Search

Application of transcranial alternating current stimulation (tACS) is thought to modulate ongoing brain oscillations in a frequency-dependent manner. However, recent studies report various and sometimes inconsistent results regarding its capacity to induce changes in cortical activity beyond the stimulation period. Here, thirty healthy volunteers participated in a randomized, cross-over, sham-controlled, double-blind study using EEG to measure the offline effects of tACS on alpha and beta power. Sham and high current density tACS (1 mA; 10 Hz and 20 Hz; 0.32 mA/cm2) were applied for 20 min over bilateral sensorimotor areas and EEG was recorded at rest before and after stimulation for 20 min. Bilateral tACS was not associated with significant changes in local alpha and beta power frequencies at stimulation sites (C3 and C4 electrodes). Overall, the present results fail to provide evidence that bilateral tACS with high current density applied over sensorimotor regions at 10 and 20 Hz reliably modulates offline brain oscillation power at the stimulation site. These results may have implications for the design and implementation of future protocols aiming to induce sustained changes in brain activity, including in clinical populations.

Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such as excitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of the pathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer’s disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy.

Introduction : Les enfants qui ont un vécu des traumas complexes sont à risque de développer de graves difficultés d’attachement, d’autorégulation et de comportement. Des études exploratoires démontrent que la pratique du yoga permet d’améliorer leur fonctionnement et diminuer leurs symptômes d’internalisation et d’externalisation. Objectifs : Le programme Namaste, une adaptation du manuel « Yoga-Based Psychotherapy » (Beltran et al. 2014) vise l’amélioration de l’autorégulation et de la santé mentale. Cette étude a pour objectif de documenter ses effets chez les enfants qui ont vécu des traumas complexes. Méthode : Douze séances ont été animées auprès d’enfants âgés de 6 à 13 ans suivis par un centre de protection de l’enfance. Les séances combinaient des postures de yoga, des exercices de respiration, et d’autres activités favorisant l’autorégulation et la socialisation. Le fonctionnement et les symptômes des enfants ont été mesurés avec le questionnaire BASC-3 avant et après l’intervention. Deux études de cas détaillées décrivent les impacts potentiels de cette intervention. Résultats : Les deux études de cas démontrent des impacts positifs sur les symptômes d’internalisation et d’externalisation ainsi que l’autorégulation, mais aucun effet sur l’estime de soi et les compétences sociales. Implications : Le programme Namaste pourrait être une intervention prometteuse pour améliorer le fonctionnement et réduire les symptômes psychologiques chez cette population. L’intégration des principes du yoga sensible aux traumas, la modalité de groupe et l’accent mis sur l’autorégulation semblent des éléments-clés. D’autres études de plus grande envergure sont nécessaires pour confirmer les impacts positifs potentiels de cette intervention.

Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) has emerged as a powerful tool to non-invasively probe brain circuits in humans, allowing for the assessment of several cortical properties such as excitability and connectivity. Over the past decade, this technique has been applied to various clinical populations, enabling the characterization and development of potential TMS-EEG predictors and markers of treatments and of the pathophysiology of brain disorders. The objective of this article is to present a comprehensive review of studies that have used TMS-EEG in clinical populations and to discuss potential clinical applications. To provide a technical and theoretical framework, we first give an overview of TMS-EEG methodology and discuss the current state of knowledge regarding the use of TMS-EEG to assess excitability, inhibition, plasticity and connectivity following neuromodulatory techniques in the healthy brain. We then review the insights afforded by TMS-EEG into the pathophysiology and predictors of treatment response in psychiatric and neurological conditions, before presenting recommendations for how to address some of the salient challenges faced in clinical TMS-EEG research. Finally, we conclude by presenting future directions in line with the tremendous potential of TMS-EEG as a clinical tool.

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy.

