Mapping Of Motor Areas Research Articles

Systematic determination of muscle groups and optimal stimulation intensity for simultaneous TMS mapping of multiple muscles in the upper limb.

Transcranial magnetic stimulation has been used to assess plastic changes in the cortical motor representations of targeted muscles. The present study explored the optimal settings and stimulation intensity for simultaneous motor mapping of multiple upper-limb muscles across segments. In 15 healthy volunteers, we evaluated cortical representations simultaneously from one muscle in the shoulder, two in the upper arm, two in the forearm, and two intrinsic hand muscles, using five stimulation intensities, ranging from 40% to 100% of the maximum stimulator output. We represented the motor map area acquired at each intensity as a percentage of the maximum for each muscle. We defined a motor map area between 25% and 75% of the maximum as the optimal area size with sufficient scope for both up- and down-regulation, and stimulation intensities producing the map area size within this range as the optimal intensities. We found that motor maps with optimal area sizes could be produced simultaneously for the four distal muscles of the forearm and hand in most participants when the stimulation intensity was set at 120-140% of the resting motor threshold (RMT) of the first dorsal interosseous. For the remaining three proximal muscles, motor maps with optimal area sizes were produced only in a few participants, even when using a higher intensity (180-220% RMT). These findings suggest that cortical representations can be assessed simultaneously in a group of distal muscles using a relatively low stimulation intensity, while a separate operation is required to assess that of the proximal muscles.

Differences in neurometabolites and transcranial magnetic stimulation motor maps in children with attention-deficit/hyperactivity disorder.

Background:Although much is known about cognitive dysfunction in attention-deficit/hyperactivity disorder (ADHD), few studies have examined the pathophysiology of disordered motor circuitry. We explored differences in neurometabolite levels and transcranial magnetic stimulation (TMS)–derived corticomotor representations among children with ADHD and typically developing children.Methods:We used magnetic resonance spectroscopy (MRS) protocols to measure excitatory (glutamate + glutamine [Glx]) and inhibitory (γ-aminobutyric acid [GABA]) neurometabolite levels in the dominant primary motor cortex (M1) and the supplementary motor area (SMA) in children with ADHD and typically developing children. We used robotic neuronavigated TMS to measure corticospinal excitability and create corticomotor maps.Results:We collected data from 26 medication-free children with ADHD (aged 7–16 years) and 25 typically developing children (11–16 years). Children with ADHD had lower M1 Glx (p = 0.044, d = 0.6); their mean resting motor threshold was lower (p = 0.029, d = 0.8); their map area was smaller (p = 0.044, d = 0.7); and their hotspot density was higher (p = 0.008, d = 0.9). M1 GABA levels were associated with motor map area (p = 0.036).Limitations: Some TMS data were lost because the threshold of some children exceeded 100% of the machine output. The relatively large MRS voxel required to obtain sufficient signal-to-noise ratio and reliably measure GABA levels encompassed tissue beyond the M1, making this measure less anatomically specific.Conclusion:The neurochemistry and neurophysiology of key nodes in the motor network may be altered in children with ADHD, and the differences appear to be related to each other. These findings suggest potentially novel neuropharmacological and neuromodulatory targets for ADHD.

Software architecture for closed-loop multi-locus transcranial magnetic stimulation

Abstract In the Connect2Brain project (ERC Synergy grant #810377), multi-locus transcranial magnetic stimulation will be controlled by neurophysiological feedback signals in a closed-loop mode. Because of the complicated connections between different software components, medical device regulations, and real-time requirements, a well-designed software architecture is necessary. We present an open platform that allows seamless, extendable integration of various software components, such as neuronavigation (InVesalius Navigator), the control user interface for multi-locus TMS, and a stimulation sequence planner for designing stimulation patterns on predefined stimulation targets. We also create a domain-specific language for defining complex stimulation sequences. The stimulation tasks enabled by the architecture include repeated stimulation with varying, pre-defined parameters, multi-pulse stimulation across multiple loci, mapping of motor areas, and automatically determining the stimulus location and direction to elicit maximal motor response. We follow the microservice architecture principles and use Apache Kafka as the messaging platform. Later, we will extend the architecture to the closed-loop feedback-controlled stimulation, based on electroencephalography and motor-evoked potential data. Apache Kafka is a messaging system with high throughput and low latency, which are desirable features in a control system that processes real-time signals with relatively high dimensionality and sampling frequency. It includes automatic logging of the events, facilitating easy recording and playback of the experiments. Furthermore, a microservice architecture enables developing services using different programming languages, which is beneficial when developing the software in an academic setting by researchers with varying development backgrounds. We adhere to the best practices of writing software by designing clear, well-documented application programming interfaces, ensuring modularity, and following modern development processes, such as periodic code reviews. Our work creates an open-source infrastructure that the other researchers can use and build upon, and takes a step towards standardizing stimulation protocols by introducing a unified representation for various stimulation patterns. Keywords: Software architecture, Neuronavigation, Stimulation sequence planning, Brain-computer interface

