Cortical Muscle Representations Research Articles

Precise motor mapping with transcranial magnetic stimulation.

We describe a routine to precisely localize cortical muscle representations within the primary motor cortex with transcranial magnetic stimulation (TMS) based on the functional relation between induced electric fields at the cortical level and peripheral muscle activation (motor-evoked potentials; MEPs). Besides providing insights into structure-function relationships, this routine lays the foundation for TMS dosing metrics based on subject-specific cortical electric field thresholds. MEPs for different coil positions and orientations are combined with electric field modeling, exploiting the causal nature of neuronal activation to pinpoint the cortical origin of the MEPs. This involves constructing an individual head model using magnetic resonance imaging, recording MEPs via electromyography during TMS and computing the induced electric fields with numerical modeling. The cortical muscle representations are determined by relating the TMS-induced electric fields to the MEP amplitudes. Subsequently, the coil position to optimally stimulate the origin of the identified cortical MEP can be determined by numerical modeling. The protocol requires 2 h of manual preparation, 10 h for the automated head model construction, one TMS session lasting 2 h, 12 h of computational postprocessing and an optional second TMS session lasting 30 min. A basic level of computer science expertise and standard TMS neuronavigation equipment suffices to perform the protocol.

The role of overlap and distribution of robotic TMS motor maps in children's hand function

Abstract Introduction: Robotic transcranial magnetic stimulation (TMS) can be used to map individual hand muscles in primary motor cortex (M1). Distribution and overlap of such cortical representations are unknown in children. We quantified Jaccard Overlap (JO) (map similarity/overlap) and Earth Mover’s Distance (EMD) (map dissimilarity/distribution) of hand muscle representations to explore motor map organization and associations with function. Methods: Typically developing, right-handed children received bilateral neuronavigated robotic TMS motor mapping. A 12x12 grid (7mm spacing) was placed over the hand knob of left and right M1. Four TMS pulses were delivered per grid-point. Motor evoked potentials from the primary muscle (first dorsal interosseous, FDI), created 2D/3D maps that were compared to abductor pollicus brevis (APB), abductor digiti minimi (ADM) and wrist extensor (WEX). JO and EMD for each were evaluated within and between hemispheres using Friedman ANOVAs and Wilcoxon Tests. Associations between map metrics and motor performance (Purdue Pegboard Task, PPT) were explored with Spearman correlations. Results: Maps were obtainable and well tolerated in all 24 participants (12-18 years old, 50% female). JO and EMD were comparable between hemispheres. EMD within each hemisphere differed with anatomically approximated muscles exhibiting higher map JO and lower EMD. Within each hemisphere, cortical representation JO differed between muscle pairs. Differences in JO and EMD were greater in the dominant hemisphere. Left hemisphere JO FDI-APB correlated with right hand PPT scores. EMD and JO in the right hemisphere did not correlate with left hand motor performance. Conclusion: JO and EMD of hand muscle cortical representations may be useful measures for investigating M1 physiology and plasticity. Comparable JO and EMD between right and left hands suggest symmetrical hemispheric motor organization in healthy children. Keywords: Robotic Transcranial Magnetic Stimulation (TMS), Motor Mapping, Motor Performance, Pediatrics

Efficient high-resolution TMS mapping of the human motor cortex by nonlinear regression

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field.Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modeled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin.We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results.Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications.

Mapping of multiple muscles with transcranial magnetic stimulation: absolute and relative test-retest reliability.

The spatial accuracy of transcranial magnetic stimulation (TMS) may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here, we investigate the within‐limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid‐based sulcus‐informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5–10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI‐based analysis, we studied normalized MNI MCRs. For the reliability assessment, we calculated intraclass correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within‐limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We, thus, provide novel evidence that inter‐muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions.

Short-Interval Intracortical Facilitation Improves Efficacy in nTMS Motor Mapping of Lower Extremity Muscle Representations in Patients with Supra-Tentorial Brain Tumors.

