Motor Cortical Representation Research Articles

Navigated Transcranial Magnetic Stimulation and Diffusion Tensor Imaging Tractography in Insular Glioma Surgery.

The surgical resection of insular gliomas is associated with a high rate of postoperative morbidity as they grow close to descending motor fibers and lenticulostriate arteries. It is believed that intraoperative perforator infarctions are the determining factor for patients' postoperative outcome, while the majority of patients with intraoperative ischemic events do not develop postoperative motor deficits. This study aims to evaluate whether navigated transcranial magnetic stimulation (nTMS) and nTMS-based fiber tracking could be valuable for the preoperative assessment of patients with insular gliomas. Thirty-two patients with insular gliomas were presurgically examined by nTMS. The resting motor threshold and cortical representation areas of legs, hands, and face were identified on both hemispheres. Motor evoked potential positive stimulation points were then used as a region of interest for diffusion tensor imaging tractographies. Somatotopic fiber tracking was performed enabling analyses of the spatial relation between tumor and cortico-spinal tract (CST) as well as the extraction of fiber tract integrity, measured by fractional anisotropy and the apparent diffusion coefficient. The performance of nTMS mappings of the motor cortex and reconstruction of descending motor fibers for legs, hands, and facial functioning was successful in all patients. Higher preoperative resting motor threshold ratios and a distance between tumor and CST of <3 mm were associated with a permanent deterioration in motor function (P = .029 and P = .007). Shorter distances between CST and tumorous tissue were correlated with lowered peritumoral fractional anisotropy values, suggesting alterations in fiber tract integrity. Lower interhemispheric peritumoral fractional anisotropy ratios showed an association with new postoperative motor deficits (P = .017). nTMS-based diffusion tensor imaging tractography enables somatotopic tract visualization and provides a valuable tool for preoperative planning, intraoperative orientation, and individual risk stratification. Thus, it may be beneficial to increase safety in insular glioma resection surgery.

Реорганизация кортикоспинального тракта при постаноксических состояниях у детей: серия клинических наблюдений

Predicting the outcome of postanoxic conditions, particularly with respect to motor control, is an important task in rehabilitation. We describe a series of case reports of reorganization of cortical motor representations (primary motor cortex (PMC), premotor cortex (PC), supplementary motor area (SMA), and cortico-spinal tract) in children with postanoxic conditions of different origins using voxel-based morphometry, diffusion tensor imaging, and diagnostic transcranial magnetic stimulation. Our results demonstrate the ability to restore the volume of cortico-spinal motor projections in patients with less severe atrophic changes of the PMC, PC, and SMA, as well as stably reproducible motor evoked potentials of a larger area at a lower motor threshold of their registration. Patients with severe atrophic changes of the PMC had a worse prognosis for recovery, even if the pyramidal tracts were preserved and increased in volume over time. These case reports rather confirm the importance of synaptogenesis in the recovery of motor functions in patients with a formed motor act, given the variability of the density of pyramidal tracts during the reorganization of brain structures. KEYWORDS: corticospinal tract, primary motor cortex, premotor cortex, supplementary motor area, postanoxic condition, transcranial magnetic stimulation, motor-evoked potential, tractography. FOR CITATION: Kan'shina D.S., Ublinskiy M.V., Mel'nikov I.A., Valliulina S.A., Akhadov T.A., Nikitin S.S., Zykov V.P., Drozhevskaya E.E. Cortico-spinal reorganization in postanoxic conditions in children: a series of case reports. Russian Journal of Woman and Child Health. 2024;7(3):286–292 (in Russ.). DOI: 10.32364/2618-8430-2024-7-3-14.

Machine Learning-assisted Quantitative Mapping of Intracortical Axonal Plasticity Following a Focal Cortical Stroke in Rodents.

Stroke destroys neurons and their connections leading to focal neurological deficits. Although limited, many patients exhibit a certain degree of spontaneous functional recovery. Structural remodeling of the intracortical axonal connections is implicated in the reorganization of cortical motor representation maps, which is considered to be an underlying mechanism of the improvement in motor function. Therefore, an accurate assessment of intracortical axonal plasticity would be necessary to develop strategies to facilitate functional recovery following a stroke. The present study developed a machine learning-assisted image analysis tool based on multi-voxel pattern analysis in fMRI imaging. Intracortical axons originating from the rostral forelimb area (RFA) were anterogradely traced using biotinylated dextran amine (BDA) following a photothrombotic stroke in the mouse motor cortex. BDA-traced axons were visualized in tangentially sectioned cortical tissues, digitally marked, and converted to pixelated axon density maps. Application of the machine learning algorithm enabled sensitive comparison of the quantitative differences and the precise spatial mapping of the post-stroke axonal reorganization even in the regions with dense axonal projections. Using this method, we observed a substantial extent of the axonal sprouting from the RFA to the premotor cortex and the peri-infarct region caudal to the RFA. Therefore, the machine learningassisted quantitative axonal mapping developed in this study can be utilized to discover intracortical axonal plasticity that may mediate functional restoration following stroke.