Abnormal changes in motor cortical maps in humans with spinal cord injury.

The functional role of motor cortical reorganization following spinal cord injury (SCI) remains largely unknown. Here, we tested motor maps in a hand muscle at rest and during voluntary contraction of the hand with and without voluntary contraction of a proximal arm muscle. Motor map area in participants with SCI decreased during hand voluntary contraction and further decreased during additional contraction of a proximal arm muscle compared with rest. In contrast, motor map area in controls increased during the same motor tasks. Participants with SCI with more severe sensory deficits in the hand showed larger decreases in motor map area. Ten minutes of hand muscle-tendon vibration increased the motor map area during voluntary contraction in SCI participants. These novel findings suggest that abnormal changes in motor cortical maps during voluntary contraction after SCI can be reshaped by sensory input, knowledge that can have implications for rehabilitation. Motor cortical representations reorganize following cervical spinal cord injury (SCI). The functional role of this reorganization remains largely unknown. Using neuronavigated transcranial magnetic stimulation, we examined motor cortical maps during voluntary contraction in humans with chronic cervical SCI and age-matched controls. We constructed motor maps in the first dorsal interosseous (FDI) muscle at rest and during voluntary contraction of the FDI with and without voluntary contraction of the biceps brachi (BB). The role of sensory input into this reorganization was examined by muscle-tendon vibration. We found that, at rest, motor maps were larger in SCI (22.3cm2 ) compared with control (12.6cm2 , P<0.001) participants. Motor map area increased during voluntary contraction of the FDI (120.7%) and further increased during contraction of the BB (143.9%) compared with rest in control subjects; however, motor map area decreased during voluntary contraction of the FDI (69.5%) and further decreased during contraction of the BB (55.5%) in individuals with SCI. SCI participants with larger decreases in map area during voluntary contraction of the FDI were those with larger sensory deficits in the hand and 10min of hand muscle-tendon vibration increased motor map area. These results provide the first evidence of abnormal changes in motor cortical maps in humans with chronic SCI during voluntary contraction, suggesting that sensory input can help to reshape this reorganization.

Machine learning may predict individual hand motor activation from resting-state fMRI in patients with brain tumors in perirolandic cortex

The study aimed to evaluate the predictive validity of the neural network (NN) method for presurgical mapping of motor areas using resting-state functional MRI (rs-fMRI) data of patients with brain tumor located in the perirolandic cortex (PRC). A total of 109 patients with brain tumors occupying PRC underwent rs-fMRI and hand movement task-based fMRI (tb-fMRI) scans. Using a NN model trained on fMRI data of 47 healthy controls, individual task activation maps were predicted from their rs-fMRI data. NN-predicted maps were compared with task activation and independent component analysis (ICA)-derived maps. Spatial Pearson's correlation coefficients (CC) matrices and Dice coefficients (DC) between task activation and predicted activation using NN (DCNN_Act) and ICA (DCICA_Act) were calculated and compared using non-parametric tests. The effects of tumor types and head motion on predicted maps were demonstrated. The CC matrix of NN-predicted maps showed higher diagonal values compared with ICA-derived maps (p < 0.001). DCNN_Act were higher than DCICA_Act (p < 0.001) for patients with or without motor deficits. Lower DCs were found in subjects with head motion greater than one voxel. DCs were higher on the nontumor side than on the tumor side (p < 0.001), especially in the glioma group compared with meningioma and metastatic groups. This study indicated that the NN approach could predict individual motor activation using rs-fMRI data and could have promising clinical applications in brain tumor patients with anatomical and functional reorganizations. • The neural network machine learning approach successfully predicted hand motor activation in patients with a tumor in the perirolandic cortex, despite space-occupying effects and possible functional reorganization. • Compared to the conventional independent component analysis, the neural network approach utilizing resting-state fMRI data yielded a higher correlation to the active task hand activation data. • The Dice coefficient of machine learning-predicted activation vs. task fMRI activation was different between tumor and nontumor side, also between tumor types, which might indicate different effects of possible neurovascular uncoupling on resting-state and task fMRI.