The aim of this study was to assess the effects of ice applied to the oral cavity on the excitability of corticobulbar projections to the swallowing muscles. The subjects were 8 healthy adult volunteers (mean age 29.0 ± 4.9 years). Motor-evoked potentials (MEPs) were recorded from the suprahyoid muscle complex using surface electrodes. Two blocks of 20 MEPs with a test stimulus intensity of 120% of the resting motor threshold were recorded at rest (baseline). Subjects then underwent 5-min thermal stimulation by either of 3 different types: (1) "ice-stick inside mouth," (2) "ice-stick on neck," and (3) "room temperature inside mouth." Blocks of 20 MEPs were then recorded immediately and at 5-min intervals for the following 15 min. There was a significant difference in the effects of the 3 interventions on the amplitude of the MEPs following stimulation (two-way ANOVA: INTERVENTION × TIME; F8,84 = 3.76, p

Electromagnetic noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation and transcranial electrical stimulation, are widely used in research and represent emerging clinical treatment options for many brain disorders. The brain-wide neurobiological effects of electromagnetic NIBS, however, are not yet fully characterized. The combination of NIBS with molecular brain imaging is a powerful tool for the investigation of these effects. Here, we conducted a systematic review of all published studies investigating the effects of all forms of electromagnetic NIBS using molecular imaging (positron emission tomography, single photon emission computed tomography). A meta-analysis was also conducted when sufficient studies employed similar methodologies. A total of 239 articles were identified, of which 71 were included in the review. Information was extracted about the study design, NIBS parameters, imaging parameters, and observed local and remote effects caused by the stimulation. Regional cerebral blood flow and glucose metabolism were the most common outcome measures, followed by dopamine neurotransmission. While the vast majority of studies obtained remote effects of stimulation in interconnected regions, approximately half of the studies showed local effects at the stimulation site. Our meta-analysis on motor cortex stimulation also showed consistent remote effects. The literature review demonstrates that although the local effects of NIBS as captured by molecular imaging are sometimes modest, there are robust remote changes in brain activity and neurotransmitter function. Finally, we discuss the potential pitfalls and methodological issues and identify gaps in the current knowledge that could be addressed using these techniques.

Physical activity has been associated with widespread anatomical and functional brain changes that occur following acute exercise or, in the case of athletes, throughout life. High levels of physical activity through the practice of sports also lead to better general health and increased cognitive function. Athletes are at risk, however, of suffering a concussion, the effects of which have been extensively described for brain function and anatomy. The level to which these effects are modulated by increased levels of fitness is not known. Here, we review literature describing the effects of physical activity and sports concussions on white matter, grey matter, neurochemistry and cortical excitability. We suggest that the effects of sports concussion can be coufounded by the effects of exercise. Indeed, available data show that the brain of athletes is different from that of healthy individuals with a non-active lifestyle. As a result, sports concussions take place in a context where structural/functional plasticity has occurred prior to the concussive event. The sports concussion literature does not permit, at present, to separate the effects of intense and repeated physical activity, and the abrupt removal from such activities, from those of concussion on brain structure and function.

The objective of the study was to determine whether repetitive hits to the head at a subclinical level are associated with structural and functional brain abnormalities and whether these effects are influenced by high levels of fitness associated with intense physical activity. Seventy-two college students were recruited: 24 nonathletic, 24 athletes practicing a varsity contact sport, and 24 athletes practicing a varsity noncontact sport. They were recruited for a neuropsychological evaluation and a magnetic resonance imaging session that included magnetic resonance spectroscopy of primary motor cortex (M1) and prefrontal cortex and susceptibility-weighted imaging. There was no evidence for reduced cognitive performance or presence of micro bleeds in contact sports athletes. Abnormalities in contact sports athletes were found for myo-inositol concentration (mIns) in M1, where levels were significantly higher compared with noncontact sports athletes (p = 0.016) and nonathletes (p = 0.029). In prefrontal cortex, glutamate + glutamine (Glx) was significantly reduced in contact sports athletes compared with noncontact sports athletes (p = 0.016), and a similar reduction was observed for gamma-aminobutyric acid (GABA) levels (p = 0.005). Varsity contact sports are associated with area-specific alterations in mIns concentration in the primary motor cortex. In the prefrontal cortex, high levels of fitness could modulate the effects of head impact exposure on prefrontal metabolite concentration. Indeed, although athletes in contact and noncontact sports show different neurometabolic profiles, they do not differ from sedentary controls.

