Hand Motor Cortex Research Articles

Multimodal and Repeated Localization of Primary Hand Motor Function to the Lateral Postcentral Gyrus in a Case of Frontal Motor Area Brain Metastasis

BACKGROUND AND IMPORTANCE: The human motor homunculus is a well-known topographical map of the functional-anatomical relationships of the precentral gyrus. Within this homunculus, the primary hand motor area is considered one of the least plastic functional-anatomical relationships. Only a few cases in the literature describe relocation of functional hand representation away from the classical anatomical location. These cases have been reported in the context of children, primary gliomas, or arteriovenous malformations. CLINICAL PRESENTATION: Here, we describe a unique case where the area of lowest hand motor stimulation threshold (ie, hand motor representation) was found in the postcentral gyrus in an older adult with a metastasis in the premotor area of the brain. This localization was based on intraoperative cortical stimulation–evoked motor potentials and confirmed with electrophysiological phase reversal and MRI-based neuronavigation. This mapping was repeated and consistent 2 months later during a reoperation for recurrence. In addition, the remapped anatomical location was found in an area that was active during finger tapping on preoperative functional MRI. CONCLUSION: These findings suggest that neuroplastic remapping of hand motor cortex to the postcentral gyrus can occur in brain metastases even in adults. This has implications for planning tumor resections and interventional neurorehabilitation strategies, and it suggests that the motor homunculus may have more plastic potential in adulthood than previously recognized.

Water and brain function: effects of hydration status on neurostimulation with transcranial magnetic stimulation.

Neurostimulation/neurorecording are tools to study, diagnose, and treat neurological/psychiatric conditions. Both techniques depend on volume conduction between scalp and excitable brain tissue. Here, we examine how neurostimulation with transcranial magnetic stimulation (TMS) is affected by hydration status, a physiological variable that can influence the volume of fluid spaces/cells, excitability, and cellular/global brain functioning. Normal healthy adult participants (32, 9 males) had common motor TMS measures taken in a repeated-measures design from dehydrated (12-h overnight fast/thirst) and rehydrated (identical dehydration protocol followed by rehydration with 1 L water in 1 h) testing days. The target region was left primary motor cortex hand area. Response at the target muscle was recorded with electromyography. Urinalysis confirmed hydration status. Motor hotspot shifted in half of participants. Motor threshold decreased in rehydration, indicating increased excitability. Even after redosing/relocalizing TMS to the new threshold/hotspot, rehydration still showed evidence of increased excitability: recruitment curve measures generally shifted upward and the glutamate-dependent paired-pulse protocol, short intracortical facilitation (SICF), was increased. Short intracortical inhibition (SICI), long intracortical inhibition (LICI), long intracortical facilitation (LICF), and cortical silent period (CSP) were relatively unaffected. The hydration perturbations were mild/subclinical based on the magnitude/speed and urinalysis. Motor TMS measures showed evidence of expected physiological changes of osmotic challenges. Rehydration showed signs of macroscopic and microscopic volume changes including decreased scalp-cortex distance (brain closer to stimulator) and astrocyte swelling-induced glutamate release. Hydration may be a source of variability affecting any techniques dependent on brain volumes/volume conduction. These concepts are important for researchers/clinicians using such techniques or dealing with the wide variety of disease processes involving water balance.NEW & NOTEWORTHY Hydration status can affect brain volumes and excitability, which should affect techniques dependent on electrical volume conduction, including neurostimulation/recording. We test the previously unknown effects of hydration on neurostimulation with TMS and briefly review relevant physiology of hydration. Rehydration showed lower motor threshold, shifted motor hotspot, and generally larger responses even after compensating for threshold/hotspot changes. This is important for clinical and research applications of neurostimulation/neurorecording and the many clinical disorders related to water balance.