TMS brain mapping of the pharyngeal cortical representation in healthy subjects

BackgroundBrain mapping is fundamental to understanding brain organization and function. However, a major drawback to the traditional Brodmann parcellation technique is the reliance on the use of postmortem specimens. It has therefore historically been difficult to make any comparison regarding functional data from different regions or hemispheres within the same individual. Moreover, this method has been significant limited by subjective boundaries and classification criteria and therefore suffer from reproducibility issues. The development of transcranial magnetic stimulation (TMS) offers an alternative approach to brain mapping, specifically the motor cortical regions by eliciting quantifiable functional reactions. ObjectiveTo precisely describe the motor cortical topographic representation of pharyngeal constrictor musculature using TMS and to further map the brain for use as a tool to study brain plasticity. Methods51 healthy subjects (20 male/31 female, 19–26 years old) were tested using single-pulse TMS combined with intraluminal catheter-guided high-resolution manometry and a standardized grid cap. We investigated various parameters of the motor-evoked potential (MEP) that include the motor map area, amplitude, latency, center of gravity (CoG) and asymmetry index. ResultsCortically evoked response latencies were similar for the left and right hemispheres at 6.79 ± 0.22 and 7.24 ± 0.27 ms, respectively. The average scalp positions (relative to the vertex) of the pharyngeal motor cortical representation were 10.40 ± 0.19 (SE) cm medio-lateral and 3.20 ± 0.20 (SE) cm antero-posterior in the left hemisphere and 9.65 ± 0.24 (SE) cm medio-lateral and 3.18 ± 0.23 (SE) cm antero-posterior in the right hemisphere. The mean motor map area of the pharynx in the left and right hemispheres were 9.22 ± 0.85(SE) cm2and 10.12 ± 1.24(SE) cm2, respectively. The amplitudes of the MEPs were 35.94 ± 1.81(SE)uV in the left hemisphere and 34.49 ± 1.95(SE)uV in the right hemisphere. By comparison, subtle but consistent differences in the degree of the bilateral hemispheric representation were also apparent both between and within individuals. ConclusionThe swallowing musculature has a bilateral motor cortical representation across individuals, but is largely asymmetric within single subjects. These results suggest that TMS mapping using a guided intra-pharyngeal EMG catheter combined with a standardized gridded cap might be a useful tool to localize brain function/dysfunction by linking brain activation to the corresponding physical reaction.

Tongue Force Training Induces Plasticity of the Lingual Motor Cortex in Young Adult and Aged Rats.

Tongue exercise programs are used clinically for dysphagia in aged individuals and have been shown to improve lingual strength. However, the neural mechanisms of age-related decline in swallowing function and its association with lingual strength are not well understood. Using an established rat model of aging and tongue exercise, we hypothesized that the motor cortex of aged rats would have a smaller lingual motor map area than young adult rats and would increase in size as a function of tongue exercise. Over 8 weeks, rats either underwent a progressive resistance tongue exercise program (TE), learned the task but did not exercise (trained controls, TC), or were naïve untrained controls (UC). Cortical motor map areas for tongue and jaw were determined using intracortical microstimulation (ICMS). Rats in the TE and TC groups had a significantly larger motor cortex region for the tongue than the UC group. Lingual cortical motor area was not correlated with protrusive tongue force gains and did not differ significantly with age. These results suggest that learning a novel tongue force skill was sufficient to induce plasticity of the lingual motor cortex yet increasing tongue strength with progressive resistance exercise did not significantly expand the lingual motor area beyond the gains that occurred through the skilled learning component.