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.

No evidence for a difference in lateralization and distinctiveness level of transcranial magnetic stimulation-derived cortical motor representations over the adult lifespan.

This study aimed to investigate the presence and patterns of age-related differences in TMS-based measures of lateralization and distinctiveness of the cortical motor representations of two different hand muscles. In a sample of seventy-three right-handed healthy participants over the adult lifespan, the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) cortical motor representations of both hemispheres were acquired using transcranial magnetic stimulation (TMS). In addition, dexterity and maximum force levels were measured. Lateralization quotients were calculated for homolog behavioral and TMS measures, whereas the distinctiveness between the FDI and ADM representation within one hemisphere was quantified by the center of gravity (CoG) distance and cosine similarity. The presence and patterns of age-related changes were examined using linear, polynomial, and piecewise linear regression. No age-related differences could be identified for the lateralization quotient of behavior or cortical motor representations of both intrinsic hand muscles. Furthermore, no evidence for a change in the distinctiveness of the FDI and ADM representation with advancing age was found. In conclusion this work showed that lateralization and distinctiveness of cortical motor representations, as determined by means of TMS-based measures, remain stable over the adult lifespan.

Sling Exercise Can Drive Cortical Representation of the Transversus Abdominis and Multifidus Muscles in Patients With Chronic Low Back Pain.

ObjectiveThe transversus abdominis (TrA) and multifidus (MF) muscles are essential in preventing chronic low back pain (CLBP) recurrence by maintaining segmental stabilization and stiffness. Sling exercise is a high-level core stability training to effectively improve the activities of the TrA and MF muscles. However, the neural mechanism for sling exercise-induced neural plasticity change in the primary motor cortex (M1) remains unclear. This study aimed to investigate the role of sling exercise in the reorganization of the motor cortical representation of the TrA and MF muscles.MethodsTwenty patients with CLBP and 10 healthy individuals were recruited. For map volume, area, the center of gravity (CoG) location (medial-lateral location and anterior-posterior location), and latency, two-way ANOVA was performed to compare the effects of groups (the CLBP-pre, CLBP-post, and healthy groups) and the two muscles (the TrA and MF muscles). The Visual Analog Scale (VAS), the Oswestry Disability Index (ODI), and postural balance stability were assessed at baseline and at the end of 2 weeks of sling exercise. Linear correlations between VAS or ODI and CoG locations were assessed by Pearson's correlation test.Results2 weeks of sling exercise induced both the anterior-medial (P < 0.001) and anterior-posterior (P = 0.025) shifts of the MF muscle representation at the left motor cortex in patients with CLBP. Anterior-medial (P = 0.009) shift of the TrA muscle representation at the right motor cortex was observed in patients with CLBP. The motor cortical representation of the two muscles in patients with CLBP after sling exercise (TrA: 2.88 ± 0.27 cm lateral and 1.53 ± 0.47 cm anterior of vertex; MF: 3.02 ± 0.48 cm lateral and 1.62 ± 0.40 cm anterior of vertex) closely resembled that observed in healthy individuals (TrA: 2.83 ± 0.48 cm lateral and 2.00 ± 0.43 cm anterior of vertex; MF: 2.94 ± 0.43 cm lateral and 1.77 ± 0.48 cm anterior of vertex). The VAS and the ODI were reduced following the sling exercise (VAS: P < 0.001; ODI: P < 0.001).ConclusionThis study provides evidence that sling training can drive plasticity changes in the motor system, which corresponds with the reduction in pain and disability levels in patients with CLBP. This study was registered in the Chinese Clinical Trial Registry (Clinical Trial Registration Number: ChiCTR2100045904, http://www.chictr.org.cn/showproj.aspx?proj=125819).Clinical Trial RegistrationChiCTR2100045904.