The new morphologic classification of the hand motor cortex with magnetic resonance imaging in glioma patients

PurposeThe hand motor cortex (HMC) is a reliable anatomical landmark for identifying the precentral gyrus. The current study aimed to investigate the morphology of HMC on axial MRI of glioma patients, propose a new morphological classification of HMC and analyze the effect of tumors on the morphology of HMC. MethodsA retrospective study of 276 adult right-handed glioma patients was conducted. The morphology of HMC was assessed using T2 axial images. Subsequently, the distribution of morphological subtypes was compared between the bilateral hemispheres and the tumor-affected and healthy hemispheres. Finally, the influence of tumor pathology on the morphology of HMC was investigated. ResultsA new morphological classification of HMC with four subtypes (Ω, ε, Ω-ε and ε-Ω) was proposed. No significant difference was identified in the distribution of morphological subtypes between the bilateral hemispheres (p = 0.0901, Chi-square test), or between the tumor-affected and healthy hemispheres (p = 0.3507, Chi-square test), and the morphology of HMC between the bilateral hemispheres were consistent (p < 0.0001, Kappa test). In addition, a significant difference was identified in the distribution of morphological subtypes between astrocytic and oligodendroglial tumors (p = 0.0135, Chi-square test). ConclusionIn the current study, we proposed a new morphological classification of HMC, and found that tumor could affect the morphology of HMC in glioma patients. The results can help our clinical practice, enabling us to further understand the spatial structure of the cerebral hemispheres.

Transcranial magnetic stimulation over supramarginal gyrus stimulates primary motor cortex directly and impairs manual dexterity: implications for TMS focality.

Based on human motor cortex, the effective spatial resolution of transcranial magnetic stimulation (TMS) is often described as 5-20 mm, because small changes in TMS coil position can have large effects on motor-evoked potentials (MEPs). MEPs are often studied at rest, with muscles relaxed. During muscle contraction and movement, corticospinal excitability is higher, thresholds for effective stimulation are lower, and MEPs can be evoked from larger regions of scalp, so the effective spatial resolution of TMS is larger. We found that TMS over the supramarginal gyrus (SMG) impaired manual dexterity in the grooved pegboard task. It also resulted in short-latency MEPs in hand muscles, despite the coil being 55 mm away from the motor cortex hand area (M1). MEPs might be evoked by either a specific corticospinal connection from SMG or a remote but direct electromagnetic stimulation of M1. To distinguish these alternatives, we mapped MEPs across the scalp during rest, isotonic contraction, and manual dexterity tasks and ran electric field simulations to model the expected M1 activation from 27 scalp locations and four coil orientations. We also systematically reviewed studies using TMS during movement. Across five experiments, TMS over SMG reliably evoked MEPs during hand movement. These MEPs were consistent with direct M1 stimulation and substantially decreased corticospinal thresholds during natural movement. Systematic review suggested that 54 published experiments may have suffered from similar motor activation confounds. Our results have implications for the assumed spatial resolution of TMS, and especially when TMS is presented within 55 mm of the motor cortex.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS) is often described as having an effective spatial resolution of ∼10 mm, because of the limited area of the scalp on which TMS produces motor-evoked potentials (MEPs) in resting muscles. We find that during natural hand movement TMS evokes MEPs from a much larger scalp area, in particular when stimulating over the supramarginal gyrus 55 mm away. Our results show that TMS can be effective at much larger distances than generally assumed.

GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study

Introduction: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABA_A receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls. Methods: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [¹¹C]flumazenil positron emission tomography to assess GABA_A receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABA_A receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABA_A receptor activity, long-interval intracortical inhibition representing GABA_B receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability. Results: No significant differences in baseline GABA_A receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABA_A receptor availability and TMS outcomes. Changes in GABA_A receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT. Conclusion: We found that a change in GABA_A receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Females with painful temporomandibular disorders present higher intracortical facilitation relative to pain-free controls.

