Exploring the Structural Plasticity Mechanism of Corticospinal Tract during Stroke Rehabilitation Based Automated Fiber Quantification Tractography.

BACKGROUND: Corticospinal tract (CST) is the principal motor pathway; we aim to explore the structural plasticity mechanism in CST during stroke rehabilitation. METHODS: A total of 25 patients underwent diffusion tensor imaging before rehabilitation (T1), 1-month post-rehabilitation (T2), 2 months post-rehabilitation (T3), and 1-year post-discharge (T4). The CST was segmented, and fractional anisotropy (FA), axial diffusion (AD), mean diffusivity (MD), and radial diffusivity (RD) were determined using automated fiber quantification tractography. Baseline level of laterality index (LI) and motor function for correlation analysis. RESULTS: The FA values of all segments in the ipsilesional CST (IL-CST) were lower compared with normal CST. Repeated measures analysis of variance showed time-related effects on FA, AD, and MD of the IL-CST, and there were similar dynamic trends in these 3 parameters. At T1, FA, AD, and MD values of the mid-upper segments of IL-CST (around the core lesions) were the lowest; at T2 and T3, values for the mid-lower segments were lower than those at T1, while the values for the mid-upper segments gradually increased; at T4, the values for almost entire IL-CST were higher than before. The highest LI was observed at T2, with a predominance in contralesional CST. The LIs for the FA and AD at T1 were positively correlated with the change rate of motor function. CONCLUSIONS: IL-CST showed aggravation followed by improvement from around the lesion to the distal end. Balance of interhemispheric CST may be closely related to motor function, and LIs for FA and AD may have predictive value for mild-to-moderate stroke rehabilitation. Clinical Trial Registration. URL: http://www.chictr.org.cn; Unique Identifier: ChiCTR1800019474.

Corticospinal inhibition investigated in relation to upper extremity motor function in cervical spinal cord injury.

OBJECTIVE: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI. METHODS: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T). RESULTS: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores. CONCLUSIONS: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP. SIGNIFICANCE: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI.

Radiological correlates of pseudobulbar affect: Corticobulbar and cerebellar components in primary lateral sclerosis.

INTRODUCTION: Pseudobulbar affect (PBA) is a distressing symptom of a multitude of neurological conditions affecting patients with a rage of neuroinflammatory, neurovascular and neurodegenerative conditions. It manifests in disproportionate emotional responses to minimal or no contextual stimulus. It has considerable quality of life implications and treatment can be challenging. METHODS: A prospective multimodal neuroimaging study was conducted to explore the neuroanatomical underpinnings of PBA in patients with primary lateral sclerosis (PLS). All participants underwent whole genome sequencing and screening for C9orf72 hexanucleotide repeat expansions, a comprehensive neurological assessment, neuropsychological screening (ECAS, HADS, FrSBe) and PBA was evaluated by the emotional lability questionnaire. Structural, diffusivity and functional MRI data were systematically evaluated in whole-brain (WB) data-driven and region of interest (ROI) hypothesis-driven analyses. In ROI analyses, functional and structural corticobulbar connectivity and cerebello-medullary connectivity alterations were evaluated separately. RESULTS: Our data-driven whole-brain analyses revealed associations between PBA and white matter degeneration in descending corticobulbar as well as in commissural tracts. In our hypothesis-driven analyses, PBA was associated with increased right corticobulbar tract RD (p = 0.006) and decreased FA (p = 0.026). The left-hemispheric corticobulbar tract, as well as functional connectivity, showed similar tendencies. While uncorrected p-maps revealed both voxelwise and ROI trends for associations between PBA and cerebellar measures, these did not reach significance to unequivocally support the "cerebellar hypothesis". CONCLUSIONS: Our data confirm associations between cortex-brainstem disconnection and the clinical severity of PBA. While our findings may be disease-specific, they are consistent with the classical cortico-medullary model of pseudobulbar affect.

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.

Increased intensity of unintended mirror muscle contractions after cervical spinal cord injury is associated with changes in interhemispheric and corticomuscular coherences.