Unilateral nasal obstruction affects development of cortical orofacial motor representation in the cortical masticatory area of growing rats

The cortical masticatory area (CMA) regulates masticatory movements. However, there is limited information regarding the effect of respiratory disturbances on the functional development of the CMA. This study aimed to examine the effect of chronic unilateral nasal obstruction (UNO) on the CMA during the growth period. Forty-eight 8-day-old male Wistar albino rats were randomized into control (CONT, n = 24) and UNO (n = 24) groups. Arterial oxygen saturation (SpO2) and the number of positive intracortical microstimulation (ICMS) sites in the anterior digastric (AD) muscle were recorded at 5, 7, and 9 weeks of age. ICMS was performed under anesthesia. The CONT group exhibited significantly higher SpO2 values than the UNO group at each age. Furthermore, the number of positive ICMS sites in the AD muscle was significantly higher in the UNO group than in the CONT group at each age. The right AD was more strongly affected by UNO than the left AD. In addition, it was found that the P-area was more strongly affected by UNO than the A-area. These findings suggest that UNO during development induces changes in the motor representation in the CMA, which may affect respiratory and orofacial functions in rats. Therefore, we suggest that the development of respiratory dysfunction needs to be monitored and corrected promptly to avoid complications in physiological function.

Forearm and Hand Muscles Exhibit High Coactivation and Overlapping of Cortical Motor Representations

Most of the motor mapping procedures using navigated transcranial magnetic stimulation (nTMS) follow the conventional somatotopic organization of the primary motor cortex (M1) by assessing the representation of a particular target muscle, disregarding the possible coactivation of synergistic muscles. In turn, multiple reports describe a functional organization of the M1 with an overlapping among motor representations acting together to execute movements. In this context, the overlap degree among cortical representations of synergistic hand and forearm muscles remains an open question. This study aimed to evaluate the muscle coactivation and representation overlapping common to the grasping movement and its dependence on the stimulation parameters. The nTMS motor maps were obtained from one carpal muscle and two intrinsic hand muscles during rest. We quantified the overlapping motor maps in size (area and volume overlap degree) and topography (similarity and centroid Euclidean distance) parameters. We demonstrated that these muscle representations are highly overlapped and similar in shape. The overlap degrees involving the forearm muscle were significantly higher than only among the intrinsic hand muscles. Moreover, the stimulation intensity had a stronger effect on the size compared to the topography parameters. Our study contributes to a more detailed cortical motor representation towards a synergistic, functional arrangement of M1. Understanding the muscle group coactivation may provide more accurate motor maps when delineating the eloquent brain tissue during pre-surgical planning.

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

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

Functional connectome reorganization relates to post-stroke motor recovery and structural and functional disconnection

Motor recovery following ischemic stroke is contingent on the ability of surviving brain networks to compensate for damaged tissue. In rodent models, sensory and motor cortical representations have been shown to remap onto intact tissue around the lesion site, but remapping to more distal sites (e.g. in the contralesional hemisphere) has also been observed. Resting state functional connectivity (FC) analysis has been employed to study compensatory network adaptations in humans, but mechanisms and time course of motor recovery are not well understood. Here, we examine longitudinal FC in 23 first-episode ischemic pontine stroke patients and utilize a graph matching approach to identify patterns of functional connectivity reorganization during recovery. We quantified functional reorganization between several intervals ranging from 1 week to 6 months following stroke, and demonstrated that the areas that undergo functional reorganization most frequently are in cerebellar/subcortical networks. Brain regions with more structural and functional connectome disruption due to the stroke also had more remapping over time. Finally, we show that functional reorganization is correlated with the extent of motor recovery in the early to late subacute phases, and furthermore, individuals with greater baseline motor impairment demonstrate more extensive early subacute functional reorganization (from one to two weeks post-stroke) and this reorganization correlates with better motor recovery at 6 months. Taken together, these results suggest that our graph matching approach can quantify recovery-relevant, whole-brain functional connectivity network reorganization after stroke.

TMS Motor Mapping Methodology and Reliability: A Structured Review.

Motor cortical representation can be probed non-invasively using a transcranial magnetic stimulation (TMS) technique known as motor mapping. The mapping technique can influence features of the maps because of several controllable elements. Here we review the literature on six key motor mapping parameters, as well as their influence on outcome measures and discuss factors impacting their selection. 132 of 1,587 distinct records were examined in detail and synthesized to form the basis of our review. A summary of mapping parameters, their impact on outcome measures and feasibility considerations are reported to support the design and interpretation of TMS mapping studies.

Effect of Bilateral Opercular Syndrome on Speech Perception.