This study aimed to investigate cortical excitability differences in the primary motor cortex (M1) hand representation between individuals with temporomandibular disorders (TMD) and healthy controls. We assessed resting motor thresholds, motor-evoked potentials (MEPs), intracortical inhibition, and intracortical facilitation and explored potential associations with clinical and psychosocial characteristics in the TMD group. We recruited 36 female participants with TMD and 17 pain-free controls. Transcranial magnetic stimulation (TMS) was used to assess M1 cortical excitability. Correlations between clinical and psychosocial factors and cortical excitability measures were also evaluated. Patients with TMD showed significantly higher intracortical facilitation at 12ms (z = 1.98, p = 0.048) and 15ms (z = 2.65, p = 0.008) when compared to controls. Correlations revealed associations between intracortical facilitation and pain interference, sleep quality, depressive symptoms, and pain catastrophizing in the TMD group. Females with TMD exhibit heightened motor cortex intracortical facilitation in the hand representation, potentially indicating altered cortical excitability beyond the motor face area. This suggests a role for cortical excitability in TMD pathophysiology, influenced by psychosocial factors. Understanding cortical excitability in TMD may inform targeted interventions. Psychosocial variables may play a role in cortical excitability, emphasizing the multidimensional nature of TMD-related pain. Further research is needed to confirm and expand upon these findings, with potential implications for the management of TMD and related pain conditions.

Probing the inhibitory motor circuits in adductor laryngeal dystonia during a dystonia-unrelated task

BackgroundThe pathophysiology of adductor laryngeal dystonia (AdLD) remains unknown; however, there is growing evidence that dystonia is associated with disruptions in the inhibitory regulation of sensorimotor cortical areas. Using functional MRI (fMRI) and transcranial magnetic stimulation (TMS) complementarily, we previously demonstrated an overly activated laryngeal motor cortex and revealed correlations between blood-oxygen-level dependent (BOLD) activation and intracortical inhibition in a phonation (dystonia-related) task in adductor laryngeal dystonia (AdLD). ObjectiveHere, we aimed to characterize the brain-based findings in the primary motor cortex (M1) during a dystonia-unrelated (finger tapping) task in AdLD and controls (CTL). MethodsWe examined the between-group differences in task-dependent BOLD activation and intracortical inhibition, measured by the TMS-evoked cortical silent period (cSP), in the M1. The correlations between fMRI and TMS responses were assessed. ResultsThere is more broadly dispersed BOLD activation, not confined to the hand motor cortex, and reduced intracortical inhibition in AdLD compared to CTL. Further, there are more positive correlations between cSP and BOLD activation in a task unrelated to dystonic symptoms in AdLD compared with CTL. This is in contrast to our previous work that demonstrated fewer positive correlations in AdLD during a dystonic phonation task. ConclusionsIn unaffected musculature activation, there is dispersed BOLD activation that is correlated with intracortical inhibition suggesting a possible compensatory strategy in the non-dystonic muscles.

Real world demonstration of hand motor mapping using the structural connectivity atlas

BackgroundLocating the hand-motor-cortex (HMC) is an essential component within many neurosurgeries. Despite advancements in these localization methods there are still downfalls for each. Additionally, the importance of presurgical planning calls for increasingly accurate and efficient methods of locating specific cortical regions. ObjectiveIn this study we aimed to test the ability of the Structural Connectivity Atlas (SCA), a machine-learning based method to parcellate the human cortex, to locate the HMC in a small cohort study. MethodsUsing MRI and DTI images obtained from adult subjects (n = 11), personalized brain maps were created for each individual based on a SCA paired with the Brainnetome region for the HMC. Subjects received single pulse TMS, over the HMC region through the use of a neuronavigation system. If they responded with motor movement, this was recorded. The SCA identified HMC region was compared to the visual-determined HMC through identifying the Omega fold on the Precentral Gyrus, which was completed by a trained neuroanatomist. A Kendall’s Tau B correlation was conducted between anatomical match and visual movement. ResultsThis study concluded that the SCA was capable of locating the HMC in healthy and distorted brains. Overall, the SCA defined the anatomical area of the HMC in 90 % of subjects and triggered a motor response in 61 %. ConclusionThe SCA could be suitable for incorporation into presurgical planning practices due to its ability to map anatomically abnormal brains. Further studies on larger cohorts and targeting different areas of cortex could be beneficial.