Mirror contractions refer to unintended contractions of the contralateral homologous muscles during voluntary unilateral contractions or movements. Exaggerated mirror contractions have been found in several neurological diseases and indicate dysfunction or lesion of the cortico-spinal pathway. The present study investigates mirror contractions and the associated interhemispheric and corticomuscular interactions in adults with spinal cord injury (SCI) - who present a lesion of the cortico-spinal tract - compared to able-bodied participants (AB). Eight right-handed adults with chronic cervical SCI and ten age-matched right-handed able-bodied volunteers performed sets of right elbow extensions at 20% of maximal voluntary contraction. Electromyographic activity (EMG) of the right and left elbow extensors, interhemispheric coherence over cerebral sensorimotor regions evaluated by electroencephalography (EEG) and corticomuscular coherence between signals over the cerebral sensorimotor regions and each extensor were quantified. Overall, results revealed that participants with SCI exhibited (1) increased EMG activity of both active and unintended active limbs, suggesting more mirror contractions, (2) reduced corticomuscular coherence between signals over the left sensorimotor region and the right active limb and increased corticomuscular coherence between the right sensorimotor region and the left unintended active limb, (3) decreased interhemispheric coherence between signals over the two sensorimotor regions. The increased corticomuscular communication and decreased interhemispheric communication may reflect a reduced inhibition leading to increased communication with the unintended active limb, possibly resulting to exacerbated mirror contractions in SCI. Finally, mirror contractions could represent changes of neural and neuromuscular communication 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.

Behavioral recovery after a spinal deafferentation injury in monkeys does not correlate with extent of corticospinal sprouting.

A long held view in the spinal cord injury field is that corticospinal terminal sprouting is needed for new connections to form, that then mediate behavioral recovery. This makes sense, but tells us little about the relationship between corticospinal sprouting extent and recovery potential. The inference has been that more extensive axonal sprouting predicts greater recovery, though there is little evidence to support this. Here we addressed this by comparing behavioral data from monkeys that had received one of two established deafferentation spinal injury models in monkeys (Darian-Smith et al., 2014, Fisher et al., 2019, 2020). Both injuries cut similar afferent pools supplying the thumb, index and middle fingers of one hand but each resulted in a very different corticospinal tract (CST) sprouting response. Following a cervical dorsal root lesion, the somatosensory CST retracted significantly, while the motor CST stayed largely intact. In contrast, when a dorsal column lesion was combined with the DRL, somatosensory and motor CSTs sprouted dramatically within the cervical cord. How these two responses relate to the behavioral outcome was not clear. Here we analyzed the behavioral outcome for the two lesions, and provide a clear example that sprouting extent does not track with behavioral recovery.

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.

Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery.

Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.

Motor Organization in Schizencephaly: Outcomes of Transcranial Magnetic Stimulation and Diffusion Tensor Imaging of Motor Tract Projections Correlate with the Different Domains of Hand Function.

OBJECTIVE: Schizencephaly is a rare congenital malformation that causes motor impairment. To determine the treatment strategy, each domain of the motor functions should be appropriately evaluated. We correlated a color map of diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) with the hand function test (HFT) to identify the type of hand function that each test (DTI and TMS) reflects. Further, we attempted to demonstrate the motor neuron organization in schizencephaly. METHOD: This retrospective study was conducted on 12 patients with schizencephaly. TMS was conducted in the first dorsal interosseous (FDI), biceps (BB), and deltoid muscles of the upper extremity, and contralateral MEP (cMEP) and ipsilateral MEP (iMEP) were recorded. The HFT included the grip strength, box and block (B&B), and 9-hole peg test. The schizencephalic cleft was confirmed using magnetic resonance imaging, and the corticospinal tract (CST) was identified using the color map of DTI. The symmetry indices for the peduncle and CST at pons level were calculated as the ratios of the cross-sectional area of the less-affected side and that of the more-affected side. RESULT: In the more-affected hemisphere TMS, no iMEP was obtained. In the less-affected hemisphere TMS, the iMEP response was detected in 9 patients and cMEP in all patients, which was similar to the pattern observed in unilateral lesion. Paretic hand grip strength was strongly correlated with the presence of iMEP (p = 0.044). The symmetry index of the color map of DTI was significantly correlated with the B&B (p = 0.008, R 2 = 0.416), whereas the symmetry index of the peduncle was not correlated with all HFTs. CONCLUSION: In patients with schizencephaly, the iMEP response rate is correlated with the hand function related to strength, while the symmetricity of the CST by the color map of DTI is correlated with the hand function associated with dexterity. Additionally, we suggest the possible motor organization pattern of schizencephaly following interhemispheric competition.

Functional and Structural Changes in the Corticospinal Tract of Streptozotocin-Induced Diabetic Rats.

This study aimed to reveal functional and morphological changes in the corticospinal tract, a pathway shown to be susceptible to diabetes. Type 1 diabetes was induced in 13-week-old male Wistar rats administered streptozotocin. Twenty-three weeks after streptozotocin injection, diabetic animals and age-matched control animals were used to demonstrate the conduction velocity of the corticospinal tract. Other animals were used for morphometric analyses of the base of the dorsal funiculus of the corticospinal tract in the spinal cord using both optical and electron microscopy. The conduction velocity of the corticospinal tract decreased in the lumbar spinal cord in the diabetic animal, although it did not decrease in the cervical spinal cord. Furthermore, atrophy of the fibers of the base of the dorsal funiculus was observed along their entire length, with an increase in the g-ratio in the lumbar spinal cord in the diabetic animal. This study indicates that the corticospinal tract fibers projecting to the lumbar spinal cord experience a decrease in conduction velocity at the lumbar spinal cord of these axons in diabetic animals, likely caused by a combination of axonal atrophy and an increased g-ratio due to thinning of the myelin sheath.