Simple SummaryPresurgical motor mapping of cortical muscle representations by single-pulse navigated transcranial magnetic stimulation (sp-nTMS) is used to localize and enclose motor function in patients harboring motor-eloquent lesions. This study investigates paired-pulse nTMS (pp-nTMS) with biphasic pulses for motor mapping of lower extremity (lE) muscle representations, showing that significantly lower stimulation intensities are needed while reliable motor maps can be achieved even in the most demanding patient cases in whom conventionally used sp-nTMS fails. Thus, novel pp-nTMS with biphasic pulses may have potential to considerably facilitate improvements of currently used nTMS-based mapping procedures in the preoperative workup of neurooncological patients.Navigated transcranial magnetic stimulation (nTMS) is increasingly used for mapping of motor function prior to surgery in patients harboring motor-eloquent brain lesions. To date, single-pulse nTMS (sp-nTMS) has been predominantly used for this purpose, but novel paired-pulse nTMS (pp-nTMS) with biphasic pulse application has been made available recently. The purpose of this study was to systematically evaluate pp-nTMS with biphasic pulses in comparison to conventionally used sp-nTMS for preoperative motor mapping of lower extremity (lE) muscle representations. Thirty-nine patients (mean age: 56.3 ± 13.5 years, 69.2% males) harboring motor-eloquent brain lesions of different entity underwent motor mapping of lE muscle representations in lesion-affected hemispheres and nTMS-based tractography of the corticospinal tract (CST) using data from sp-nTMS and pp-nTMS with biphasic pulses, respectively. Compared to sp-nTMS, pp-nTMS enabled motor mapping with lower stimulation intensities (61.8 ± 13.8% versus 50.7 ± 11.6% of maximum stimulator output, p < 0.0001), and it provided reliable motor maps even in the most demanding cases where sp-nTMS failed (pp-nTMS was able to provide a motor map in five patients in whom sp-nTMS did not provide any motor-positive points, and pp-nTMS was the only modality to provide a motor map in one patient who also did not show motor-positive points during intraoperative stimulation). Fiber volumes of the tracked CST were slightly higher when motor maps of pp-nTMS were used, and CST tracking using pp-nTMS data was also possible in the five patients in whom sp-nTMS failed. In conclusion, application of pp-nTMS with biphasic pulses enables preoperative motor mapping of lE muscle representations even in the most challenging patients in whom the motor system is at high risk due to lesion location or resection.

Neck rotation modulates motor-evoked potential duration of proximal muscle cortical representations in healthy adults

Transcranial magnetic stimulation (TMS) produces motor-evoked potentials (MEP) used to infer changes in corticomotor excitability. In humans, neck rotation can probe reticulospinal input on corticomotor output. This study investigated the effect of neck rotation on MEP duration in a proximal and distal upper limb muscle and compared responses between rest and preactivation. Single-pulse TMS to motor cortex was used to evoke MEPs at two stimulus intensities in 18 healthy adults (20-40years). Surface electromyography recorded MEPs from the non-dominant biceps brachii (BB) and first dorsal interosseous (FDI). Participants were seated with the target muscle at rest or 10% preactivated, and head rotated ipsilateral, contralateral, or in neutral position. The primary outcome was MEP tail, defined as the mean difference in MEP duration between active and rest trials. Secondary outcomes were MEP duration and amplitude. MEP tail was modulated by neck rotation in the proximal BB (P = 0.03) but not distal FDI (P > 0.19), with shorter duration during ipsilateral or contralateral rotation relative to neutral. In a neutral neck position, MEP duration was prolonged by muscle preactivation and higher TMS intensities in the FDI and BB (P < 0.03). Neck rotation attenuated the prolongation of MEP duration during preactivation in the BB, but not the FDI. Neck rotation had no effect on MEP amplitude for either muscle (P > 0.05). Modulation of the late portion of the MEP by rotation of the neck could indicate subcortical projections to alpha-motoneuron pools are stronger in proximal than distal upper limb muscles. These findings may have relevance for using MEP duration as a neural biomarker in neurological diseases.