Speech perception ability and structural neuroimaging were investigated in two cases of bilateral opercular syndrome. Due to bilateral ablation of the motor control center for the lower face and surrounds, these rare cases provide an opportunity to evaluate the necessity of cortical motor representations for speech perception, a cornerstone of some neurocomputational theories of language processing. Speech perception, including audiovisual integration (i.e., the McGurk effect), was mostly unaffected in these cases, although verbal short-term memory impairment hindered performance on several tasks that are traditionally used to evaluate speech perception. The results suggest that the role of the cortical motor system in speech perception is context-dependent and supplementary, not inherent or necessary.

Developmental and Interventional Plasticity of Motor Maps after Perinatal Stroke.

Within the perinatal stroke field, there is a need to establish preclinical models where putative biomarkers for motor function can be examined. In a mouse model of perinatal stroke, we evaluated motor map size and movement latency following optogenetic cortical stimulation against three factors of post-stroke biomarker utility: (1) correlation to chronic impairment on a behavioral test battery; (2) amenability to change using a skilled motor training paradigm; and (3) ability to distinguish individuals with potential to respond well to training. Thy1-ChR2-YFP mice received a photothrombotic stroke at postnatal day 7 and were evaluated on a battery of motor tests between days 59 and 70. Following a cranial window implant, mice underwent longitudinal optogenetic motor mapping both before and after 3 weeks of skilled forelimb training. Map size and movement latency of both hemispheres were positively correlated with impaired spontaneous forelimb use, whereas only ipsilesional hemisphere map size was correlated with performance in skilled reaching. Map size and movement latency did not show groupwise changes with training; however, mice with the smallest pretraining map sizes and worst impairments demonstrated the greatest expansion of map size in response to skilled forelimb training. Overall, motor map size showed utility as a potential biomarker for impairment and training-induced modulation in specific individuals. Future assessment of the predictive capacity of post-stroke motor representations for behavioral outcome in animal models opens the possibility of dissecting how plasticity mechanisms contribute to recovery following perinatal stroke.SIGNIFICANCE STATEMENT We investigated the utility of two cortical motor representation measures (motor map size and movement onset latency) as potential biomarkers for post-stroke motor recovery in a mouse model of perinatal stroke. Both motor map size and movement latency were associated with functional recovery after perinatal stroke, with map size showing an additional association between training responsiveness and severity of impairment. Overall, both motor map size and movement onset latency show potential as neurophysiological correlates of recovery. As such, future studies of perinatal stroke rehabilitation and neuromodulation should include these measures to help explain neurophysiological changes that might be occurring in response to treatment.

A New Neurorehabilitative Postsurgery Intervention for Facial Palsy Based on Smile Observation and Hand-Mouth Motor Synergies.

Objective To perform a preliminary test of a new rehabilitation treatment (FIT-SAT), based on mirror mechanisms, for gracile muscles after smile surgery. Method A pre- and postsurgery longitudinal design was adopted to study the efficacy of FIT-SAT. Four patients with bilateral facial nerve paralysis (Moebius syndrome) were included. They underwent two surgeries with free muscle transfers, one year apart from each other. The side of the face first operated on was rehabilitated with the traditional treatment, while the second side was rehabilitated with FIT-SAT. The FIT-SAT treatment includes video clips of an actor performing a unilateral or a bilateral smile to be imitated (FIT condition). In addition to this, while smiling, the participants close their hand in order to exploit the overlapped cortical motor representation of the hand and the mouth, which may facilitate the synergistic activity of the two effectors during the early phases of recruitment of the transplanted muscles (SAT). The treatment was also aimed at avoiding undesired movements such as teeth grinding. Discussion. Results support FIT-SAT as a viable alternative for smile rehabilitation after free muscle transfer. We propose that the treatment potentiates the effect of smile observation by activating the same neural structures responsible for the execution of the smile and therefore by facilitating its production. Closing of the hand induces cortical recruitment of hand motor neurons, recruiting the transplanted muscles, and reducing the risk of associating other unwanted movements such as teeth clenching to the smile movements.

Functional DTI tractography in brainstem cavernoma surgery

OBJECTIVE Surgical resection of brainstem cavernomas is associated with high postoperative morbidity due to the density of local vulnerable structures. Classical mapping of pathways by diffusion tensor imaging (DTI) has proven to be unspecific and confusing in many cases. In the current study, the authors aimed to establish a more reliable, specific, and objective method for somatotopic visualization of the descending motor pathways with navigated transcranial magnetic stimulation (nTMS)–based DTI fiber tracking. METHODS Twenty-one patients with brainstem cavernomas were examined with nTMS prior to surgery. The resting motor threshold (RMT) and cortical representation areas of hand, leg, and facial function were determined on both hemispheres. Motor evoked potential (MEP)–positive stimulation spots were then set as seed points for tractography. Somatotopic fiber tracking was performed at a fractional anisotropy (FA) value of 75% of the individual FA threshold. RESULTS Mapping of the motor cortex and tract reconstruction for hand, leg, and facial function was successful in all patients. The somatotopy of corticospinal and corticonuclear tracts was also clearly depicted on the brainstem level. Higher preoperative RMT values were associated with a postoperative motor deficit (p &lt; 0.05) and correlated with a lower FA threshold (p &lt; 0.05), revealing structural impairment of the corticospinal tract (CST) prior to surgery. In patients with a new deficit, the distance between the lesion and CST was below 1 mm. CONCLUSIONS nTMS-based fiber tracking enables objective somatotopic tract visualization on the brainstem level and provides a valuable instrument for preoperative planning, intraoperative orientation, and individual risk stratification. nTMS may thus increase the safety of surgical resection of brainstem cavernomas.

Familiarity with a Tool Influences Peripersonal Space and Primary Motor Cortex Excitability of Muscles Involved in Haptic Contact

Long-term experience with a tool stably enlarges peripersonal space (PPS). Also, gained experience with a tool modulates internal models of action. The aim of this work was to understand whether the familiarity with a tool influences both PPS and motor representation. Toward this goal, we tested in 13 expert fencers through a multisensory integration paradigm the embodiment in their PPS of a personal (pE) or a common (cE) épée. Then, we evaluated the primary motor cortex excitability of proximal (ECR) and distal (APB) muscles during a motor imagery (MI) task of an athletic gesture when athletes handled these tools. Results showed that pE enlarges subjects’ PPS, while cE does not. Moreover, during MI, handling tools increased cortical excitability of ECR muscle. Notably, APB’s cortical excitability during MI only increased with pE as a function of its embodiment in PPS. These findings indicate that the familiarity with a tool specifically enlarges PPS and modulates the cortical motor representation of those muscles involved in the haptic contact with it.

TMS coil orientation and muscle activation influence lower limb intracortical excitability

IntroductionPrevious research with transcranial magnetic stimulation (TMS) indicates that coil orientation (TMS current direction) and muscle activation state (rest or active) modify corticospinal and intracortical excitability of upper limb muscles. However, the extent to which these factors influence corticospinal and intracortical excitability of lower limb muscles is unknown. This study aimed to examine how variations in coil orientation and muscle activation affect corticospinal and intracortical excitability of tibialis anterior (TA), a lower leg muscle. MethodsIn 21 young (21.6 ± 3.3 years, 11 female) adults, TMS was administered to the motor cortical representation of TA in posterior-anterior (PA) and mediolateral (ML) orientations at rest and during muscle activation. Single-pulse TMS measures of motor evoked potential amplitude, in addition to resting and active motor thresholds, were used to index corticospinal excitability, whereas paired-pulse TMS measures of short-interval intracortical inhibition (SICI) and facilitation (SICF), and long-interval intracortical inhibition (LICI), were used to assess excitability of intracortical circuits. ResultsFor single-pulse TMS, motor thresholds and test TMS intensity were lower for ML stimulation (all P < 0.05). In a resting muscle, ML TMS produced greater SICI (P < 0.001) and less SICF (both P < 0.05) when compared with PA TMS. In contrast, ML TMS in an active muscle resulted in reduced SICI but increased SICF (both P ≤ 0.001) when compared with PA TMS. ConclusionTMS coil orientation and muscle activation influence measurements of intracortical excitability recorded in the tibialis anterior, and are therefore important considerations in TMS studies of lower limb muscles.

Poststroke Impairment and Recovery Are Predicted by Task-Specific Regionalization of Injury.

Lesion size and location affect the magnitude of impairment and recovery following stroke, but the precise relationship between these variables and functional outcome is unknown. Herein, we systematically varied the size of strokes in motor cortex and surrounding regions to assess effects on impairment and recovery of function. Female Sprague Dawley rats (N = 64) were evaluated for skilled reaching, spontaneous limb use, and limb placement over a 7 week period after stroke. Exploration and reaching were also tested in a free ranging, more naturalistic, environment. MRI voxel-based analysis of injury volume and its likelihood of including the caudal forelimb area (CFA), rostral forelimb area (RFA), hindlimb (HL) cortex (based on intracranial microstimulation), or their bordering regions were related to both impairment and recovery. Severity of impairment on each task was best predicted by injury in unique regions: impaired reaching, by damage in voxels encompassing CFA/RFA; hindlimb placement, by damage in HL; and spontaneous forelimb use, by damage in CFA. An entirely different set of voxels predicted recovery of function: damage lateral to RFA reduced recovery of reaching, damage medial to HL reduced recovery of hindlimb placing, and damage lateral to CFA reduced recovery of spontaneous limb use. Precise lesion location is an important, but heretofore relatively neglected, prognostic factor in both preclinical and clinical stroke studies, especially those using region-specific therapies, such as transcranial magnetic stimulation.SIGNIFICANCE STATEMENT By estimating lesion location relative to cortical motor representations, we established the relationship between individualized lesion location, and functional impairment and recovery in reaching/grasping, spontaneous limb use, and hindlimb placement during walking. We confirmed that stroke results in impairments to specific motor domains linked to the damaged cortical subregion and that damage encroaching on adjacent regions reduces the ability to recover from initial lesion-induced impairments. Each motor domain encompasses unique brain regions that are most associated with recovery and likely represent targets where beneficial reorganization is taking place. Future clinical trials should use individualized therapies (e.g., transcranial magnetic stimulation, intracerebral stem/progenitor cells) that consider precise lesion location and the specific functional impairments of each subject since these variables can markedly affect therapeutic efficacy.

Case studies in neuroscience: deep brain stimulation changes upper limb cortical motor maps in dystonia.

Deep brain stimulation of the globus pallidus pars interna (GPi-DBS) is an effective treatment for primary dystonia; however, its therapeutic mechanism is poorly understood. Because improvement is gradual, GPi-DBS treatment likely involves short- and long-term mechanisms. Abnormal plasticity resulting in somatotopic reorganization is involved in the development of dystonia and has been proposed as a possible mechanism for this gradual improvement, yet it has not been directly investigated. We hypothesized that GPi-DBS will lead to progressive changes in the cortical representations (motor maps) of upper limb muscles. Neuronavigated robotic transcranial magnetic stimulation was used to map the cortical representation of five upper limb muscles in six healthy controls and a 45-yr-old female cervical dystonia patient before (Pre) and at four time points (Post5 to Post314), 5 to 314 days after GPi-DBS. Motor map area and volume decreased in all muscles following GPi-DBS, while changes in overlap and center of gravity distance between muscles were variable. Despite these motor map changes, only dystonic tremor improved after a year of DBS; neck position worsened slightly. These preliminary findings suggest that GPi-DBS may reduce the cortical representation and excitability of upper limb muscles in dystonia and that these changes can occur without clinical improvement.NEW & NOTEWORTHY Neuronavigated robotic transcranial magnetic stimulation was used to investigate changes in upper limb muscle representation in a cervical dystonia patient before and at four time points up to 314 days after globus pallidus pars interna deep brain stimulation (GPi-DBS). GPi-DBS altered excitability and motor cortical representation of upper limb muscles; however, these changes were not associated with clinical improvement.

Alterations of hand sensorimotor function and cortical motor representations over the adult lifespan.

Using a cross sectional design, we aimed to identify the effect of aging on sensorimotor function and cortical motor representations of two intrinsic hand muscles, as well as the course and timing of those changes. Furthermore, the link between cortical motor representations, sensorimotor function, and intracortical inhibition and facilitation was investigated. Seventy-seven participants over the full adult lifespan were enrolled. For the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscle, cortical motor representations, GABAA-mediated short-interval intracortical inhibition (SICI), and glutamate-mediated intracortical facilitation (ICF) were assessed using transcranial magnetic stimulation over the dominant primary motor cortex. Additionally, participants’ dexterity and force were measured. Linear, polynomial, and piecewise linear regression analyses were conducted to identify the course and timing of age-related differences. Our results demonstrated variation in sensorimotor function over the lifespan, with a marked decline starting around the mid-thirties. Furthermore, an age-related reduction in cortical motor representation volume and maximal MEP of the FDI, but not for ADM, was observed, occurring mainly until the mid-forties. Area of the cortical motor representation did not change with advancing age. Furthermore, cortical motor representations, sensorimotor function, and measures of intracortical inhibition and facilitation were not interrelated.