Increased paired stimuli enhance corticospinal-motoneuronal plasticity in humans with spinal cord injury.

Paired corticospinal-motoneuronal stimulation (PCMS) has been used to enhance corticospinal excitability and functional outcomes in humans with spinal cord injury (SCI). Here, we examined the effect of increasing the number of paired pulses on PCMS-induced plasticity. During PCMS, corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the hand motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle 1-2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve. We tested motor-evoked potentials (MEPs) elicited by TMS over the hand motor cortex and electrical stimulation at the cervicomedullary junction (CMEPs) in the FDI muscle before and after 180 paired pulses (PCMS-180) followed up by another 180 paired pulses (PCMS-360) in humans with and without chronic incomplete cervical SCI. The nine-hole-peg-test (9HPT) was measured before and after PCMS paired pulses in individuals with SCI. We found that the size of MEPs and CMEPs increased after PCMS-180 in both groups compared with baseline and further increased after PCMS-360 in participants with SCI, suggesting a spinal origin for these effects. Notably, in people with SCI, the time to complete the 9HPT decreased after PCMS-180 and further decreased after PCMS-360 compared with baseline but not when the 9HPT was repeated overtime. Our findings demonstrate that increasing the number of PCMS paired pulses potentiates corticospinal excitability and voluntary motor output after SCI, likely through spinal plasticity. This proof-of-principle study suggests that increasing the PCMS dose represents a strategy to boost voluntary motor output after SCI.NEW & NOTEWORTHY Paired corticospinal-motoneuronal stimulation (PCMS) has been used to enhance corticospinal excitability and functional outcomes in humans with spinal cord injury (SCI). Here, we demonstrate that 360 paired pulses resulted in larger increases in motor-evoked potential size in a hand muscle and in a better ability to complete the nine-hold-peg-test compared with 180 paired pulses in people with SCI. This proof-of-principle study suggests that increasing the PCMS dose represents a strategy to boost motor output after SCI.

Imagined paralysis reduces motor cortex excitability.

Mental imagery is a powerful capability that engages similar neurophysiological processes that underlie real sensory and motor experiences. Previous studies show that motor cortical excitability can increase during mental imagery of actions. In this study, we focused on possible inhibitory effects of mental imagery on motor functions. We assessed whether imagined arm paralysis modulates motor cortical excitability in healthy participants, as measured by motor evoked potentials (MEPs) of the hand induced by near‐threshold transcranial magnetic stimulation (TMS) over the primary motor cortex hand area. We found lower MEP amplitudes during imagined arm paralysis when compared to imagined leg paralysis or baseline stimulation without paralysis imagery. These results show that purely imagined bodily constraints can selectively inhibit basic motor corticospinal functions. The results are discussed in the context of motoric embodiment/disembodiment.

HABIT+tDCS: a study protocol of a randomised controlled trial (RCT) investigating the synergistic efficacy of hand-arm bimanual intensive therapy (HABIT) plus targeted non-invasive brain stimulation to improve upper extremity function in school-age children with unilateral cerebral palsy

IntroductionUnilateral spastic cerebral palsy (USCP) is characterised by movement deficits primarily on one body side. The best available upper extremity (UE) therapies are costly and intensive. Thus, there is an...

Morphologic Variants of the Hand Motor Cortex in Developing Brains from Neonates through Childhood Assessed by MR Imaging.