Corticospinal Motor Circuit Plasticity After Spinal Cord Injury: Harnessing Neuroplasticity to Improve Functional Outcomes.

Spinal cord injury (SCI) is a devastating condition that affects approximately 294,000 people in the USA and several millions worldwide. The corticospinal motor circuitry plays a major role in controlling skilled movements and in planning and coordinating movements in mammals and can be damaged by SCI. While axonal regeneration of injured fibers over long distances is scarce in the adult CNS, substantial spontaneous neural reorganization and plasticity in the spared corticospinal motor circuitry has been shown in experimental SCI models, associated with functional recovery. Beneficially harnessing this neuroplasticity of the corticospinal motor circuitry represents a highly promising therapeutic approach for improving locomotor outcomes after SCI. Several different strategies have been used to date for this purpose including neuromodulation (spinal cord/brain stimulation strategies and brain-machine interfaces), rehabilitative training (targeting activity-dependent plasticity), stem cells and biological scaffolds, neuroregenerative/neuroprotective pharmacotherapies, and light-based therapies like photodynamic therapy (PDT) and photobiomodulation (PMBT). This review provides an overview of the spontaneous reorganization and neuroplasticity in the corticospinal motor circuitry after SCI and summarizes the various therapeutic approaches used to beneficially harness this neuroplasticity for functional recovery after SCI in preclinical animal model and clinical human patients' studies.

The Strength of the Corticospinal Tract Not the Reticulospinal Tract Determines Upper-Limb Impairment Level and Capacity for Skill-Acquisition in the Sub-Acute Post-Stroke Period.

Background. Upper-limb impairment in patients with chronic stroke appears to be partly attributable to an upregulated reticulospinal tract (RST). Here, we assessed whether the impact of corticospinal (CST) and RST connectivity on motor impairment and skill-acquisition differs in sub-acute stroke, using transcranial magnetic stimulation (TMS)-based proxy measures. Methods. Thirty-eight stroke survivors were randomized to either reach training 3-6 weeks post-stroke (plus usual care) or usual care only. At 3, 6 and 12 weeks post-stroke, we measured ipsilesional and contralesional cortical connectivity (surrogates for CST and RST connectivity, respectively) to weak pre-activated triceps and deltoid muscles with single pulse TMS, accuracy of planar reaching movements, muscle strength (Motricity Index) and synergies (Fugl-Meyer upper-limb score). Results. Strength and presence of synergies were associated with ipsilesional (CST) connectivity to the paretic upper-limb at 3 and 12 weeks. Training led to planar reaching skill beyond that expected from spontaneous recovery and occurred for both weak and strong ipsilesional tract integrity. Reaching ability, presence of synergies, skill-acquisition and strength were not affected by either the presence or absence of contralesional (RST) connectivity. Conclusion. The degree of ipsilesional CST connectivity is the main determinant of proximal dexterity, upper-limb strength and synergy expression in sub-acute stroke. In contrast, there is no evidence for enhanced contralesional RST connectivity contributing to any of these components of impairment. In the sub-acute post-stroke period, the balance of activity between CST and RST may matter more for the paretic phenotype than RST upregulation per se.

Contribution of altered corticospinal microstructure to gait impairment in children with cerebral palsy.

OBJECTIVE: Corticospinal tract (CST) injury may lead to motor disorders in children with Cerebral Palsy (CP). However, the precise underlying mechanisms are still ambiguous. We aimed to characterize the CST structure and function in children with CP and determine their contributions to balance and gait impairments. METHOD: Twenty-six children with spastic CP participated. Transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) were utilized to characterize CST structure and function. Common clinical measures were used to assess gait speed, endurance and balance, and mobility. RESULTS: CST structure and function were significantly altered in children with CP. Different abnormal patterns of CST structure were identified as either abnormal appearance of brain hemispheres (Group-1) or semi-normal CST appearance (Group-2). We found significant correlations between the DTI parameters of the more affected CST and gait features only in Group-1. CONCLUSION: CST structure and function are abnormal in children with CP and these abnormalities may contribute to balance and gait impairment in some children with CP. SIGNIFICANCE: Our findings may lead to the development of further investigations on the mechanisms underlying gait impairment in children with CP and on decision-making for more effective rehabilitation.