Early movement restriction leads to maladaptive plasticity in the sensorimotor cortex and to movement disorders

Motor control and body representations in the central nervous system are built, i.e., patterned, during development by sensorimotor experience and somatosensory feedback/reafference. Yet, early emergence of locomotor disorders remains a matter of debate, especially in the absence of brain damage. For instance, children with developmental coordination disorders (DCD) display deficits in planning, executing and controlling movements, concomitant with deficits in executive functions. Thus, are early sensorimotor atypicalities at the origin of long-lasting abnormal development of brain anatomy and functions? We hypothesize that degraded locomotor outcomes in adulthood originate as a consequence of early atypical sensorimotor experiences that induce developmental disorganization of sensorimotor circuitry. We showed recently that postnatal sensorimotor restriction (SMR), through hind limb immobilization from birth to one month, led to enduring digitigrade locomotion with ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and clear signs of spinal hyperreflexia in adult rats, suggestive of spasticity; each individual disorder likely interplaying in self-perpetuating cycles. In the present study, we investigated the impact of postnatal SMR on the anatomical and functional organization of hind limb representations in the sensorimotor cortex and processes representative of maladaptive neuroplasticity. We found that 28 days of daily SMR degraded the topographical organization of somatosensory hind limb maps, reduced both somatosensory and motor map areas devoted to the hind limb representation and altered neuronal response properties in the sensorimotor cortex several weeks after the cessation of SMR. We found no neuroanatomical histopathology in hind limb sensorimotor cortex, yet increased glutamatergic neurotransmission that matched clear signs of spasticity and hyperexcitability in the adult lumbar spinal network. Thus, even in the absence of a brain insult, movement disorders and brain dysfunction can emerge as a consequence of reduced and atypical patterns of motor outputs and somatosensory feedback that induce maladaptive neuroplasticity. Our results may contribute to understanding the inception and mechanisms underlying neurodevelopmental disorders, such as DCD.

Alteration of occlusal vertical dimension induces signs of neuroplastic changes in corticomotor control of masseter muscles: Preliminary findings.

To investigate the effect of altering occlusal vertical dimension (OVD) in patients with severe attrition on corticomotor control of the masseter muscles as assessed by navigated transcranial magnetic stimulation (nTMS). Seven patients (58.6±8.4years) with decreased OVD due to severe attrition were given mandibular occlusal splints to alter the OVD with the instruction to wear during the whole awake time for a period of four weeks. Motor-evoked potentials (MEPs) and the motor cortex maps of the masseter muscles and first dorsal interosseous (FDI) muscles as control were recorded by nTMS at baseline and at least 4weeks after the alteration of OVD. The stimulus-response curves of MEPs were analysed with two-way repeated-measures ANOVA, and the numerical rating scale scores, motor thresholds, onset latencies, motor cortex maps and centre of gravity (COG) were analysed with paired t tests. There was a significant increase in the amplitude of the masseter muscle MEPs (P=0.036), but no change in the motor cortex map areas (P=0.111) four weeks after the alteration of OVD. Furthermore, there was no significant difference in either the amplitude of the FDI muscle MEPs (P=0.466) or the motor cortex map areas (P=0.230) before and after OVD alteration. The results suggest that alteration of OVD in patients with severe attrition was associated with signs of neuroplastic changes in the corticomotor control of the masseter muscles. The results of the study may add to our understanding of the putative mechanisms related to cortical changes in response to OVD alterations.