Issues of diagnostic and therapeutic use of transcranial magnetic stimulation in patients with writing cramp

To study diagnostic and therapeutic values of transcranial magnetic stimulation (TMS) in writing cramp (WC). Twelve right-handed patients with WC were enrolled in the study. All patients underwent low-frequency repetitive TMS (rTMS) of the premotor cortex of contralateral to affected hand hemisphere. The clinical efficacy was assessed using the Writer's Cramp Rating Scale (WCRS) and the Medical Outcomes Study-Short Form (MOS-SF-36). Before and after last rTMS session, motor mapping of Abductor pollicis brevis muscle (APB) was performed using navigated TMS (nTMS). Localization, area, and amplitude-weighted area of the APB muscle cortical representations were compared with the healthy controls. After the rTMS course, the dynamics of the studied parameters was assessed. Ten sessions of low-frequency rTMS of premotor cortex reduced the severity of WS clinical symptoms with a duration of effect of at least 1 month (p<0.05). There was no statistically significant difference between the area and the weighted area of cortical muscle representations between patients and healthy controls or in patients before and after rTMS. When assessing the localization of cortical muscle representations, two trends were noted: in 4 patients, the localization remained stable, with a shift in the center of gravity of less than 4 mm; in the other 8 patients, a shift in the center of mass of more than 5 mm was noted. No significant correlation between the stability of the cortical muscle representations (the magnitude of the shift in the center of gravity) and the improvement on the WCRS were found. The low-frequency rTMS of the premotor cortex of the contralateral to affected hand hemisphere can be used as an adjuvant therapy for WC. The TMS-motor mapping study did not show its diagnostic value.

Navigated TMS mapping using the grid-based algorithm to evaluate the reorganization of cortical muscle representation in amyotrophic lateral sclerosis

Introduction. Motor cortex mapping using navigated transcranial magnetic stimulation (TMS) is a promising method for assessing motor cortex reorganization in amyotrophic lateral sclerosis (ALS). The use of the grid-based algorithm allows the mapping protocol to be standardized and can help to reduce the variability of the assessed parameters. Study aim — to analyse the reorganization features of the cortical representations of hand muscles in patients with classical ALS using navigated TMS mapping with a grid-based algorithm. Materials and methods. The study included 14 patients with classical ALS and 9 healthy volunteers. Navigated TMS mapping of the cortical representations of the right abductor pollicis brevis (APB) muscle was performed using a predetermined grid (7×7 square cells) centred around a ‘hot spot’. Five stimuli with an intensity of 110% of the individual resting motor threshold (RMT) were randomly applied to each cell. The RMT and area of cortical representation of the APB muscle were analysed, amplitude or probability weighted. Results. Patients with ALS showed a statistically significant decrease in the weighted amplitude of the area of cortical representations of the APB muscle compared with healthy volunteers. The RMT, area and weighted probability area of the cortical representations of the APB muscle did not differ significantly between the groups. A statistically significant correlation between RMT and severity of dysfunction and upper motor neuron damage was found in patients with ALS, based on the clinical data. There were no statistically significant correlations between cortical representation parameters and the clinical symptoms in patients with ALS. Conclusion. Navigated TMS mapping of the motor cortex with a grid-based algorithm in patients with ALS revealed a decrease in the weighted amplitude of the cortical representation area of the APB muscle. It is important to clarify the role of navigated TMS mapping with the proposed algorithm in the diagnosis, prognosis and monitoring of ALS.

