acute decrease in phosphene threshold was observed, followed by a significant increase by day 5. Phosphene threshold returned to preblindfold levels within 2 h of light re-exposure. Thus, light deprivation is characterized by a transient increase in visual cortical excitability, followed by a sustained decrease in visual cortex excitability that quickly returns to baseline levels after re-exposure to light.

Brain Stimulation in Poststroke Rehabilitation

Cerebrovascular Diseases (Basel, Switzerland). 2007  |  Pubmed ID: 17971652

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.

Diminishing Risk-taking Behavior by Modulating Activity in the Prefrontal Cortex: a Direct Current Stimulation Study

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Nov, 2007  |  Pubmed ID: 18003828

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.

Transcranial Direct Stimulation and Fluoxetine for the Treatment of Depression

European Psychiatry : the Journal of the Association of European Psychiatrists. Jan, 2008  |  Pubmed ID: 18023968

Processing Nouns and Verbs in the Left Frontal Cortex: a Transcranial Magnetic Stimulation Study

Journal of Cognitive Neuroscience. Apr, 2008  |  Pubmed ID: 18052789

Neuropsychological and neurophysiological studies suggest that the production of verbs in speech depends on cortical regions in the left frontal lobe. However, the precise topography of these regions, and their functional roles in verb production, remains matters of debate. In an earlier study with repetitive transcranial magnetic stimulation (rTMS), we showed that stimulation to the left anterior midfrontal gyrus disrupted verb production, but not noun production, in a task that required subjects to perform simple morphological alternations. This result raises a number of questions: for example, is the effect of stimulation focal and specific to that brain region? Is the behavioral effect limited to rule-based, regular transformations, or can it be generalized over the grammatical category? In the present study, we used rTMS to suppress the excitability of distinct parts of the left prefrontal cortex to assess their role in producing regular and irregular verbs compared to nouns. We compared rTMS to sham stimulation and to stimulation of homologous areas in the right hemisphere. Response latencies increased for verbs, but were unaffected for nouns, following stimulation to the left anterior midfrontal gyrus. No significant interference specific for verbs resulted after stimulation to two other areas in the left frontal lobe, the posterior midfrontal gyrus and Broca's area. These results therefore reinforce the idea that the left anterior midfrontal cortex is critical for processing verbs. Moreover, none of the regions stimulated was preferentially engaged in the production of regular or irregular inflection, raising questions about the role of the frontal lobes in processing inflectional morphology.

Transcranial Magnetic Stimulation in Child Neurology: Current and Future Directions

Journal of Child Neurology. Jan, 2008  |  Pubmed ID: 18056688

Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation based on the principle of electromagnetic induction, where small intracranial electric currents are generated by a powerful, rapidly changing extracranial magnetic field. Over the past 2 decades TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disease in adults, but has been used on a more limited basis in children. We reviewed the literature to identify potential diagnostic and therapeutic applications of TMS in child neurology and also its safety in pediatrics. Although TMS has not been associated with any serious side effects in children and appears to be well tolerated, general safety guidelines should be established. The potential for applications of TMS in child neurology and psychiatry is significant. Given its excellent safety profile and possible therapeutic effect, this technique should develop as an important tool in pediatric neurology over the next decade.

Spontaneous Fluctuations in Posterior Alpha-band EEG Activity Reflect Variability in Excitability of Human Visual Areas

Cerebral Cortex (New York, N.Y. : 1991). Sep, 2008  |  Pubmed ID: 18093905

Neural activity fluctuates dynamically with time, and these changes have been reported to be of behavioral significance, despite occurring spontaneously. Through electroencephalography (EEG), fluctuations in alpha-band (8-14 Hz) activity have been identified over posterior sites that covary on a trial-by-trial basis with whether an upcoming visual stimulus will be detected or not. These fluctuations are thought to index the momentary state of visual cortex excitability. Here, we tested this hypothesis by directly exciting human visual cortex via transcranial magnetic stimulation (TMS) to induce illusory visual percepts (phosphenes) in blindfolded participants, while simultaneously recording EEG. We found that identical TMS-stimuli evoked a percept (P-yes) or not (P-no) depending on prestimulus alpha-activity. Low prestimulus alpha-band power resulted in TMS reliably inducing phosphenes (P-yes trials), whereas high prestimulus alpha-values led the same TMS-stimuli failing to evoke a visual percept (P-no trials). Additional analyses indicated that the perceptually relevant fluctuations in alpha-activity/visual cortex excitability were spatially specific and occurred on a subsecond time scale in a recurrent pattern. Our data directly link momentary levels of posterior alpha-band activity to distinct states of visual cortex excitability, and suggest that their spontaneous fluctuation constitutes a visual operation mode that is activated automatically even without retinal input.

Studying the Neurobiology of Social Interaction with Transcranial Direct Current Stimulation--the Example of Punishing Unfairness

Cerebral Cortex (New York, N.Y. : 1991). Sep, 2008  |  Pubmed ID: 18158325

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.

Transcranial Magnetic Stimulation and Brain Atrophy: a Computer-based Human Brain Model Study

Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale. Apr, 2008  |  Pubmed ID: 18193208

This paper is aimed at exploring the effect of cortical brain atrophy on the currents induced by transcranial magnetic stimulation (TMS). We compared the currents induced by various TMS conditions on several different MRI derived finite element head models of brain atrophy, incorporating both decreasing cortical volume and widened sulci. The current densities induced in the cortex were dependent upon the degree and type of cortical atrophy and were altered in magnitude, location, and orientation when compared to healthy head models. Predictive models of the degree of current density attenuation as a function of the scalp-to-cortex distance were analyzed, concluding that those which ignore the electromagnetic field-tissue interactions lead to inaccurate conclusions. Ultimately, the precise site and population of neural elements stimulated by TMS in an atrophic brain cannot be predicted based on healthy head models which ignore the effects of the altered cortex on the stimulating currents. Clinical applications of TMS should be carefully considered in light of these findings.

Transcranial Direct Current Stimulation of the Prefrontal Cortex Modulates the Desire for Specific Foods

Appetite. Jul, 2008  |  Pubmed ID: 18243412

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.

Cumulative Sessions of Repetitive Transcranial Magnetic Stimulation (rTMS) Build Up Facilitation to Subsequent TMS-mediated Behavioural Disruptions

The European Journal of Neuroscience. Feb, 2008  |  Pubmed ID: 18279329

A single session of repetitive transcranial magnetic stimulation (rTMS) can induce behavioural effects that outlast the duration of the stimulation train itself (off-line effects). Series of rTMS sessions on consecutive days are being used for therapeutic applications in a variety of disorders and are assumed to lead to the build-up of cumulative effects. However, no studies have carefully assessed this notion. In the present study we applied 30 daily sessions of 1 Hz rTMS (continuous train of 20 min) to repeatedly modulate activity in the posterior parietal cortex and associated neural systems in two intact cats. We assessed the effect on visuospatial orientation before and after each stimulation session. Cumulative sessions of rTMS progressively induced visuospatial neglect-like 'after-effects' of greater magnitude (from 5-10% to 40-50% error levels) and increasing spatial extent (from 90-75 degrees to 45-30 degrees eccentricity locations), affecting the visual hemifield contralateral to the stimulated hemisphere. Nonetheless, 60 min after each TMS session, visual detection-localization abilities repeatedly returned to baseline levels. Furthermore, no lasting behavioural effect could be demonstrated at any time across the study, when subjects were tested 1 or 24 h post-rTMS. We conclude that the past history of periodically cumulative rTMS sessions builds up a lasting 'memory', resulting in increased facilitation to subsequent TMS-induced disruptions. Such a phenomenon allows a behavioural effect of progressively higher magnitude, but equal duration, in response to individual TMS interventions.

Transient Suppression of Seizures by Repetitive Transcranial Magnetic Stimulation in a Case of Rasmussen's Encephalitis

Epilepsy & Behavior : E&B. Jul, 2008  |  Pubmed ID: 18304879

Repetitive transcranial magnetic stimulation (rTMS) has been applied with variable success to terminate the seizures of epilepsia partialis continua. The rationale for using this technique to suppress ongoing seizures is the capacity of rTMS to interrupt ongoing neuronal activity, and to produce a lasting decrease in cortical excitability with low-frequency (1 Hz) stimulation. We report a case of epilepsia partialis continua in a child with Rasmussen's encephalitis, in whom seizures were transiently suppressed by 1-Hz rTMS delivered in nine daily 30-minute sessions. In this case, total ictal time was significantly reduced during stimulation, but the daily baseline seizure rate remained unchanged. Notably, the detection and quantification of this short-lived improvement were enabled by recording EEG continuously during the rTMS session. Thus, we present this case to illustrate a potential utility of combined continuous EEG recording and rTMS in seizure treatment.

Cortical Stimulation of the Prefrontal Cortex with Transcranial Direct Current Stimulation Reduces Cue-provoked Smoking Craving: a Randomized, Sham-controlled Study

The Journal of Clinical Psychiatry. Jan, 2008  |  Pubmed ID: 18312035

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.

Interhemispheric Transfer Deficit in Alexithymia: a Transcranial Magnetic Stimulation Study

Psychotherapy and Psychosomatics. 2008  |  Pubmed ID: 18332615

A deficit in interhemispheric transfer was hypothesized in alexithymia more than 30 years ago, following the observation that split-brain patients manifest certain alexithymic characteristics. However, direct evidence of interhemispheric transfer deficit has never been provided. This study investigated the hypothesis of a transcallosal interhemispheric transfer deficit in alexithymia by means of paired-pulse transcranial magnetic stimulation.

Baseline Cortical Excitability Determines Whether TMS Disrupts or Facilitates Behavior

Journal of Neurophysiology. May, 2008  |  Pubmed ID: 18337360

Transcranial magnetic stimulation (TMS) is increasingly used to modify brain activity noninvasively and to study brain-behavior relations. However, results can be variable and the conditions that affect the functional efficacy of TMS remain unclear. Here we show that on-line TMS can either facilitate or suppress perceptual functions depending on the baseline level of activity of the targeted brain region. When TMS was applied over the motion selective region V5/MT during a simple motion-detection task, subjects' motion-detection ability was impaired. Similarly, suppression of V5/MT activity using off-line 1 Hz repetitive TMS (rTMS) disrupted performance in a subsequent motion-detection task. However, paradoxically, on-line V5/MT TMS had a facilitatory effect on motion detection if V5/MT had been suppressed by off-line 1-Hz rTMS prior to the motion-detection task. These results demonstrate that TMS can have an unexpected facilitatory effect on behavior when the targeted neural population is in a suppressed state. Our findings provide further evidence for the view that the effects of TMS are modulated by the initial activation state of the targeted neural population.

Noninvasive Brain Stimulation for Parkinson's Disease and Dystonia

Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics. Apr, 2008  |  Pubmed ID: 18394576

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.

An Open-label, Prospective Study of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Long-term Treatment of Refractory Depression: Reproducibility and Duration of the Antidepressant Effect in Medication-free Patients

The Journal of Clinical Psychiatry. Jun, 2008  |  Pubmed ID: 18505308

Several studies have assessed the acute antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), and many have revealed positive results. However, the impact of rTMS throughout the long course of major depressive disorder (MDD) and the efficacy of rTMS in the treatment of depressive relapses still remain to be elucidated.

Psychopathy and the Mirror Neuron System: Preliminary Findings from a Non-psychiatric Sample

Psychiatry Research. Aug, 2008  |  Pubmed ID: 18599127

Recent advances in social neuroscience suggest a link between empathy and the mirror neuron system (MNS). Impaired empathy is one of the core diagnostic features of psychopathic personality disorder. In the present study, we investigated whether psychopathic personality traits in a non-psychiatric sample were related to MNS function. Healthy participants viewed short videos known to activate the sensorimotor MNS for pain (a needle penetrating a human hand) while transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEP) were recorded as a measure of motor cortex excitability. Individual psychopathic personality traits were assessed using the Psychopathic Personality Inventory (PPI) and correlated with the MEP findings. Consistent with previous data, observation of the painful stimulus was associated with a significant reduction in the amplitude of the TMS-induced MEP. Interestingly, the level of corticospinal excitability modulation was positively correlated with individual scores on the coldheartedness subscale of the PPI, such that individuals with the greatest MEP reduction were the ones scoring highest on the coldheartedness measure. These data suggest the existence of a functional link between 'motor empathy' and psychopathy.

The Continuous Wagon Wheel Illusion and the 'when' Pathway of the Right Parietal Lobe: a Repetitive Transcranial Magnetic Stimulation Study

PloS One. 2008  |  Pubmed ID: 18682842

A continuous periodic motion stimulus can sometimes be perceived moving in the wrong direction. These illusory reversals have been taken as evidence that part of the motion perception system samples its inputs as a series of discrete snapshots -although other explanations of the phenomenon have been proposed, that rely on the spurious activation of low-level motion detectors in early visual areas. We have hypothesized that the right inferior parietal lobe ('when' pathway) plays a critical role in timing perceptual events relative to one another, and thus we examined the role of the right parietal lobe in the generation of this "continuous Wagon Wheel Illusion" (c-WWI). Consistent with our hypothesis, we found that the illusion was effectively weakened following disruption of right, but not left, parietal regions by low frequency repetitive transcranial magnetic stimulation (1 Hz, 10 min). These results were independent of whether the motion stimulus was shown in the left or the right visual field. Thus, the c-WWI appears to depend on higher-order attentional mechanisms that are supported by the 'when' pathway of the right parietal lobe.

Novelty Seeking Modulates Medial Prefrontal Activity During the Anticipation of Emotional Stimuli

Psychiatry Research. Oct, 2008  |  Pubmed ID: 18703319

In a functional magnetic resonance imaging experiment, expectancy cues signaling emotional stimuli were used to study the personality trait of novelty seeking. BOLD responses to emotional expectancy were positively correlated with novelty-seeking scores in the medial prefrontal cortex. This correlation was strongest for the sub-dimension of exploratory excitability.

The 'when' Parietal Pathway Explored by Lesion Studies

Current Opinion in Neurobiology. Apr, 2008  |  Pubmed ID: 18708141

The perception of events in space and time is at the root of our interactions with the environment. The precision with which we perceive visual events in time enables us to act upon objects with great accuracy and the loss of such functions due to brain lesions can be catastrophic. We outline a visual timing mechanism that deals with the trajectory of an object's existence across time, a crucial function when keeping track of multiple objects that temporally overlap or occur sequentially. Recent evidence suggests these functions are served by an extended network of areas, which we call the 'when' pathway. Here we show that the when pathway is distinct from and interacts with the well-established 'where' and 'what' pathways.