Knowledge of anatomic markers of the hand motor cortex is essential in the evaluation and treatment of motor neurologic diseases for both adults and developing populations. However, hand motor cortex variants in developing brains remain to be investigated. Our objective was to observe morphologic variants of the hand motor cortex in developing brains from neonates through childhood. In this study, 542 participants (0∼15 years of age) were retrospectively enrolled and divided into different age groups. The hand motor cortex morphology was evaluated on the basis of 3D T1WI. Variations in hand motor cortex variants were compared among different age groups. Inter-gender and interhemispheric differences of hand motor cortex variants were also evaluated. Various hand motor cortex variants could be observed in developing brains, even in the neonatal period. One new morphologic shape, "immature Ω," was found in neonates and infants. The proportion of this new shape decreased dramatically during the first year after birth, then disappeared after 1 year of age. It persisted for a longer time in the right hemisphere and in males. However, sex or hemispheric effects on the distribution of the proportion of variants were not statistically significant. Furthermore, the proportion of concordance of the bilateral hand motor cortex showed an increasing trend with age (P = .006), higher in females than males. Various hand motor cortex variants already existed at birth. The distribution of proportions of different variants developmentally varied during the first year after birth and became stable after 1 year of age. The concordance of the bilateral hand motor cortex could be influenced by age and sex.

Plasticity in the developing brain: neurophysiological basis for lesion-induced motor reorganization.

The plasticity of the developing brain can be observed following injury to the motor cortex and/or corticospinal tracts, the most commonly injured brain area in the pre- or peri-natal period. Factors such as the timing of injury, lesion size and lesion location may affect a single hemisphere’s ability to acquire bilateral motor representation. Bilateral motor representation of single hemisphere origin is most likely to occur if brain injury occurs before the age of 2 years; however, the link between injury aetiology, reorganization type and functional outcome is largely understudied. We performed a retrospective review to examine reorganized cortical motor maps identified through transcranial magnetic stimulation in a cohort of 52 patients. Subsequent clinical, anthropometric and demographic information was recorded for each patient. Each patient’s primary hand motor cortex centre of gravity, along with the Euclidian distance between reorganized and normally located motor cortices, was also calculated. The patients were classified into broad groups including reorganization type (inter- and intrahemispheric motor reorganization), age at the time of injury (before 2 years and after 2 years) and injury aetiology (developmental disorders and acquired injuries). All measures were analysed to find commonalities between motor reorganization type and injury aetiology, function and centre of gravity distance. There was a significant effect of injury aetiology on type of motor reorganization (P < 0.01), with 60.7% of patients with acquired injuries and 15.8% of patients with developmental disorders demonstrating interhemispheric motor reorganization. Within the interhemispheric motor reorganization group, ipsilaterally and contralaterally projecting hand motor cortex centres of gravity overlapped, indicating shared cortical motor representation. Furthermore, the data suggest significantly higher prevalence of bilateral motor representation from a single hemisphere in cases of acquired injuries compared to those of developmental origin. Functional outcome was found to be negatively affected by acquired injuries and interhemispheric motor reorganization relative to their respective counterparts with developmental lesions and intrahemispheric motor reorganization. These results provide novel information regarding motor reorganization in the developing brain via an unprecedented cohort sample size and transcranial magnetic stimulation. Transcranial magnetic stimulation is uniquely suited for use in understanding the principles of motor reorganization, thereby aiding in the development of more efficacious therapeutic techniques to improve functional recovery following motor cortex injury.