F140. Effects of tDCS and HD-tDCS on motor learning and motor maps in children

Perinatal stroke is the leading cause of hemiparetic cerebral palsy (CP). We have shown non-invasive brain stimulation enhances motor learning in healthy and hemiparetic children using transcranial-direct-current-stimulation (tDCS). High-definition (HD-tDCS) may offer additional potential but is unstudied in pediatrics. Motor maps are individualized representations of primary motor cortex (M1) topography measurable with single pulse TMS. Advances in MRI-guided imaging and robotic TMS may facilitate rapid and accurate motor mapping. How motor maps are altered by motor learning and tDCS are unknown. We aimed to determine the effects of tDCS/HD-tDCS enhanced motor learning on motor maps in children, hypothesizing tDCS-enhanced learning is associated with motor map enlargement. AMPED (Accelerated Motor learning in PEDiatrics) is a randomized, sham-controlled trial (NCT03193580). Participants are healthy, right handed children aged 12–18 years. TMS motor mapping is performed using neuronavigated (Brainisght2), robotic (Axilum) TMS. A 10 × 10, 7 mm grid is placed over M1 with 4 stimulations per point generating motor evoked potentials (MEP) of individual hand muscles. Primary outcome is motor map area (volume, center of gravity, cortical excitability are secondary). Motor function is assessed with Purdue Pegboard (primary), Jebsen-Taylor Test, and Serial Reaction Time Task. Participants are randomized into three groups: right M1 1 mA tDCS, HD-tDCS, or sham. All practiced the PPT daily (8 trails) during stimulation with the left hand for 5 consecutive days. Safety and tolerability is assessed daily. All outcomes are repeated on day 5 and at 6 weeks. Two-way repeated measure ANOVA examined changes in performance and motor maps across groups and sessions. Fifteen of 24 participants have completed the study (median age 16.4, 67% female). Blinded interim analysis grouped interventions as A, B, or C. PPT scores improved across all groups (p < 0.001) mean improvement was 3.93(SD:1.3) and comparable across groups: A 4.3(SD 1.7), B 3.1(SD 1.2), C 3.7(SD 1.2). Motor maps were obtained without complication except two subjects could not complete bi-hemispheric mapping due to time constraints. Motor map outcomes differed at baseline between hemispheres −109.31 mm2 (SD 675.46). Following intervention, map area decreased in group C(−147 ± 65.7), p < 0.04) but change in area was not different between groups. Similar findings were observed for secondary outcomes. Procedures were well tolerated with no adverse events. Trials combining tDCS or HD-tDCS enhanced motor learning with robotic TMS motor mapping are feasible in children. Completion of the sample will determine how HD-tDCS enhancement of motor learning compares to tDCS, with potential to advance therapeutic applications in children with CP.

T126. Mapping contralesional motor cortex using robotic transcranial magnetic stimulation in children with perinatal stroke

Introduction Children with perinatal stroke have motor deficits lateralized to one side of the body (hemiparetic cerebral palsy, HCP). Motor control of the affected limb often resides in the contralesional hemisphere with preservation of ipsilateral corticospinal connections. Intensive therapies can improve hand function but mechanisms and predictors of response are unknown. Individualized maps of the motor cortex may provide insight but only two studies have examined this where manual motor mapping was tedious and potentially insensitive. This study aimed to determine the feasibility of using robotic transcranial magnetic stimulation (TMS) motor mapping to better characterize integrated motor maps of the contralesional hemisphere and their association with clinical function. Methods Ten children with unilateral perinatal stroke and HCP (aged 8–19 years) participated in a randomized controlled, double-blinded clinical trial. Children were engaged in a 2-week, goal-directed, child-friendly intensive intervention (constraint and bimanual therapies). Children were randomized to receive 20 min/day of contralesional motor cortex (M1) transcranial direct current stimulation (tDCS) or sham (1:1). Robotic TMS (Axilum Robotics) applied 4 single-pulses to each target on a custom map (12 × 12, 7 mm spacing) over the motor cortex at baseline and within one-week after intervention. Surface electromyography was recorded in bilateral first dorsal interosseous (FDI). Primary neurophysiological measures included the percentage overlap (sites inducing a motor evoked potential (MEP) in both FDI/sites inducing an MEP in the affected FDI), and area of bilateral FDI maps. Clinical outcome was assessed with the Jebsen-Taylor Test of Hand Function (JTTHF). Paired t-tests were performed to examine therapy-associated changes in all measures. Results All children completed the intervention. Two children with incomplete clinical assessments were excluded. Contralesional motor maps were successfully probed by using TMS robot. Motor map parameters did not correlate with clinical scores at baseline (p > 0.1). Percentage overlap of bilateral FDI in the contralesional M1 did not change (n = 7, baseline = 74.5 ± 29.5%, post = 71.7 ± 27.1%, p = 0.86). Averaged motor map areas of unaffected FDI may have increased from 1245 ± 854 mm2 at baseline to 1583 ± 981 mm2 after intervention (n = 10, p = 0.21). Motor map areas of the affected FDI did not change after intervention (n = 7, baseline = 1365 ± 951 mm2, post = 1358 ± 844 mm2,p = 0.98). On average, children moved 23.5 ± 20.8 s faster (12.6 ± 9.6%) with the more-affected hand in JTTHF after intervention (p = 0.02). Change in performance was not associated with change in motor map parameters. Conclusion Our preliminary findings demonstrated that it is feasible to study motor map characteristics using a TMS robot in children with HCP. The utility of using such motor maps as biomarkers to understand and predict treatment outcome will become clearer with completion of larger samples within this and other trials.