Neural and Behavioral Correlates of Drawing in an Early Blind Painter: a Case Study

Brain Research. Nov, 2008  |  Pubmed ID: 18710656

Humans rely heavily on vision to identify objects in the world and can create mental representations of the objects they encounter. Objects can also be identified and mentally represented through haptic exploration. However, it is unclear whether prior visual experience is necessary to generate these internal representations. Subject EA, an early blind artist, provides insight into this question. Like other blind individuals, EA captures the external world by touch. However, he is also able to reveal his internal representations through highly detailed drawings that are unequivocally understandable by a sighted person. We employed fMRI to investigate the neural correlates associated with EA's ability to transform tactilely explored three-dimensional objects into drawings and contrasted these findings with a series of control conditions (e.g. nonsensical scribbling as a sensory-motor control). Activation during drawing (compared to scribbling) occurred in brain areas normally associated with vision, including the striate cortex along with frontal and parietal cortical regions. Some of these areas showed overlap when EA was asked to mentally imagine the pictures he had to draw (albeit to a lesser anatomical extent and signal magnitude). These results have important implications as regards our understanding of the ways in which tactile information can generate mental representations of shapes and scenes in the absence of normal visual development. Furthermore, these findings suggest the occipital cortex plays a key role in supporting mental representations even without prior visual experience.

Rapid and Reversible Recruitment of Early Visual Cortex for Touch

PloS One. 2008  |  Pubmed ID: 18728773

The loss of vision has been associated with enhanced performance in non-visual tasks such as tactile discrimination and sound localization. Current evidence suggests that these functional gains are linked to the recruitment of the occipital visual cortex for non-visual processing, but the neurophysiological mechanisms underlying these crossmodal changes remain uncertain. One possible explanation is that visual deprivation is associated with an unmasking of non-visual input into visual cortex.

Impaired Interhemispheric Interactions in Patients with Major Depression

The Journal of Nervous and Mental Disease. Sep, 2008  |  Pubmed ID: 18791428

Previous studies have shown that patients with major depression have an interhemispheric imbalance between right and left prefrontal and motor cortex. We aimed to investigate the interhemispheric interactions in patients with major depression using repetitive transcranial magnetic stimulation (rTMS). Thirteen patients with major depression and 14 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS (applied to the left primary motor cortex) was assessed in the left and right motor cortex and these results were compared with those in healthy subjects. There was a significant difference in the interhemispheric effects between patients with depression and healthy subjects. In healthy subjects, 1 Hz rTMS significantly decreased corticospinal excitability in the stimulated, left hemisphere and increased it in the contralateral, right hemisphere. In depressed subjects, 1 Hz rTMS also decreased corticospinal excitability in the left hemisphere; however, it induced no significant changes in corticospinal excitability in the contralateral, right hemisphere. In addition, there was a significant correlation between the degree of interhemispheric modulation and the severity of the depression as indexed by the Beck Depression Inventory scores. Our findings showing a decreased interhemispheric modulation in patients with major depression are consistent with the notion that mood disorders are associated with slow interhemispheric switching mechanisms.

State-dependency of Transcranial Magnetic Stimulation

Brain Topography. Sep, 2008  |  Pubmed ID: 18791818

Transcranial magnetic stimulation (TMS), a tool that allows noninvasive modulation of cortical neural activity, has become an important tool in cognitive neuroscience and is being increasingly explored in neurotherapeutics. Amongst the factors that are likely to influence its efficacy, the importance of the baseline cortical activation state on the impact of TMS has not received much attention. However, this state-dependency is important as the neural impact of any external stimulus represents an interaction with the ongoing brain activity at the time of stimulation. The effects of any external stimulus are therefore not only determined by the properties of that stimulus but also by the activation state of the brain. Here we review the existing evidence on the state-dependency of TMS and propose how its systematic study can provide unique insights into brain function and significantly enhance the effectiveness of TMS in investigations on the neural basis of perception and cognition. We also describe novel approaches based on this state-dependency which can be used to investigate the properties of distinct neural subpopulations within the stimulated region. Furthermore, we discuss how state-dependency can explain the functional mechanisms through which TMS impairs perception and behavior.

A Randomized, Double-blind Clinical Trial on the Efficacy of Cortical Direct Current Stimulation for the Treatment of Major Depression

The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). Mar, 2008  |  Pubmed ID: 17559710

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.

Safety of 6-Hz Primed Low-frequency RTMS in Stroke

Neurorehabilitation and Neural Repair. Mar-Apr, 2008  |  Pubmed ID: 17876070

Suppression of activity in the contralesional motor cortex may promote recovery of function after stroke. Furthermore, the known depressant effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) can be increased and prolonged by preceding it with 6-Hz priming stimulation.

Prefrontal Cortex Modulation Using Transcranial DC Stimulation Reduces Alcohol Craving: a Double-blind, Sham-controlled Study

Drug and Alcohol Dependence. Jan, 2008  |  Pubmed ID: 17640830

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.

Concepts Are More Than Percepts: the Case of Action Verbs

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Oct, 2008  |  Pubmed ID: 18971476

Several regions of the posterior-lateral-temporal cortex (PLTC) are reliably recruited when participants read or listen to action verbs, relative to other word and nonword types. This PLTC activation is generally interpreted as reflecting the retrieval of visual-motion features of actions. This interpretation supports the broader theory, that concepts are comprised of sensory-motor features. We investigated an alternative interpretation of the same activations: PLTC activity for action verbs reflects the retrieval of modality-independent representations of event concepts, or the grammatical types associated with them, i.e., verbs. During a functional magnetic resonance imaging scan, participants made semantic-relatedness judgments on word pairs varying in amount of visual-motion information. Replicating previous results, several PLTC regions showed higher responses to words that describe actions versus objects. However, we found that these PLTC regions did not overlap with visual-motion regions. Moreover, their response was higher for verbs than nouns, regardless of visual-motion features. For example, the response of the PLTC is equally high to action verbs (e.g., to run) and mental verbs (e.g., to think), and equally low to animal nouns (e.g., the cat) and inanimate natural kind nouns (e.g., the rock). Thus, PLTC activity for action verbs might reflect the retrieval of event concepts, or the grammatical information associated with verbs. We conclude that concepts are abstracted away from sensory-motor experience and organized according to conceptual properties.

Seizure Suppression by EEG-guided Repetitive Transcranial Magnetic Stimulation in the Rat

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Dec, 2008  |  Pubmed ID: 18977170

To test the anticonvulsive potential of a range of repetitive transcranial magnetic stimulation (rTMS) frequencies by novel methods for simultaneous EEG and rTMS in a rat seizure model.

Release of Premotor Activity After Repetitive Transcranial Magnetic Stimulation of Prefrontal Cortex

Social Neuroscience. 2008  |  Pubmed ID: 18979382

In the present study we aimed to explore by means of repetitive transcranial magnetic stimulation (rTMS) the reciprocal influences between prefrontal cortex (PFC) and premotor cortex (PMC). Subjects were asked to observe on a computer monitor different pictures representing manipulations of different kind of tools. They had to produce a movement (go condition) or to keep the resting position (no-go condition) at the appearance of different cue signals represented by different colors shown alternatively on the hands manipulating the tools or on the picture background. Motor evoked potentials (MEPs) were collected at the offset of the visual stimuli before and after a 10 minute, 1 Hz rTMS train applied to the dorsolateral PFC (Experiment 1), to the PMC (Experiment 2) or to the primary motor cortex (Experiment 3). Following rTMS to the PFC, MEPs increased in the go condition when the cue for the go command was presented on the hand. In contrast, following rTMS to the PMC, in the same condition, MEPs were decreased. rTMS to the primary motor cortex did not produce any modulation. Results are discussed according to the presence of a visual-motor matching system in the PMC and to the role of the PFC in the attention-related processes. We hypothesize that the perceptual analysis for action selection within the PFC was modulated by rTMS and its temporary functional inactivation in turn influenced the premotor areas for motor programming.

State of the Art: Pharmacologic Effects on Cortical Excitability Measures Tested by Transcranial Magnetic Stimulation

Brain Stimulation. Jul, 2008  |  Pubmed ID: 20633382

The combination of brain stimulation techniques like transcranial magnetic stimulation (TMS) with CNS active drugs in humans now offers a unique opportunity to explore the physiologic effects of these substances in vivo in the human brain. Motor threshold, motor evoked potential size, motor evoked potential intensity curves, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, short-interval intracortical facilitation, long-interval intracortical inhibition and short latency afferent inhibition represent the repertoire for investigating drug effects on motor cortical excitability by TMS. Here we present an updated overview on the pharmacophysiologic mechanisms with special emphasis on methodologic pitfalls and possible future developments or requirements.

Consensus: Motor Cortex Plasticity Protocols

Brain Stimulation. Jul, 2008  |  Pubmed ID: 20633383

Noninvasive transcranial stimulation is being increasingly used by clinicians and neuroscientists to alter deliberately the status of the human brain. Important applications are the induction of virtual lesions (for example, transient dysfunction) to identify the importance of the stimulated brain network for a certain sensorimotor or cognitive task, and the induction of changes in neuronal excitability, synaptic plasticity or behavioral function outlasting the stimulation, for example, for therapeutic purposes. The aim of this article is to review critically the properties of the different currently used stimulation protocols, including a focus on their particular strengths and weaknesses, to facilitate their appropriate and conscientious application.

Controversy: Does Repetitive Transcranial Magnetic Stimulation/ Transcranial Direct Current Stimulation Show Efficacy in Treating Tinnitus Patients?

Brain Stimulation. Jul, 2008  |  Pubmed ID: 20633385

Tinnitus affects 10% of the population, its pathophysiology remains incompletely understood, and treatment is elusive. Functional imaging has demonstrated a relationship between the intensity of tinnitus and the degree of reorganization in the auditory cortex. Experimental studies have further shown that tinnitus is associated with synchronized hyperactivity in the auditory cortex. Therefore, targeted modulation of auditory cortex has been proposed as a new therapeutic approach for chronic tinnitus.

Transcranial Direct Current Stimulation: State of the Art 2008

Brain Stimulation. Jul, 2008  |  Pubmed ID: 20633386

Effects of weak electrical currents on brain and neuronal function were first described decades ago. Recently, DC polarization of the brain was reintroduced as a noninvasive technique to alter cortical activity in humans. Beyond this, transcranial direct current stimulation (tDCS) of different cortical areas has been shown, in various studies, to result in modifications of perceptual, cognitive, and behavioral functions. Moreover, preliminary data suggest that it can induce beneficial effects in brain disorders. Brain stimulation with weak direct currents is a promising tool in human neuroscience and neurobehavioral research. To facilitate and standardize future tDCS studies, we offer this overview of the state of the art for tDCS.

Efficacy of Repetitive Transcranial Magnetic Stimulation/transcranial Direct Current Stimulation in Cognitive Neurorehabilitation

Brain Stimulation. Oct, 2008  |  Pubmed ID: 20633391

Cognitive deficits are a common consequence of neurologic disease, in particular, of traumatic brain injury, stroke, and neurodegenerative disorders, and there is evidence that specific cognitive training may be effective in cognitive rehabilitation. Several investigations emphasize the fact that interacting with cortical activity, by means of cortical stimulation, can positively affect the short-term cognitive performance and improve the rehabilitation potential of neurologic patients. In this respect, preliminary evidence suggests that cortical stimulation may play a role in treating aphasia, unilateral neglect, and other cognitive disorders. Several possible mechanisms can account for the effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) on cognitive performance. They all reflect the potential of these methods to improve the subject's ability to relearn or to acquire new strategies for carrying out behavioral tasks. The responsible mechanisms remain unclear but they are most likely related to the activation of impeded pathways or inhibition of maladaptive responses. Modifications of the brain activity may assist relearning by facilitating local activity or by suppressing interfering activity from other brain areas. Notwithstanding the promise of these preliminary findings, to date no systematic application of these methods to neurorehabilitation research has been reported. Considering the potential benefit of these interventions, further studies taking into consideration large patient populations, long treatment periods, or the combination of different rehabilitation strategies are needed. Brain stimulation is indeed an exciting opportunity in the field of cognitive neurorehabilitation, which is clearly in need of further research.

Consensus: Can Transcranial Direct Current Stimulation and Transcranial Magnetic Stimulation Enhance Motor Learning and Memory Formation?

Brain Stimulation. Oct, 2008  |  Pubmed ID: 20633394

Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this article is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance, and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short-lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations, including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurologic and psychiatric disorders.

Consensus: "Can TDCS and TMS Enhance Motor Learning and Memory Formation?"

Brain Stimulation. Oct, 2008  |  Pubmed ID: 19802336

Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this paper is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurological and psychiatric disorders.

Research with Transcranial Magnetic Stimulation in the Treatment of Aphasia

Current Neurology and Neuroscience Reports. Nov, 2009  |  Pubmed ID: 19818232

Repetitive transcranial magnetic stimulation (rTMS) has been used to improve language behavior, including naming, in stroke patients with chronic, nonfluent aphasia. Part 1 of this article reviews functional imaging studies related to language recovery in aphasia. Part 2 reviews the rationale for using rTMS to treat nonfluent aphasia (based on functional imaging) and presents our current rTMS protocol. We present language results from our rTMS studies as well as imaging results from overt naming functional MRI scans obtained before and after a series of rTMS treatments. Part 3 presents results from a pilot study in which rTMS treatments were followed immediately by constraint-induced language therapy. Part 4 reviews our diffusion tensor imaging study examining the possible connectivity of the arcuate fasciculus to different parts of Broca's area (pars triangularis, pars opercularis) and to the ventral premotor cortex. The potential role of mirror neurons in the right pars opercularis and ventral premotor cortex in aphasia recovery is discussed.

Safety, Ethical Considerations, and Application Guidelines for the Use of Transcranial Magnetic Stimulation in Clinical Practice and Research

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Dec, 2009  |  Pubmed ID: 19833552

This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.

Consensus Paper: Combining Transcranial Stimulation with Neuroimaging

Brain Stimulation. Apr, 2009  |  Pubmed ID: 20633405

In the last decade, combined transcranial magnetic stimulation (TMS)-neuroimaging studies have greatly stimulated research in the field of TMS and neuroimaging. Here, we review how TMS can be combined with various neuroimaging techniques to investigate human brain function. When applied during neuroimaging (online approach), TMS can be used to test how focal cortex stimulation acutely modifies the activity and connectivity in the stimulated neuronal circuits. TMS and neuroimaging can also be separated in time (offline approach). A conditioning session of repetitive TMS (rTMS) may be used to induce rapid reorganization in functional brain networks. The temporospatial patterns of TMS-induced reorganization can be subsequently mapped by using neuroimaging methods. Alternatively, neuroimaging may be performed first to localize brain areas that are involved in a given task. The temporospatial information obtained by neuroimaging can be used to define the optimal site and time point of stimulation in a subsequent experiment in which TMS is used to probe the functional contribution of the stimulated area to a specific task. In this review, we first address some general methodologic issues that need to be taken into account when using TMS in the context of neuroimaging. We then discuss the use of specific brain mapping techniques in conjunction with TMS. We emphasize that the various neuroimaging techniques offer complementary information and have different methodologic strengths and weaknesses.

Neuromodulation in Hypoxic-ischemic Injury

Brain Stimulation. Jul, 2009  |  Pubmed ID: 20633417

Report of Seizure Induced by Continuous Theta Burst Stimulation

Brain Stimulation. Oct, 2009  |  Pubmed ID: 20160904

Transcranial DC Stimulation Coupled with TENS for the Treatment of Chronic Pain: a Preliminary Study

The Clinical Journal of Pain. Oct, 2009  |  Pubmed ID: 19920718

Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation.