Theta burst stimulation (TBS) has been proposed as a novel treatment for major depression (MD). However, randomized and sham-controlled trials (RCTs) published to date have yielded heterogeneous clinical results and we have thus carried out the present systematic review and exploratory meta-analysis of RCTs to evaluate this issue. We searched the literature for RCTs on TBS for MD from January 2001 through September 2016 using MEDLINE, EMBASE, PsycINFO, and CENTRAL. We then performed a random-effects meta-analysis with the main outcome measures including pre-post score changes in the Hamilton Depression Rating Scale (HAM-D) as well as rates of response, remission and dropout. Data were obtained from 5 RCTs, totalling 221 subjects with MD. The pooled Hedges' g for pre-post change in HAM-D scores was 1.0 (p = 0.003), indicating a significant and large-sized difference in outcome favouring active TBS. Furthermore, active TBS was associated with significantly higher response rates when compared to sham TBS (35.6% vs. 17.5%, respectively; p = 0.005), although the groups did not differ in terms of rates of remission (18.6% vs. 10.7%, respectively; p = 0.1) and dropout (4.2% vs. 7.8%, respectively; p = 0.5). Finally, subgroup analyses indicated that bilateral TBS and unilateral intermittent TBS seem to be the most promising protocols. In conclusion, although TBS is a promising novel therapeutic intervention for MD, future studies should identify more clinically-relevant stimulation parameters as well as neurobiological predictors of treatment outcome, and include larger sample sizes, active comparators and longer follow-up periods.

The search for biological targets in psychiatric disorders is essential to better understand illness mechanisms and also to monitor and predict response to currently available therapeutic interventions. To this end, the combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) has emerged as a powerful clinical research tool. TMS-EEG allows cortical properties, such as excitability, inhibition, oscillatory activity, and connectivity, to be directly probed within a specific region of the cortex. This review will summarize the state of the current literature on TMS-EEG and its potential to uncover biological targets in psychiatric illnesses, with a focus on major depressive disorder, bipolar disorder, and schizophrenia. Collectively, the reviewed studies suggest that alterations in gamma-aminobutyric acid-mediated inhibition and gamma oscillations in the dorsolateral prefrontal cortex and neighboring frontal regions are potential shared biomarkers in psychiatry, highlighting the potential of TMS-EEG to help identify translational biomarkers.

Since the initial demonstration of linear effects of stimulation duration and intensity on the strength of after-effects associated with transcranial direct current stimulation (tDCS), few studies have systematically assessed how varying these parameters modulates corticospinal excitability. Therefore, the objective of this study was to systematically evaluate the effects of anodal tDCS on corticospinal excitability at two stimulation intensities (1 mA, 2 mA) and durations (10 min, 20 min), and determine the value of several variables in predicting response. Two groups of 20 individuals received, in two separate sessions, 1 and 2 mA anodal tDCS (left primary motor cortex (M1)-right supra-orbital montage) for either 10- or 20-min. Transcranial magnetic stimulation was delivered over left M1 and motor evoked potentials (MEPs) of the contralateral hand were recorded prior to tDCS and every 5 min for 20-min post-tDCS. The following predictive variables were evaluated: I-wave recruitment, stimulation intensity, baseline M1 excitability and inter-trial MEP variability. Results show that anodal tDCS failed to significantly modulate corticospinal excitability in all conditions. Furthermore, low response rates were identified across all parameter combinations. No baseline measure was significantly correlated with increases in MEP amplitude. However, a decrease in inter-trial MEP variability was linked to response to anodal tDCS. In conclusion, the present findings are consistent with recent reports showing high levels of inter-subject variability in the neurophysiological response to tDCS, which may partly explain inconsistent group results. Furthermore, the level of variability in the neurophysiological outcome measure, i.e. MEPs, appears to be related to response.

