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Transcranial static magnetic stimulation (tSMS) has been focused as a new non-invasive brain stimulation, which can suppress the human cortical excitability just below the magnet. However, the non-regional effects of tSMS via brain network have been rarely studied so far. We investigated whether tSMS over the left primary motor cortex (M1) can facilitate the right M1 in healthy subjects, based on the hypothesis that the functional suppression of M1 can cause the paradoxical functional facilitation of the contralateral M1 via the reduction of interhemispheric inhibition (IHI) between the bilateral M1. This study was double-blind crossover trial. We measured the corticospinal excitability in both M1 and IHI from the left to right M1 by recording motor evoked potentials from first dorsal interosseous muscles using single-pulse and paired-pulse transcranial magnetic stimulation before and after the tSMS intervention for 30 min. We found that the corticospinal excitability of the left M1 decreased, while that of the right M1 increased after tSMS. Moreover, the evaluation of IHI revealed the reduced inhibition from the left to the right M1. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of tSMS in human.

Objective: To identify cortical regions engaged during the sustained attention to response task (SART) and characterize changes in their activity associated with the neurodegenerative condition amyotrophic lateral sclerosis (ALS). Methods: High-density electroencephalography (EEG) was recorded from 33 controls and 23 ALS patients during a SART paradigm. Differences in associated event-related potential peaks were measured for Go and NoGo trials. Sources active during these peaks were localized, and ALS-associated differences were quantified. Results: Go and NoGo N2 and P3 peak sources were localized to the left primary motor cortex, bilateral dorsolateral prefrontal cortex (DLPFC), and lateral posterior parietal cortex (PPC). NoGo trials evoked greater bilateral medial PPC activity during N2 and lesser left insular, PPC and DLPFC activity during P3. Widespread cortical hyperactivity was identified in ALS during P3. Changes in the inferior parietal lobule and insular activity provided very good discrimination (AUROC > 0.75) between patients and controls. Activation of the right precuneus during P3 related to greater executive function in ALS, indicative of a compensatory role. Interpretation: The SART engages numerous frontal and parietal cortical structures. SART–EEG measures correlate with specific cognitive impairments that can be localized to specific structures, aiding in differential diagnosis.

Across a series of studies, our laboratory has shown that the efficiency of action stopping is associated with the strength of GABAA-mediated short-intracortical inhibition (SICI) as measured using transcranial magnetic stimulation (TMS). However, these studies used fixed TMS parameters, which may not optimally probe GABAA receptor activity for each individual. In the present study, we measured the relationship between stopping efficiency and SICI using a range of TMS parameters. Participants completed a right-hand unimanual stop signal task to obtain a measure of stopping efficiency. Resting-state SICI was measured from the left primary motor cortex using six combinations of interstimulus intervals and conditioning pulse intensities. We also established the parameters which generated the strongest SICI (SICImax) and weakest SICI (SICImin) for each individual. We found that stopping efficiency was significantly predicted by SICI using various TMS parameters, including SICImax. Interestingly, SICImin accounted for a similar proportion of variance in stopping efficiency as SICI measured using other TMS parameters. The findings suggest that the relationship between stopping efficiency and SICI is robust, reliable, and not influenced by the extent to which SICI is optimally probed.

Professional boxers train to reduce their body mass before a match to refine their body movements. To test the hypothesis that the well-defined movements of boxers are represented within the motor loop (cortico-striatal circuit), we first elucidated the brain structure and functional connectivity specific to boxers and then investigated plasticity in relation to boxing matches. We recruited 21 male boxers 1 month before a match (Time1) and compared them to 22 age-, sex-, and body mass index (BMI)-matched controls. Boxers were longitudinally followed up within 1 week prior to the match (Time2) and 1 month after the match (Time3). The BMIs of boxers significantly decreased at Time2 compared with those at Time1 and Time3. Compared to controls, boxers presented significantly higher gray matter volume in the left putamen, a critical region representing motor skill training. Boxers presented significantly higher functional connectivity than controls between the left primary motor cortex (M1) and left putamen, which is an essential region for establishing well-defined movements. Boxers also showed significantly higher structural connectivity in the same region within the motor loop from Time1 to Time2 than during other periods, which may represent the refined movements of their body induced by training for the match.

Objective: This article presents the development and validation of a new robotic system for Transcranial Magnetic Stimulation (TMS), characterized by a new control approach, and an ad-hoc calibration methodology, specifically devised for the TMS application. Methods: The robotic TMS platform is composed of a 7 dof manipulator, controlled by an impedance control, and a camera-based neuronavigation system. The proposed calibration method was optimized on the workspace useful for the specific TMS application (spherical shell around the subject's head), and tested on three different hand-eye and robot-world calibration algorithms. The platform functionality was tested on six healthy subjects during a real TMS procedure, over the left primary motor cortex. Results: employing our method significantly decreases ( $p ) the calibration error by 34% for the position and 19% for the orientation. The robotic TMS platform achieved greater orientation accuracy than the expert operators, significantly reducing orientation errors by 46% ( $p ). No significant differences were found in the position errors and in the amplitude of the motor evoked potentials (MEPs) between the robot-aided TMS and the expert operators. Conclusion: The proposed calibration represents a valid method to significantly reduce the calibration errors in robot-aided TMS applications. Results showed the efficacy of the proposed platform (including the control algorithm) in administering a real TMS procedure, achieving better coil positioning than expert operators, and similar results in terms of MEPs. Significance: This article spotlights how to improve the performance of a robotic TMS platform, providing a reproducible and low-cost alternative to the few devices commercially available.