Functional Recruitment of Visual Cortex for Sound Encoded Object Identification in the Blind

Neuroreport. Jan, 2009  |  Pubmed ID: 19104453

Individuals using a visual-to-auditory sensory substitution device (SSD) called 'The vOICe' can identify objects in their environment through images encoded by sound. We have shown that identifying objects with this SSD is associated with activation of occipital visual areas. Here, we show that repetitive transcranial magnetic stimulation (rTMS) delivered to a specific area of occipital cortex (identified by functional MRI) profoundly impairs a blind user's ability to identify objects. rTMS delivered to the same site had no effect on a visual imagery task. The task and site-specific disruptive effect of rTMS in this individual suggests that the cross-modal recruitment of occipital visual areas is functional in nature and critical to the patient's ability to process and decode the image sounds using this SSD.

Meta-analysis of the Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Negative and Positive Symptoms in Schizophrenia

Schizophrenia Research. Mar, 2009  |  Pubmed ID: 19138833

A growing body of evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can alleviate negative and positive symptoms of refractory schizophrenia. However, trials to date have been small and results are mixed.

Feasibility of a Home Constraint-induced Movement Therapy for Hand Weakness After Stroke

Journal of Rehabilitation Medicine : Official Journal of the UEMS European Board of Physical and Rehabilitation Medicine. Jan, 2009  |  Pubmed ID: 19197578

Suppression of Ipsilateral Motor Cortex Facilitates Motor Skill Learning

The European Journal of Neuroscience. Feb, 2009  |  Pubmed ID: 19200062

The primary motor cortex (M1) plays a critical role in early aspects of motor skill learning. Given the notion of inter-hemispheric competition, unilateral disruption of M1 may increase excitability of the unaffected motor cortex and thus improve motor learning with the ipsilateral hand. We applied slow-frequency repetitive transcranial magnetic stimulation (rTMS) before the initiation of practice of a simple motor skill. Participants were randomly divided into three stimulation groups: (i) ipsilateral M1; (ii) contralateral M1; and (iii) Cz (control site). The mean execution time and error rate were recorded in four sessions distributed over 2 days. Disruption of M1 with rTMS slowed down skill acquisition with the contralateral hand, albeit non significantly, but paradoxically enhanced learning with the ipsilateral hand. This was evidenced by a significant decrease of execution time at the end of day 1 in the group that received rTMS over the ipsilateral M1 compared with both control groups (Cz and contralateral M1 stimulation). This supports the notion of inter-hemispheric competition and provides novel insights that may be applicable to neurorehabilitation.

M1 Contributes to the Intrinsic but Not the Extrinsic Components of Motor-skills

Cortex; a Journal Devoted to the Study of the Nervous System and Behavior. Oct, 2009  |  Pubmed ID: 19243742

Procedural skills consist of several components that can be simultaneously acquired. During a motor-learning task we can distinguish between how a "movement" is performed (intrinsic component) and the spatial-related (extrinsic) component of this movement. The intrinsic movement component is thought to be supported by motor loops, including primary motor cortex (M1) as assessed with neuroimaging studies. Here we want to test further whether M1 makes a critical contribution to the movement rather than spatial-related component of skill-learning. To this purpose, we used repetitive Transcranial Magnetic Stimulation (rTMS) and the serial reaction time (SRT) task. Twenty right-handed participants performed the SRT-task starting with their left or right hand. After this learning session, participants switched to the untrained hand by performing original (spatial-related) and mirror-ordered (movement-based) sequences. rTMS was applied to M1 ipsi- or contralateral to the transfer-hand and both sequences were retested. Results revealed rTMS-interference with motor-skill transfer of mirror-ordered but not original sequences, showing that M1 is critically involved in the retrieval/transformation of the intrinsic but not the extrinsic movement coordinates. rTMS-interference in the mirror-condition consisted of both (i) disruption and (ii) release of motor-skill transfer depending on the stimulated hemisphere and on transfer-hand. The pattern of results suggests (i) contralateral (right) M1 involvement in retrieval/transformation of motor information during left-hand reproduction of previously acquired right-hand motor-skills; and (ii) modulatory interactions of inhibitory nature from the dominant (left) to the non-dominant (right) M1 in the same transfer-condition. These results provide further evidence that M1 is essential to intrinsic movement-based skill-learning and novel insight on models of motor-learning and hemispheric specialization, suggesting the involvement of interhemispheric inhibition.

Using Non-invasive Brain Stimulation to Augment Motor Training-induced Plasticity

Journal of Neuroengineering and Rehabilitation. 2009  |  Pubmed ID: 19292910

Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date.

Temporal Lobe Cortical Electrical Stimulation During the Encoding and Retrieval Phase Reduces False Memories

PloS One. 2009  |  Pubmed ID: 19319182

A recent study found that false memories were reduced by 36% when low frequency repetitive transcranial magnetic stimulation (rTMS) was applied to the left anterior temporal lobe after the encoding (study) phase. Here we were interested in the consequences on a false memory task of brain stimulation throughout the encoding and retrieval task phases. We used transcranial direct current stimulation (tDCS) because it has been shown to be a useful tool to enhance cognition. Specifically, we examined whether tDCS can induce changes in a task assessing false memories. Based on our preliminary results, three conditions of stimulation were chosen: anodal left/cathodal right anterior temporal lobe (ATL) stimulation ("bilateral stimulation"); anodal left ATL stimulation (with a large contralateral cathodal electrode--referred as "unilateral stimulation") and sham stimulation. Our results showed that false memories were reduced significantly after the two active conditions (unilateral and bilateral stimulation) as compared with sham stimulation. There were no significant changes in veridical memories. Our findings show that false memories are reduced by 73% when anodal tDCS is applied to the anterior temporal lobes throughout the encoding and retrieval stages, suggesting a possible strategy for improving certain aspects of learning.

Treatment of Depression with Transcranial Direct Current Stimulation (tDCS): a Review

Experimental Neurology. Sep, 2009  |  Pubmed ID: 19348793

Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.

Invasive Cortical Stimulation to Promote Recovery of Function After Stroke: a Critical Appraisal

Stroke; a Journal of Cerebral Circulation. May, 2009  |  Pubmed ID: 19359643

Residual motor deficits frequently linger after stroke. Search for newer effective strategies to promote functional recovery is ongoing. Brain stimulation, as a means of directing adaptive plasticity, is appealing. Animal studies and Phase I and II trials in humans have indicated safety, feasibility, and efficacy of combining rehabilitation and concurrent invasive cortical stimulation. However, a recent Phase III trial showed no advantage of the combination. We critically review results of various trials and discuss the factors that contributed to the distinctive result.

Approaches to Rehabilitation for Visual Field Defects Following Brain Lesions

Expert Review of Medical Devices. May, 2009  |  Pubmed ID: 19419286

Visual field defects often result from stroke and brain injury. The resulting visual impairment can be debilitating for patients, impeding daily activities such as reading and mobility. Historically, it was believed that there was little opportunity for restoration of function following visual system damage. However, the development of various visual rehabilitative strategies suggests that visual field defects are partially repairable and a certain degree of function can be improved. While this provides hope for patients, many of these strategies have been met with skepticism within the clinical and scientific communities. Further development of these strategies through carefully designed studies could validate their efficacy and reveal underlying mechanisms. Novel techniques, aimed at enhancing the effect of these rehabilitative strategies, are also discussed.

The Middle Range of the Number Line Orients Attention to the Left Side of Visual Space

Cognitive Neuropsychology. May, 2009  |  Pubmed ID: 19449241

Mental representation of numbers is believed to be spatial in nature, with small numbers occupying the left and large numbers the right side of a putative mental number line. Consistent with this, presentation of numbers from the low and high ends of the mental number line induces covert shifts of spatial attention to the left and right side of visual space, respectively. However, the effect of the presentation of the middle range (containing numbers below and above the midpoint) of the number line on visual perception has so far not been studied. Here we show in two experiments, using a line bisection task and a simple target detection task, that processing of middle-range numbers affects allocation of visuospatial attention in a similar way as processing of small numbers, with attention shifted to the left side of space. We suggest that this pattern of results arises due to "anchoring" heuristics that participants use in number processing.

Linburg's Syndrome, Can It Cause Focal Dystonia?

Movement Disorders : Official Journal of the Movement Disorder Society. Aug, 2009  |  Pubmed ID: 19514067

Growing Up Blind Does Not Change the Neural Bases of Theory of Mind

Proceedings of the National Academy of Sciences of the United States of America. Jul, 2009  |  Pubmed ID: 19553210

Humans reason about the mental states of others; this capacity is called Theory of Mind (ToM). In typically developing adults, ToM is supported by a consistent group of brain regions: the bilateral temporoparietal junction (TPJ), medial prefrontal cortex (MPFC), precuneus (PC), and anterior temporal sulci (aSTS). How experience and intrinsic biological factors interact to produce this adult functional profile is not known. In the current study we investigate the role of visual experience in the development of the ToM network by studying congenitally blind adults. In experiment 1, participants listened to stories and answered true/false questions about them. The stories were either about mental or physical representations of reality (e.g., photographs). In experiment 2, participants listened to stories about people's beliefs based on seeing or hearing; people's bodily sensations (e.g., hunger); and control stories without people. Participants judged whether each story had positive or negative valance. We find that ToM brain regions of sighted and congenitally blind adults are similarly localized and functionally specific. In congenitally blind adults, reasoning about mental states leads to activity in bilateral TPJ, MPFC, PC, and aSTS. These brain regions responded more to passages about beliefs than passages about nonbelief representations or passages about bodily sensations. Reasoning about mental states that are based on seeing is furthermore similar in congenitally blind and sighted individuals. Despite their different developmental experience, congenitally blind adults have a typical ToM network. We conclude that the development of neural mechanisms for ToM depends on innate factors and on experiences represented at an abstract level, amodally.

Safety of 1 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) in Patients with Titanium Skull Plates

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Jul, 2009  |  Pubmed ID: 19560399

Abnormal Corticospinal Excitability in Traumatic Diffuse Axonal Brain Injury

Journal of Neurotrauma. Dec, 2009  |  Pubmed ID: 19604100

This study aimed to investigate the cortical motor excitability characteristics in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A variety of excitatory and inhibitory transcranial magnetic stimulation (TMS) paradigms were applied to primary motor cortices of 17 patients and 11 healthy controls. The parameters of testing included resting motor threshold (MT), motor evoked potential (MEP) area under the curve, input-output curves, MEP variability, and silent period (SP) duration. The patient group overall revealed a higher MT, smaller MEP areas, and narrower recruitment curves compared to normal controls (p < 0.05). The alterations in excitability were more pronounced with an increase in DAI severity (p < 0.005) and the presence of motor impairment (p < 0.05), while co-existence of focal lesions did not affect the degree of MEP changes. MEP variability was significantly lower in the group with motor impairment only (p < 0.05). The intracortical inhibition, as revealed by SP duration, did not exhibit any significant differences in any of the patient groups. In conclusion, our findings expand the concept that impairment of the excitatory and inhibitory phenomena in the motor cortex does not proceed in parallel and demonstrate distinct patterns of aberrations in TBI. Furthermore, these data suggest that alterations in the corticospinal excitatory mechanisms are determined predominantly by the severity of DAI, and show a significant relationship with clinical motor dysfunction following severe trauma diffusely affecting the motor cortical connections. In severe TBI, motor and functional recovery might be linked to restitution of normal corticospinal mechanisms, indexed by normalization of the cortical excitability parameters.

The Mental Number Line Modulates Visual Cortical Excitability

Neuroscience Letters. Oct, 2009  |  Pubmed ID: 19616067

The mental number line has been shown to exert an influence on the visuo-spatial allocation of attention, with presentation of numbers from the low and high ends of the mental number line inducing covert shifts of spatial attention to the left and right side of visual space, respectively. In the present study we used transcranial magnetic stimulation (TMS) to investigate whether this attentional modulation influences excitability of the early visual cortex. By using the phosphene threshold as a measure of visual cortical excitability, we show (in 10 subjects) that number priming modulates excitability of the early visual cortex in a topographic fashion: low numbers, associated with left side of space, increase the excitability of the right early visual cortex (the stimulation of which induces phosphenes in the left hemifield) and decrease the excitability of the left early visual cortex (the stimulation of which induces phosphenes in the right hemifield). The opposite pattern of results was observed for high numbers. Our results suggest that the attentional shifts induced by the mental number line are manifested at the earliest cortical stages of visual processing.

Overt Naming FMRI Pre- and Post-TMS: Two Nonfluent Aphasia Patients, with and Without Improved Naming Post-TMS

Brain and Language. Oct, 2009  |  Pubmed ID: 19695692

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post-a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received 10, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a 'good responder' with improved naming and phrase length; P2 was a 'poor responder' without improved naming. Pre-TMS (10 years poststroke), P1 had significant activation in R and L sensorimotor cortex, R IFG, and in both L and R SMA during overt naming fMRI (28% pictures named). At 3 mo. post-TMS (42% named), P1 showed continued activation in R and L sensorimotor cortex, R IFG, and in R and L SMA. At 16 mo. post-TMS (58% named), he also showed significant activation in R and L sensorimotor cortex mouth and R IFG. He now showed a significant increase in activation in the L SMA compared to pre-TMS and at 3 mo. post-TMS (p < .02; p < .05, respectively). At 16 mo. there was also greater activation in L than R SMA (p < .08). At 46 mo. post-TMS (42% named), this new LH pattern of activation continued. He improved on the Boston Naming Test from 11 pictures named pre-TMS, to scores ranging from 14 to 18 pictures, post-TMS (2-43 mo. post-TMS). His longest phrase length (Cookie Theft picture) improved from three words pre-TMS, to 5-6 words post-TMS. Pre-TMS (1.5 years poststroke), P2 had significant activation in R IFG (3% pictures named). At 3 and 6 mo. post-TMS, there was no longer significant activation in R IFG, but significant activation was present in R sensorimotor cortex. On all three fMRI scans, P2 had significant activation in both the L and R SMA. There was no new, lasting perilesional LH activation across sessions for this patient. Over time, there was little or no change in his activation. His naming remained only at 1-2 pictures during all three fMRI scans. His BNT score and longest phrase length remained at one word, post-TMS. Lesion site may play a role in each patient's fMRI activation pattern and response to TMS treatment. P2, the poor responder, had an atypical frontal lesion in the L motor and premotor cortex that extended high, near brain vertex, with deep white matter lesion near L SMA. P2 also had frontal lesion in the posterior middle frontal gyrus, an area important for naming (Duffau et al., 2003); P1 did not. Additionally, P2 had lesion inferior and posterior to Wernicke's area, in parts of BA 21 and 37, whereas P1 did not. The fMRI data of our patient who had good response following TMS support the notion that restoration of the LH language network is linked in part, to better recovery of naming and phrase length in nonfluent aphasia.