O12 RTMS therapy on M1 modifies the facial motor map in chronic neuropathic pain

Objectives Despite the poorly known mechanism of action, high-frequency rTMS targeted somatotopically to M1, is beneficial to treat therapy-resistant chronic neuropathic pain in about half of the patients. According to previous literature hand motor representation area is diminished in chronic pain. We hypothesized that face motor map is altered in chronic pain and will be restored after rTMS treatment. Another aim was to find the different patterns of plastic cortical reshaping. Methods 13 patients with severe unilateral, chronic atypical facial pain were examined before therapy (2 five-day rTMS treatment courses (2400 or 3600 pulses daily), separated by 6 weeks), and 4–5 days after the last treatment session. Motor mapping was performed at 105% rMT of the mentalis muscle using a grid (2 stimuli per square) to determine the extent of representation area on the hemisphere contralateral to painful side. Mapping was analyzed for hotspot, center-of-gravity (CoG) and representation area, calculated using spline-interpolation method. Patient scored the effect of treatment using patient global impression of change (PGIC). Results The hotspots and CoGs were located in anatomically expected areas. In group level, the rTMS did not cause any shift in mediolateral or anteroposterior axis, or affect the extent of representation areas. However, there were several patients in whom the area significantly largened or became more compact/dense after the treatment. Noteworthly, the motor map of facial muscles was surprisingly small in four patients, whereof three scored high benefit. Discussion The face motor maps in patients with chronic facial pain are variable in size. There was a trend of rTMS increasing the motor map. In some patients the face motor map was clearly diminished and mainly, these patients responded to treatment well. This may be related to enhanced cortical plasticity. Conclusion nTMS motor mapping is a feasible method to study neuronal plasticity in chronic pain and enlighten the effects of rTMS. However, larger amount of patient is needed to draw conclusions about patterns of cortical plasticity. Significance Motor map area may be a biomarker for treatment response in chronic facial pain.

P011 Motor recovery of the affected hand in subacute stroke correlates with changes of contralesional cortical hand motor representation

Objective To investigate the relationship between changes of cortical hand motor representation and motor recovery of the affected hand in subacute stroke. Methods 17 patients with motor impairment of the affected hand were enrolled in an in-patient neurological rehabilitation program. Hand motor function tests (Wolf Motor Function Test, Action Research Arm Test) and the neurophysiological evaluations (resting motor threshold, motor evoked potentials, motor map area size, motor map area volume, motor map area location) were obtained from both hands and hemispheres at baseline, and two, four and six weeks of in-patient neurological rehabilitation. Results There was a wide spectrum of hand motor impairment at baseline and hand motor recovery over time. Hand motor function and recovery correlated significantly with (i) reduction of cortical excitability, (ii) reduction in size and volume of cortical hand motor representation and (iii) a medial and anterior shift of cortical hand motor representation within the contralesional hemisphere. Conclusion Recovery of motor function of the affected hand after stroke is accompanied by definite changes in excitability, size, volume and location of hand motor representation over the contralesional primary motor cortex. These measures may serve as surrogate markers for the outcome of hand motor rehabilitation after stroke.

Motor Recovery of the Affected Hand in Subacute Stroke Correlates with Changes of Contralesional Cortical Hand Motor Representation

Objective. To investigate the relationship between changes of cortical hand motor representation and motor recovery of the affected hand in subacute stroke. Methods. 17 patients with motor impairment of the affected hand were enrolled in an in-patient neurological rehabilitation program. Hand motor function tests (Wolf Motor Function Test, Action Research Arm Test) and neurophysiological evaluations (resting motor threshold, motor evoked potentials, motor map area size, motor map area volume, and motor map area location) were obtained from both hands and hemispheres at baseline and two, four, and six weeks of in-patient rehabilitation. Results. There was a wide spectrum of hand motor impairment at baseline and hand motor recovery over time. Hand motor function and recovery correlated significantly with (i) reduction of cortical excitability, (ii) reduction in size and volume of cortical hand motor representation, and (iii) a medial and anterior shift of the center of gravity of cortical hand motor representation within the contralesional hemisphere. Conclusion. Recovery of motor function of the affected hand after stroke is accompanied by definite changes in excitability, size, volume, and location of hand motor representation over the contralesional primary motor cortex. These measures may serve as surrogate markers for the outcome of hand motor rehabilitation after stroke.