Objective: The aim of the study was to show that short-lasting (90 s) transcranial alternating current stimulation (tACS) at 20 Hz delivered over the left primary motor cortex (M1) is able to chang...

Studies using transcranial direct current stimulation (tDCS) typically incorporate a fade‐in, short‐stimulation, fade‐out sham (placebo) protocol, which is assumed to be indistinct from a 10–30 min active protocol on the scalp. However, many studies report that participants can dissociate active stimulation from sham, even during low‐intensity 1 mA currents. We recently identified differences in the perception of an active (10 min of 1 mA) and a sham (20 s of 1 mA) protocol that lasted for 5 min after the cessation of sham. In the present study we assessed whether delivery of a higher‐intensity 2 mA current would exacerbate these differences. Two protocols were delivered to 32 adults in a double‐blinded, within‐subjects design (active: 10 min of 2 mA, and sham: 20 s of 2 mA), with the anode over the left primary motor cortex and the cathode on the right forehead. Participants were asked “Is the stimulation on?” and “How sure are you?” at 30 s intervals during and after stimulation. The differences between active and sham were more consistent and sustained during 2 mA than during 1 mA. We then quantified how well participants were able to track the presence and absence of stimulation (i.e. their sensitivity) during the experiment using cross‐correlations. Current strength was a good classifier of sensitivity during active tDCS, but exhibited only moderate specificity during sham. The accuracy of the end‐of‐study guess was no better than chance at predicting sensitivity. Our results indicate that the traditional end‐of‐study guess poorly reflects the sensitivity of participants to stimulation, and may not be a valid method of assessing sham blinding., We quantified how well participants were able to track the presence and absence of a tDCS current (i.e. their sensitivity), using cross‐correlations. Current strength was a good classifier of sensitivity (higher for 2mA than 1mA), but the accuracy of their end‐of‐study guess was no better than chance at predicting sensitivity. The traditional end‐of‐study guess method poorly reflects the sensitivity of participants to stimulation, and may not be a valid method of assessing sham blinding.

The object of this study was to clarify how the motor imagery of foot muscle relaxation influences corticospinal excitability for the ipsilateral hand. Twelve participants volitionally relaxed their right foot from a dorsiflexed position (actual relaxation), or imaged the same movement (imagery relaxation) in response to an auditory cue. Transcranial magnetic stimulation (TMS) was delivered to the hand area of the left primary motor cortex at different time intervals after an auditory cue. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). MEP amplitudes of ECR and FCR caused by single-pulse TMS temporarily decreased during both actual relaxation and imagery relaxation as compared with those of the resting control. A correlation of MEP amplitude between actual relaxation and imagery relaxation was observed. Our findings indicate that motor imagery of muscle relaxation of the foot induced a reduction of corticospinal excitability in the ipsilateral hand muscles. This effect is likely produced via the same mechanism that functions during actual muscle relaxation.

Background Despite recent developments in navigation and modeling techniques, the type and location of the structures that are activated by transcranial magnetic stimulation (TMS) remain unknown. Objective We studied the relationships between electrophysiological measurements and electric fields induced in the brain to locate the TMS activation site. Methods The active and resting motor thresholds of the first dorsal interosseous muscle were recorded in 19 subjects (7 female, 12 male, age 22 ± 4 years) using anteromedially oriented monophasic TMS at multiple locations over the left primary motor cortex (M1). Structural MR images were used to construct electric field models of each subject's head and brain. The cortical activation site was estimated by finding where the calculated electric fields best explained the coil-location dependency of the measured MTs. Results The experiments and modeling showed individual variations both in the measured motor thresholds (MTs) and in the computed electric fields. When the TMS coil was moved on the scalp, the calculated electric fields in the hand knob region were shown to vary consistently with the measured MTs. Group-level analysis indicated that the electric fields were significantly correlated with the measured MTs. The strongest correlations ( R 2 = 0.69), which indicated the most likely activation site, were found in the ventral and lateral part of the hand knob. The site was independent of voluntary contractions of the target muscle. Conclusion The study showed that TMS combined with personalized electric field modeling can be used for high-resolution mapping of the motor cortex.

