Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.

Individual contralesional recruitment in the context of structural reserve in early motor reorganization after stroke.

The concept of structural reserve in stroke reorganization assumes that the relevance of the contralesional hemisphere strongly depends on the brain tissue spared by the lesion in the affected hemisphere. Recent studies, however, have indicated that the contralesional hemisphere's impact exhibits region-specific variability with concurrently existing maladaptive and supportive influences. This challenges traditional views, necessitating a nuanced investigation of contralesional motor areas and their interaction with ipsilesional networks. Our study focused on the functional role of contralesional key motor areas and lesion-induced connectome disruption early after stroke. Online TMS data of twenty-five stroke patients was analyzed to disentangle interindividual differences in the functional roles of contralesional primary motor cortex (M1), dorsal premotor cortex (dPMC), and anterior interparietal sulcus (aIPS) for motor function. Connectome-based lesion symptom mapping and corticospinal tract lesion quantification were used to investigate how TMS effects depend on ipsilesional structural network properties. At group and individual levels, TMS interference with contralesional M1 and aIPS but not dPMC led to improved performance early after stroke. At the connectome level, a more disturbing role of contralesional M1 was related to a more severe disruption of the structural integrity of ipsilesional M1 in the affected motor network. In contrast, a detrimental influence of contralesional aIPS was linked to less disruption of the ipsilesional M1 connectivity. Our findings indicate that contralesional areas distinctively interfere with motor performance early after stroke depending on ipsilesional structural integrity, extending the concept of structural reserve to regional specificity in recovery of function.

Evidence of the existence of multiple modules for the stroke-caused flexion synergy from Fugl-Meyer assessment scores.

Stroke-caused synergies may result from the preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or abnormal synergies, and accordingly, the controllability of individual muscles decreases. However, it is not clear whether muscles involuntarily activated by abnormal synergy vary depending on the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from the merging and reweighting of synergies in individuals without neurological deficits. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment that could characterize the neuroanatomical architecture in individuals with a wide range of impairments. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% [8/57, 95% confidence interval (5.0%, 23.1%)] of the participants with severe impairment (total Fugl-Meyer score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants underwent a different course of neural reorganization, which enhanced abnormal synergies in comparison with individuals with mild impairment (P < 0.05). These results provide evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.NEW & NOTEWORTHY We demonstrate that abnormal synergies are still selectively excited depending on the context.

Correlations in abnormal synergies between the upper and lower extremities across various phases of stroke.

The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and the lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the interlimb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. We used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis after stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy after stroke. We found that, generally, strong interlimb correlations (r > 0.65 with all P values < 0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). However, the correlations of the lower-extremity extension synergy with the upper-extremity flexion synergy and extension synergy decreased (down to r = 0.38) 360 days after stroke (P < 0.05). These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances the interlimb correlations between the flexion synergy and extension synergy. At the same time, the results imply that the recovery of CST integrity or/and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase may contribute to diversity in neural pathways in motor execution, eventually leading to reduced interlimb correlations.NEW & NOTEWORTHY For the first time, this article addresses the asynchronous relationships in the strengths of flexion and extension synergy expressions between the paretic upper extremity and lower extremity across various phases of stroke.

Subtle motor signs in children with ADHD and their white matter correlates.

Subtle motor signs are a common feature in children with attention-deficit/hyperactivity disorder (ADHD). It has long been suggested that white matter abnormalities may be involved in their presentation, though no study has directly probed this question. The aim of this study was to investigate the relationship between white matter organization and the severity of subtle motor signs in children with and without ADHD. Participants were 92 children with ADHD aged between 8 and 12 years, and 185 typically developing controls. Subtle motor signs were examined using the Physical and Neurological Examination for Soft Signs (PANESS). Children completed diffusion MRI, and fixel-based analysis was performed after preprocessing. Tracts of interest were delineated using TractSeg including the corpus callosum (CC), the bilateral corticospinal tracts (CST), superior longitudinal fasciculus, and fronto-pontine tracts (FPT). Fiber cross-section (FC) was calculated for each tract. Across all participants, lower FC in the CST was associated with higher PANESS Total score (greater motor deficits). Within the PANESS, similar effects were observed for Timed Left and Right maneuvers of the hands and feet, with lower FC of the CST, CC, and FPT associated with poorer performance. No significant group differences were observed in FC in white matter regions associated with PANESS performance. Our data are consistent with theoretical accounts implicating white matter organization in the expression of motor signs in childhood. However, rather than contributing uniquely to the increased severity of soft motor signs in those with ADHD, white matter appears to contribute to these symptoms in childhood in general.