Background Understanding how different brain regions interact with one another is at the heart of current endeavors in cognitive and basic neuroscience. Unlike most neuroimaging techniques, transcranial magnetic stimulation (TMS) allows the establishment of causal relationships in the study of the functional architecture of the human brain. While this tool is increasingly used to probe the functional and causal nature of the associations between brain regions, a comprehensive guide documenting the various existing stimulation protocols is currently lacking, limiting its use. Objective The main objective of the current work is to characterize the various dual-coil TMS protocols used to probe effective connectivity and plasticity within the motor system. In addition, we want to propose a short TMS battery that could be used in clinical and research settings. Method Articles using dual-coil TMS indexed in PubMed and Medline published between 1990 and 2015 were included in the review. Results A wide range of stimulation parameters has been used to probe connectivity and plasticity. However, a few protocols have been shown to produce robust effects, mostly inhibitory in nature. Conclusion Dual-coil TMS offers the distinctive opportunity to investigate effective connectivity and plasticity between different parts of the brain. Sites of stimulation, stimulation intensity, inter-stimulus interval and coil orientation are crucial factors to consider when using this technique. We propose a brief battery of tests that could be used to assess effective brain connectivity in clinical populations.

Agenesis of the corpus callosum (AgCC) is a congenital malformation that can occur in isolation or in association with other neurological conditions. Although the behavioral manifestations associated with AgCC have been widely studied, the effects of complete absence of the corpus callosum (CC) on cerebral cortex anatomy are still not completely understood. In this study, cortical thickness in adults with complete AgCC was compared to a group of healthy controls. Results showed highly variable patterns of cortical thickness in AgCC individuals, with few areas showing significant and consistent alterations including primary visual cortex, primary somatosensory cortex and primary motor cortex. These results suggest relatively limited effects of AgCC on cortical morphology, which are mostly restricted to primary sensory and motor areas.

The present paper systematically reviews studies using transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) to assess cortical excitability, intra-cortical inhibition/facilitation and synaptic plasticity following mild traumatic brain injury (mTBI).Articles using TMS over M1 in patients with mTBI or sport-related concussion indexed in PubMed and published between 1998 and September 2014 were included in the present review.From the 17 articles that matched search criteria, results from various TMS paradigms were summarized and divided in three main areas of interest: motor cortical excitability/facilitation, motor cortical inhibition and cortical plasticity. Although studies suggest a trend of abnormal intra-cortical inhibition following mTBI, no clear and specific pattern emerges from the surveyed data.At this time and with the possible exception of intra-cortical inhibitory measures, TMS cannot reliably detect changes in M1 excitability in individuals with mTBI or a concussion at both the acute and chronic stages of injury. This may be explained by the small number of studies and large variety of stimulation parameters. Additional longitudinal and multimodal studies are needed to better understand the nature of the excitability changes that may occur within M1 following mTBI.

Alpha (8–12 Hz) and beta (13–30 Hz) oscillations are believed to be involved in motor control. Their modulation with transcranial alternating current stimulation (tACS) has been shown to alter motor behavior and cortical excitability. The aim of the present study was to determine whether tACS applied bilaterally over sensorimotor cortex at 10 Hz and 20 Hz modulates interhemispheric interactions and corticospinal excitability. Thirty healthy volunteers participated in a randomized, cross-over, sham-controlled, double-blind protocol. Sham and active tACS (10 Hz, 20 Hz, 1 mA) were applied for 20 min over bilateral sensorimotor areas. The physiological effects of tACS on corticospinal excitability and interhemispheric inhibition were assessed with transcranial magnetic stimulation. Physiological mirror movements were assessed to measure the overflow of motor activity to the contralateral M1 during voluntary muscle contraction. Bilateral 10 Hz tACS reduced corticospinal excitability. There was no significant effect of tACS on physiological mirror movements and interhemispheric inhibition. Ten Hz tACS was associated with response patterns consistent with corticospinal inhibition in 57% of participants. The present results indicate that application of tACS at the alpha frequency can induce aftereffects in sensorimotor cortex of healthy individuals.