In-session Seizures During Low-frequency Repetitive Transcranial Magnetic Stimulation in Patients with Epilepsy

Epilepsy & Behavior : E&B. Oct, 2009  |  Pubmed ID: 19747883

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool for patients with intractable epilepsy. Although seizures during treatment have been reported as adverse events in some patients, the nature and severity of seizures that may be provoked by low-frequency rTMS in patients with epilepsy have not been extensively studied. Accordingly, this article documents seizures in patients (n=5) with intractable epilepsy and average seizure frequency greater than one per day who underwent 1-Hz rTMS for seizure suppression. We report three observations in the present case series: (1) in each instance the in-session seizure was typical in semiology to the patient's habitual seizures, (2) the duration of each documented seizure was either the same as or shorter than the patients' baseline seizures, and (3) the overall neurological outcome on follow-up was not affected by the in-session seizures. More data will be required for valid conclusions with respect to safety and tolerability of low-frequency rTMS in patients with epilepsy, but it is noteworthy from our perspective that seizures during rTMS in this series were similar to the patients' habitual seizures, occurred in patients with epilepsy with baseline seizure frequency exceeding one per day, and did not correlate with a poor neurological outcome or with absence of clinical response to rTMS.

Contrasting Early Visual Cortical Activation States Causally Involved in Visual Imagery and Short-term Memory

The European Journal of Neuroscience. Oct, 2009  |  Pubmed ID: 19788574

Whether visual imagery and visual short-term memory (STM) share the same neural resources, and the extent to which the early visual cortex (V1/V2) is involved in these processes, has been the subject of much debate. Here, we used transcranial magnetic stimulation (TMS) in two separate experiments to contrast the neural states associated with visual imagery and visual STM in the early visual cortex. In Experiment 1, we investigated V1/V2 activation states at the end of the retention phase in a visual imagery and a visual STM task. V1/V2 TMS facilitated performance in both tasks; the finding that imagery and STM interacted with TMS in the same way suggests that the two processes have similar effects on early visual cortical excitability. In Experiment 2, we investigated V1/V2 activation states at the beginning of the retention phase. V1/V2 TMS impaired performance in the visual STM task, whereas it had no effect on the imagery task. Taken together, our findings show that the late phases of the early visual cortical activation state associated with visual imagery and visual STM are similar; differences between the two processes are apparent in the early phases of the tasks. Our results also suggest that the causal role of the early visual cortex in visual STM includes both the initial translation of the visual input into working memory and the subsequent maintenance of the mental representation. Finally, our findings indicate that visual STM sensory recruitment in working memory might act via excitability modulation of V1/V2 neurons.

Estimation of Brain State Changes Associated with Behavior, Stimulation and Epilepsy

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2009  |  Pubmed ID: 19964837

Brain state dynamics vary at different spatiotemporal scales with behavior, stimulation, and disease, and may be unobserved (latent). Using a state-space model framework and subspace identification, we estimated spatiotemporally localized, latent state changes associated with the application of transcranial magnetic stimulation (TMS), to assess the effect of stimulation on brain state dynamics. State appeared to be modulated by behavior in a spatially-specific manner and small-amplitude state fluctuations were temporally locked to stimulus presentations. In addition, during and following TMS, an overall, bilateral and spatially nonspecific decrease in brain state was observed. We also estimated brain state changes during seizure evolution (independent of TMS), in focal and generalized seizures, which have very different epileptogenesis and propagation mechanisms, possibly resulting also in distinct spatiotemporal dynamics. Indeed, our preliminary results showed that in focal seizures, temporally localized dynamic state changes occur at least 1 min prior to seizure onset, with a decrease in steady-state followed by an increase which reaches a maximum during the ictal interval. In contrast, no such dynamic pattern was evident in state estimates during generalized seizures.

Repetitive Transcranial Magnetic Stimulation in the Treatment of Epilepsia Partialis Continua

Epilepsy & Behavior : E&B. Jan, 2009  |  Pubmed ID: 18832045

Repetitive transcranial magnetic stimulation (rTMS) is a technique for noninvasive focal brain stimulation by which small intracranial electrical currents are generated by a fluctuating extracranial magnetic field. In clinical epilepsy, rTMS has been applied most often interictally to reduce seizure frequency. Less often, rTMS has been used to terminate ongoing seizures, as in instances of epilepsia partialis continua (EPC). Whether ictal rTMS is effective and safe in the treatment of EPC has not been extensively studied. Here, we describe our recent experience with rTMS in the treatment of EPC, as an early step toward evaluating the safety and efficacy of rTMS in the treatment of intractable ongoing focal seizures.

Safety and Behavioral Effects of High-frequency Repetitive Transcranial Magnetic Stimulation in Stroke

Stroke; a Journal of Cerebral Circulation. Jan, 2009  |  Pubmed ID: 18845801

Electromagnetic brain stimulation might have value to reduce motor deficits after stroke. Safety and behavioral effects of higher frequencies of repetitive transcranial magnetic stimulation (rTMS) require detailed assessment.

The Role of the Angular Gyrus in the Modulation of Visuospatial Attention by the Mental Number Line

NeuroImage. Jan, 2009  |  Pubmed ID: 18848630

We tend to mentally organize numbers along a left-to-right oriented horizontal mental number line, with the smaller numbers occupying the more leftward positions. This mental number line has been shown to exert an influence on the visuospatial allocation of attention, with presentation of numbers from the low and high ends of the mental number line inducing covert shifts of spatial attention to the left and right side of visual space, respectively. However, the neural basis of this modulation is not known. Here we used transcranial magnetic stimulation (TMS) to study the role of the angular gyrus in shifts in visuospatial attention induced by the mental number line. We used a priming paradigm with a line bisection task to assess the bias in spatial allocation of visual attention induced by exposure to either small (16-24) or large (76-84) ends of the mental number line. In the Small Number Prime condition, when attention is presumably biased to the left side of visual space, TMS applied over the right angular gyrus during the delay between the prime and the target line abolished the effect of number priming. In contrast, application of TMS over the left angular gyrus had no significant effect. In the Large Number Prime condition (which shifted attention to the right side of visual space) both left and right TMS over the angular gyrus modulated the effect of number priming. This pattern of results reveals the involvement of the angular gyrus in the interaction between the mental number line and visual spatial attention.

The Role of the Parietal Lobe in Visual Extinction Studied with Transcranial Magnetic Stimulation

Journal of Cognitive Neuroscience. Oct, 2009  |  Pubmed ID: 18855545

Interhemispheric competition between homologous areas in the human brain is believed to be involved in a wide variety of human behaviors from motor activity to visual perception and particularly attention. For example, patients with lesions in the posterior parietal cortex are unable to selectively track objects in the contralesional side of visual space when targets are simultaneously present in the ipsilesional visual field, a form of visual extinction. Visual extinction may arise due to an imbalance in the normal interhemispheric competition. To directly assess the issue of reciprocal inhibition, we used fMRI to localize those brain regions active during attention-based visual tracking and then applied low-frequency repetitive transcranial magnetic stimulation over identified areas in the left and right intraparietal sulcus to asses the behavioral effects on visual tracking. We induced a severe impairment in visual tracking that was selective for conditions of simultaneous tracking in both visual fields. Our data show that the parietal lobe is essential for visual tracking and that the two hemispheres compete for attentional resources during tracking. Our results provide a neuronal basis for visual extinction in patients with parietal lobe damage.

6-Hz Primed Low-frequency RTMS to Contralesional M1 in Two Cases with Middle Cerebral Artery Stroke

Neuroscience Letters. Jan, 2010  |  Pubmed ID: 20026185

This case study contrasted two subjects with stroke who received 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) to the contralesional primary motor area (M1) to disinhibit ipsilesional M1. Functional magnetic resonance imaging (fMRI) showed that the intervention disrupted cortical activation at contralesional M1. Subject 1 showed decreased intracortical inhibition and increased intracortical facilitation following intervention during paired-pulse TMS testing of ipsilesional M1. Subject 2, whose precentral knob was totally obliterated and who did not show an ipsilesional motor evoked potential at pretest, still did not show any at posttest; however, her fMRI did show a large increase in peri-infarct zone cortical activation. Behavioral results were mixed, indicating the need for accompanying behavioral training to capitalize on the brain organization changes induced with rTMS.

Motor Cortical Hyperexcitability in Idiopathic Scoliosis: Could Focal Dystonia Be a Subclinical Etiological Factor?

European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Feb, 2010  |  Pubmed ID: 20033462

The aetiology of idiopathic scoliosis (IS) remains unknown; however, there is a growing body of evidence suggesting that the spine deformity could be the expression of a subclinical nervous system disorder. A defective sensory input or an anomalous sensorimotor integration may lead to an abnormal postural tone and therefore the development of a spine deformity. Inhibition of the motor cortico-cortical excitability is abnormal in dystonia. Therefore, the study of cortico-cortical inhibition may shed some insight into the dystonia hypothesis regarding the pathophysiology of IS. Paired pulse transcranial magnetic stimulation was used to study cortico-cortical inhibition and facilitation in nine adolescents with IS, five teenagers with congenital scoliosis (CS) and eight healthy age-matched controls. The effect of a previous conditioning stimulus (80% intensity of resting motor threshold) on the amplitude of the motor-evoked potential induced by the test stimulus (120% of resting motor threshold) was examined at various interstimulus intervals (ISIs) in both abductor pollicis brevis muscles. The results of healthy adolescents and those with CS showed a marked inhibitory effect of the conditioning stimulus on the response to the test stimulus at interstimulus intervals shorter than 6 ms. These findings do not differ from those reported for normal adults. However, children with IS revealed an abnormally reduced cortico-cortical inhibition at the short ISIs. Cortico-cortical inhibition was practically normal on the side of the scoliotic convexity while it was significantly reduced on the side of the scoliotic concavity. In conclusion, these findings support the hypothesis that a dystonic dysfunction underlies in IS. Asymmetrical cortical hyperexcitability may play an important role in the pathogenesis of IS and represents an objective neurophysiological finding that could be used clinically.

Integrating TMS with EEG: How and What For?

Brain Topography. Jan, 2010  |  Pubmed ID: 20043238

Noninvasive Brain Stimulation with High-frequency and Low-intensity Repetitive Transcranial Magnetic Stimulation Treatment for Posttraumatic Stress Disorder

The Journal of Clinical Psychiatry. Aug, 2010  |  Pubmed ID: 20051219

We aimed to investigate the efficacy of 20 Hz repetitive transcranial magnetic stimulation (rTMS) of either right or left dorsolateral prefrontal cortex (DLPFC) as compared to sham rTMS for the relief of posttraumatic stress disorder (PTSD)-associated symptoms.

Reduction of Spasticity with Repetitive Transcranial Magnetic Stimulation in Patients with Spinal Cord Injury

Neurorehabilitation and Neural Repair. Jun, 2010  |  Pubmed ID: 20053952

Spasticity with increased tone and spasms is frequent in patients after spinal cord injury (SCI). Damage to descending corticospinal pathways that normally exert spinal segmental control is thought to play an important causal role in spasticity. The authors examined whether the modulation of excitability of the primary motor cortex with high-frequency repetitive transcranial magnetic stimulation (rTMS) could modify lower limb spasticity in patients with incomplete SCI.

Modulation of Decision-making in a Gambling Task in Older Adults with Transcranial Direct Current Stimulation

The European Journal of Neuroscience. Feb, 2010  |  Pubmed ID: 20105234

Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision-making. Based on our recent findings suggesting that non-invasive brain stimulation can improve decision-making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty-eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high-risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly.

Interhemispheric Modulation Induced by Cortical Stimulation and Motor Training

Physical Therapy. Mar, 2010  |  Pubmed ID: 20110339

Interhemispheric inhibition might be a beneficial cortico-cortical interaction, but also might be maladaptive in people with neurological disorders. One recently revisited technique that has been shown to be effective in improving motor function in people with stroke using interhemispheric modulation is transcranial direct current stimulation (tDCS).

Neuroplasticity Associated with Tactile Language Communication in a Deaf-blind Subject

Frontiers in Human Neuroscience. 2010  |  Pubmed ID: 20130756

A long-standing debate in cognitive neuroscience pertains to the innate nature of language development and the underlying factors that determine this faculty. We explored the neural correlates associated with language processing in a unique individual who is early blind, congenitally deaf, and possesses a high level of language function. Using functional magnetic resonance imaging (fMRI), we compared the neural networks associated with the tactile reading of words presented in Braille, Print on Palm (POP), and a haptic form of American Sign Language (haptic ASL or hASL). With all three modes of tactile communication, indentifying words was associated with robust activation within occipital cortical regions as well as posterior superior temporal and inferior frontal language areas (lateralized within the left hemisphere). In a normally sighted and hearing interpreter, identifying words through hASL was associated with left-lateralized activation of inferior frontal language areas however robust occipital cortex activation was not observed. Diffusion tensor imaging -based tractography revealed differences consistent with enhanced occipital-temporal connectivity in the deaf-blind subject. Our results demonstrate that in the case of early onset of both visual and auditory deprivation, tactile-based communication is associated with an extensive cortical network implicating occipital as well as posterior superior temporal and frontal associated language areas. The cortical areas activated in this deaf-blind subject are consistent with characteristic cortical regions previously implicated with language. Finally, the resilience of language function within the context of early and combined visual and auditory deprivation may be related to enhanced connectivity between relevant cortical areas.

Two Phases of V1 Activity for Visual Recognition of Natural Images

Journal of Cognitive Neuroscience. Jun, 2010  |  Pubmed ID: 19413482

Present theories of visual recognition emphasize the role of interactive processing across populations of neurons within a given network, but the nature of these interactions remains unresolved. In particular, data describing the sufficiency of feedforward algorithms for conscious vision and studies revealing the functional relevance of feedback connections to the striate cortex seem to offer contradictory accounts of visual information processing. TMS is a good method to experimentally address this issue, given its excellent temporal resolution and its capacity to establish causal relations between brain function and behavior. We studied 20 healthy volunteers in a visual recognition task. Subjects were briefly presented with images of animals (birds or mammals) in natural scenes and were asked to indicate the animal category. MRI-guided stereotaxic single TMS pulses were used to transiently disrupt striate cortex function at different times after image onset (SOA). Visual recognition was significantly impaired when TMS was applied over the occipital pole at SOAs of 100 and 220 msec. The first interval has consistently been described in previous TMS studies and is explained as the interruption of the feedforward volley of activity. Given the late latency and discrete nature of the second peak, we hypothesize that it represents the disruption of a feedback projection to V1, probably from other areas in the visual network. These results provide causal evidence for the necessity of recurrent interactive processing, through feedforward and feedback connections, in visual recognition of natural complex images.

Safety and Proof of Principle Study of Cerebellar Vermal Theta Burst Stimulation in Refractory Schizophrenia

Schizophrenia Research. Dec, 2010  |  Pubmed ID: 20817483

Early invasive electrical stimulation studies suggested that enhancement of cerebellar vermal activity might prove valuable in symptomatic treatment of refractory neuropsychiatric diseases via modulation of emotion and affect. This proof of principle study aimed to test this hypothesis using noninvasive brain stimulation, and to explore the safety of this protocol in schizophrenia.

The Importance of Recognizing Paradoxes (Commentary on Madhavan Et Al.)