Motor commands for the arms and hands generally originate in contralateral motor cortex anatomically. However, ipsilateral primary motor cortex shows activity related to arm movement despite the lack of direct connections. The extent to which the activity related to ipsilateral movement is independent from that related to contralateral movement is unclear based on conflicting conclusions in prior work. Here we present the results of bilateral arm and hand movement tasks completed by two human subjects with intracortical microelectrode arrays implanted in left primary motor cortex for a clinical brain-computer interface study. Neural activity was recorded while they attempted to perform arm and hand movements in a virtual environment. This enabled us to quantify the strength and independence of motor cortical activity related to continuous movements of each arm. We also investigated the subjects’ ability to control both arms through a brain-computer interface system. Through a number of experiments, we found that ipsilateral arm movement was represented independently of, but more weakly than, contralateral arm movement. However, the representation of grasping was correlated between the two hands. This difference between hand and arm representation was unexpected, and poses new questions about the different ways primary motor cortex controls hands and arms.

BackgroundVariable effects limit the efficacy of transcranial direct current stimulation (tDCS) as a research and therapeutic tool. Conventional application of a fixed-dose of tDCS does not account for inter-individual differences in anatomy (e.g. skull thickness), which varies the amount of current reaching the brain. Individualised dose-control may reduce the variable effects of tDCS by reducing variability in electric field intensities at a cortical target site.ObjectiveTo characterise the variability in electric field intensity at a cortical site (left primary motor cortex; M1) and throughout the brain for conventional fixed-dose tDCS, and individualised dose-controlled tDCS.MethodsThe intensity and distribution of the electric field during tDCS was estimated using Realistic Volumetric Approach to Simulate Transcranial Electric Stimulation (ROAST) in 50 individual brain scans taken from the Human Connectome Project, for fixed-dose tDCS (1mA & 2mA) and individualised dose-controlled tDCS targeting left M1.ResultsWith a fixed-dose (1mA & 2mA), E-field intensity in left M1 varied by more than 100% across individuals, with substantial variation observed throughout the brain as well. Individualised dose-controlled ensured the same E-field intensity was delivered to left M1 in all individuals. Its variance in other regions of interest (right M1 and area underneath the electrodes) was comparable with fixed- and individualised-dose.ConclusionsIndividualized dose-control can eliminate the variance in electric field intensities at a cortical target site. Assuming that the current delivered to the brain directly determines its physiological and behavioural consequences, this approach may allow for reducing the known variability of tDCS effects.

BackgroundThe sense of touch is a key component of motor function. Severe spinal cord injury (SCI) should essentially eliminate sensory information transmission to the brain, that originates from skin innervated from below the lesion. We assessed the hypothesis that, following SCI, residual hand sensory information is transmitted to the brain, can be decoded amongst competing sensorimotor signals, and used to enhance the sense of touch via an intracortically controlled closed-loop brain-computer interface (BCI) system.MethodsExperiments were performed with a participant who has an AIS-A C5 SCI and an intracortical recording array implanted in left primary motor cortex (M1). Sensory stimulation and standard clinical sensorimotor functional assessments were used throughout a series of several mechanistic experiments.FindingsOur results demonstrate that residual afferent hand sensory signals surprisingly reach human primary motor cortex and can be simultaneously demultiplexed from ongoing efferent motor intention, enabling closed-loop sensory feedback during brain-computer interface (BCI) operation. The closed-loop sensory feedback system was able to detect residual sensory signals from up to the C8 spinal level. Using the closed-loop sensory feedback system enabled significantly enhanced object touch detection, sense of agency, movement speed, and other sensorimotor functions.InterpretationTo our knowledge, this is the first demonstration of simultaneously decoding multiplexed afferent and efferent activity from human cortex to control multiple assistive devices, constituting a ‘sensorimotor demultiplexing’ BCI. Overall, our results support the hypothesis that sub-perceptual neural signals can be decoded reliably and transformed to conscious perception, significantly augmenting function.FundingInternal funding was provided for this study from Battelle Memorial Institute and The Ohio State University Center for Neuromodulation.

To investigate effectiveness of two different high-frequency repetitive transcranial magnetic stimulation (rTMS) protocols on pain, fatigue, quality of life (QoL) and depression in female patients with fibromyalgia.Thirty patients were randomized into three groups. Fifteen sessions of 10 Hz (90% resting motor threshold-RMT, 1200 pulses) rTMS were applied to left primary motor cortex and left dorsolateral prefrontal cortex (DLPFC) in Group M1 (n:10) and Group DLPFC (n:10), respectively. Group sham (n = 10) received 15 sessions of sham rTMS over 3 weeks. Visual Analogue Scale, Fibromyalgia Impact Questionnaire, Fatigue Severity Scale, Short-form 36, and Beck Depression Inventory were assessed at baseline and at the end of the treatments by a blinded-experienced assessor.Significant improvements in pain, QoL, and depression scores were observed in three groups. However, improvements in depression, physical functioning, physical role functioning, and general health perceptions were greater in active rTMS groups than in sham group. Emotional role functioning was only improved in Group M1. The decrease in VAS scores was significantly greater in Group M1 when compared to sham group. Change in physical role functioning was significantly greater in Group DLPFC than in Group M1.Significant improvements in physical role functioning, physical functioning, depression, and general health perceptions were achieved in active rTMS groups. Further clinical studies on larger samples involving both sexes with longer follow-up durations are needed.