MRI of Transcallosal White Matter Helps to Predict Motor Impairment in Multiple Sclerosis

Background Altered callosal integrity has been associated with motor deficits in patients with multiple sclerosis (MS), but its contribution to disability has, to the knowledge of the authors, not been investigated by using multiparametric MRI approaches. Purpose To investigate structural and functional interhemispheric MRI substrates of global disability at different milestones and upper limb motor impairment in MS. Materials and Methods In this cross-sectional study, healthy control patients and patients with MS (between January 1, 2008, and December 31, 2016) were retrospectively selected from our hospital database. Clinical assessment included Expanded Disability Status Scale (EDSS), nine-hole peg test, and digital finger tapping test. By using structural and resting-state functional MRI sequences, probabilistic tractography of hand corticospinal tract fibers, and transcallosal fibers between hand-motor cortices (hereafter, referred to as hand-M1), supplementary motor areas (SMAs), premotor cortices (PMCs), and voxel-mirror homotopic connectivity (VMHC) were analyzed. Random forest analyses identified the MRI predictors of clinical disability at different milestones (EDSS scores of 3.0, 4.0, 6.0) and upper limb motor impairment (nine-hole peg test and finger tapping test z scores < healthy control patients 5th percentile). Results One-hundred thirty healthy control patients (median age, 39 years; interquartile range, 31-50 years; 70 women) and 340 patients with MS (median age, 43 years; interquartile range, 33-51 years; 213 women) were studied. EDSS 3.0 predictors (n = 159) were global measures of atrophy and lesions together with damage measures of corticospinal tracts and transcallosal fibers between PMCs and SMAs (accuracy, 86%; P = .001-.01). For EDSS 4.0 (n = 131), similar predictors were found in addition to damage in transcallosal fibers between hand-M1 (accuracy, 89%; P = .001-.049). No MRI predictors were found for EDSS 6.0 (n = 70). Nine-hole peg test (right, n = 161; left, n = 166) and finger tapping test (right, n = 117; left, n = 111) impairments were predicted by damage in transcallosal fibers between SMAs and PMCs (accuracy range, 69%-77%; P = .001-.049). VMHC abnormalities did not explain clinical outcomes. Conclusion Structural, not functional, abnormalities at MRI in transcallosal premotor and motor white matter fibers predicted severity of global disability and upper limb motor impairment in patients with multiple sclerosis. The informative role of such predictors appeared less evident at higher disability levels. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Barkhof and Pontillo in this issue.

Effect of Pulse Duration and Direction on Plasticity Induced by 5 Hz Repetitive Transcranial Magnetic Stimulation in Correlation With Neuronal Depolarization.

Introduction: High frequency repetitive transcranial magnetic stimulation applied to the motor cortex causes an increase in the amplitude of motor evoked potentials (MEPs) that persists after stimulation. Here, we focus on the aftereffects generated by high frequency controllable pulse TMS (cTMS) with different directions, intensities, and pulse durations.Objectives: To investigate the influence of pulse duration, direction, and amplitude in correlation to induced depolarization on the excitatory plastic aftereffects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) using bidirectional cTMS pulses.Methods: We stimulated the hand motor cortex with 5 Hz rTMS applying 1,200 bidirectional pulses with the main component durations of 80, 100, and 120 μs using a controllable pulse stimulator TMS (cTMS). Fourteen healthy subjects were investigated in nine sessions with 80% resting motor threshold (RMT) for posterior-anterior (PA) and 80 and 90% RMT anterior-posterior (AP) induced current direction. We used a model approximating neuronal membranes as a linear first order low-pass filter to estimate the strength–duration time constant and to simulate the membrane polarization produced by each waveform.Results: PA and AP 5 Hz rTMS at 80% RMT produced no significant excitation. An exploratory analysis indicated that 90% RMT AP stimulation with 100 and 120 μs pulses but not 80 μs pulses led to significant excitation. We found a positive correlation between the plastic outcome of each session and the simulated peak neural membrane depolarization for time constants >100 μs. This correlation was strongest for neural elements that are depolarized by the main phase of the AP pulse, suggesting the effects were dependent on pulse direction.Conclusions: Among the tested conditions, only 5 Hz rTMS with higher intensity and wider pulses appeared to produce excitatory aftereffects. This correlated with the greater depolarization of neural elements with time constants slower than the directly activated neural elements responsible for producing the motor output (e.g., somatic or dendritic membrane).Significance: Higher intensities and wider pulses seem to be more efficient in inducing excitation. If confirmed, this observation could lead to better results in future clinical studies performed with wider pulses.