The European Journal of Neuroscience. Sep, 2010  |  Pubmed ID: 20865821

Assessment and Modulation of Neural Plasticity in Rehabilitation with Transcranial Magnetic Stimulation

PM & R : the Journal of Injury, Function, and Rehabilitation. Dec, 2010  |  Pubmed ID: 21172687

Despite intensive efforts to improve outcomes after acquired brain injury, functional recovery is often limited. One reason for this limitation is the challenge in assessing and guiding plasticity after brain injury. In this context, transcranial magnetic stimulation (TMS), a noninvasive tool of brain stimulation, could play a major role. TMS has been shown to be a reliable tool for measuring plastic changes in the motor cortex associated with interventions in the motor system, such as motor training and motor cortex stimulation. In addition, as illustrated by the experience in promoting recovery from stroke, TMS is a promising therapeutic tool to minimize motor, speech, cognitive, and mood deficits. In this review, we will focus on stroke to discuss how TMS can provide insights into the mechanisms of neurologic recovery and how it can be used for measurement and modulation of plasticity after an acquired brain insult.

Neural Reorganization Following Sensory Loss: the Opportunity of Change

Nature Reviews. Neuroscience. Jan, 2010  |  Pubmed ID: 19935836

There is growing evidence that sensory deprivation is associated with crossmodal neuroplastic changes in the brain. After visual or auditory deprivation, brain areas that are normally associated with the lost sense are recruited by spared sensory modalities. These changes underlie adaptive and compensatory behaviours in blind and deaf individuals. Although there are differences between these populations owing to the nature of the deprived sensory modality, there seem to be common principles regarding how the brain copes with sensory loss and the factors that influence neuroplastic changes. Here, we discuss crossmodal neuroplasticity with regards to behavioural adaptation after sensory deprivation and highlight the possibility of maladaptive consequences within the context of rehabilitation.

Improved Language in a Chronic Nonfluent Aphasia Patient After Treatment with CPAP and TMS

Cognitive and Behavioral Neurology : Official Journal of the Society for Behavioral and Cognitive Neurology. Mar, 2010  |  Pubmed ID: 20299861

To present pretreatment and post-treatment language data for a nonfluent aphasia patient who received 2 treatment modalities: (1) continuous positive airway pressure (CPAP) for his sleep apnea, starting 1-year poststroke; and (2) repetitive transcranial magnetic brain stimulation (TMS), starting 2 years poststroke.

Disruption of the Right Temporoparietal Junction with Transcranial Magnetic Stimulation Reduces the Role of Beliefs in Moral Judgments

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2010  |  Pubmed ID: 20351278

When we judge an action as morally right or wrong, we rely on our capacity to infer the actor's mental states (e.g., beliefs, intentions). Here, we test the hypothesis that the right temporoparietal junction (RTPJ), an area involved in mental state reasoning, is necessary for making moral judgments. In two experiments, we used transcranial magnetic stimulation (TMS) to disrupt neural activity in the RTPJ transiently before moral judgment (experiment 1, offline stimulation) and during moral judgment (experiment 2, online stimulation). In both experiments, TMS to the RTPJ led participants to rely less on the actor's mental states. A particularly striking effect occurred for attempted harms (e.g., actors who intended but failed to do harm): Relative to TMS to a control site, TMS to the RTPJ caused participants to judge attempted harms as less morally forbidden and more morally permissible. Thus, interfering with activity in the RTPJ disrupts the capacity to use mental states in moral judgment, especially in the case of attempted harms.

Auditory Enhancement of Visual Phosphene Perception: the Effect of Temporal and Spatial Factors and of Stimulus Intensity

Neuroscience Letters. Jun, 2010  |  Pubmed ID: 20430065

Multisensory integration of information from different sensory modalities is an essential component of perception. Neurophysiological studies have revealed that audiovisual interactions occur early in time and even within sensory cortical areas believed to be modality-specific. Here we investigated the effect of auditory stimuli on visual perception of phosphenes induced by transcranial magnetic stimulation (TMS) delivered to the occipital visual cortex. TMS applied at subthreshold intensity led to the perception of phosphenes when coupled with an auditory stimulus presented within close spatiotemporal congruency at the expected retinotopic location of the phosphene percept. The effect was maximal when the auditory stimulus preceded the occipital TMS pulse by 40 ms. Follow-up experiments confirmed a high degree of temporal and spatial specificity of this facilitatory effect. Furthermore, audiovisual facilitation was only present at subthreshold TMS intensity for the phosphenes, suggesting that suboptimal levels of excitability within unisensory cortices may be better suited for enhanced crossmodal interactions. Overall, our findings reveal early auditory-visual interactions due to the enhancement of visual cortical excitability by auditory stimuli. These interactions may reflect an underlying anatomical connectivity between unisensory cortices.

Horizontal Portion of Arcuate Fasciculus Fibers Track to Pars Opercularis, Not Pars Triangularis, in Right and Left Hemispheres: a DTI Study

NeuroImage. Aug, 2010  |  Pubmed ID: 20438853

The arcuate fasciculus (AF) is a white matter pathway traditionally considered to connect left Broca's area with posterior language zones. We utilized diffusion tensor imaging (DTI) in eight healthy subjects (5 M) to track pathways in the horizontal mid-portion of the AF (hAF) to subregions of Broca's area - pars triangularis (PTr) and pars opercularis (POp); and to ventral premotor cortex (vPMC) in the right and left hemispheres (RH, LH). These pathways have previously been studied in the LH, but not in the RH. Only 1/8 subjects showed fiber tracts between PTr and hAF in the RH (also, only 1/8 in the LH). In contrast to PTr, 5/8 subjects showed fiber tracts between POp and hAF in the RH (8/8 in the LH). Fiber tracts for vPMC were similar to those of POp, where 7/8 subjects showed fiber tracts between vPMC and hAF in the RH (8/8 in the LH). Our designated hAF could have included some of the superior longitudinal fasciculus (SLF) III, because it is difficult to separate the two fiber bundles. The SLF III has been previously reported to connect supramarginal gyrus with POp and vPMC in the LH. Thus, although the present DTI study showed almost no pathways between PTr and hAF in the RH (and in the LH), robust pathways were observed between POp and/or vPMC with hAF in the RH (and in LH). These results replicate previous studies for the LH, but are new, for the RH. They could contribute to better understanding of recovery in aphasia.

Symmetry Perception in the Blind

Acta Psychologica. Jul, 2010  |  Pubmed ID: 20444438

Bilateral mirror symmetry, especially vertical symmetry, is a powerful phenomenon in spatial organization of visual shapes. However, the causes of vertical symmetry salience in visual perception are not completely clear. Here we investigated whether the perceptual salience of vertical symmetry depends on visual experience by testing a group of congenitally blind individuals in a memory task in which either horizontal or vertical symmetry was used as an incidental feature. Both blind and sighted subjects remembered more accurately configurations that were symmetrical compared to those that were not. Critically, whereas sighted subjects displayed a higher level of facilitation by vertical than horizontal symmetry, no such difference was found in the blind. This suggests that the perceptual salience of the vertical dimension is visually based.

Enhancing Plasticity Through Repeated RTMS Sessions: the Benefits of a Night of Sleep

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Dec, 2010  |  Pubmed ID: 20541968

Previous work has demonstrated that corticospinal facilitation from 20Hz repetitive transcranial magnetic stimulation (rTMS) was greater during a second rTMS session 24h after the first. We sought to determine whether such metaplasticity is dependent on a particular phase of the normal sleep-wake/circadian cycle.

Modulation of Cortical Motor Outputs by the Symbolic Meaning of Visual Stimuli

The European Journal of Neuroscience. Jul, 2010  |  Pubmed ID: 20561046

The observation of an action modulates motor cortical outputs in specific ways, in part through mediation of the mirror neuron system. Sometimes we infer a meaning to an observed action based on integration of the actual percept with memories. Here, we conducted a series of experiments in healthy adults to investigate whether such inferred meanings can also modulate motor cortical outputs in specific ways. We show that brief observation of a neutral stimulus mimicking a hand does not significantly modulate motor cortical excitability (Study 1) although, after prolonged exposure, it can lead to a relatively nonspecific modulation (Study 2). However, when such a neutral stimulus is preceded by exposure to a hand stimulus, the latter appears to serve as a prime, perhaps enabling meaning to the neutral stimulus, which then modulates motor cortical excitability in accordance with mirror neuron-driving properties (Studies 2 and 3). Overall results suggest that a symbolic value ascribed to an otherwise neutral stimulus can modulate motor cortical outputs, revealing the influence of top-down inputs on the mirror neuron system. These findings indicate a novel aspect of the human mirror neuron system: an otherwise neutral stimulus can acquire specific mirror neuron-driving properties in the absence of a direct association between motor practice and perception. This significant malleability in the way that the mirror neuron system can code otherwise meaningless (i.e. arbitrarily associated) stimuli may contribute to coding communicative signals such as language. This may represent a mirror neuron system feature that is unique to humans.

Neuromodulation of Decision-making in the Addictive Brain

Substance Use & Misuse. Sep, 2010  |  Pubmed ID: 20590399

Noninvasive brain stimulation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation and transcranial direct current stimulation can modify decision-making behaviors in healthy subjects. The same type of noninvasive brain stimulation can suppress drug craving in substance user patients, who often display impaired decision-making behaviors. We discuss the implications of these studies for the cognitive neurosciences and their translational applications to the treatment of addictions. We propose a neurocognitive model that can account for our findings and suggests a promising therapeutic role of brain stimulation in the treatment of substance abuse and addictive behavior disorders.

Effectiveness of Transcranial Direct Current Stimulation and Visual Illusion on Neuropathic Pain in Spinal Cord Injury

Brain : a Journal of Neurology. Sep, 2010  |  Pubmed ID: 20685806

The aim of this study was to evaluate the analgesic effect of transcranial direct current stimulation of the motor cortex and techniques of visual illusion, applied isolated or combined, in patients with neuropathic pain following spinal cord injury. In a sham controlled, double-blind, parallel group design, 39 patients were randomized into four groups receiving transcranial direct current stimulation with walking visual illusion or with control illusion and sham stimulation with visual illusion or with control illusion. For transcranial direct current stimulation, the anode was placed over the primary motor cortex. Each patient received ten treatment sessions during two consecutive weeks. Clinical assessment was performed before, after the last day of treatment, after 2 and 4 weeks follow-up and after 12 weeks. Clinical assessment included overall pain intensity perception, Neuropathic Pain Symptom Inventory and Brief Pain Inventory. The combination of transcranial direct current stimulation and visual illusion reduced the intensity of neuropathic pain significantly more than any of the single interventions. Patients receiving transcranial direct current stimulation and visual illusion experienced a significant improvement in all pain subtypes, while patients in the transcranial direct current stimulation group showed improvement in continuous and paroxysmal pain, and those in the visual illusion group improved only in continuous pain and dysaesthesias. At 12 weeks after treatment, the combined treatment group still presented significant improvement on the overall pain intensity perception, whereas no improvements were reported in the other three groups. Our results demonstrate that transcranial direct current stimulation and visual illusion can be effective in the management of neuropathic pain following spinal cord injury, with minimal side effects and with good tolerability.

Research with RTMS in the Treatment of Aphasia

Restorative Neurology and Neuroscience. 2010  |  Pubmed ID: 20714075

This review of our research with rTMS to treat aphasia contains four parts: Part 1 reviews functional brain imaging studies related to recovery of language in aphasia with emphasis on nonfluent aphasia. Part 2 presents the rationale for using rTMS to treat nonfluent aphasia patients (based on results from functional imaging studies). Part 2 also reviews our current rTMS treatment protocol used with nonfluent aphasia patients, and our functional imaging results from overt naming fMRI scans, obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy (CILT). Part 4 reviews our diffusion tensor imaging (DTI) study that examined white matter connections between the horizontal, midportion of the arcuate fasciculus (hAF) to different parts within Broca's area (pars triangularis, PTr; pars opercularis, POp), and the ventral premotor cortex (vPMC) in the RH and in the LH. Part 4 also addresses some of the possible mechanisms involved with improved naming and speech, following rTMS with nonfluent aphasia patients.

Modulation of Risk-taking in Marijuana Users by Transcranial Direct Current Stimulation (tDCS) of the Dorsolateral Prefrontal Cortex (DLPFC)

Drug and Alcohol Dependence. Dec, 2010  |  Pubmed ID: 20729009

Cognitive deficits that are reported in heavy marijuana users (attention, memory, affect perception, decision-making) appear to be completely reversible after a prolonged abstinence period of about 28 days. However, it remains unclear whether the reversibility of these cognitive deficits indicates that (1) chronic marijuana use is not associated with long-lasting changes in cortical networks or (2) that such changes occur but the brain adapts to and compensates for the drug-induced changes. Therefore, we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm (Risk Task) while undergoing sham or active transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Twenty-five chronic marijuana users who were abstinent for at least 24h were randomly assigned to receive left anodal/right cathodal tDCS of DLPFC (n=8), right anodal/left cathodal tDCS of DLPFC (n=9), or sham stimulation (n=8); results on Risk Task during sham/active tDCS were compared to healthy volunteers from a previously published dataset. Chronic marijuana users demonstrated more conservative (i.e. less risky) decision-making during sham stimulation. While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers, both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users. These findings reveal alterations in the decision-making neural networks among chronic marijuana users. Finally, we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana.

A Review of Combined TMS-EEG Studies to Characterize Lasting Effects of Repetitive TMS and Assess Their Usefulness in Cognitive and Clinical Neuroscience

Brain Topography. Jan, 2010  |  Pubmed ID: 19862614

Transcranial magnetic stimulation (TMS) has developed into a powerful tool for studying human brain physiology and brain-behavior relations. When applied in sessions of repeated stimulation, TMS can lead to changes in neuronal activity/excitability that outlast the stimulation itself. Such aftereffects are at the heart of the offline TMS protocols in cognitive neuroscience and neurotherapeutics. However, whether these aftereffects are of applied interest critically depends on their magnitude and duration, which should fall within an experimentally or clinically useful range without increasing risks and adverse effects. In this short review, we survey combined TMS-EEG studies to characterize the TMS-aftereffects as revealed by EEG to contribute to the characterization of the most effective and promising repetitive TMS-parameters. With one session of conventional repetitive TMS (of fixed pulse frequency), aftereffects were consistently comparable in magnitude to EEG-changes reported after learning or with fatigue, and were short-lived (<70 min). The few studies using recently developed protocols (such as theta burst stimulation) suggest comparable effect-size but longer effect-durations. Based on the reviewed data, it is expected that TMS-efficacy can be further promoted by repeating TMS-sessions, by using EEG-gated TMS to tailor TMS to current neuronal state, or by other, non-conventional TMS-protocols. Newly emerging developments in offline TMS research for cognitive neuroscience and neurotherapeutics are outlined.

Lateralization of Forelimb Motor Evoked Potentials by Transcranial Magnetic Stimulation in Rats

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Jan, 2010  |  Pubmed ID: 19900839

To approximate methods for human transcranial magnetic stimulation (TMS) in rats, we tested whether lateralized cortical stimulation resulting in selective activation of one forelimb contralateral to the site of stimulation could be achieved by TMS in the rat.