Recent studies have shown, in asymptomatic concussed athletes, metabolic disruption in the primary motor cortex (M1) and abnormal intracortical inhibition lasting for more than six months. The present study aims to assess if these neurochemical and neurophysiological alterations are persistent and linked to M1 cortical thickness.Sixteen active football players who sustained their last concussion, on average, three years prior to testing and 14 active football players who never sustained a concussion were recruited for a single session of proton magnetic resonance spectroscopy ((1)H-MRS) and transcranial magnetic stimulation (TMS). Measures of M1 and whole brain cortical thickness were acquired, and (1)H-MRS data were acquired from left M1 using a MEGA-PRESS sequence. Cortical silent period (CSP) and long-interval intracortical inhibition (LICI) were measured with TMS applied over left M1.No significant group differences were observed for metabolic concentrations, TMS measures, and cortical thickness. However, whereas GABA and glutamate levels were positively correlated in control athletes, this relationship was absent in concussed athletes.These data suggest the general absence of neurophysiologic, neurometabolic and neuroanatomical disruptions in M1 three years following the last concussive event. However, correlational analyses suggest the presence of a slight metabolic imbalance between GABA and glutamate concentrations in the primary motor cortex of concussed athletes.The present study highlights the importance of multimodal assesments of the impacts of sport concussions.

Background Studies using Transcranial Magnetic Stimulation (TMS) have demonstrated the possibility to target different neuronal populations within the primary motor cortex (M1) by changing coil orientation and stimulation intensity. The absence of a direct electrophysiological response such as motor evoked potentials has limited this investigation in areas outside M1. This problem can be solved with the use of combined TMS and electroencephalography, which allows direct recording of cortical responses to TMS pulses. Materials and methods In this work on healthy human subjects we compared early (10–70 ms) and late (70–250 ms) transcranial evoked potentials (TEP) and TMS-related spectral perturbation (TRSP) obtained by delivering magnetic pulses over the pre-SMA with variable coil orientation (0°; 90°; 180° and 270°) and stimulation intensity (100%, 120% and 140% of resting motor threshold). Results both early and late TEP were generally larger when the coil handle was pointing backwards (0[o). This result was true also for early TRSP but, surprisingly, late TRSP was greater when the coil was pointing at 180°. Additionally, stimulating the pre-SMA with a 90° orientation activated the right M1, thus limiting the spatial specificity of the stimulation. Conclusions these results suggest that parameters such as coil orientation and stimulation intensity are critical when stimulating the pre-SMA and they should be taken into account in physiological and clinical studies.

Transcranial magnetic stimulation (TMS) can provide an index of intracortical excitability/inhibition balance. However, the neurochemical substrate of these measures remains unclear. Pharmacological studies suggest the involvement of GABAA and GABAB receptors in TMS protocols aimed at measuring intracortical inhibition, but this link remains inferential. Proton magnetic resonance spectroscopy (1H-MRS) permits measurement of GABA and glutamate + glutamine (Glx) concentrations in the human brain and might help in the direct empirical assessment of the relationship between TMS inhibitory measures and neurotransmitter concentrations. In the present study, MRS-derived relative concentrations of GABA and Glx measured in the left M1 of healthy participants were correlated with TMS measures of intracortical inhibition. Glx levels were found to correlate positively with TMS-induced silent period duration, whereas no correlation was found between GABA concentration and TMS measures. The present data demonstrate that specific TMS measures of intracortical inhibition are linked to shifts in cortical Glx, rather than GABA neurotransmitter levels. Glutamate might specifically interact with GABAB receptors, where higher MRS-derived Glx concentrations seem to be linked to higher levels of receptor activity.