Contains fulltext : 159172.pdf (Publisher’s version ) (Closed access) Threat demands fast and adaptive reactions that are manifested at the physiological, behavioral, and phenomenological level and are responsive to the direction of threat and its severity for the individual. Here, we investigated the effects of threat directed toward or away from the observer on motor corticospinal excitability and explicit recognition. Sixteen healthy right-handed volunteers completed a transcranial magnetic stimulation (TMS) task and a separate three-alternative forced-choice emotion recognition task. Single-pulse TMS to the left primary motor cortex was applied to measure motor evoked potentials from the right abductor pollicis brevis in response to dynamic angry, fearful, and neutral bodily expressions with blurred faces directed toward or away from the observer. Results showed that motor corticospinal excitability increased independent of direction of anger compared with fear and neutral. In contrast, anger was better recognized when directed toward the observer compared with when directed away from the observer, while the opposite pattern was found for fear. The present results provide evidence for the differential effects of threat direction on explicit recognition and motor corticospinal excitability. In the face of threat, motor corticospinal excitability increases independently of the direction of anger, indicative of the importance of more automatic reactions to threat. 10 p.

Navigated transcranial magnetic stimulation (TMS) in combination with electromyography (EMG) recordings can be used to map the brain regions in which TMS evokes motor-evoked potentials (MEPs) in certain muscles. Navigated TMS (nTMS) is used increasingly to identify the functional motor area of different muscles for clinical applications, including neurosurgical planning. However, the accuracy of TMS-based mapping of functional motor areas may depend on the TMS-induced current direction due to anisotropic cortical morphology, complicating association of the functional motor maps with neuroanatomical structures. Furthermore, it is not clear how well nTMS can distinguish nearby muscle representations on the cortical surface. We therefore investigated the functional motor maps obtained with posterior-to-anterior (PA) and lateral-to-medial (LM) TMS-induced currents within a spatially defined area by stimulating targets in a grid of locations over the left primary motor cortex in 8 healthy participants. Results were compared to functional MRI (fMRI) activation maps obtained using a voluntary opposing thumb movement task. We found that TMS applied with PA-induced currents identifies a motor area that is located significantly more anterior (8.7 – 10.4 mm depending on the muscle) with respect to an MEP motor area identified using LM-induced currents for the same muscle. Motor maps obtained with LM-induced currents show more overlap with the motor map identified using fMRI compared to PA-induced currents. In conclusion, the spatial representation of the MEP motor map identified by TMS is dependent on the direction of the induced current. These findings suggest that the application of nTMS using an LM-induced current direction corresponds best with the hand motor area as measured with fMRI.

Motor preparation involves inhibitory and excitatory processes that influence the scaling and efficiency of movement. Understanding the modulation of these processes when predictability is altered can provide insight as to how individuals prepare for temporally-urgent scenarios where the lower limbs are engaged. This study aimed to determine the influence of task predictability on preparatory corticospinal excitability during a 3 s foreperiod. It was hypothesized that during preparation for an unpredictable choice (go/no-go) reaction time task, corticospinal excitability would be facilitated compared to the responses measured for the predictable (simple) reaction time task. Twenty-eight healthy young adults participated in two reaction time tasks (predictable and unpredictable) using a go/no-go paradigm. During the foreperiod, transcranial magnetic stimulation was applied over the left primary motor cortex to elicit a motor-evoked potential in the right tibialis anterior muscle. Task predictability had a significant effect on corticospinal excitability when controlling for task order [F(1,25) = 7.124, p = 0.013], with the unpredictable task augmenting corticospinal excitability to a greater extent than the predictable task. When the predictable condition was performed first, MEP amplitude was 109.2 ± 14.3% of baseline for the predictable task and 124.0 ± 15.4% for the unpredictable task. In contrast, when the unpredictable condition was performed first, MEP amplitude was 119.5 ± 14.4% for the unpredictable task and 126.6 ± 10.1% for the predictable task. These results suggest that unpredictability may require individuals to have a heightened attention to incoming stimuli, thereby increasing corticospinal excitability, which can be maintained in subsequent predictable scenarios.