Resection of Motor Eloquent Metastases Aided by Preoperative nTMS-Based Motor Maps—Comparison of Two Observational Cohorts

Preoperative mapping of motor areas with navigated transcranial magnetic stimulation (nTMS) has been shown to improve surgical outcomes for peri-Rolandic lesions and, in particular, for gliomas. However, the impact of this technique on surgical outcomes for peri-Rolandic metastatic lesions is yet unknown. To investigate the impact of nTMS on surgical outcomes for peri-Rolandic metastatic lesions, various clinical parameters were analyzed in our international study group. Two prospectively enrolled cohorts were compared by investigating patients receiving preoperative nTMS (2010-2015; 120 patients) and patients who did not receive preoperative nTMS (2006-2015; 130 patients). Tumor location, pathology, size, and preoperative deficits were comparable. The nTMS group showed a lower rate of residual tumor on postoperative magnetic resonance imaging (odds ratio 0.3025; 95% confidence interval 0.1356-0.6749). On long-term follow-up, surgery-related paresis was decreased in the nTMS group (nTMS vs. non-nTMS; improved: 30.8 vs. 13.1%, unchanged: 65.8 vs. 73.8%, worse: 3.4 vs. 13.1% of patients; p = 0.0002). Moreover, the nTMS group received smaller craniotomies (nTMS: 16.7 ± 8.6 cm2 vs. non-nTMS: 25.0 ± 17.1 cm2; p < 0.0001). Surgical time differed significantly between the two groups (nTMS: 128.8 ± 49.4 min vs. non-nTMS: 158.0 ± 65.8 min; p = 0.0002). This non-randomized study suggests that preoperative motor mapping by nTMS may improve the treatment of patients undergoing surgical resection of metastases in peri-Rolandic regions. These findings suggest that further evaluation with a prospective, randomized trial may be warranted.

Closed-loop afferent electrical stimulation for recovery of hand function in individuals with motor incomplete spinal injury: early clinical results.

Afferent electrical stimulation is known to augment the effect of rehabilitative therapy through use-dependent cortical plasticity. Experiments pairing transcranial magnetic stimulation (TMS) with peripheral nerve stimulation (PNS) have shown a timing-dependent effect on motor evoked potential (MEP) amplitude suggesting that PNS applied in closed-loop (CL) mode could augment this effect through positive reinforcement. We present early results from a clinical trial in which an EEG brain-machine interface (BMI) was used to apply PNS to two subjects in response to motor intent detected from sensorimotor cortex in a cue-driven hand grip task. Both subjects had stable incomplete cervical spinal cord injury (SCI) with impaired upper limb function commensurate with the injury level. Twelve sessions of CL-PNS applied over a 4-6 week period yielded results suggesting improved hand grip strength and increased task-related modulation of the EEG in one hand of both subjects, and increased TMS-measured motor map area in one. These observations suggest that rehabilitation using such interactive therapies could benefit affected individuals.

Can short-term oral fine motor training affect precision of task performance and induce cortical plasticity of the jaw muscles?

The aim was to test the hypothesis that short-term oral sensorimotor training of the jaw muscles would increase the precision of task performance and induce neuroplastic changes in the corticomotor pathways, related to the masseter muscle. Fifteen healthy volunteers performed six series with ten trials of an oral sensorimotor task. The task was to manipulate and position a spherical chocolate candy in between the anterior teeth and split it into two equal halves. The precision of the task performance was evaluated by comparing the ratio between the two split halves. A series of "hold-and-split" tasks was also performed before and after the training. The hold force and split force along with the electromyographic (EMG) activity of jaw muscles were recorded. Motor-evoked potentials and cortical motor maps of the right masseter muscle were evoked by transcranial magnetic stimulation. There was a significant effect of series on the precision of the task performance during the short-term oral sensorimotor training (P<0.002). The hold force during the "hold-and-split" task was significantly lower after training than before the short-term training (P=0.011). However, there was no change in the split force and the EMG activity of the jaw muscles before and after the training. Further, there was a significant increase in the amplitude of the motor-evoked potentials (P<0.016) and in the motor cortex map areas (P=0.033), after the short-term oral sensorimotor training. Therefore, short-term oral sensorimotor task training increased the precision of task performance and induced signs of neuroplastic changes in the corticomotor pathways, related to the masseter muscle.