It is known that transcranial direct current stimulation (tDCS) can induce polarity-specific shifts in brain excitability of the primary motor cortex (M1) with anodal tDCS enhancing and cathodal tDCS reducing cortical excitability. However, less is known about its impact on specific intracortical inhibitory mechanisms, such as γ-aminobutyric acid B (GABAB)-mediated inhibition. Consequently, the aim of the present study was to assess the impact of anodal and cathodal tDCS on M1 intracortical inhibition in healthy individuals. Long-interval intracortical inhibition (LICI) and cortical silent period (CSP) duration, both presumably mediated by GABAB receptors, were assessed using transcranial magnetic stimulation immediately before and after a 20 min session of tDCS over the left M1. Anodal tDCS significantly enhanced motor evoked potential size and reduced CSP duration, whereas it had no effect on LICI. Cathodal stimulation did not significantly modulate motor evoked potential size, CSP duration or LICI. This study provides evidence that anodal tDCS, presumably by synaptic plasticity mechanisms, has a direct effect on GABAB-meditated inhibition assessed by the CSP, but not by LICI. Our results further suggest that CSP and LICI probe distinct intracortical inhibitory mechanisms as they are differentially modulated by anodal tDCS. Finally, these data may have clinical value in patients in whom a pathological increase in CSP duration is present, such as schizophrenia.

The recent development of non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) has allowed the non-invasive assessment of cerebellar function in humans. Early studies showed that cerebellar activity, as reflected in the excitability of the dentate-thalamo-cortical pathway, can be assessed with paired stimulation of the cerebellum and the primary motor cortex (M1) (cerebellar inhibition of motor cortex, CBI). Following this, many attempts have been made, using techniques such as repetitive TMS and transcranial electrical stimulation (TES), to modulate the activity of the cerebellum and the dentate-thalamo-cortical output, and measure their impact on M1 activity. The present article reviews literature concerned with the impact of non-invasive stimulation of cerebellum on M1 measures of excitability and “plasticity” in both healthy and clinical populations. The main conclusion from the 27 reviewed articles is that the effects of cerebellar “plasticity” protocols on M1 activity are generally inconsistent. Nevertheless, two measurements showed relatively reproducible effects in healthy individuals: reduced response of M1 to sensorimotor “plasticity” (paired-associative stimulation, PAS) and reduced CBI following repetitive TMS and TES. We discuss current challenges, such as the low power of reviewed studies, variability in stimulation parameters employed and lack of understanding of physiological mechanisms underlying CBI.

PURPOSE. The aim of the present study was to assess, in healthy individuals, the impact of M1-M1 tDCS on primary motor cortex excitability using transcranial magnetic stimulation and sensorimotor metabolite concentration using (1)H-MRS. METHODS. For both experiments, each participant received the three following interventions (20 min tDCS, 1mA): left-anodal/right-cathodal, left-cathodal/right-anodal, sham. The effects of tDCS were assessed via motor evoked potentials (experiment 1) and metabolite concentrations (experiment 2) immediately after and 12 minutes following the end of stimulation and compared to baseline measurement. RESULTS. No effect of M1-M1 tDCS on corticospinal excitability was found. Similarly, M1-M1 tDCS did not significantly modulate metabolite concentrations. High inter-subject variability was noted. Response rate analysis showed a tendency towards inhibition following left-anodal/right-cathodal tDCS in 50% of participants and increased GABA levels in 45% of participants. CONCLUSION. In line with recent studies showing important inter-subject variability following M1-supraorbital tDCS, the present data show that M1-M1 stimulation is also associated with large response variability. The absence of significant effects suggests that current measures may lack sensitivity to assess changes in M1 neurophysiology and metabolism associated with M1-M1 tDCS.

Humans have a natural tendency towards symmetrical movements, which rely on a distributed cortical network that allows for complex unimanual movements. Studies on healthy humans using rTMS have shown that disruption of this network, and particularly the dorsal premotor cortex (dPMC), can result in increased physiological mirror movements. The aim of the present set of experiments was to further investigate the role of dPMC in restricting motor output to the contralateral hand and determine whether physiological mirror movements could be decreased in healthy individuals. Physiological mirror movements were assessed before and after transcranial direct current stimulation (tDCS) over right and left dPMC in three conditions: bilateral, unilateral left and unilateral right stimulation. Mirror EMG activity was assessed immediately before, 0, 10 and 20 min after tDCS. Results show that physiological mirroring increased significantly in the hand ipsilateral to cathodal stimulation during bilateral stimulation of the dPMC, 10 and 20 min after stimulation compared to baseline. There was no significant modulation of physiological mirroring in the hand ipsilateral to anodal stimulation in the bilateral condition or following unilateral anodal or unilateral cathodal stimulation. The present data further implicate the dPMC in the control of unimanual hand movements and show that physiological mirroring can be increased but not decreased with dPMC tDCS.