Objective The aim of the present study was to investigate the effect of the transcranial direct current stimulation (tDCS) on motor cortex excitability in healthy children and adolescents. Methods We applied 1 mA anodal or cathodal tDCS for 10 min on the left primary motor cortex of 19 healthy children and adolescents (mean age 13.9 ± 0.4 years). In order to prove whether the effects of tDCS may be attributed to the stimulation intensity, 10 children and adolescents were studied again using 0.5 mA anodal and cathodal tDCS. Sham stimulation was used as a control. Results Compared with sham stimulation, both 1 mA anodal and cathodal tDCS resulted in a significant increase of Motor evoked potentials (MEP) amplitudes which remained to be prominent even one hour after the end of stimulation. Interestingly, the 0.5 mA cathodal tDCS decreased cortico-spinal excitability whereas the 0.5 mA anodal stimulation did not result in any effect. Conclusion For the first time, the study demonstrates age-specific influences of tDCS on cortical excitability of the primary motor cortex. Significance Thus, the stimulation protocols of the tDCS have to be optimized according to age by planning studies in pediatric population.

Action observation has been suggested to be an effective adjunct to physical practice in motor (re)learning settings. However, optimal viewing conditions for interventions are yet to be established. Single-pulse transcranial magnetic stimulation (TMS) was used to investigate the effect of two different screen positions and participants’ screen position viewing preference on the amplitude of motor evoked potentials (MEPs) during observation of a ball pinch action. Twenty-four participants observed four blocked conditions that contained either a dynamic index finger-thumb ball pinch or a static hand holding a ball in a similar position on a horizontally or vertically positioned screen. TMS was delivered to the hand representation of the left primary motor cortex and MEPs were recorded from the first dorsal interosseous muscle of the right hand. Initial analysis of the normalized MEP amplitude data showed no significant differences between conditions. In a follow-up procedure, participants engaged in individual semi-structured interviews and completed a questionnaire designed to assess viewing affect and screen position viewing preference. The MEP data were subsequently split by screen position preference and re-analyzed using a 2 × 2 repeated measures ANOVA. Main effects indicated that participants who preferred the horizontal screen position (n = 16) demonstrated significantly greater MEP amplitudes during observation of the ball-pinch action compared to the static hand condition irrespective of screen position, and during the horizontal compared to the vertical screen position irrespective of video type. These results suggest that ensuring anatomical and perceptual congruency with the physical task, alongside consideration of participants’ screen position viewing preferences, may be an important part of optimizing action observation interventions.

Patients with supernumerary phantom limb report experiencing an additional limb duplicating its physical counterpart, usually following a stroke with sensorimotor disturbances. Here, we report a short‐lasting case of a right upper supernumerary phantom limb with unusual visuomotor features in a healthy participant during a pure Jacksonian motor seizure unexpectedly induced by continuous Theta‐Burst Stimulation over the left primary motor cortex. Electromyographic correlates of the event followed the phenomenological pattern of sudden appearance and brutal dissolution of the phantom, adding credit to the hypothesis that supernumerary phantom limb results from a dynamic resolution of conflictual multimodal information.

Previous behavioral and neuroimaging studies have suggested that the motor properties associated with graspable objects may be automatically accessed when people passively view these objects. We directly tested this by measuring the excitability of the motor pathway when participants viewed pictures of graspable objects that were presented during the attentional blink (AB), when items frequently go undetected. Participants had to identify two briefly presented objects separated by either a short or long SOA. Motor-evoked potentials were measured from the right hand in response to a single TMS pulse delivered over the left primary motor cortex 250 msec after the onset of the second target. Behavioral results showed poorer identification of objects at short SOA compared with long SOA, consistent with an AB, which did not differ between graspable and nongraspable objects. However, motor-evoked potentials measured during the AB were significantly higher for graspable objects than for nongraspable objects, irrespective of whether the object was successfully identified or undetected. This provides direct evidence that the motor system is automatically activated during visual processing of objects that afford a motor action.

Bimanual visuomotor movement training (BMT) enhances the excitability of human preparatory premotor and primary motor (M1) cortices compared to unimanual movement. This occurs when BMT involves mirror symmetrical movements of both upper-limbs (in-phase) but not with non-symmetrical movements (anti-phase). The neural mechanisms mediating the effect of BMT is unclear, but may involve interhemispheric connections between homologous M1 representations as well as the dorsal premotor cortices (PMd). The purpose of this study is to assess how intermittent theta burst stimulation (iTBS) of the left PMd affects left M1 excitability, and the possible combined effects of iTBS to left PMd applied before a single session of BMT. Left M1 excitability was quantified using transcranial magnetic stimulation (TMS) in terms of both the amplitudes and spatial extent of motor evoked potentials (MEPs) for the extensor carpi radialis (ECR) before and multiple time points following (1) BMT, (2) iTBS to left PMd or (3) iTBS to left PMd and BMT. Although there was not a greater increase in either specific measure of M1 excitability due to the combination of the interventions, iTBS applied before BMT showed that both the spatial extent and global MEP amplitude for the ECR became larger in parallel, whereas the spatial extent was enhanced with BMT alone and global MEP amplitude was enhanced with iTBS to left PMd alone. These results suggest that the modulation of rapid functional M1 excitability associated with BMT and iTBS of the left PMd could operate under related early markers of neuro-plastic mechanisms, which may be expressed in concurrent and distinct patterns of M1 excitability. Critically, this work may guide rehabilitation training and stimulation techniques that modulate cortical excitability after brain injury.

Background Evidence from recent clinical trials suggests that transcranial direct current stimulation (tDCS) may have potential in treating neuropsychiatric disorders. However, the optimal frequency at which tDCS sessions should be administered is unknown. Objective/Hypothesis This study investigated the effects of daily or second daily tDCS sessions on motor cortical excitability, over a 5-day period. Methods Twelve healthy volunteers received daily or second daily sessions of tDCS to the left primary motor cortex over the study period, in a randomized, intraindividual crossover design. Motor cortical excitability was assessed before and after tDCS at each session through responses to transcranial magnetic stimulation. Results Over a fixed 5-day period, tDCS induced greater increases in MEP amplitude when given daily rather than second daily. Analyses showed that this difference reflected greater cumulative effects between sessions rather than a greater response to each individual tDCS session. Conclusions These results demonstrate that in the motor cortex of healthy volunteers, tDCS alters cortical excitability more effectively when given daily rather than second daily over a 5-day period.

Currently, Granger-Geweke causality models have been widely applied to investigate the dynamic direction relationships among brain regions. In a previous study, we have found that the right hand finger-tapping task can produce relatively reliable brain response. As an extension of our previous study, we developed an algorithm based on the classical Granger- Geweke causality model to further investigate the effective connectivity of three brain regions (left primary motor cortex (M1), supplementary motor area (SMA) and right cerebellum) that showed the most robust brain activations. Our computational results not only confirm the strong linear feedback among SMA, M1 and right cerebellum, but also demonstrate that M1 is the hub of these three regions indicated by the anatomy research. Moreover, the model predicts the high intermediate node density existing in the area between SMA and M1, which will stimulate the imaging experimentalists to carry out new experiments to validate this postulation.

Mirror therapy is one of the promising rehabilitation therapeutic interventions but the neural basis of the therapeutic effect remains unknown. It has been reported that the 20-Hz rhythmic activity is induced in the primary motor cortex after median nerve stimulation and the amount of the induced activity is decreased when the primary motor cortex is activated. In the present study, to elucidate the neural mechanisms underlying mirror therapy, we investigated whether the mirror reflection of a hand holding a pencil modulates the stimulus-induced 20-Hz activity. Neuromagnetic brain activities were recorded from 11 healthy right-handed subjects while they were viewing their hand holding a pencil or its mirror reflection. The right median nerve was stimulated and the stimulus-induced 20-Hz activity over the left rolandic cortex dominantly innervating right-hand movements was quantified. The stimulus-induced 20-Hz activity was strongly suppressed when subjects viewed the right hand holding a pencil or the mirror reflection of the left hand looking like the right hand holding a pencil, compared with when subjects viewed the left hand holding a pencil or the mirror reflection of the right hand looking like the left hand holding a pencil. These results suggest that the human left primary motor cortex is strongly activated when the subjects view not only the right hand holding a pencil but also the mirror reflection of the left hand looking like the right hand holding a pencil. This may be one of the neural mechanisms responsible for the therapeutic effect of mirror therapy.

Fearful facial expressions are danger signals that rapidly trigger a cascade of neurobiological processes defensibly associated with action preparation. However, direct evidence for the activating effects of fearful facial expressions on the motor system is absent. The current transcranial magnetic stimulation (TMS) study investigated whether fearful facial expressions selectively increase corticospinal motor tract (CST) excitability. Focal TMS was applied over the left primary motor cortex during the exposure of fearful, happy, and neutral facial expressions in 12 healthy right-handed volunteers. Changes in CST excitability using the motor evoked potential (MEP) were recorded. Results showed significant selective increases in MEP to fearful facial expressions. These findings provide the first direct evidence for selective increases in CST excitability to threat and contribute to evolutionary views on emotion and action preparedness.

Transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) exhibit considerable trial-to-trial variability, potentially reducing the sensitivity and reproducibility of this measure. While increasing the number of trials will improve accuracy, prolonged recording blocks are not always feasible. In this study, we investigated the minimum number of trials required to provide a measure of human corticospinal excitability that is stable both within and between sessions. Single-pulse TMS was applied to the left primary motor cortex, and MEPs were recorded from the right first dorsal interosseous muscle. Approximately 20-30 trials were required to provide a stable measure of MEP amplitude with high within- and between-session reliability. Extending the number of trials beyond 30 provided no additional benefit. Collecting 30 trials may be optimal for reliably estimating corticospinal excitability using TMS. These findings may have significant implications for using TMS to measure corticospinal excitability in both basic and clinical research settings. Refereed/Peer-reviewed

A non-invasive DC electroencephalographic (DC-EEG) method was developed to record and analyze focal low-frequency (

Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions.