Transcranial Magnetic Stimulation Provides Means to Assess Cortical Plasticity and Excitability in Humans with Fragile X Syndrome and Autism Spectrum Disorder

Frontiers in Synaptic Neuroscience. 2010  |  Pubmed ID: 21423512

Fragile X Syndrome (FXS) is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of fragile X mental retardation protein affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation paradigms have recently been developed to non-invasively investigate cortical excitability using paired pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS) in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity). The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD), and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of non-invasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

Sensitive Period for a Multimodal Response in Human Visual Motion Area MT/MST

Current Biology : CB. Nov, 2010  |  Pubmed ID: 20970337

The middle temporal complex (MT/MST) is a brain region specialized for the perception of motion in the visual modality. However, this specialization is modified by visual experience: after long-standing blindness, MT/MST responds to sound. Recent evidence also suggests that the auditory response of MT/MST is selective for motion. The developmental time course of this plasticity is not known. To test for a sensitive period in MT/MST development, we used fMRI to compare MT/MST function in congenitally blind, late-blind, and sighted adults. MT/MST responded to sound in congenitally blind adults, but not in late-blind or sighted adults, and not in an individual who lost his vision between ages of 2 and 3 years. All blind adults had reduced functional connectivity between MT/MST and other visual regions. Functional connectivity was increased between MT/MST and lateral prefrontal areas in congenitally blind relative to sighted and late-blind adults. These data suggest that early blindness affects the function of feedback projections from prefrontal cortex to MT/MST. We conclude that there is a sensitive period for visual specialization in MT/MST. During typical development, early visual experience either maintains or creates a vision-dominated response. Once established, this response profile is not altered by long-standing blindness.

Transcranial Magnetic Stimulation: a Historical Evaluation and Future Prognosis of Therapeutically Relevant Ethical Concerns

Journal of Medical Ethics. Mar, 2011  |  Pubmed ID: 21106996

Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including marketing, off-label use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand.

Modulatory Effects of Theta Burst Stimulation on Cerebellar Nonsomatic Functions

Cerebellum (London, England). Sep, 2011  |  Pubmed ID: 21132574

Clinical and functional imaging studies suggest that the cerebellar vermis is involved in the regulation of a range of nonsomatic functions including cardiovascular control, thirst, feeding behavior, and primal emotions. Cerebello-hypothalamic circuits have been postulated to be a potential neuroanatomical substrate underlying this modulation. We tested this putative relationship between the cerebellar vermis and nonsomatic functions by stimulating the cerebellum noninvasively via neuronavigated transcranial magnetic stimulation. In this randomized, counter-balanced, within-subject study, intermittent theta burst stimulation (TBS) was applied on three different days to the vermis and the right and left cerebellar hemispheres of 12 right-handed normal subjects with the aim of modulating activity in the targeted cerebellar structure. TBS-associated changes were investigated via cardiovascular monitoring, a series of emotionally arousing picture stimuli, subjective analog scales for primal emotions, and the Profile of Mood States test. All 36 sessions of cerebellar stimulation were tolerated well without serious adverse events. Cardiovascular monitoring pointed to a mild but significant decrease in heart rate subsequent to vermal stimulation; no changes were detected in systolic or diastolic blood pressure measurements. Subjective ratings detected a significant increase in Thirst and a trend toward increased Appetite following vermal stimulation. These observations are consistent with existing neurophysiological and neuroimaging data indicating a role for the cerebellum in the regulation of visceral responses. In conjunction with the modulatory function of the cerebellum, our results suggest a role for the vermis in somatovisceral integration likely through cerebello-hypothalamic pathways. Further research is warranted to elucidate the potential mechanisms underlying the cerebellar modulation of nonsomatic functions.

Measures of Cortical Inhibition by Paired-pulse Transcranial Magnetic Stimulation in Anesthetized Rats

Journal of Neurophysiology. Feb, 2011  |  Pubmed ID: 21160011

Paired-pulse transcranial magnetic stimulation (ppTMS) is a noninvasive method to measure cortical inhibition in vivo. Long interpulse interval (50-500 ms) ppTMS (LI-ppTMS) provokes intracortical inhibitory circuits and can reveal pathologically impaired cortical inhibition in disorders such as epilepsy. Adaptation of ppTMS protocols to rodent disease models is highly desirable to facilitate basic and translational research. We previously adapted single-pulse TMS (spTMS) methods to rats, but ppTMS has yet to be applied. Specifically, whether ppTMS elicits an inhibitory response in rodents is unknown. ppTMS in rats also requires anesthesia, a setting under which the preservation of these measures is undetermined. We therefore tested, in anesthetized rats, whether anesthetic choice affects spTMS-motor-evoked potentials (MEPs), LI-ppTMS in rats, as in humans, elicits intracortical inhibition of the MEP, and rat LI-ppTMS inhibition is acutely impaired in a seizure model. Rats were anesthetized with pentobarbital (PB) or ketamine-atropine-xylazine (KAX) and stimulated unilaterally over the motor cortex while recording bilateral brachioradialis MEPs. LI-ppTMS was applied analogous to human long interval intracortical inhibition (LICI) protocols, and acute changes in inhibition were evaluated following injection of the convulsant pentylenetetrazole (PTZ). We find that spTMS-evoked MEPs were reliably present under either anesthetic, and that LI-ppTMS elicits inhibition of the conditioned MEP in rats, similar to human LICI, by as much as 58 ± 12 and 71 ± 11% under PB and KAX anesthesia, respectively. LI-ppTMS inhibition was reduced to as much as 53% of saline controls following PTZ injection, while spTMS-derived measures of corticospinal excitability were unchanged. Our data show that regional inhibition, similar to human LICI, is present in rats, can be elicited under PB or KAX anesthesia, and is reduced following convulsant administration. These results suggest a potential for LI-ppTMS as a biomarker of impaired cortical inhibition in murine disease models.

Single Pulse TMS-induced Modulations of Resting Brain Neurodynamics Encoded in EEG Phase

Brain Topography. Jun, 2011  |  Pubmed ID: 21203817

Integration of electroencephalographic (EEG) recordings and transcranial magnetic stimulation (TMS) provides a useful framework for quantifying stimulation-induced modulations of neural dynamics. Amplitude and frequency modulations by different TMS protocols have been previously investigated, but the study of stimulation-induced effects on EEG phase has been more limited. We examined changes in resting brain dynamics following single TMS pulses, focusing on measures in the phase domain, to assess their sensitivity to stimulation effects. We observed a significant, approximately global increase in EEG relative phase following prolonged (>20 min) single-pulse TMS. In addition, we estimated higher rates of phase fluctuation from the slope of estimated phase curves, and higher numbers of phase resetting intervals following TMS over motor cortex, particularly in frontal and centro-parietal/parietal channels. Phase changes were only significantly different from their pre-TMS values at the end of the stimulation session, which suggests that prolonged single-pulse TMS may result in cumulative changes in neural activity reflected in the phase of the EEG. This is a novel result, as prior studies have reported only transient stimulation-related effects in the amplitude and frequency domains following single-pulse TMS.

An Estimate of Placebo Effect of Repetitive Transcranial Magnetic Stimulation in Epilepsy

Epilepsy & Behavior : E&B. Feb, 2011  |  Pubmed ID: 21216200

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool in epilepsy. In recent years, several open-label trials have shown an encouraging reduction in seizure frequency in patients with epilepsy. However, the data from controlled trials are mixed with respect to antiepileptic rTMS efficacy, and the field would benefit from further carefully controlled trials. Prior to initiating new trials, it is important assess the magnitude of the placebo effect of presently used sham rTMS methods.

Safety of Theta Burst Transcranial Magnetic Stimulation: a Systematic Review of the Literature

Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society. Feb, 2011  |  Pubmed ID: 21221011

Theta burst stimulation (TBS) protocols have recently emerged as a method to transiently alter cortical excitability in the human brain through repetitive transcranial magnetic stimulation. TBS involves applying short trains of stimuli at high frequency repeated at intervals of 200 milliseconds. Because repetitive transcranial magnetic stimulation is known to carry a risk of seizures, safety guidelines have been established. TBS has the theoretical potential of conferring an even higher risk of seizure than other repetitive transcranial magnetic stimulation protocols because it delivers high-frequency bursts. In light of the recent report of a seizure induced by TBS, the safety of this new protocol deserves consideration. We performed an English language literature search and reviewed all studies published from May 2004 to December 2009 in which TBS was applied. The adverse events were documented, and crude risk was calculated. The majority of adverse events attributed to TBS were mild and occurred in 5% of subjects. Based on this review, TBS seems to be a safe and efficacious technique. However, given its novelty, it should be applied with caution. Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS and intensity dosing studies to assess the seizure risk associated with various stimulation parameters (e.g., frequency, intensity, and location).

Improved Motion Perception and Impaired Spatial Suppression Following Disruption of Cortical Area MT/V5

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jan, 2011  |  Pubmed ID: 21273412

As stimulus size increases, motion direction of high-contrast patterns becomes increasingly harder to perceive. This counterintuitive behavioral result, termed "spatial suppression," is hypothesized to reflect center-surround antagonism-a receptive field property ubiquitous in sensory systems. Prior research proposed that spatial suppression of motion signals is a direct correlate of center-surround antagonism within cortical area MT. Here, we investigated whether human MT/V5 is indeed causally involved in spatial suppression of motion signals. The key assumption is that a disruption of neural mechanisms that play a critical role in spatial suppression could allow these normally suppressed motion signals to reach perceptual awareness. Thus, our hypothesis was that a disruption of MT/V5 should weaken spatial suppression and, consequently, improve motion perception of large, moving patterns. To disrupt MT/V5, we used offline 1 Hz transcranial magnetic stimulation (TMS)-a method that temporarily attenuates normal functioning of the targeted cortex. Early visual areas were also targeted as a control site. The results supported our hypotheses and showed that disruption of MT/V5 improved motion discrimination of large, moving stimuli, presumably by weakening surround suppression strength. This effect was specific to MT/V5 stimulation and contralaterally presented stimuli. Evidently, the critical neural constraints limiting motion perception of large, high-contrast stimuli involve MT/V5. Additionally, our findings mimic spatial suppression deficits that are observed in several patient populations and implicate impaired MT/V5 processes as likely neural correlates for the reported perceptual abnormalities in the elderly, patients with schizophrenia and those with a history of depression.

Focused Ultrasound Modulates Region-specific Brain Activity

NeuroImage. Jun, 2011  |  Pubmed ID: 21354315

We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders.

Language Processing in the Occipital Cortex of Congenitally Blind Adults

Proceedings of the National Academy of Sciences of the United States of America. Mar, 2011  |  Pubmed ID: 21368161

Humans are thought to have evolved brain regions in the left frontal and temporal cortex that are uniquely capable of language processing. However, congenitally blind individuals also activate the visual cortex in some verbal tasks. We provide evidence that this visual cortex activity in fact reflects language processing. We find that in congenitally blind individuals, the left visual cortex behaves similarly to classic language regions: (i) BOLD signal is higher during sentence comprehension than during linguistically degraded control conditions that are more difficult; (ii) BOLD signal is modulated by phonological information, lexical semantic information, and sentence-level combinatorial structure; and (iii) functional connectivity with language regions in the left prefrontal cortex and thalamus are increased relative to sighted individuals. We conclude that brain regions that are thought to have evolved for vision can take on language processing as a result of early experience. Innate microcircuit properties are not necessary for a brain region to become involved in language processing.

Transcranial Brain Stimulation: Clinical Applications and Future Directions

Neurosurgery Clinics of North America. Apr, 2011  |  Pubmed ID: 21435574

Noninvasive brain stimulation is a valuable investigative tool and has potential therapeutic applications in cognitive neuroscience, neurophysiology, psychiatry, and neurology. Transcranial magnetic stimulation (TMS) is particularly useful to establish and map causal brain-behavior relations in motor and nonmotor cortical areas. Neuronavigated TMS is able to provide precise information related to the individual's functional anatomy that can be visualized and used during surgical interventions and critically aid in presurgical planning, reducing the need for riskier and more cumbersome intraoperative or invasive mapping procedures. This article reviews methodological aspects, clinical applications, and future directions of TMS-based mapping.

Longitudinal Changes of Resting-state Functional Connectivity During Motor Recovery After Stroke

Stroke; a Journal of Cerebral Circulation. May, 2011  |  Pubmed ID: 21441147

Functional MRI (fMRI) studies could provide crucial information on the neural mechanisms of motor recovery in patients with stroke. Resting-state fMRI is applicable to patients with stroke who are not capable of proper performance of the motor task. In this study, we explored neural correlates of motor recovery in patients with stroke by investigating longitudinal changes in resting-state functional connectivity of the ipsilesional primary motor cortex (M1).

Harnessing Neuroplasticity for Clinical Applications

Brain : a Journal of Neurology. Jun, 2011  |  Pubmed ID: 21482550

Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

Changes in Cortical Plasticity Across the Lifespan

Frontiers in Aging Neuroscience. 2011  |  Pubmed ID: 21519394

Deterioration of motor and cognitive performance with advancing age is well documented, but its cause remains unknown. Animal studies dating back to the late 1970s reveal that age-associated neurocognitive changes are linked to age-dependent changes in synaptic plasticity, including alterations of long-term potentiation and depression (LTP and LTD). Non-invasive brain stimulation techniques enable measurement of LTP- and LTD-like mechanisms of plasticity, in vivo, in humans, and may thus provide valuable insights. We examined the effects of a 40-s train of continuous theta-burst stimulation (cTBS) to the motor cortex (600 stimuli, three pulses at 50 Hz applied at a frequency of 5 Hz) on cortico-spinal excitability as measured by the motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation before and after cTBS in the contralateral first dorsal interosseus muscle. Thirty-six healthy individuals aged 19-81 years old were studied in two sites (Boston, USA and Barcelona, Spain). The findings did not differ across study sites. We found that advancing age is negatively correlated with the duration of the effect of cTBS (r = -0.367; p = 0.028) and the overall amount of corticomotor suppression induced by cTBS (r = -0.478; p = 0.003), and positively correlated with the maximal suppression of amplitude on motor evoked responses in the target muscle (r = 0.420; p = 0.011). We performed magnetic resonance imaging (MRI)-based individual morphometric analysis in a subset of subjects to demonstrate that these findings are not explained by age-related brain atrophy or differences in scalp-to-brain distance that could have affected the TBS effects. Our findings provide empirical evidence that the mechanisms of cortical plasticity area are altered with aging and their efficiency decreases across the human lifespan. This may critically contribute to motor and possibly cognitive decline.

Transcranial Magnetic Stimulation: a Neuroscientific Probe of Cortical Function in Schizophrenia

Biological Psychiatry. Jul, 2011  |  Pubmed ID: 21571254

Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, functional near infrared spectroscopy, magnetoencephalography, and electroencephalography, to explore neocortical function. With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiologic modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology. Thus, TMS could be a useful tool in the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose.