Relationship Between Motor Function, DTI, and Neurophysiological Parameters in Patients with Stroke in the Recovery Rehabilitation unit.

OBJECTIVES: We investigated the relationship between pyramidal tract evaluation indexes (i.e., diffusion tensor imaging, transcranial magnetic stimulation (TMS)-induced motor-evoked potential (MEP), and central motor conduction time (CMCT) on admission to the recovery rehabilitation unit) and motor functions at discharge in patients with ischemic or hemorrhagic stroke. MATERIALS AND METHODS: Seventeen patients were recruited (12 men; 57.9 ± 10.3 years). The mean fractional anisotropy (FA) values of the right and left posterior limbs of the internal capsule were estimated using a computer-automated method. We determined the ratios of FA values in the affected and unaffected hemispheres (rFA), TMS-induced MEP, and the ratios of CMCT in the affected and unaffected hemispheres (rCMCT) and examined their association with motor functions (Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT)) at discharge. RESULTS: Higher rFA values of the posterior limb of the internal capsule on admission to the recovery rehabilitation unit led to a better recovery of upper limb function (FMA: r = 0.78, p < 0.001; ARAT: r = 0.74, p = 0.001). Patients without MEP had poorer recovery of upper limb function than those with MEP (FMA: p < 0.001; ARAT: p = 0.001). The higher the rCMCT, the poorer the recovery of upper limb function (ARAT: r = -0.93, p < 0.001). However, no association was observed between the pyramidal tract evaluation indexes and recovery of lower limb motor function. CONCLUSIONS: Evaluating the pyramidal tract is useful for predicting upper limb function prognosis, but not for lower limb function prognosis.

Improved white matter integrity after contralateral seventh cervical nerve transfer measured by tractographic representation.

Contralateral C7 (CC7) nerve transfer surgery was shown to significantly improve the spasticity condition and the motor function of paralyzed arms. However, the involvement of the white matter tract in the recovery process is not well established. We here investigated the possible biologic explanation for this phenomenon. A 62-year-old female patient, who suffered from spastic hemiparesis due to intracranial hemorrhage, underwent CC7 transfer surgery 13 years after the initial stroke event. Six months after the surgery, the patient's Modified Ashworth Scale and Fugl-Myere score improved, even though no specific rehabilitation programs were applied. Diffusion tensor imaging (DTI) was performed before and 6 months after the surgery. The pre-surgery DTI showed both ipsilesional and contralesional CST from the cerebral peduncles to the cortices. After surgery, however, only the contralesional CST was observed. In conclusion, functional alterations of the brain white matter tract after CC7 nerve transfer surgery possibly provided a neurophysiological substrate for ameliorating the spasticity and improving the motor function in a spastic hemiplegia patient.

The Use of Motor-Evoked Potentials in Clinical Trials in Multiple Sclerosis.

SUMMARY: Motor-evoked potentials (MEPs) can be used to assess the integrity of the descending corticospinal tract in the laboratory. Evoked potentials (EPs) have been widely used in the past for the diagnosis of multiple sclerosis (MS), but they are now becoming more useful in assessing the prognosis of the disease. Motor-evoked potentials have been included in EP scales that have demonstrated good correlations with clinical disability. Soon after the onset of MS, it is possible to detect an ongoing process of neurodegeneration and axonal loss. Axonal loss is probably responsible for the disability and disease progression that occurs in MS. Given the good correlations of EPs in detecting disease progression in MS, they have been used to monitor the effects of drugs used to treat the disease. Several clinical trials used MEPs as part of their EP evaluation, but MEPs have never been used as a measure of efficacy in clinical trials testing neuroprotective agents, although MEPs could be a very promising tool to measure neuroprotection and remyelination resulting from these drugs. To be used in multicenter clinical trials, MEP readings should be comparable between centers. Standardized multicenter EP assessment with central reading has been demonstrated to be feasible and reliable. Although MEP measurements have been correlated with clinical scores and other measures of neurodegeneration, further validation of MEP amplitude measurements is needed regarding their validity, reliability, and sensitivity before they can be routinely used in clinical drug trials in MS.

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.

Recurrent ipsilateral hemiparesis in a patient with both uncrossed corticospinal tracts and reorganization of cortical motor areas - An opportune visitation of the motor tracts.

We report the case of a patient who experienced recurrent ipsilateral hemiparesis in the setting of predominantly-uncrossed corticospinal tracts, with concomitant neuronal reorganization of the cortical motor maps, and the presence of aberrant interhemispheric connections. Their presence was supported by our results from diffusion tensor imaging tractography, functional magnetic resonance imaging, and transcranial magnetic stimulation. To our knowledge, this has never been reported before, and provides valuable insights into the mechanisms behind post-stroke motor recovery.

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.