Time-Frequency Analysis of Motor-Evoked Potential in Patients with Stroke vs Healthy Subjects: a Transcranial Magnetic Stimulation Study

Conventional analysis of motor-evoked potential (MEP) is performed in time domain using amplitude and latency, which encapsulates information relevant to the cortical excitability of the brain. The study investigated the importance of time-frequency analysis by comparing MEPs in time-frequency domains (TFD) of healthy versus stroke survivors. Six healthy subjects and ten patients with stroke were enrolled. Single-pulse transcranial magnetic stimulation (TMS) at resting motor threshold (RMT) was given at extensor digitorum communis muscle cortical representation to obtain MEP. MEPs were obtained at resting motor threshold (100% RMT subjects and patients), supra-threshold range (100–170% RMT), and different voluntary contractions (100% RMT) to subjects. Fast Fourier transform and continuous wavelet transform (CWT) were used for analysis. Frequency spectrum showed 98% and 66% of signal power in 0–100 Hz for subjects and patients, respectively. Top 10, top 25, and top 50 percentile power of CWT were calculated for each MEP. Frequency spectrum of top 10 and top 25 percentile power of subjects were different (p < 0.05) and dispersed to 0–500 Hz for patients; both groups having a 40-Hz peak. Total power of MEP was found to be low (p < 0.05) in patients as compared to subjects and top 10, top 25, and top 50 percentile power showed decrease. Clinical scores—MAS and FM—were observed to be correlated to frequency and time-frequency features (p < 0.05). Frequency spectrum belonging top 10 percentile power of different level voluntary contractions showed statistical significance (p < 0.05). However, no significant differences were observed for MEPs at different supra-threshold intensities. Results suggest time-frequency analysis might provide objective ways to quantify TMS measures for stroke patients.

P79-F Disrupted muscle cortical representations in amyotrophic lateral sclerosis studied by navigated TMS mapping

Background The search for biomarkers in amyotrophic lateral sclerosis (ALS) can provide pathophysiological insights and is important for early diagnosis and monitoring of the disease progression. Mapping muscle cortical representations using navigated transcranial magnetic stimulation (nTMS) is a noninvasive method for probing corticospinal excitability. We aimed at studying nTMS map parameters as potential biomarkers in ALS. Methods We examined 12 ALS patients (4 women, age median 49, quartiles 40, 55) and 7 healthy controls (5 women, age median 37, quartiles 35, 41). Navigated TMS mapping was performed at the intensity of 110% of the resting motor threshold (RMT) with motor evoked potentials (MEPs) recorded from the abductor pollicis brevis muscle (APB). We used a 7 × 7 stimulation point grid, with 5 stimuli per cell in a pseudorandom order. We analyzed the RMT, the area of cells with at least one suprathreshold MEP, the area weighted by the probability of a suprathreshold MEP, and the area weighted by the mean MEP amplitude. Results The groups were not significantly different in age. The RMT was higher in ALS (p = 0.01, Mann-Whitney). Among the studied representation parameters, only the area weighted by the mean MEP amplitude showed a significant difference, with lower values in ALS patients than in controls (p = 0.02). Conclusions The results suggest that the extent of the APB motor representation in ALS patients is not significantly altered, whereas the excitability and amplitude-weighted area are reduced. Thus, it is important to study motor representation parameters other than the extent as potential ALS biomarkers. Funding RSF17-75-10062.

P21-T The influence of the navigated TMS mapping protocol on the accuracy of motor representation characteristics

Background Navigated transcranial magnetic stimulation enables noninvasive mapping of muscle cortical representations for research and clinical purposes. Several mapping protocols are in use, with no consensus regarding the optimal one and insufficient data about their influence on the mapping accuracy. We aimed to determine this influence for protocols that employ a stimulation point grid. Methods We mapped the abductor pollicis brevis muscle representations in 8 healthy volunteers (3 women, age median 28, quartiles 24, 29) three times on consecutive days. We used a 7 × 7 stimulation grid, with 10 stimuli per cell applied in a pseudorandom order at an intensity of 110% of the resting motor threshold. The grid size was chosen to cover on average 98% of the area of 121 representations previously mapped without grid. The studied parameters were the area of cells with mean motor evoked potential (MEP) amplitude above 50 μV, the area of cells with at least one (or 6) suprathreshold MEP, the area weighted by the mean amplitude (or the probability of suprathreshold MEP), and the location of the center of gravity. Results Parameter accuracy significantly increased with the number of stimuli. The area weighted by the probability of suprathreshold MEP had the highest accuracy and differed significantly between sessions in three subjects. Conclusions The obtained accuracy dependencies can guide the choice of a sufficient number of stimuli for a given problem, e.g. the detection of significant area changes between sessions in our dataset was possible with at least 7 stimuli per cell. Funding RSF17-75-10062.