Plasma Apo-E mediated corticospinal tract abnormalities and suicidality in patients with major depressive disorder.

This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E's mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085).

Touch and tactile neuropathic pain sensitivity are set by corticospinal projections.

Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain1-4. Mental influence on perception is largely assumed to occur locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway5, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons. Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain. Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn. This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia. These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain.

Tumor-Specific Alterations in Motor Cortex Excitability and Tractography of the Corticospinal Tract-A Navigated Transcranial Magnetic Stimulation Study.

BACKGROUND: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. METHODS: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance - LTD) were measured. RESULTS: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p < 0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). CONCLUSIONS: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas.

A Concise Guide to D-Wave Monitoring during Intramedullary Spinal Cord Tumour Surgery.

D-waves (also called direct waves) result from the direct activation of fast-conducting, thickly myelinated corticospinal tract (CST) fibres after a single electrical stimulus. During intraoperative neurophysiological monitoring, D-waves are used to assess the long-term motor outcomes of patients undergoing surgery for intramedullary spinal cord tumours, selected cases of intradural extramedullary tumours and surgery for syringomyelia. In the present manuscript, we discuss D-wave monitoring and its role as a tool for monitoring the CST during spinal cord surgery. We describe the neurophysiological background and provide some recommendations for recording and stimulation, as well as possible future perspectives. Further, we introduce the concept of anti D-wave and present an illustrative case with successful recordings.

Modulation of Both Intrinsic and Extrinsic Factors Additively Promotes Rewiring of Corticospinal Circuits after Spinal Cord Injury.

Axon regeneration after spinal cord injury (SCI) is limited by both a decreased intrinsic ability of neurons to grow axons and the growth-hindering effects of extrinsic inhibitory molecules expressed around the lesion. Deletion of phosphatase and tensin homolog (Pten) augments mechanistic target of rapamycin (mTOR) signaling and enhances the intrinsic regenerative response of injured corticospinal neurons after SCI. Because of the variety of growth-restrictive extrinsic molecules, it remains unclear how inhibition of conserved inhibitory signaling elements would affect axon regeneration and rewiring after SCI. Moreover, it remains unknown how a combinatorial approach to modulate both extrinsic and intrinsic mechanisms can enhance regeneration and rewiring after SCI. In the present study, we deleted RhoA and RhoC, which encode small GTPases that mediate growth inhibition signals of a variety of extrinsic molecules, to remove global extrinsic pathways. RhoA/RhoC double deletion in mice suppressed retraction or dieback of corticospinal axons after SCI. In contrast, Pten deletion increased regrowth of corticospinal axons into the lesion core. Although deletion of both RhoA and Pten did not promote axon regrowth across the lesion or motor recovery, it additively promoted rewiring of corticospinal circuits connecting the cerebral cortex, spinal cord, and hindlimb muscles. Our genetic findings, therefore, reveal that a combinatorial approach to modulate both intrinsic and extrinsic factors can additively promote neural circuit rewiring after SCI.SIGNIFICANCE STATEMENT SCI often causes severe motor deficits because of damage to the corticospinal tract (CST), the major neural pathway for voluntary movements. Regeneration of CST axons is required to reconstruct motor circuits and restore functions; however, a lower intrinsic ability to grow axons and extrinsic inhibitory molecules severely limit axon regeneration in the CNS. Here, we investigated whether suppression of extrinsic inhibitory cues by genetic deletion of Rho as well as enhancement of the intrinsic pathway by deletion of Pten could enable axon regrowth and rewiring of the CST after SCI. We show that simultaneous elimination of extrinsic and intrinsic signaling pathways can additively promote axon sprouting and rewiring of the corticospinal circuits. Our data demonstrate a potential molecular approach to reconstruct motor pathways after SCI.