Introduction Corticospinal excitability is transiently suppressed during motor preparation (Greenhouse et al., 2015 ) and when cancelling a prepared movement (Hoshiyama et al., 1997 ). Because MEPs are suppressed even in task-irrelevant muscles Greenhouse et al., 2015 , Hoshiyama et al., 1997 ), it has been proposed that there is a “global” inhibitory signal (Greenhouse et al., 2015) . Objectives We tested the whether the inhibition is global or specific to different excitatory interneuron circuits in primary motor cortex (M1). Materials & methods A controllable pulse parameter TMS (cTMS; Rogue Resolutions Ltd.) device was used to activate distinct interneuron circuits in M1 by changing the coil orientation (posterior–anterior, PA; anterior–posterior, AP) and TMS pulse width (30–120 μs). Motor evoked potentials (MEPs) were elicited in the first dorsal interosseous muscle(s) using short AP- (AP30) and long PA-directed (PA120) pulses at various stages during: (1) a left/right choice reaction time task (CRTT) in which a non-informative warning cue appeared 0.5 s prior to the imperative signal indicated the required response; and (2) a Go/No-Go task in which a non-informative warning cue appeared 2 s prior to a Go or No-Go signal indicating to respond or not respond. Because TMS pulse specificity is greatest at low stimulus intensities, experiments were conducted with weak voluntary contraction (5–10% maximum) to reduce stimulus threshold. Results AP30 pulses evoked MEPs with a longer latency than PA120 pulses, confirming that different excitatory interneurons were recruited by the different pulse. [RH1] In the CRTT, the amplitude of AP30-evoked MEPs was suppressed at the time of the imperative stimulus in both responding and non-responding hands, whereas responses to PA120 stimuli were unaffected (Fig. 1A) Download : Download high-res image (366KB) Download : Download full-size image .[RH2] In the Go/No-Go task, AP30 and PA120 MEPs were suppressed to a similar extent in the No-Go condition near to the expected onset of movement (Fig. 1B). Conclusion During motor preparation for the CRTT there was a selective suppression of one interneuron circuit in M1. In contrast, a global inhibition of corticospinal excitability was observed following a decision not to move. The implication is that the mechanisms underlying each form of inhibition are at least partially distinct.

Activity of the primary motor cortex (M1) during action observation is thought to reflect motor resonance. Here, we conducted three studies using transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) of the first dorsal interosseus muscle (FDI) during action observation to determine: (i) the time course of M1 corticospinal excitability during the observation of a simple finger movement; (ii) the specificity of M1 modulation in terms of type of movement and muscle; and (iii) the relationship between M1 activity and measures of empathy and autistic traits. In a first study, we administered single-pulse TMS at 30-ms intervals during the observation of simple finger movements. Results showed enhanced corticospinal excitability occurring between 60 and 90 ms after movement onset. In a second experiment, TMS-induced MEPs were recorded from the FDI and abductor digiti minimi muscles while pulses were delivered 90 ms after movement onset during observation of simple finger movement and dot movement. Increased corticospinal excitability was restricted to finger movement and was present in both muscles. Finally, in an exploratory experiment, single-pulse TMS was administered at 30, 90 and 150 ms after movement onset, and participants were asked to complete the Empathy Quotient (EQ) and the Autism Spectrum Quotient (AQ). Correlational analysis revealed a significant link between motor facilitation at 90 ms and the EQ and AQ scores. These results suggest that corticospinal excitability modulation seen at M1 during action observation is the result of a rapid and crude automatic process, which may be related to social functioning.

Purpose: Recent studies investigating the effects of mild traumatic brain injury (mTBI) suggest the presence of unbalanced excitatory and inhibitory mechanisms within primary motor cortex (M1). Whether these abnormalities are associated with impaired synaptic plasticity remains unknown. 11 12 13 Methods: The effects of continuous theta burst stimulation (cTBS) on transcranial magnetic stimulation-induced motor evoked potentials (MEPs) were assessed on average two weeks and six weeks following mTBI in five individuals. 14 15 Results: The procedure was well-tolerated by all participants. Continuous TBS failed to induce a significant reduction of MEP amplitudes two weeks after the injury, but response to cTBS normalized six weeks following injury, as a majority of patients became asymptomatic. 16 17 18 Conclusions: These preliminary results suggest that cTBS can be used to assess M1 synaptic plasticity in subacute phase following mTBI and may provide insights into neurobiological substrates of symptoms and consequences of mTBI. 19 20

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood 33. To help improve this understanding, proton magnetic resonance spectroscopy (1H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as γ-aminobutyric acid (GABA) and glutamate in a region-specific manner 41. In fact, a recent study demonstrated that 1H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration 34. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with 1H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices 27,30,31. Methodological factors to consider and possible modifications to the protocol are also discussed.

To perform strictly unilateral movements, the brain relies on a large cortical and subcortical network. This network enables healthy adults to perform complex unimanual motor tasks without the activation of contralateral muscles. However, mirror movements (involuntary movements in ipsilateral muscles that can accompany intended movement) can be seen in healthy individuals if a task is complex or fatiguing, in childhood, and with increasing age. Lateralization of movement depends on complex interhemispheric communication between cortical (i.e., dorsal premotor cortex, supplementary motor area) and subcortical (i.e., basal ganglia) areas, probably coursing through the corpus callosum (CC). Here, we will focus on transcallosal interhemispheric inhibition (IHI), which facilitates complex unilateral movements and appears to play an important role in handedness, pathological conditions such as Parkinson’s disease, and stroke recovery.

Sports concussions affect thousands of individuals every year and are a major public health concern. Still, little is known about the long-term and cumulative effects of concussions on brain neurophysiology. The principal objective of this study was to investigate the long-lasting effects of multiple sports concussions on sensorimotor integration and somatosensory processing in a sample of 12 concussed athletes and 14 non-concussed athletes of similar age (mean, 23 years) and education (mean, 16 years). Right median nerve stimulation was paired with transcranial magnetic stimulation (TMS) of the left primary motor cortex to investigate sensorimotor integration with short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) at five interstimulus intervals (18, 20, 22, 100, 200 msec). Somatosensory evoked potentials (SEP) were recorded from the left centro-parietal region. We also investigated primary motor cortex inhibitory mechanisms with three TMS protocols: cortical silent period, long interval intracortical inhibition, and short interval intracortical inhibition. Motor evoked potentials were recorded from the right abductor pollicis brevis muscle. No differences were observed between groups for SAI, LAI, and SEP. However, cortical silent period duration was prolonged and long interval intracortical inhibition was enhanced in the concussed group. These findings suggest that multiple sports concussions lead to specific, long-term neurophysiological dysfunctions of intracortical inhibitory mechanisms in primary motor cortex while somatosensory processing and sensorimotor integration are spared. This study provides additional evidence for the presence of specific and stable alterations of GABA(B) receptor activity in primary motor cortex that may be of clinical value for prognosis and diagnosis.

It is now well established that the human brain is endowed with a mechanism that pairs action perception with its execution. This system has been extensively studied using visual stimuli and recent evidence suggests that it is also responsive to the sound of motor actions. Here, we presented action (finger and tongue clicks) and acoustically matched sounds to investigate action-related sound processing in a 12-year-old child undergoing intracranial monitoring of epileptic seizures. Electroencephalography grids were located over a large portion of the right hemisphere, including motor cortex. Wavelet analysis carried out on electrodes overlying the functionally defined hand representation of the motor cortex revealed early (100 ms) and late (250-450 ms) decreases in mu rhythm power (12 and 20 Hz) selective for natural finger-clicks compared with control sounds. These data suggest the presence of a rapid, multimodal resonance mechanism modulating motor cortex activity.