Mapping the homunculus: agreement between fMRI and TMS-based motor cortex hand, trunk and leg representations

Mapping the homunculus: agreement between fMRI and TMS-based motor cortex hand, trunk and leg representations

Effects and safety of high-frequency repetitive transcranial magnetic stimulation in trigeminal neuralgia

Background. Trigeminal neuralgia is the most common cause of facial pain. Insufficient effectiveness and frequent side effects of pharmacological therapy, as well as the risk of complications of invasive neurosurgical manipulations, determine the relevance of the development of new treatment approaches, one of which is repetitive transcranial magnetic stimulation (rTMS).The aim of the study is to determine the effectiveness of high‑frequency rTMS of the primary motor cortex in terms of pain intensity and quality of life in patients with trigeminal neuralgia, as well as to assess the safety of the stimulation course.Materials and methods. This open‑label non‑randomized single arm study included 20 patients with classic trigeminal neuralgia according to the ICHD‑3 classification. All patients received 10 sessions of navigated high‑frequency rTMS of the primary motor cortex (hand area) of the hemisphere, contralateral to pain syndrome localization. The maximum and average pain intensity was assessed before and after 10 rTMS sessions according to a Numeric Pain Rating Scale (NPRS), as well as quality of life was measured according to the SF‑36 questionnaire, and the severity of affective disorders according was measured to the Beck Depression Inventory (BDI). Safety and tolerability of rTMS were assessed using self‑developed questionnaires for adverse events that occurred during stimulation and within 24 hours after the previous session.Results. A significant decrease in the maximum (p = 0.01) and average (p &lt;0.01) pain intensity was shown after 10 sessions of rTMS. In 50 % of patients, the maximum pain intensity decreased by more than 30 % vs baseline. Significant changes were detected in the physical health measure of SF‑36 quality of life questionnaire, particularly, in the “bodily pain” domain, as well as in such aspects of the mental health measure as “vitality” and “social functioning”. The severity of affective disorders did not change significantly. A favorable profile of rTMS tolerability has been demonstrated.Conclusion. An open‑label study showed the possible effectiveness of 10 sessions of high‑frequency rTMS to reduceт the pain intensity in patients with trigeminal neuralgia. For the first time, the spectrum of adverse events both during stimulation and within a day after its completion was systematically analyzed.

Neural mechanisms underlying the Rubber Hand Illusion: A systematic review of related neurophysiological studies.

IntroductionMany researchers took advantage of the well‐established rubber hand illusion (RHI) paradigm to explore the link between the sense of body ownership and the different brain structures and networks. Here, we aimed to review the studies that have investigated this phenomenon by means of neurophysiological techniques.MethodsThe MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: “Rubber hand illusion” AND “Transcranial magnetic stimulation (TMS)” OR “Evoked potentials (EP)” OR “Event related potentials (ERP)” OR “Electroencephalography (EEG)”.ResultsTranscranial magnetic stimulation studies revealed a significant excitability drop in primary motor cortex hand circuits accompanying the disembodiment of the real hand during the RHI experience and that the perceived ownership over the rubber hand is associated with normal parietal–motor communication. Moreover, TMS provided causal evidence that the extrastriate body area is involved in the RHI and subsequently in body representation, while neuromodulation of ventral premotor area and the inferior parietal lobe did not result in an enhancement of embodiment. EP and ERP studies suggest that pre‐existing body representations may affect larger stages of tactile processing and support predictive coding models of the functional architecture of multisensory integration in bodily perceptual experience. High‐frequency oscillations on EEG play a role in the integrative processing of stimuli across modalities, and EEG activity in γ band activity in the parietal area reflects the visuotactile integration process. EEG studies also revealed that RHI is associated with the neural circuits underlying motor control and that premotor areas play a crucial role in mediating illusory body ownership.ConclusionNeurophysiological studies shed new light on our understanding of the different aspects that contribute to the formation of a coherent self‐awareness in humans.

First and Second Language at Hand: A Chronometric Transcranial-Magnetic Stimulation Study on Semantic and Motor Resonance

According to embodied theories, motor and language processing bidirectionally interact: Motor activation modulates behavior in lexico-semantic tasks (semantic resonance), and understanding motor-related words entails activation of the corresponding motor brain areas (motor resonance). Whereas many studies investigated such interaction in the first language (L1), only few did so in a second language (L2), focusing on motor resonance. Here, we directly compared L1 and a late L2, for the first time both in terms of semantic and motor resonance and both in terms of magnitude and timing, by taking advantage of single-pulse TMS. Twenty-five bilinguals judged, in each language, whether hand motor-related ("grasp") and non-motor-related verbs ("believe"), were physical or mental. Meanwhile, we applied TMS on the hand motor cortex at 125, 275, 350, and 500 msec post verb onset, and recorded behavioral responses and TMS-induced motor evoked potentials. TMS induced faster responses for L1 versus L2 motor and nonmotor verbs at 125 msec (three-way interaction β = -0.0442, 95% CI [0.0814, -0.0070]), showing a semantic resonance effect at an early stage of word processing in L1 but not in L2. Concerning motor resonance, TMS-induced motor evoked potentials at 275 msec revealed higher motor cortex excitability for L2 versus L1 processing (two-way interaction β = 0.095, 95% CI [0.017, 0.173]). These findings confirm action-language interaction at early stages of word recognition, provide further evidence that L1 and L2 are differently embodied, and call for an update of existing models of bilingualism and embodiment, concerning both language representations and processing.

Clinical Utility of Transcranial Magnetic Stimulation (TMS) in the Presurgical Evaluation of Motor, Speech, and Language Functions in Young Children With Refractory Epilepsy or Brain Tumor: Preliminary Evidence.

Accurate presurgical mapping of motor, speech, and language cortices, while crucial for neurosurgical planning and minimizing post-operative functional deficits, is challenging in young children with neurological disease. In such children, both invasive (cortical stimulation mapping) and non-invasive functional mapping imaging methods (MEG, fMRI) have limited success, often leading to delayed surgery or adverse post-surgical outcomes. We therefore examined the clinical utility of transcranial magnetic stimulation (TMS) in young children who require functional mapping. In a retrospective chart review of TMS studies performed on children with refractory epilepsy or a brain tumor, at our institution, we identified 47 mapping sessions in 36 children 3 years of age or younger, in whom upper and lower extremity motor mapping was attempted; and 13 children 5–6 years old in whom language mapping, using a naming paradigm, was attempted. The primary hand motor cortex was identified in at least one hemisphere in 33 of 36 patients, and in both hemispheres in 27 children. In 17 children, primary leg motor cortex was also successfully identified. The language cortices in temporal regions were successfully mapped in 11 of 13 patients, and in six of them language cortices in frontal regions were also mapped, with most children (n = 5) showing right hemisphere dominance for expressive language. Ten children had a seizure that was consistent with their clinical semiology during or immediately following TMS, none of which required intervention or impeded completion of mapping. Using TMS, both normal motor, speech, and language developmental patterns and apparent disease induced reorganization were demonstrated in this young cohort. The successful localization of motor, speech, and language cortices in young children improved the understanding of the risk-benefit ratio prior to surgery and facilitated surgical planning aimed at preserving motor, speech, and language functions. Post-operatively, motor function was preserved or improved in nine out of 11 children who underwent surgery, as was language function in all seven children who had surgery for lesions near eloquent cortices. We provide feasibility data that TMS is a safe, reliable, and effective tool to map eloquent cortices in young children.