Neuronal activity reorganization in motor cortex for successful locomotion after a lesion in the ventrolateral thalamus.

Thalamic stroke leads to ataxia if the cerebellum-receiving ventrolateral thalamus (VL) is affected. The compensation mechanisms for this deficit are not well understood, particularly the roles that single neurons and specific neuronal subpopulations outside the thalamus play in recovery. The goal of this study was to clarify neuronal mechanisms of the motor cortex involved in mitigation of ataxia during locomotion when part of the VL is inactivated or lesioned. In freely ambulating cats, we recorded the activity of neurons in layer V of the motor cortex as the cats walked on a flat surface and horizontally placed ladder. We first reversibly inactivated ∼10% of the VL unilaterally using glutamatergic transmission antagonist CNQX and analyzed how the activity of motor cortex reorganized to support successful locomotion. We next lesioned 50%-75% of the VL bilaterally using kainic acid and analyzed how the activity of motor cortex reorganized when locomotion recovered. When a small part of the VL was inactivated, the discharge rates of motor cortex neurons decreased, but otherwise the activity was near normal, and the cats walked fairly well. Individual neurons retained their ability to respond to the demand for accuracy during ladder locomotion; however, most changed their response. When the VL was lesioned, the cat walked normally on the flat surface but was ataxic on the ladder for several days after lesion. When ladder locomotion normalized, neuronal discharge rates on the ladder were normal, and the shoulder-related group was preferentially active during the stride's swing phase.NEW & NOTEWORTHY This is the first analysis of reorganization of the activity of single neurons and subpopulations of neurons related to the shoulder, elbow, or wrist, as well as fast- and slow-conducting pyramidal tract neurons in the motor cortex of animals walking before and after inactivation or lesion in the thalamus. The results offer unique insights into the mechanisms of spontaneous recovery after thalamic stroke, potentially providing guidance for new strategies to alleviate locomotor deficits after stroke.

Lateral Corticospinal Tract and Dorsal Column Damage: Predictive Relationships With Motor and Sensory Scores at Discharge From Acute Rehabilitation After Spinal Cord Injury.

OBJECTIVE: To determine if lateral corticospinal tract (LCST) integrity demonstrates a significant predictive relationship with future ipsilateral lower extremity motor function (LEMS) and if dorsal column (DC) integrity demonstrates a significant predictive relationship with future light touch (LT) sensory function post spinal cord injury (SCI) at time of discharge from inpatient rehabilitation. DESIGN: Retrospective analyses of imaging and clinical outcomes. SETTING: University and academic hospital. PARTICIPANTS: A total of 151 participants (N=151) with SCI. INTERVENTIONS: Inpatient rehabilitation. MAIN OUTCOME MEASURES: LEMS and LT scores at discharge from inpatient rehabilitation. RESULTS: In 151 participants, right LCST spared tissue demonstrated a significant predictive relationship with right LEMS percentage recovered (ß=0.56; 95% confidence interval [CI], 0.37-0.73; R=0.43; P<.001). Left LCST spared tissue demonstrated a significant predictive relationship with left LEMS percentage recovered (ß=0.66; 95% CI, 0.50-0.82; R=0.51; P<.001). DC spared tissue demonstrated a significant predictive relationship with LT percentage recovered (ß=0.69; 95% CI, 0.52-0.87; R=0.55; P<.001). When subgrouping the participants into motor complete vs incomplete SCI, motor relationships were no longer significant, but the sensory relationship remained significant. Those who had no voluntary motor function but recovered some also had significantly greater LCST spared tissue than those who did not recover motor function. CONCLUSIONS: LCST demonstrated significant moderate predictive relationships with lower extremity motor function at the time of discharge from inpatient rehabilitation, in an ipsilesional manner. DC integrity demonstrated a significant moderate predictive relationship with recovered function of LT. With further development, these neuroimaging methods might be used to predict potential deficits after SCI and to provide corresponding targeted interventions.