Targeted Motor Rehabilitation Dissociates Corticobulbar Versus Corticospinal Dysfunction in an Animal Model of Parkinson’s Disease

Background. Recent evidence suggests that motor training may be beneficial for slowing the onset of motor impairments in Parkinson’s disease (PD). Objective. To examine the impact of targeted rehabilitation on limb motor and cranial motor function and the corresponding corticospinal and corticobulbar circuits in a rodent model of PD. Methods. Baseline performance of limb (reaching) and cranial (licking) motor function were established prior to and 6 weeks following unilateral intrastriatal 6-hydroxydopamine (6-OHDA) infusions. Animals then received 6 weeks of limb motor rehabilitation (LMR) or cranial motor rehabilitation (CMR), after which motor performance was reassessed. Intracortical microstimulation (ICMS) was used to generate motor maps of corresponding corticospinal (forelimb) and corticobulbar (tongue) movement representations within the motor cortex ipsilateral to the 6-OHDA infusion. Quantitative tyrosine hydroxylase (TH) immunohistochemistry was performed to determine levels of striatal TH depletion in 6-OHDA animals using near infrared densitometry. Results. (1) unilateral intrastriatal dopamine depletion impaired both reaching accuracy and lick force; (2) targeted LMR ameliorated impairments in reaching performance; however, CMR did not improve lick force impairments; (3) unilateral dopamine depletion significantly reduced forelimb but not tongue motor map topography; (4) LMR partially restored forelimb motor maps, whereas CMR did not alter tongue motor maps; and (5) significant correlations were observed between skilled reaching accuracy, forelimb motor map area, and TH depletion, but no relationships were revealed for cranial motor function, motor maps, or TH depletion. Conclusions: These data demonstrate dissociation between striatal dopamine depletion, limb versus cranial motor function, and targeted motor rehabilitation in a rodent model of PD.

Training-induced cortical plasticity compared between three tongue-training paradigms

The primary aim of this study was to investigate the effect of different training types and secondary to test gender differences on the training-related cortical plasticity induced by three different tongue-training paradigms: (1) therapeutic tongue exercises (TTE), (2) playing computer games with the tongue using the Tongue Drive System (TDS) and (3) tongue-protrusion task (TPT). Forty-eight participants were randomized into three groups with 1h of TTE, TDS, or TPT. Stimulus–response curves of motor evoked potentials (MEPs) and motor cortex mapping for tongue muscles and first dorsal interosseous (FDI) (control) were established using transcranial magnetic stimulation at three time-points: (1) before tongue-training, (2) immediately after training, (3) 1h after training. Subject-based reports of motivation, fun, pain and fatigue were evaluated on 0–10 numerical rating scales after training. The resting motor thresholds of tongue MEPs were lowered by training with TDS and TPT (P<0.011) but not by TTE (P=0.167). Tongue MEP amplitudes increased after training with TDS and TPT (P<0.030) but not with TTE (P=0.302). Men had higher MEPs than women in the TDS group (P<0.045) at all time-points. No significant effect of tongue-training on FDI MEPs was observed (P>0.335). The tongue cortical motor map areas were not significantly increased by training (P>0.142). Training with TDS was most motivating and fun (P<0.001) and TTE was rated the most painful (P<0.001). Fatigue level was not different between groups (P>0.071). These findings suggest a differential effect of tongue-training paradigms on training-induced cortical plasticity and subject-based scores of fun, motivation and pain in healthy participants.

Interaction of Motor Training and Intermittent Theta Burst Stimulation in Modulating Motor Cortical Plasticity: Influence of BDNF Val66Met Polymorphism

Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.