In the present study, we used transcranial magnetic stimulation (TMS) to investigate the changes in the excitability of the left primary motor cortex (M1) innervating the hand muscles and in short-interval intracortical inhibition (SICI) during speech describing hand or leg movements. In experiment 1, we investigated the effects of the contents of speech on the amplitude of the motor evoked potentials (MEPs) induced during reading aloud and silent reading. In experiment 2, we repeated experiment 1 with an additional condition, the non-vocal oral movement (No-Voc OM) condition, and investigated the change in SICI induced in each condition using the paired TMS paradigm. The MEP observed in the reading aloud and No-Voc OM conditions exhibited significantly greater amplitudes than those seen in the silent reading conditions, irrespective of the content of the sentences spoken by the subjects or the timing of the TMS. There were no significant differences in SICI between the experimental conditions. Our findings suggest that the increased excitability of the left M1 hand area detected during speech was mainly caused by speech-related oral movements and the activation of language processing-related brain functions. The increased left M1 excitability was probably also mediated by neural mechanisms other than reduced SICI; i.e., disinhibition.

We present a patient with a low-grade glioma restricted to the ‘face area’ of the left primary motor cortex. Little is known about functional consequences of surgery within this specific part of the brain. After surgery there were only mild and transient deficits. We suggest that original functions had already reorganized to direct perilesional areas.

Repetitive transcranial magnetic stimulation (rTMS) affects cortical excitability according to the frequency of stimulation. Few data are available on the influence of rTMS applied over the primary motor cortex (M1) on motor performances in healthy volunteers. The aim of this study was to determine, through kinematic analysis, whether rTMS over the left M1 changes initiation and performance of movement executed with the contralateral arm. Nine healthy males completed a set of motor tasks, consisting of a single-joint rapid movement between two objects performed under three different behavioral conditions (self-initiated; externally triggered known, during which the subject could see where the target was positioned in advance; externally triggered unknown, during which the subject could not see where the target was positioned until he reached it). The tasks were performed in a randomized order in three different sessions, with a seven-day interval between each session: (1) without stimulation (baseline); (2) immediately after 1-Hz rTMS; (3) immediately after 10-Hz rTMS. We measured reaction time, movement time, calculated as the sum of the time taken to reach the target from movement onset (T1) and that taken to reach the target to movement termination (T2), acceleration and deceleration time on the velocity profile, as well as the ratio between them, and maximum speed and maximum acceleration. Reaction time, movement time, and T2 significantly increased after 1-Hz rTMS and decreased after 10-Hz rTMS, while the other parameters remained unchanged. Our results suggest that rTMS may modify both initiation and performance of a voluntary movement.

Increasing evidences show that the linguistic representation of motor activities induces simulative processes that involve motor neural systems normally engaged in actual execution of movements. However, other researches suggest that the motor cortex is not an integral part of the network for action-word representation but is recruited only to execute tasks that critically require the retrieval of sensorimotor attributes associated with words. In order to enlighten this controversial literature, three groups of healthy participants were submitted to transcranial direct current stimulation (tDCS) (cathodal, anodal and sham stimulations) of the left primary motor cortex during the execution of a picture recognition task. Results show that cathodal stimulation improves the participants' ability to detect either mismatching motor vs. no motor sentence-drawing associations, while no significant difference has not been reported for compatible associations. The current result is in line with the suggestion that motor regions play a critical role in detecting dissonant outcomes.

We report on a patient with a meningioma whose hand motor function appeared to be reorganized mainly into the face somatotopy of the primary motor cortex (M1) following meningioma removal, using functional RMI (fMRI). A 76-year-old right-handed woman showed leukomalactic lesions in the left fronto-parietal lobes and subcortical white matter, including the upper portion of the precentral knob after meningioma removal. She recovered motor function to the point that she was able to extend the affected fingers against gravity at 6 weeks and extend the affected fingers against resistance at 12 weeks. The right primary sensori-motor cortex centered on the precentral knob was activated during movement of the unaffected (left) hand. By contrast, the face somatotopy and inferior portion of the precentral knob of the left primary motor cortex were activated during movement of the right hand. Peak activations were present at the left face somatotopy of the primary motor cortex during movement of the right hand and the right precentral knob during movement of the left hand. Motor function of the affected hand appeared to be reorganized mainly into the face somatotopy of the primary motor cortex and partially into the lower portion of the precentral knob after meningioma removal.

The purpose of the present study was to investigate the effect of the repetition rate of a simple movement on the magnitude of neuronal recruitment at maximal effort in humans. Nine right-handed healthy subjects [age: 27.4 +/- 4.8 yr, stature: 174.5 +/- 12.2 cm, body-weight 74.3 +/- 16.6 kg (Mean +/- SD)] participated in this study. We measured the regional cerebral hemodynamics using 24-channel near infrared spectroscopy (NIRS). An auditory-cued, repetitive flexion movement of the right index finger against a button was performed as the finger-tapping task at maximal effort (ME), at 25% of maximal effort (25% ME) and at 50% of maximal effort (50% ME). The increase of the left primary motor cortex hemodynamics during movement relative to the hemodynamics under the resting condition was calculated for each pair of movement conditions. The frequency of finger-tapping was 1.61 +/- 0.18 Hz (25% ME trial), 3.23 +/- 0.36 Hz (50% ME trial), and 6.46 +/- 0.72 Hz (ME trial). The left primary motor cortex showed significant activation under all conditions. The change in total hemoglobin ([tHb]) between the ME trial and the resting value (1.19 +/- 0.93 mmol.mm) was significantly higher than those between the resting value and the 25% ME trial (0.04 +/- 0.04 mmol.mm) or the 50% ME trial (0.08 +/- 0.11 mmol x mm) (p < 0.05). There was a 29.8-fold increase of the [tHb] value between the 50% ME trial and the ME trial, but only a 2-fold increase of the [tHb] value between the 25% ME trial and the 50% ME trial. These results demonstrated that the rate of change in regional cerebral hemoglobin at a maximal effort finger-tapping task was much higher than that at a low frequency finger-tapping task.

We used transcranial magnetic stimulation (TMS) in combination with positron emission tomography (PET) to investigate the effective connectivity of four cortical regions within the same study. By employing [17F]-[CH3F] ([17F]-fluoromethane) as a radiotracer of blood-flow, we were able to obtain increased sensitivity compared to [15O]-H2O for both cortical and subcortical structures. The brain areas investigated were left primary motor cortex, right primary visual cortex, and left and right prefrontal areas. We found that each site of stimulation yielded a different pattern of activation/deactivation consistent with its anatomical connectivity. Moreover, we found that TMS of prefrontal and motor cortical areas gave rise to trans-synaptic activation of subcortical circuits.

Independent use of both hands is characteristic of human action in daily life. By nature, however, in-phase bimanual movements, for example clapping, are easier to accomplish than anti-phase movements, for example playing the piano. It is commonly agreed that interhemispheric interactions play a central role in the coordination of bimanual movements. However, the spatial, temporal, and physiological properties of the interhemispheric signals that coordinate different modes of bimanual movements are still not completely understood. More precisely, do individual interhemispheric connectivity parameters have behavioral relevance for bimanual rapid anti-phase coordination? To address this question, we measured movement-related interhemispheric interactions, i.e., inhibition and facilitation, and correlated them with the performance during bimanual coordination. We found that movement-related facilitation from right premotor to left primary motor cortex (rPMd-lM1) predicted performance in anti-phase bimanual movements. It is of note that only fast facilitation during the preparatory period of a movement was associated with success in anti-phase movements. Modulation of right to left primary motor interaction (rM1-lM1) was not related to anti-phase but predicted bimanual in-phase and unimanual behavior. These data suggest that strictly timed modulation of interhemispheric rPMd-lM1 connectivity is essential for independent high-frequency use of both hands. The rM1-lM1 results indicate that adjustment of connectivity between homologous M1 may be important for the regulation of homologous muscle synergies.

Brain activities of three subjects performing a right-hand tapping task were measured by near-infrared spec-troscopy (NIRS). In experiments, the hemoglobin concentration change in the subjects’ brains while they learned a new movement was analyzed. The results of these tests show that the channels covering the left primary motor cortex recorded a decreasing tendency in oxyHb when the subjects were repeating the tapping task. In contrast, the channels covering the supplementary motor cortex recorded an increasing tendency of oxyHb. Thease results suggest that the functional load on the brain decreases and the brain’s active domain changes during motor learning.

Pathways of the human mirror neuron system are activated during both, action observation and action execution, including lateralized activation of respective areas, as shown by observed right-or left-hand actions. Here, we investigated whether execution-dependent motor cortex excitability is affected by prior interaction between transcranial random noise stimulation (tRNS) and action observation. Sham or real tRNS (1 mA) was applied for 10-minute over the left primary motor cortex during action observation. In the main experiments, participants received sham or real tRNS while they watched a video showing repeated tapping tasks, involving either the right-hand (experiment 1, congruent action observation), or a mirror-reversed video showing the same performance (experiment 2), followed by action execution of the right-hand. In control experiments 1-3, participants received real tRNS while observing a perceptual sequence, watching a landscape picture, or observing the left-hand performing the action (the sequence was identical to experiment 1), followed by action execution of the right-hand. In control experiment 4, participants received real tRNS during congruent action observation, and then took 6-min rest. Motor-evoked potentials (MEP) were recorded before action observation, a perceptual sequence or a landscape picture, immediately after, and after action execution, or an interval of 6-min, dependent on the respective experimental condition. MEPs in the right first dorsal interosseous muscle increased significantly after real tRNS combined with congruent action observation, and after action execution compared to the sham session in experiment 1 and control experiments. We conclude that prior interaction between real tRNS and action observation of mirror-matched movements modulates subsequent execution-dependent motor cortex excitability.