Parallel modulation of interhemispheric inhibition and the size of a cortical hand muscle representation during active contraction.

Interhemispheric inhibition (IHI) between motor cortexes is thought to suppress unwanted mirror movements during voluntary behaviors and can be assessed using paired-pulse transcranial magnetic stimulation (TMS). The magnitude of IHI may be related to the size of the cortical representation for a given muscle as a mechanism for facilitating unimanual control. To date, the relationship between IHI and cortical muscle representations remains unknown. Fifteen healthy, right-handed individuals participated in the present study. IHI was examined in the right first dorsal interosseous (FDI) muscle by delivering conditioning TMS to ipsilateral (right) primary motor cortex (M1) followed by a test TMS pulse to contralateral (left) M1. The size of the FDI representation in M1 was determined by delivering suprathreshold TMS over a 5 × 5-cm grid centered on the FDI motor hotspot of the left M1. Both IHI and cortical territory were obtained during three conditions: rest, contralateral (right) FDI contraction, and ipsilateral (left) FDI contraction. Results indicate a significant association between IHI and the size of the FDI representation only in the context of contraction and not when the FDI muscle was relaxed. Specifically, reduced IHI corresponded to larger cortical FDI representations during both contralateral and ipsilateral contraction. These data demonstrate that, for a muscle of the hand, the magnitude of IHI and the cortical territory are associated within the context of muscle contraction. NEW & NOTEWORTHY This study provides evidence from noninvasive brain stimulation that communication between the motor cortexes of the two hemispheres plays a role in shaping the motor cortical map that outputs to a hand muscle during active contraction of that muscle. This relationship exists only when the hand muscle is contracted. The findings presented further our understanding of motor control during unilateral movement and may inform future research targeting clinical populations that exhibit impaired unilateral control.

Accuracy of Estimating the Area of Cortical Muscle Representations from TMS Mapping Data Using Voronoi Diagrams.

Motor evoked potentials (MEPs) caused by transcranial magnetic stimulation (TMS) provide a possibility of noninvasively mapping cortical muscle representations for clinical and research purposes. The interpretation of such results is complicated by the high variability in MEPs and the lack of a standard optimal mapping protocol. Comparing protocols requires the determination of the accuracy of estimated representation parameters (such as the area), which is problematic without ground truth data. We addressed this problem and obtained two main results: (1) the development of a bootstrapping-based approach for estimating the within-session variability and bias of representation parameters and (2) estimations of the area and amplitude-weighted area accuracies for motor representations using this approach. The method consists in the simulation of TMS mapping results by subsampling MEPs from a single map with a large number of stimuli. We studied the extensor digitorum communis (EDC) and flexor digitorum superficialis (FDS) muscle maps of 15 healthy subjects processed using Voronoi diagrams. We calculated the (decreasing) dependency of the errors in the area and weighted area on the number of stimuli. This result can be used to choose a number of stimuli sufficient for studying the effects of a given size (e.g., the protocol with 150 stimuli leads to relative errors of 7% for the area and 11% for the weighted area in 90% of the maps). The approach is applicable to other parameters (e.g., the center of gravity) and other map processing methods, such as spline interpolation.

Optimization of the Navigated TMS Mapping Algorithm for Accurate Estimation of Cortical Muscle Representation Characteristics.