Distinct Corticospinal and Reticulospinal Contributions to Voluntary Control of Elbow Flexor and Extensor Muscles in Humans with Tetraplegia.

Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps.SIGNIFICANCE STATEMENT Although a number of individuals with cervical incomplete spinal cord injury show limited functional recovery of elbow extensors compared with elbow flexor muscles, to date, the neural mechanisms underlying this asymmetrical recovery remain unknown. Here, we provide for the first time evidence for increased reticulospinal inputs to biceps but not triceps brachii and loss of corticospinal drive to triceps brachii in humans with tetraplegia. We propose that this reorganization in descending control contributes to the asymmetrical recovery between elbow flexor and extensor muscles after cervical spinal cord injury.

Multimodal Assessment of the Motor System in Patients With Chronic Ischemic Stroke.

BACKGROUND AND PURPOSE: Despite continuing efforts in the multimodal assessment of the motor system after stroke, conclusive findings on the complementarity of functional and structural metrics of the ipsilesional corticospinal tract integrity and the role of the contralesional hemisphere are still lacking. This research aimed to find the best combination of motor system metrics, allowing the classification of patients into 3 predefined groups of upper limb motor recovery. METHODS: We enrolled 35 chronic ischemic stroke patients (mean 47 [26-66] years old, 29 [6-58] months poststroke) with a single supratentorial lesion and unilateral upper extremity weakness. Patients were divided into 3 groups, depending on upper limb motor recovery: good, moderate, and bad. Nonparametric statistical tests and regression analysis were used to investigate the relationships among microstructural (fractional anisotropy (FA) ratio of the corticospinal tracts at the internal capsule (IC) level (classic method) and along the length of the tracts (Fréchet distance), and of the corpus callosum) and functional (motor evoked potentials [MEPs] for 2 hand muscles) motor system metrics. Stratification rules were also tested using a decision tree classifier. RESULTS: IC FA ratio in the IC and MEP absence were both equally discriminative of the bad motor outcome (96% accuracy). For the 3 recovery groups' classification, the best parameter combination was IC FA ratio and the Fréchet distance between the contralesional and ipsilesional corticospinal tract FA profiles (91% accuracy). No other metrics had any additional value for patients' classification. MEP presence differed for 2 investigated muscles. CONCLUSIONS: This study demonstrates that better separation between 3 motor recovery groups may be achieved when considering the similarity between corticospinal tract FA profiles along its length in addition to region of interest-based assessment and lesion load calculation. Additionally, IC FA ratio and MEP absence are equally important markers for poor recovery, while for MEP probing it may be important to investigate more than one hand muscle.

Differences in brain structure and theta burst stimulation-induced plasticity implicate the corticomotor system in loss of function after musculoskeletal injury.

Traumatic musculoskeletal injury (MSI) may involve changes in corticomotor structure and function, but direct evidence is needed. To determine the corticomotor basis of MSI, we examined interactions among skeletomotor function, corticospinal excitability, corticomotor structure (cortical thickness and white matter microstructure), and intermittent theta burst stimulation (iTBS)-induced plasticity. Nine women with unilateral anterior cruciate ligament rupture (ACL) 3.2 ± 1.1 yr prior to the study and 11 matched controls (CON) completed an MRI session followed by an offline plasticity-probing protocol using a randomized, sham-controlled, double-blind, cross-over study design. iTBS was applied to the injured (ACL) or nondominant (CON) motor cortex leg representation (M1LEG) with plasticity assessed based on changes in skeletomotor function and corticospinal excitability compared with sham iTBS. The results showed persistent loss of function in the injured quadriceps, compensatory adaptations in the uninjured quadriceps and both hamstrings, and injury-specific increases in corticospinal excitability. Injury was associated with lateralized reductions in paracentral lobule thickness, greater centrality of nonleg corticomotor regions, and increased primary somatosensory cortex leg area inefficiency and eccentricity. Individual responses to iTBS were consistent with the principles of homeostatic metaplasticity; corresponded to injury-related differences in skeletomotor function, corticospinal excitability, and corticomotor structure; and suggested that corticomotor adaptations involve both hemispheres. Moreover, iTBS normalized skeletomotor function and corticospinal excitability in ACL. The results of this investigation directly confirm corticomotor involvement in chronic loss of function after traumatic MSI, emphasize the sensitivity of the corticomotor system to skeletomotor events and behaviors, and raise the possibility that brain-targeted therapies could improve recovery.NEW & NOTEWORTHY Traumatic musculoskeletal injuries may involve adaptive changes in the brain that contribute to loss of function. Our combination of neuroimaging and theta burst transcranial magnetic stimulation (iTBS) revealed distinct patterns of iTBS-induced plasticity that normalized differences in muscle and brain function evident years after unilateral knee ligament rupture. Individual responses to iTBS corresponded to injury-specific differences in brain structure and physiological activity, depended on skeletomotor deficit severity, and suggested that corticomotor adaptations involve both hemispheres.

Evidence for interhemispheric imbalance in stroke patients as revealed by combining transcranial magnetic stimulation and electroencephalography.

Interhemispheric interactions in stroke patients are frequently characterized by abnormalities, in terms of balance and inhibition. Previous results showed an impressive variability, mostly given to the instability of motor-evoked potentials when evoked from the affected hemisphere. We aim to find reliable interhemispheric measures in stroke patients with a not-evocable motor-evoked potential from the affected hemisphere, by combining transcranial magnetic stimulation (TMS) and electroencephalography. Ninteen stroke patients (seven females; 61.26 ± 9.8 years) were studied for 6 months after a first-ever stroke in the middle cerebral artery territory. Patients underwent four evaluations: clinical, cortical, corticospinal, and structural. To test the reliability of our measures, the evaluations were repeated after 3 weeks. To test the sensitivity, 14 age-matched healthy controls were compared to stroke patients. In stroke patients, stimulation of the affected hemisphere did not result in any inhibition onto the unaffected. The stimulation of the unaffected hemisphere revealed a preservation of the inhibition mechanism onto the affected. This resulted in a remarkable interhemispheric imbalance, whereas this mechanism was steadily symmetric in healthy controls. This result was stable when cortical evaluation was repeated after 3 weeks. Importantly, patients with a better recovery of the affected hand strength were the ones with a more stable interhemispheric balance. Finally, we found an association between microstructural integrity of callosal fibers, suppression of interhemispheric TMS-evoked activity and interhemispheric connectivity. We provide direct and sensitive cortical measures of interhemispheric imbalance in stroke patients. These measures offer a reliable means of distinguishing healthy and pathological interhemispheric dynamics.

Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury.

Rehabilitative exercise in humans with spinal cord injury aims to engage residual neural networks to improve functional recovery. We hypothesized that exercise combined with non-invasive stimulation targeting spinal synapses further promotes functional recovery. Twenty-five individuals with chronic incomplete cervical, thoracic, and lumbar spinal cord injury were randomly assigned to 10 sessions of exercise combined with paired corticospinal-motor neuronal stimulation (PCMS) or sham-PCMS. In an additional experiment, we tested the effect of PCMS without exercise in 13 individuals with spinal cord injury with similar characteristics. During PCMS, 180 pairs of stimuli were timed to have corticospinal volleys evoked by transcranial magnetic stimulation over the primary motor cortex arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles (depending on the injury level), 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of a peripheral nerve. Participants exercised for 45 min after all protocols. We found that the time to complete subcomponents of the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) and the 10-m walk test decreased on average by 20% after all protocols. However, the amplitude of corticospinal responses elicited by transcranial magnetic stimulation and the magnitude of maximal voluntary contractions in targeted muscles increased on overage by 40-50% after PCMS combined or not with exercise but not after sham-PCMS combined with exercise. Notably, behavioural and physiological effects were preserved 6 months after the intervention in the group receiving exercise with PCMS but not in the group receiving exercise combined with sham-PCMS, suggesting that the stimulation contributed to preserve exercise gains. Our findings indicate that targeted non-invasive stimulation of spinal synapses might represent an effective strategy to facilitate exercise-mediated recovery in humans with different degrees of paralysis and levels of spinal cord injury.

The Influence of Cortico-Cerebellar Structural Connectivity on Cortical Excitability in Chronic Stroke.

Brain imaging has recently evidenced that the structural state of distinct reciprocal cortico-cerebellar fiber tracts, the dentato-thalamo-cortical tract (DTCT), and the cortico-ponto-cerebellar tract (CPCeT), significantly influences residual motor output in chronic stroke patients, independent from the level of damage to the corticospinal tract (CST). Whether such structural information might also directly relate to measures of cortical excitability is an open question. Eighteen chronic stroke patients with supratentorial ischemic lesions and 17 healthy controls underwent transcranial magnetic stimulation to assess recruitment curves of motor evoked potentials of both hemispheres. Diffusion-weighted imaging and probabilistic tractography were applied to reconstruct reciprocal cortico-cerebellar motor tracts between the primary motor cortex and the cerebellum. Tract-related microstructure was estimated by means of fractional anisotropy, and linear regression modeling was used to relate it to cortical excitability. The main finding was a significant association between cortical excitability and the structural integrity of the DTCT, the main cerebellar outflow tract, independent from the level of damage to the CST. A comparable relationship was neither detectable for the CPCeT nor for the healthy controls. This finding contributes to a mechanistic understanding of the putative supportive role of the cerebellum for residual motor output by facilitating cortical excitability after stroke.

Uncrossed corticospinal tracts presenting as transient tumor-related symptomatology.

Ipsilateral corticospinal innervation is rare. No prior cases have described ipsilateral tumor-associated symptoms as the presentation of an uncrossed corticospinal tract. Herein, we describe a case associated with a left frontal tumor, presenting with transient ipsilateral hemiparesis and aphasia. Due to the fluctuating symptomatology, we suspected a cerebrovascular cause and initially performed a workup for stroke. Ipsilateral motor innervation was discovered with intraoperative monitoring during the resection of the tumor, and confirmed with postoperative diffusion tensor imaging (DTI). Neurosurgeons should be aware of uncrossed motor system, and include it in the differential of ipsilateral deficit in patients with intracranial tumors.

The prediction of need of using ankle-foot orthoses in stroke patients based on findings of a transcranial magnetic stimulation study.

Ankle-foot orthoses (AFOs) are widely prescribed for stroke rehabilitation. We investigated the potential of transcranial magnetic stimulation (TMS) at an early stage, after stroke, to predict the need of using AFOs in stroke patients. We recruited 35 patients who could walk with intermittent support of one person or independently 3 months after onset of stroke. The patients included in the study were classified into two groups: a TMS (+) group (n = 10), in which motor-evoked potential (MEP) in the affected tibialis anterior (TA) was present, and a TMS (-) group (n = 25), in which the MEP in the affected TA was absent. Three months after the onset of stroke, we investigated whether patients were using AFOs or not. We also checked the motor function of the affected lower extremity using the Medical Research Council (MRC) scale. After 3 months of onset of stroke in the TMS (+) group, 4 patients (40%) were using an AFO during ambulation. In the TMS (-) group, 21 patients (84%) were using an AFO. The probability of using AFOs in the 2 groups were significantly different. Additionally, 3 months after the onset of stroke, the MRC scores of ankle dorsiflexor power, on the affected side, were significantly higher in the TMS (+) group. Early TMS evaluation of the corticospinal tract to the TA appears to be useful for predicting the need of using AFOs in stroke patients during the recovery phase.