Brain Stimulation over Broca's Area Differentially Modulates Naming Skills in Neurotypical Adults and Individuals with Asperger's Syndrome

The European Journal of Neuroscience. Jul, 2011  |  Pubmed ID: 21676037

In the present study we tested the hypothesis that, in subjects with Asperger's syndrome (ASP), the dynamics of language-related regions might be abnormal, so that repetitive transcranial magnetic stimulation (rTMS) over Broca's area leads to differential behavioral effects as seen in neurotypical controls. We conducted a five-stimulation-site, double-blind, multiple crossover, pseudo-randomized, sham-controlled study in 10 individuals with ASP and 10 age- and gender-matched healthy subjects. Object naming was assessed before and after low-frequency rTMS of the left pars opercularis, left pars triangularis, right pars opercularis and right pars triangularis, and sham stimulation, as guided stereotaxically by each individual's brain magnetic resonance imaging. In ASP participants, naming improved after rTMS of the left pars triangularis as compared with sham stimulation, whereas rTMS of the adjacent left opercularis lengthened naming latency. In healthy subjects, stimulation of parts of Broca's area did not lead to significant changes in naming skills, consistent with published data. Overall, these findings support our hypothesis of abnormal language neural network dynamics in individuals with ASP. From a methodological point of view, this work illustrates the use of rTMS to study the dynamics of brain-behavior relations by revealing the differential behavioral impact of non-invasive brain stimulation in a neuropsychiatric disorder.

Cognitive, Mood, and Electroencephalographic Effects of Noninvasive Cortical Stimulation with Weak Electrical Currents

The Journal of ECT. Jun, 2011  |  Pubmed ID: 20938352

: The use of noninvasive cortical electrical stimulation with weak currents has significantly increased in basic and clinical human studies. Initial, preliminary studies with this technique have shown encouraging results; however, the safety and tolerability of this method of brain stimulation have not been sufficiently explored yet. The purpose of our study was to assess the effects of direct current (DC) and alternating current (AC) stimulation at different intensities in order to measure their effects on cognition, mood, and electroencephalogram.

Screening Questionnaire Before TMS: an Update

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Aug, 2011  |  Pubmed ID: 21227747

Noninvasive Brain Stimulation in Alzheimer's Disease: Systematic Review and Perspectives for the Future

Experimental Gerontology. Aug, 2011  |  Pubmed ID: 21511025

A number of studies have applied transcranial magnetic stimulation (TMS) to physiologically characterize Alzheimer's disease (AD) and to monitor effects of pharmacological agents, while others have begun to therapeutically use TMS and transcranial direct current stimulation (tDCS) to improve cognitive function in AD. These applications are still very early in development, but offer the opportunity of learning from them for future development.

Spatial Biases in Peripersonal Space in Sighted and Blind Individuals Revealed by a Haptic Line Bisection Paradigm

Journal of Experimental Psychology. Human Perception and Performance. Aug, 2011  |  Pubmed ID: 21517214

Our representation of peripersonal space does not always accurately reflect the physical world. An example of this is pseudoneglect, a phenomenon in which neurologically normal individuals bisect to the left of the veridical midpoint, reflecting an overrepresentation of the left portion of space compared with the right one. Consistent biases have also been observed in the vertical and radial planes. It is an open question whether these biases depend on normal visual experience for their occurrence. Here we systematically investigated this issue by testing blindfolded sighted and early blind individuals in a haptic line bisection task. Critically, we found a robust leftward bias in all participants. In the vertical and radial planes, sighted participants showed a consistent downward and proximal bias. Conversely, the directional bias in blind participants was dependent on the final movement direction; thus, there was no general bias in either direction. These findings are discussed in terms of different reference frames adopted by sighted and blind participants when encoding space.

Spinal Associative Stimulation: a Non-invasive Stimulation Paradigm to Modulate Spinal Excitability

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Nov, 2011  |  Pubmed ID: 21524606

Repetitive, paired peripheral and transcranial stimulation targeting the cerebral cortex can increase cortical excitability, outlasting the stimulation period. It is unknown whether paired stimulation specifically targeting the spinal cord can modulate spinal excitability. We tested whether the H-reflex facilitation from a sub-threshold conditioning TMS pulse could modulate spinal excitability if delivered repetitively.

Brain Responses to Food Images During the Early and Late Follicular Phase of the Menstrual Cycle in Healthy Young Women: Relation to Fasting and Feeding

The American Journal of Clinical Nutrition. Aug, 2011  |  Pubmed ID: 21593494

Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown.

Commentary on Kratz Et Al "seizure in a Nonpredisposed Individual Induced by Single-pulse Transcranial Magnetic Stimulation"

The Journal of ECT. Jun, 2011  |  Pubmed ID: 21602643

Clinical Effects and Brain Metabolic Correlates in Non-invasive Cortical Neuromodulation for Visceral Pain

European Journal of Pain (London, England). Jan, 2011  |  Pubmed ID: 20822942

Chronic visceral pain is frequent, extremely debilitating, and generally resistant to pharmacological treatment. It has been shown that chronic visceral inflammation, through altered afferent visceral sensory input, leads to plastic changes in the central nervous system that ultimately sustain pain. Therefore approaches aiming at modulation of brain activity are attractive candidates to control visceral pain.

Reward-seeking Behavior in Human Narcolepsy

Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine. Jun, 2011  |  Pubmed ID: 21677900

The hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing and addiction. Because individuals with narcolepsy with cataplexy have low hypocretin levels, we hypothesized that they may be less prone to risk- and reward-seeking behaviors, including substance abuse.

Noninvasive Brain Stimulation in Traumatic Brain Injury

The Journal of Head Trauma Rehabilitation. Jun, 2011  |  Pubmed ID: 21691215

OBJECTIVE:: To review novel techniques of noninvasive brain stimulation (NBS), which may have value in assessment and treatment of traumatic brain injury (TBI). METHODS:: Review of the following techniques: transcranial magnetic stimulation, transcranial direct current stimulation, low-level laser therapy, and transcranial Doppler sonography. Furthermore, we provide a brief overview of TMS studies to date. MAIN FINDINGS:: We describe the rationale for the use of these techniques in TBI, discuss their possible mechanisms of action, and raise a number of considerations relevant to translation of these methods to clinical use. Depending on the stimulation parameters, NBS may enable suppression of the acute glutamatergic hyperexcitability following TBI and/or counter the excessive GABAergic effects in the subacute stage. In the chronic stage, brain stimulation coupled to rehabilitation may enhance behavioral recovery, learning of new skills, and cortical plasticity. Correlative animal models and comprehensive safety trials seem critical to establish the use of these modalities in TBI. CONCLUSIONS:: Different forms of NBS techniques harbor the promise of diagnostic and therapeutic utility, particularly to guide processes of cortical reorganization and enable functional restoration in TBI. Future lines of safety research and well-designed clinical trials in TBI are warranted to determine the capability of NBS to promote recovery and minimize disability.

[The Use of Noninvasive Brain Stimulation in Childhood Psychiatric Disorders: New Diagnostic and Therapeutic Opportunities and Challenges]

Revista De Neurologia. Aug, 2011  |  Pubmed ID: 21780073

Novel diagnostic and therapeutic approaches based on noninvasive brain stimulation offer some promise in the field of childhood psychiatric disorders. There are two primary methods of noninvasive brain stimulation currently available: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Both noninvasive neuromodulation techniques appear to rely on modulating brain plasticity and thus open new hopes in the treatment of brain circuit and plasticity disorders. Since many childhood psychiatric disorders involve disturbances in the timing or mechanisms of plasticity within frontostriatal circuits, and the developing brain shows a greater capacity of brain plasticity, noninvasive brain stimulation might induce greater benefits in this population than in adults. Although the utilization of TMS and tDCS remains limited in children, there is enough evidence for their rational, safe use in this population. In this paper, we review the principles of noninvasive brain stimulation and the diagnostic and therapeutic applications in child-hood psychiatric disorders in order to inform its development into safe and reliable diagnostic and effective therapeutic approaches in pediatric psychiatry.

RTMS Stimulation to Induce Plastic Changes at the Language Motor Area in a Patient with a Left Recidivant Brain Tumor Affecting Broca's Area

Neurocase. Jul, 2011  |  Pubmed ID: 21780986

Introduction. Extent of resection is one of the most powerful predictors of outcome in surgery of gliomas. Tumors located within areas governing eloquence may impede a total tumor resection. Functional plasticity may be induced by therapeutic means, such as cortical stimulation with repetitive transcranial magnetic stimulation (rTMS). Thus, rTMS is a potential tool to induce an improvement of functions of eloquence menaced by brain tumors.  Material and Methods.We report a case of a 59-year-old woman operated for a left sided precentral oligodendroglioma with awake intraoperative stimulation, whose tumor could not be completely removed because it affected areas governing language. Nine months later the tumor progressed and the motor language functions worsened. We submitted the patient to rTMS directed to Broca's area, next to the anterior pole of the tumor, with the aim of improving motor language function before a new tumor resection attempt. We performed 12 daily sessions of theta-burst rTMS followed by intensive language rehabilitation for 10 minutes, and 5 different aspects of language were measured before, immediately after and 10 minutes after each session. Results.Repetition and nomination worsened immediately after each rTMS session, and improved after 10 min of rehabilitation. However, basal values improved globally along the experiment. Also, the impact of rTMS on motor language was increasingly less along the procedure. Conclusions.rTMS induces changes in Broca's area and this effect can be potentially used to improve language function in tumors located at or close to eloquent cortical areas .

Down-regulation of Negative Emotional Processing by Transcranial Direct Current Stimulation: Effects of Personality Characteristics

PloS One. 2011  |  Pubmed ID: 21829522

Evidence from neuroimaging and electrophysiological studies indicates that the left dorsolateral prefrontal cortex (DLPFC) is a core region in emotional processing, particularly during down-regulation of negative emotional conditions. However, emotional regulation is a process subject to major inter-individual differences, some of which may be explained by personality traits. In the present study we used transcranial direct current stimulation (tDCS) over the left DLPFC to investigate whether transiently increasing the activity of this region resulted in changes in the ratings of positive, neutral and negative emotional pictures. Results revealed that anodal, but not cathodal, tDCS reduced the perceived degree of emotional valence for negative stimuli, possibly due to an enhancement of cognitive control of emotional expression. We also aimed to determine whether personality traits (extraversion and neuroticism) might condition the impact of tDCS. We found that individuals with higher scores on the introversion personality dimension were more permeable than extraverts to the modulatory effects of the stimulation. The present study underlines the role of the left DLPFC in emotional regulation, and stresses the importance of considering individual personality characteristics as a relevant variable, although replication is needed given the limited sample size of our study.

Characterizing Brain Cortical Plasticity and Network Dynamics Across the Age-span in Health and Disease with TMS-EEG and TMS-fMRI

Brain Topography. Oct, 2011  |  Pubmed ID: 21842407

Brain plasticity can be conceptualized as nature's invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable 'starting-points' and different 'slopes of change' defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer's disease.

Recruitment of Occipital Cortex During Sensory Substitution Training Linked to Subjective Experience of Seeing in People with Blindness

PloS One. 2011  |  Pubmed ID: 21853098

Over three months of intensive training with a tactile stimulation device, 18 blind and 10 blindfolded seeing subjects improved in their ability to identify geometric figures by touch. Seven blind subjects spontaneously reported 'visual qualia', the subjective sensation of seeing flashes of light congruent with tactile stimuli. In the latter subjects tactile stimulation evoked activation of occipital cortex on electroencephalography (EEG). None of the blind subjects who failed to experience visual qualia, despite identical tactile stimulation training, showed EEG recruitment of occipital cortex. None of the blindfolded seeing humans reported visual-like sensations during tactile stimulation. These findings support the notion that the conscious experience of seeing is linked to the activation of occipital brain regions in people with blindness. Moreover, the findings indicate that provision of visual information can be achieved through non-visual sensory modalities which may help to minimize the disability of blind individuals, affording them some degree of object recognition and navigation aid.

A Developmental Framework of Brain and Cognition from Infancy to Old Age

Brain Topography. Oct, 2011  |  Pubmed ID: 21858551

Reversal of TMS-induced Motor Twitch by Training is Associated with a Reduction in Excitability of the Antagonist Muscle

Journal of Neuroengineering and Rehabilitation. 2011  |  Pubmed ID: 21861922

A single session of isolated repetitive movements of the thumb can alter the response to transcranial magnetic stimulation (TMS), such that the related muscle twitch measured post-training occurs in the trained direction. This response is attributed to transient excitability changes in primary motor cortex (M1) that form the early part of learning. We investigated; (1) whether this phenomenon might occur for movements at the wrist, and (2) how specific TMS activation patterns of opposing muscles underlie the practice-induced change in direction.

TMS Suppression of Right Pars Triangularis, but Not Pars Opercularis, Improves Naming in Aphasia

Brain and Language. Dec, 2011  |  Pubmed ID: 21864891

This study sought to discover if an optimum 1 cm(2) area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions.

Combining Visual Rehabilitative Training and Noninvasive Brain Stimulation to Enhance Visual Function in Patients with Hemianopia: a Comparative Case Study

PM & R : the Journal of Injury, Function, and Rehabilitation. Sep, 2011  |  Pubmed ID: 21944300

To standardize a protocol for promoting visual rehabilitative outcomes in post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT).

Modulation of Large-scale Brain Networks by Transcranial Direct Current Stimulation Evidenced by Resting-state Functional MRI

Brain Stimulation. Sep, 2011  |  Pubmed ID: 21962981

BACKGROUND: Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. OBJECTIVE: We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. METHODS: Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). RESULTS: After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. CONCLUSIONS: Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.

Neural Correlates of the Antinociceptive Effects of Repetitive Transcranial Magnetic Stimulation on Central Pain After Stroke

Neurorehabilitation and Neural Repair. Oct, 2011  |  Pubmed ID: 21980153

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. OBJECTIVE: . The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. METHODS: Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. RESULTS: Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. CONCLUSION: Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.

Resonating with Others: the Effects of Self-construal Type on Motor Cortical Output

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Oct, 2011  |  Pubmed ID: 21994369

"Self-construal" refers to how individuals view and make meaning of the self, and at least two subtypes have been identified. Interdependent self-construal is a view of the self that includes relationships with others, and independent self-construal is a view of the self that does not include relations with others. It has been suggested that priming these two types of self-construal affects the cognitive processing style that an individual adopts, especially with regard to context sensitivity. Specifically, an interdependent self-construal is thought to promote attention to others and social context to a greater degree than an independent self-construal. To investigate this assertion, we elicited motor-evoked potentials with transcranial magnetic stimulation during an action observation task in which human participants were presented with either interdependent or independent self-construal prime words. Priming interdependent self-construal increased motor cortical output whereas priming independent self-construal did not, compared with a no-priming baseline condition. These effects, likely mediated by changes in the mirror system, essentially tune the individual to, or shield the individual from, social input. Interestingly, the pattern of these self-construal-induced changes in the motor system corroborates with previously observed self-construal effects on overt behavioral mimicry in social settings, and as such, our results provide strong evidence that motor resonance likely mediates nonconscious mimicry in social settings. Finally, these self-construal effects may lead to the development of interventions for disorders of deficient or excessive social influence, like certain autism spectrum and compulsive imitative disorders.

Fundamentals of Transcranial Electric and Magnetic Stimulation Dose: Definition, Selection, and Reporting Practices

Brain Stimulation. Nov, 2011  |  Pubmed ID: 22305345

BACKGROUND: The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. METHODS: This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. RESULTS: The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. CONCLUSIONS: We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated.

Safety and Tolerability of Repetitive Transcranial Magnetic Stimulation in Patients with Pathologic Positive Sensory Phenomena: a Review of Literature

Brain Stimulation. Jun, 2011  |  Pubmed ID: 22322098

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable therapeutic and diagnostic tool. rTMS appears particularly promising for disorders characterized by positive sensory phenomena that are attributable to alterations in sensory cortical excitability. Among these are tinnitus, auditory and visual hallucinations, and pain syndromes. OBJECTIVE: Despite studies addressing rTMS efficacy in suppression of positive sensory symptoms, the safety of stimulation of potentially hyperexcitable cortex has not been fully addressed. We performed a systematic literature review and metaanalysis to describe the rTMS safety profile in these disorders. METHODS: Using the PubMed database, we performed an English-language literature search from January 1985 to April 2011 to review all pertinent publications. Per study, we noted and listed pertinent details. From these data we also calculated a crude per-subject risk for each adverse event. RESULTS: One hundred six publications (n = 1815) were identified with patients undergoing rTMS for pathologic positive sensory phenomena. Adverse events associated with rTMS were generally mild and occurred in 16.7% of subjects. Seizure was the most serious adverse event, and occurred in three patients with a 0.16% crude per-subject risk. The second most severe adverse event involved aggravation of sensory phenomena, occurring in 1.54%. CONCLUSIONS: The published data suggest rTMS for the treatment or diagnosis of pathologic positive sensory phenomena appears to be a relatively safe and well-tolerated procedure. However, published data are lacking in systematic reporting of adverse events, and safety risks of rTMS in these patient populations will have to be addressed in future prospective trials.

Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions

Brain Stimulation. Apr, 2011  |  Pubmed ID: 22037126

BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. METHODS: We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. MAIN FINDINGS/DISCUSSION: We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.

Neurophysiological Investigation of Congenital Mirror Movements in a Patient with Agenesis of the Corpus Callosum

Brain Stimulation. Mar, 2011  |  Pubmed ID: 22037131

We describe a patient with complete agenesis of the corpus callosum and congenital mirror movements in which primary motor cortex (M1) excitability of both hemispheres was assessed with transcranial magnetic stimulation. Voluntary contraction of the index finger was associated with bilateral electromyographic activity in the first dorsal interosseus muscle. Motor-evoked potentials of identical latencies were produced bilaterally after unilateral M1 stimulation. Measures of intracortical inhibition and facilitation were within normal limits bilaterally although a shorter contralateral silent period was found for both hemispheres. Taken together, the current data suggest a pattern of M1 excitability very similar to that found in patients with congenital mirror movements and no other motor abnormality.

Minimal Heating of Aneurysm Clips During Repetitive Transcranial Magnetic Stimulation

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Nov, 2011  |  Pubmed ID: 22119800

A Sensitive Period for Language in the Visual Cortex: Distinct Patterns of Plasticity in Congenitally Versus Late Blind Adults

Brain and Language. Dec, 2011  |  Pubmed ID: 22154509

Recent evidence suggests that blindness enables visual circuits to contribute to language processing. We examined whether this dramatic functional plasticity has a sensitive period. BOLD fMRI signal was measured in congenitally blind, late blind (blindness onset 9-years-old or later) and sighted participants while they performed a sentence comprehension task. In a control condition, participants listened to backwards speech and made match/non-match to sample judgments. In both congenitally and late blind participants BOLD signal increased in bilateral foveal-pericalcarine cortex during response preparation, irrespective of whether the stimulus was a sentence or backwards speech. However, left occipital areas (pericalcarine, extrastriate, fusiform and lateral) responded more to sentences than backwards speech only in congenitally blind people. We conclude that age of blindness onset constrains the non-visual functions of occipital cortex: while plasticity is present in both congenitally and late blind individuals, recruitment of visual circuits for language depends on blindness during childhood.

Drummer's Lower Limb Dystonia

Journal of Neurology. Dec, 2011  |  Pubmed ID: 22160433

Transcranial Magnetic Stimulation Modulates the Brain's Intrinsic Activity in a Frequency-dependent Manner

Proceedings of the National Academy of Sciences of the United States of America. Dec, 2011  |  Pubmed ID: 22160708

Intrinsic activity in the brain is organized into networks. Although constrained by their anatomical connections, functional correlations between nodes of these networks reorganize dynamically. Dynamic organization implies that couplings between network nodes can be reconfigured to support processing demands. To explore such reconfigurations, we combined repetitive transcranial magnetic stimulation (rTMS) and functional connectivity MRI (fcMRI) to modulate cortical activity in one node of the default network, and assessed the effect of this upon functional correlations throughout the network. Two different frequencies of rTMS to the same default network node (the left posterior inferior parietal lobule, lpIPL) induced two topographically distinct changes in functional connectivity. High-frequency rTMS to lpIPL decreased functional correlations between cortical default network nodes, but not between these nodes and the hippocampal formation. In contrast, low frequency rTMS to lpIPL did not alter connectivity between cortical default network nodes, but increased functional correlations between lpIPL and the hippocampal formation. These results suggest that the default network is composed of (at least) two subsystems. More broadly, the finding that two rTMS stimulation regimens to the same default network node have distinct effects reveals that this node is embedded within a network that possesses multiple, functionally distinct relationships among its distributed partners.

Transcranial Magnetic Stimulation and Aphasia Rehabilitation

Archives of Physical Medicine and Rehabilitation. Jan, 2012  |  Pubmed ID: 22202188

Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve naming in chronic stroke patients with nonfluent aphasia since 2005. In part 1, we review the rationale for applying slow, 1-Hz, rTMS to the undamaged right hemisphere in chronic nonfluent aphasia patients after a left hemisphere stroke; and we present a transcranial magnetic stimulation (TMS) protocol used with these patients that is associated with long-term, improved naming post-TMS. In part 2, we present results from a case study with chronic nonfluent aphasia where TMS treatments were followed immediately by speech therapy (constraint-induced language therapy). In part 3, some possible mechanisms associated with improvement after a series of TMS treatments in stroke patients with aphasia are discussed.

Contribution of Axonal Orientation to Pathway-dependent Modulation of Excitatory Transmission by Direct Current Stimulation in Isolated Rat Hippocampus

Journal of Neurophysiology. Jan, 2012  |  Pubmed ID: 22219028

Transcranial direct current stimulation (tDCS) is a method for modulating cortical excitability by weak constant electrical current that is applied through scalp electrodes. Although often described in terms of anodal or cathodal stimulation, depending on which scalp electrode pole is proximal to the cortical region of interest, it is the orientation of neuronal structures relative to the DC vector that determines the effect of tDCS. To investigate the contribution of neural pathway orientation, we studied DCS-mediated neuromodulation in an in vitro rat hippocampal slice preparation. We examined the contribution of dendritic orientation to the DCS neuromodulatory effect by recording field excitatory postsynaptic potentials (fEPSPs) in apical and basal dendrites of CA1 neurons within a constant DC field. In addition, we assessed the contribution of axonal orientation by recording CA1 and CA3 apical fEPSPs generated by stimulation of oppositely oriented Schaffer collateral and mossy fiber axons, respectively, during DCS. Finally, non-synaptic excitatory signal propagation was measured along antidromically-stimulated CA1 axons at different DCS amplitudes and polarity. We find that modulation of both the fEPSP and population spike depend on axonal orientation relative to the electric field vector. Axonal orientation determines whether the DC field is excitatory or inhibitory and dendritic orientation affects the magnitude, but not the overall direction, of the DC effect. These data suggest that tDCS may oppositely affect neurons in a stimulated cortical volume if these neurons are excited by oppositely orientated axons in a constant electrical field.

Why the Assessment of Causality in Brain-Behavior Relations Requires Brain Stimulation

Journal of Cognitive Neuroscience. Jan, 2012  |  Pubmed ID: 22264196

A central aim in cognitive neuroscience is to explain how neural activity gives rise to perception and behavior; the causal link of paramount interest is thus from brain to behavior. Functional neuroimaging studies, however, tend to provide information in the opposite direction by informing us how manipulation of behavior may affect neural activity. Although this may provide valuable insights into neuronal properties, one cannot use such evidence to make inferences about the behavioral significance of the observed activations; if A causes B, it does not necessarily follow that B causes A. In contrast, brain stimulation techniques enable us to directly modulate brain activity as the source of behavior and thus establish causal links.

Comparison of Visual Field Training for Hemianopia With Active Versus Sham Transcranial Direct Cortical Stimulation

Neurorehabilitation and Neural Repair. Jan, 2012  |  Pubmed ID: 22291042

BACKGROUND: Vision Restoration Therapy (VRT) aims to improve visual field function by systematically training regions of residual vision associated with the activity of suboptimal firing neurons within the occipital cortex. Transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability. OBJECTIVE: Assess the possible efficacy of tDCS combined with VRT. METHODS: The authors conducted a randomized, double-blind, demonstration-of-concept pilot study where participants were assigned to either VRT and tDCS or VRT and sham. The anode was placed over the occipital pole to target both affected and unaffected lobes. One hour training sessions were carried out 3 times per week for 3 months in a laboratory. Outcome measures included objective and subjective changes in visual field, recording of visual fixation performance, and vision-related activities of daily living (ADLs) and quality of life (QOL). RESULTS: Although 12 participants were enrolled, only 8 could be analyzed. The VRT and tDCS group demonstrated significantly greater expansion in visual field and improvement on ADLs compared with the VRT and sham group. Contrary to expectations, subjective perception of visual field change was greater in the VRT and sham group. QOL did not change for either group. The observed changes in visual field were unrelated to compensatory eye movements, as shown with fixation monitoring. CONCLUSIONS: The combination of occipital cortical tDCS with visual field rehabilitation appears to enhance visual functional outcomes compared with visual rehabilitation alone. TDCS may enhance inherent mechanisms of plasticity associated with training.

A New Measure of Cortical Inhibition by Mechanomyography and Paired-pulse Transcranial Magnetic Stimulation in Unanesthetized Rats

Journal of Neurophysiology. Feb, 2012  |  Pubmed ID: 22013238

Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive tool for measuring cortical inhibition in humans, particularly in patients with disorders of cortical inhibition such as epilepsy. However, ppTMS protocols in rodent disease models, where mechanistic insight into the ppTMS physiology and into disease processes may be obtained, have been limited due to the requirement for anesthesia and needle electromyography. To eliminate the confounding factor of anesthesia and to approximate human ppTMS protocols in awake rats, we adapted the mechanomyogram (MMG) method to investigate the ppTMS inhibitory phenomenon in awake rats and then applied differential pharmacology to test the hypothesis that long-interval cortical inhibition is mediated by the GABA(A) receptor. Bilateral hindlimb-evoked MMGs were elicited in awake rats by long-interval ppTMS protocols with 50-, 100-, and 200-ms interstimulus intervals. Acute changes in ppTMS-MMG were measured before and after intraperitoneal injections of saline, the GABA(A) agonist pentobarbital (PB), and GABA(A) antagonist pentylenetetrazole (PTZ). An evoked MMG was obtained in 100% of animals by single-pulse stimulation, and ppTMS resulted in predictable inhibition of the test-evoked MMG. With increasing TMS intensity, MMG amplitudes increased in proportion to machine output to produce reliable input-output curves. Simultaneous recordings of electromyography and MMG showed a predictable latency discrepancy between the motor-evoked potential and the evoked MMG (7.55 ± 0.08 and 9.16 ± 0.14 ms, respectively). With pharmacological testing, time course observations showed that ppTMS-MMG inhibition was acutely reduced following PTZ (P < 0.05), acutely enhanced after PB (P < 0.01) injection, and then recovered to pretreatment baseline after 1 h. Our data support the application of the ppTMS-MMG technique for measuring the cortical excitability in awake rats and provide the evidence that GABA(A) receptor contributes to long-interval paired-pulse cortical inhibition. Thus ppTMS-MMG appears a well-tolerated biomarker for measuring GABA(A)-mediated cortical inhibition in rats.

Hearing Shapes Our Perception of Time: Temporal Discrimination of Tactile Stimuli in Deaf People

Journal of Cognitive Neuroscience. Feb, 2012  |  Pubmed ID: 21916563

Confronted with the loss of one type of sensory input, we compensate using information conveyed by other senses. However, losing one type of sensory information at specific developmental times may lead to deficits across all sensory modalities. We addressed the effect of auditory deprivation on the development of tactile abilities, taking into account changes occurring at the behavioral and cortical level. Congenitally deaf and hearing individuals performed two tactile tasks, the first requiring the discrimination of the temporal duration of touches and the second requiring the discrimination of their spatial length. Compared with hearing individuals, deaf individuals were impaired only in tactile temporal processing. To explore the neural substrate of this difference, we ran a TMS experiment. In deaf individuals, the auditory association cortex was involved in temporal and spatial tactile processing, with the same chronometry as the primary somatosensory cortex. In hearing participants, the involvement of auditory association cortex occurred at a later stage and selectively for temporal discrimination. The different chronometry in the recruitment of the auditory cortex in deaf individuals correlated with the tactile temporal impairment. Thus, early hearing experience seems to be crucial to develop an efficient temporal processing across modalities, suggesting that plasticity does not necessarily result in behavioral compensation.

Evoked Potentials and Quantitative Thermal Testing in Spinal Cord Injury Patients with Chronic Neuropathic Pain

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Mar, 2012  |  Pubmed ID: 21852190

Neuropathic pain (NP) is a common symptom following spinal cord injury (SCI). NP may be associated with altered processing of somatosensory pathways in dermatomes rostral to the injury level. To explore this possibility, the characteristics of contact heat evoked potentials (CHEPs) and quantitative thermal testing (QTT) were studied at and above the lesion level in SCI patients with NP. The goal was to determine processing abnormalities correlated with data from clinical evaluations.

Treatment of Auditory Verbal Hallucinations with Transcranial Magnetic Stimulation in a Patient with Psychotic Major Depression: One-year Follow-up

Neurocase. Feb, 2012  |  Pubmed ID: 21614723

Auditory verbal hallucinations (AVH) in patients with schizophrenia can respond to repetitive transcranial magnetic stimulation (TMS). We report the therapeutic utility of rTMS in a 48-year-old patient with a 20-year history of severe depression (five suicidal gestures and previous failure of ECT) and internal AVH. First, 20 Hz rTMS to the left prefrontal cortex for 3 weeks significantly improved depression (BDI-II: 89% change, lasting 14 months along with weekly/bi-weekly maintenance treatments), but AVH remained unchanged. The patient also underwent a further course of the left temporo-parietal 1 Hz rTMS and amelioration of AVH severity was achieved (PSYRATS-AH: 53% change) and maintained at 1-year follow-up. AVH respond to rTMS in disorders other than schizophrenia. Furthermore, targeted rTMS to different brain regions can address diverse symptoms in neuropsychiatric conditions.