Navigated transcranial magnetic stimulation (nTMS) mapping of cortical muscle representations allows noninvasive assessment of the state of a healthy or diseased motor system, and monitoring changes over time. These applications are hampered by the heterogeneity of existing mapping algorithms and the lack of detailed information about their accuracy. We aimed to find an optimal motor evoked potential (MEP) sampling scheme in the grid-based mapping algorithm in terms of the accuracy of muscle representation parameters. The abductor pollicis brevis (APB) muscles of eight healthy subjects were mapped three times on consecutive days using a seven-by-seven grid with ten stimuli per cell. The effect of the MEP variability on the parameter accuracy was assessed using bootstrapping. The accuracy of representation parameters increased with the number of stimuli without saturation up to at least ten stimuli per cell. The detailed sampling showed that the between-session representation area changes in the absence of interventions were significantly larger than the within-session fluctuations and thus could not be explained solely by the trial-to-trial variability of MEPs. The results demonstrate that the number of stimuli has no universally optimal value and must be chosen by balancing the accuracy requirements with the mapping time constraints in a given problem.

Human motor cortical organization is influenced by handedness

Although there is some evidence that handedness is associated with structural and functional differences in the motor cortex, findings remain inconclusive. Here, we evaluated whether handedness influences the location, size and overlap of the cortical representations of upper limb muscles across hemispheres in right- versus left-handed individuals. Using transcranial magnetic stimulation, the cortical representations of abductor pollicis brevis, flexor carpi radialis and biceps brachii muscles were mapped bilaterally with a 6 by 5 grid space. Results indicate that right-handers had more lateral and posterior representations in the non-dominant hemisphere as well as greater overall cortical territory compared to left-handers. Right- and left-handers did not differ in the extent of overlap between muscle representations. Our findings suggest that human motor cortical organization of upper limb muscles is indeed influenced by handedness, specifically with regard to the location of non-dominant cortical muscle representations and the size of cortical territory dedicated to upper limb muscle representations.

Diagnostic and therapeutic issues of using transcranial magnetic stimulation in patients with writer's cramp

To assess diagnostic and therapeutic values of transcranial magnetic stimulation (TMS) in patients with writer's cramp (WC). Twelve right-handed patients with WC were enrolled in the study. All patients underwent low-frequency repetitive TMS (rTMS) over the premotor cortex of the hemisphere contralateral to the affected hand. The clinical efficacy was assessed using the Writer's Cramp Rating Scale (WCRS) and the Medical Outcomes Study-Short Form (MOS-SF-36). Before and after the last rTMS session, motor mapping of abductor pollicis brevis muscle (APB) was performed using navigated TMS (nTMS). Localization, area, and amplitude-weighted area of the APB muscle cortical representations were compared with the healthy controls. The dynamics of the mentioned above parameters after the rTMS course was assessed. Ten sessions of low-frequency rTMS over premotor cortex reduced the severity of WC clinical symptoms, with a duration of effect of at least 1 month (p<0.05). There was no significant difference between the area and the weighted area of cortical muscle representations between patients and healthy controls or in patients before and after rTMS. When assessing the localization of cortical muscle representations, two trends were noted: in 4 patients, the localization remained stable, with a shift in the center of gravity of less than 4 mm; in the other 8 patients, a shift in the center of gravity of more than 5 mm was noted. No significant correlations between the stability of the cortical muscle representations (the magnitude of the shift in the center of gravity) and the improvement on the WCRS scale were found. The low-frequency rTMS over the premotor cortex of the hemisphere contralateral to the affected hand can be used as an adjuvant therapy for WC. The TMS-motor mapping study did not show its diagnostic value.

TMSmap - Software for Quantitative Analysis of TMS Mapping Results.

The use of the MRI-navigation system ensures accurate targeting of TMS. This, in turn, results in TMS motor mapping becoming a routinely used procedure in neuroscience and neurosurgery. However, currently, there is no standardized methodology for assessment of TMS motor-mapping results. Therefore, we developed TMSmap—free standalone graphical interface software for the quantitative analysis of the TMS motor mapping results (http://tmsmap.ru/). In addition to the estimation of standard parameters (such as the size of cortical muscle representation and the center of gravity location), it allows estimation of the volume of cortical representations, excitability profile of the cortical surface map, and the overlap between cortical representations. The input data for the software includes the coordinates of the coil position (or electric field maximum) and the corresponding response in each stimulation point. TMSmap has been developed for versatile assessment and comparison of TMS maps relating to different experimental interventions including, but not limited to longitudinal, pharmacological and clinical studies (e.g., stroke recovery). To illustrate the use of TMSmap we provide examples of the actual TMS motor-mapping analysis of two healthy subjects and one chronic stroke patient.

Efficient Mapping of the Motor Cortex with Navigated Biphasic Paired-Pulse Transcranial Magnetic Stimulation.

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate cortical muscle representations. Usually, single TMS pulses are targeted to the motor cortex with the help of neuronavigation and by measuring motor evoked potential (MEP) amplitudes from the peripheral muscles. The efficacy of single-pulse TMS to induce MEPs has been shown to increase by applying facilitatory paired-pulse TMS (ppTMS). Therefore, the aim was to study whether the facilitatory ppTMS could enable more efficient motor mapping. Biphasic single-pulse TMS and ppTMS with inter-stimulus intervals (ISIs) of 1.4 and 2.8ms were applied to measure resting motor thresholds (rMTs) as a percentage of the maximal stimulator output and to determine the cortical representation areas of the right first dorsal interosseous muscle in healthy volunteers. The areas, shapes, hotspots, and center of gravities (CoGs) of the representations were calculated. Biphasic ppTMS with ISI of 1.4ms resulted in lower rMTs than those obtained with the other protocols (p = 0.001). With ISI of 2.8ms, rMT was lower than with single-pulse TMS (p = 0.032). The ppTMS mapping was thus performed with lower intensity than when using single-pulse TMS. The areas, shapes, hotspots, and CoGs of the muscle representations were in agreement. Hence, biphasic ppTMS has potential in the mapping of cortical hand representations in healthy individuals as an alternative for single-pulses, but with lower stimulation intensity by utilizing cortical facilitatory mechanism. This could improve application of nTMS in subjects with low motor tract excitability.

Differentiation of motor evoked potentials elicited from multiple forearm muscles: An investigation with high-density surface electromyography

Transcranial magnetic stimulation (TMS) is a non-invasive method to measure corticospinal excitability of the primary motor cortex. However, motor evoked potentials (MEPs) elicited by TMS in a target muscle are variable; inconsistent MEPs may be due to overlapping cortical muscle representations and/or volume conduction from neighbouring muscles. The source of variable muscle responses may not be apparent using conventional bipolar electromyography (EMG), particularly over areas with several distinct neighbouring muscles (e.g. the forearm). High-density surface EMG (HDsEMG) may provide a useful means to investigate the underlying variability in amplitude and spatial distribution of MEPs. Here, we investigated the spatial distribution of MEPs in the forearm extensors using HDsEMG. HDsEMG consisted of a 16×5 grid of surface electrodes placed on the right (dominant) dorsal forearm over the extensor carpi radialis (ECR), ulnaris (ECU) and extensor digitorum communis finger extensors (EDC). MEP amplitude and distribution were recorded from 100 to 170% of resting (RMT) and active motor threshold (AMT). The distribution of MEPs was correlated to the activity recorded during selective, isometric contractions of the ECR, ECU, middle (EDC-D3) and ring (EDC-D4) finger extensors to determine the spatial distribution of MEPs in the forearm extensors. Although ECR was the hotspot, resting MEP spatial distribution was primarily correlated to that of EDC-D4 and ECU. With background ECR activation, the spatial distribution of MEPs correlated strongly with ECR. Further, while holding a background ECR contraction, EDC-D4 and ECU MEPs increased with greater stimulation intensity. Our results suggest that HDsEMG provides a useful way to differentiate which wrist extensor muscles are activated by TMS.

Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players.

Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere.