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There is neuroanatomical and clinical evidence that the corticospinal tract governs the patterns of pareses in sporadic ALS. These patterns are mirrored by phylogenetically young monosynaptic corticomotor neuronal connections. It is well known that, clinically, dysfunction of the deltoid muscle contributes considerably to the early disability of the ALS patient. In this study, we prospectively compared the degree of pareses of the deltoid muscle with the triceps and biceps brachii in N = 71 patients (426 muscles). We could show that the extent of involvement of the deltoid muscle early in the disease process resembles that of the biceps rather than the triceps brachii. This pattern is consistent with functional data of the corticospinal monosynaptic connectivity of all three muscles., Competing Interests: Declarations. Conflicts of interest: None., (© 2025. The Author(s).)

Background: Primary motor cortex (M1) organization and quadriceps femoris excitability may change after anterior cruciate ligament injury (ACLi) and anterior cruciate ligament reconstruction (ACLr), as demonstrated by transcranial magnetic stimulation (TMS) studies., Objective: To systematically review studies evaluating changes in quadriceps femoris corticospinal and intracortical excitability in subjects with ACLi and ACLr., Methods: Database searches were conducted in PubMed, Embase, Scopus, and ScienceDirect, with the last search performed on November 23, 2023. Newcastle-Ottawa Scale and a specific checklist for evaluating descriptions in studies using TMS assessment were used. Continuous variables were expressed as mean and standard deviation and represented by the estimated difference from the mean and 95% confidence interval (CI). Heterogeneity was assessed by Chi 2 and I 2 and the level of statistical significance was 5%., Results: Fourteen studies, comprising 381 individuals, using TMS were identified. Meta-analysis results showed significantly higher motor threshold (MT) in ACLi/ACLr individuals compared to healthy controls ( p  < .01, mean difference 6.72). Additionally, MTs were significantly higher on the uninjured side compared to healthy controls ( p  < .0001, mean difference 3.82). Motor-evoked potentials (MEP) amplitude was significantly higher on the uninjured side compared to the injured side ( p  < .00001, mean difference 0.01). Short-interval intracortical inhibition (SICI) amplitude was significantly lesser on the injured limb compared to the uninjured side ( p  < .00001, mean difference 0.50)., Conclusion: Quadriceps MT and SICI are altered in ACLi and ACLr populations, and minor alterations were identified in MEP, demonstrating brain changes related to anterior cruciate ligament injury and/or reconstruction.

Purpose: Direct-wave (D-wave) neuromonitoring is a direct measure of corticospinal tract integrity that detects potential injury during spinal cord surgery. Epidural placement of electrodes used for D-wave measurements can result in high electrical impedances resulting in substantial signal noise that can compromise signal interpretation. Subdural electrode placement may offer a solution., Methods: Medical records for consecutive patients with epidural and subdural D-wave monitoring were reviewed. Demographic and clinical information including preoperative and postoperative motor strength were recorded. Neuromonitoring charts were reviewed to characterize impedances and signal amplitudes of D-waves recorded epidurally (before durotomy) and subdurally (following durotomy). Nonparametric statistics were used to compare epidural and subdural D-waves., Results: Ten patients (50% women, median age 50.5 years) were analyzed, of which five patients (50%) were functionally independent (modified McCormick grade ≤ II) preoperatively. D-waves were successfully acquired by subdural electrodes in eight cases and by epidural electrodes in three cases. Subdural electrode placement was associated with lower impedance values ( P = 0.011) and a higher baseline D-wave amplitude ( P = 0.007) relative to epidural placement. No association was observed between D-wave obtainability and functional status, and no adverse events relating to subdural electrode placement were encountered., Conclusions: Subdural electrode placement allows successful D-wave acquisition with accurate monitoring, clearer waveforms, and a more optimal signal-to-noise ratio relative to epidural placement. For spinal surgeries where access to the subdural compartment is technically safe and feasible, surgeons should consider subdural placement when monitoring D-waves to optimize clinical interpretation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Acute intermittent hypoxia (AIH) enhances human motor function after incomplete spinal cord injury. Although the underlying mechanisms in humans are unknown, emerging evidence indicates that AIH facilitates corticospinal excitability to the upper limb. However, the functional relevance of this plasticity remains unexplored, and it is unclear whether similar plasticity can be induced for lower limb motor areas. We recently demonstrated that AIH improves motor adaptation, motor savings, and metabolic efficiency during split-belt walking. Thus, we hypothesized that AIH increases lower limb excitability and that these enhancements would predict the magnitude of motor learning and the corresponding reductions in net metabolic power. We assessed tibialis anterior (TA) excitability using transcranial magnetic stimulation and quantified changes in spatiotemporal asymmetries and net metabolic power in response to split-belt speed perturbations. We show that AIH enhances TA excitability, and that the magnitude of this facilitation positively correlates with greater spatiotemporal adaptation. Notably, we demonstrate a novel association between increased excitability and reduced net metabolic power during motor adaptation and motor savings. Together, our results suggest that AIH-induced gains in excitability predict both the magnitude of motor learning and the associated metabolic efficiency. Determining indices of AIH-induced improvements in motor performance is critical for optimizing its therapeutic reach., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The importance of corticospinal tract (CST) integrity in upper limb recovery poststroke is well established, but its association with standing balance and walking remains unclear. This meta-analysis aimed to establish the relationship between CST and non-CST motor tract integrity, and clinical scores of standing balance and walking poststroke., Methods: In July 2024, five databases were searched for studies, focusing on diffusion MRI metrics and clinical scores of standing balance and/or walking independence poststroke. Meta-analyses were conducted to pool correlation coefficients (r) and group differences (d) based on CST integrity., Results: Twenty-two studies were included. Cross-sectional analysis showed no correlation ( r  < .25) between CST metrics and the functional ambulation category (FAC) in the sub-acute phase. Weak prognostic associations were found for CST-FA and CST-FN with FAC. Significant FAC score differences were found between preserved- and disrupted CST groups in the sub-acute (d = .79) and chronic (d = 1.07) phase and for prognostic analysis (d = 1.40). Non-CST metrics showed no cross-sectional associations and mixed prognostic associations., Conclusions: CST integrity was not significantly associated with standing balance or walking independence in the sub-acute phase. Early CST integrity showed weak prognostic value for walking at 6 months. Multimodal longitudinal research is needed to improve lower limb recovery prognostics.

The ability of neurons to sense and respond to damage is crucial for maintaining homeostasis and facilitating nervous system repair. For some cell types, notably dorsal root ganglia and retinal ganglion cells, extensive profiling has uncovered a significant transcriptional response to axon injury, which influences survival and regenerative outcomes. In contrast, the injury responses of most supraspinal cell types, which display limited regeneration after spinal damage, remain mostly unknown. In this study, we used single-nuclei sequencing in adult male and female mice to profile the transcriptional responses of diverse supraspinal cell types to spinal injury. Surprisingly, thoracic spinal injury induced only modest changes in gene expression across all populations, including corticospinal tract (CST) neurons. Additionally, CST neurons exhibited minimal response to cervical injury but showed a much stronger reaction to intracortical axotomy, with upregulation of numerous regeneration and apoptosis-related transcripts shared with injured DRG and RGC neurons. Thus, the muted response of CST neurons to spinal injury is linked to the injury's distal location, rather than intrinsic cellular characteristics. More broadly, these findings indicate that a central challenge for enhancing regeneration after a spinal injury is the limited detection of distant injuries and the subsequent modest baseline neuronal response., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Introduction: Functional electrical stimulation (FES) is used to retrain motor function in neurological disorders but typically requires multiple sessions and shows limited benefits in chronic cases. Low-intensity transcranial focused ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) method offering greater focality and deeper penetration than current NIBS techniques. TUS delivered in a theta burst pattern (tbTUS) for 80 s produces neuroplastic changes with long-term potentiation-like effects lasting up to 60 min in healthy adults. Since tbTUS increases cortical excitability, combining it with FES may enhance neuroplasticity. We hypothesized that combining tbTUS with FES would result in increased corticospinal excitability compared to FES alone and lead to greater improvement in fine motor skills as assessed by Nine-Hole Peg Test (NHPT) scores., Methods: Fifteen healthy participants underwent two study visits consisting of real or sham tbTUS of the left motor cortex immediately followed by 30 min of FES of the first dorsal interosseous (FDI) and the opponens pollicis (OP) muscles for fine motor function training of the right hand. Motor-evoked potentials (MEPs) were recorded from the right FDI, OP, and abductor digiti minimi (ADM) muscles at baseline (BL), immediately after real or sham tbTUS (T0), immediately after 30 min of FES training (T45), and at 15 (T65) and 30 min (T80) post-FES. NHPT was delivered at BL and at T80., Results: Data from 14 participants were analyzed. It showed a significant decrease in MEP amplitudes of FDI and OP at T45 following only real tbTUS+FES with a return to BL at T80. No significant changes were seen in the NHPT scores in either condition., Conclusion: Real tbTUS+FES combined with voluntary movement results in immediate corticospinal inhibition with a return to BL at ∼20 min post-stimulation suggestive of homeostatic metaplasticity. These findings highlight the potential of tbTUS+FES as a neuromodulatory intervention, warranting further exploration in neurological conditions for therapeutic applications., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Multiple sclerosis (MS) is a central nervous system disease involving gray and white matters. Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) could help identify potential markers of disease evolution, disability, and treatment response. This work evaluates the relationship between intracortical inhibition and facilitation, motor cortex lesions, and corticospinal tract (CST) integrity. Consecutive adult patients with progressive MS were included. Sociodemographic and clinical data were collected. MRI was acquired to assess primary motor cortex lesions (double inversion and phase-sensitive inversion recovery) and CST integrity (diffusion tensor imaging). TMS outcomes were obtained: motor evoked potentials (MEP) latency, resting motor threshold, short-interval intracortical facilitation (ICF) and inhibition. Correlation analysis was performed. Twenty-five patients completed the study (13 females, age: 55.60 ± 11.49 years, Expanded Disability Status Score: 6.00 ± 1.25). Inverse correlations were found between ICF mean and each of CST radial diffusivity (RD) (ρ =-0.56; p < 0.01), CST apparent diffusion coefficient (ADC) (ρ=-0.44; p = 0.03), and disease duration (ρ=-0.46; p = 0.02). MEP latencies were directly correlated with disability scores (ρ = 0.55; p < 0.01). High ADC/RD and low ICF have been previously reported in patients with MS. While the former could reflect structural damage of the CST, the latter could hint towards an aberrant synaptic transmission as well as a depletion of facilitatory compensatory mechanisms that helps overcoming functional decline. The findings suggest concomitant structural and functional abnormalities at later disease stages that would be accompanied with a heightened disability. The results should be interpreted with caution mainly because of the small sample size that precludes further comparisons (e.g., treated vs. untreated patients, primary vs. secondary progressive MS). The role of these outcomes as potential MS biomarkers merit to be further explored., Competing Interests: Declarations. Competing interests: SA declares having received compensation from Sanofi Aventis, France; Novartis, France; Exoneural Network AB, Sweden and Ottobock, France. MC received compensation from Janssen Global Services LLC, Exoneural Network AB, Sweden, and Ottobock, France. The remaining authors declare no conflicts of interest. Data will be made available by the corresponding author upon reasonable requests., (© 2024. The Author(s).)

This review verified the extent, variety, quality and main findings of studies that have tested the neurophysiological and clinical effects of muscle tendon vibration (VIB) in individuals with sensorimotor impairments. The search was conducted on PubMed, CINAHL, and SportDiscuss up to April 2024. Studies were selected if they included humans with neurological impairments, applied VIB and used at least one measure of corticospinal excitability using transcranial magnetic stimulation (TMS). Two investigators assessed the studies' quality using critical appraisal checklists and extracted relevant data. The 10 articles included were diverse in populations and methods, generally rated as 'average' to 'good' quality. All studies reported an increased corticospinal excitability in the vibrated muscle, but the effects of VIB on non-vibrated muscles remain unclear. Positive clinical changes in response to VIB were reported in a few studies, such as a decreased spasticity and improved sensorimotor function. These changes were sometimes correlated with corticospinal effects, suggesting a link between VIB-induced plasticity and clinical improvements. Despite the limited and heterogeneous literature, this review supports the facilitatory influence of VIB on motor outputs controlling vibrated muscles, even with altered sensorimotor functions. It highlights knowledge gaps and suggests future research directions on VIB mechanisms and clinical implications.

Background: There is no clear consensus on the anatomical substrates required for recovery from lower limb (LL) impairment after stroke. Knowledge of biomarkers, such as white matter integrity (WMI), could fill this knowledge gap., Objectives: To analyze the associations between WMI of the corticospinal tract (CST) and corticoreticulospinal pathway (CRP) and LL motor impairment after stroke, in terms of synergistic control and muscle strength. It also explores whether any associations depend on time post-stroke., Methods: In April 2023, PubMed, Web of Science, and Scopus databases were systematically searched for studies associating WMI of the CST and CRP and LL motor impairment after stroke. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scales., Results: Nineteen studies were included, 15 about the association between CST and motor impairment, and 4 concerning CST and CRP. Associations were consistently found between higher WMI of the CST and greater muscle strength, but not with synergistic control. There were no clear associations between WMI of the CRP and muscle strength, and associations could not be analyzed for synergistic control. The results could not determine whether the associations are time dependent., Conclusions: The results of this review supported using WMI of the CST to understand LL muscle strength after stroke. However, the same cannot be said for LL synergistic control due to the small number of studies. There was no clear evidence of an association between WMI of the CRP and LL muscle strength or synergistic control due to mixed results or a lack of studies., Competing Interests: Conflicts of interest The authors declare no competing interest., (Copyright © 2024 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Transcranial magnetic stimulation (TMS) interventions could feasibly treat stroke-related motor impairments, but their effects are highly variable. Brain state-dependent TMS approaches are a promising solution to this problem, but inter-individual variation in lesion location and oscillatory dynamics can make translating them to the poststroke brain challenging. Personalized brain state-dependent approaches specifically designed to address these challenges are needed., Methods: As a first step towards this goal, we tested a novel machine learning-based EEG-TMS system that identifies personalized brain activity patterns reflecting strong and weak corticospinal tract (CST) activation (strong and weak CST states) in healthy adults in real-time. Participants completed a single-session study that included the acquisition of a TMS-EEG-EMG training dataset, personalized classifier training, and real-time EEG-informed single-pulse TMS during classifier-predicted personalized CST states., Results: MEP amplitudes elicited in real-time during classifier-predicted personalized strong CST states were significantly larger than those elicited during corresponding weak and random CST states. MEP amplitudes elicited in real-time during classifier-predicted personalized strong CST states were also significantly less variable than those elicited during corresponding weak CST states. Personalized CST states lasted for ∼1-2 s at a time and ∼1 s elapsed between consecutive similar states. Individual participants exhibited unique differences in spectro-spatial EEG patterns between classifier-predicted personalized strong and weak CST states., Conclusion: Our results show for the first time that personalized whole-brain EEG activity patterns predict CST activation in real-time in healthy humans. These findings represent a pivotal step towards using personalized brain state-dependent TMS interventions to promote poststroke CST function., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Hussain reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to determine the maximum safe spatial-peak pulse-average intensity (I SPPA ) of low-intensity focused ultrasound stimulation (LIFUS) in stroke patients and explore its effect on motor learning and corticospinal excitability., Methods: We adopted the classic 3 + 3 design to escalate I SPPA (estimated in-vivo transcranial value) from 0, 1, 2, 4, 6, to 8 W/cm 2 . Stopping rules were pre-defined: 2 nd -degree scalp burn, clinical seizure, new lesion on diffusion-weighted imaging or major reduction in apparent diffusion coefficient, and participant discontinuation due to any reason. We applied 12-min LIFUS over the ipsilesional motor cortex while participants were concurrently practicing 3 blocks of a motor sequence learning (MSL) task using the affected hand. We measured MSL (response time) and corticospinal excitability (motor evoked potential) pre- and post-stimulation and compared MSL and corticospinal excitability between the LOW (0, 1, and 2 W/cm 2 ) and HIGH (4, 6, and 8 W/cm 2 ) groups., Results: I SPPA was escalated to 8 W/cm 2 with 18 stroke participants without meeting the stopping rules. Compared to the LOW, more participants in the HIGH performed better on MSL (6/9 vs. 0/9, p = 0.009) and showed a sign of greater corticospinal excitability (7/9 vs. 5/9, p = 0.62)., Interpretation: Our phase-I safety study suggests that one session of LIFUS up to 8 W/cm 2 I SPPA is safe and feasible in stroke patients, and LIFUS at high intensity induces positive changes in both MSL and corticospinal excitability. The next logical step is to conduct a phase-II trial testing the efficacy of LIFUS and continuously monitoring its safety profiles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wuwei Feng is the grant recipient of an innovative project award from the American Heart Association. Wuwei Feng & Xiaoning Jiang have an ultrasound stimulation related provisional patent filed to United States Patent and Trademark Office. The rest of co-authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

In a recently developed associative rehabilitative brain-computer interface (BCI) system, electroencephalography (EEG) is used to identify the most active phase of the motor cortex during attempted movement and deliver precisely timed peripheral stimulation during training. This approach has been demonstrated to facilitate corticospinal excitability and functional recovery in patients with lower limb weakness following stroke. The current study expands those findings by investigating changes in corticospinal excitability following the associative BCI intervention in patients with post stroke with upper limb weakness. In a randomized controlled trial, 24 patients with subacute stroke, subdivided into an intervention group and a "sham" control group, performed 30 wrist extensions. The intervention comprised 30 pairings of single peripheral nerve stimulation at the motor threshold, timed so that the generated afferent volley arrived at the motor cortex during the peak negativity of the movement-related cortical potential (MRCP), which was identified with EEG. The sham group underwent the same intervention, though the intensity of the nerve stimulation was below the perception threshold. Immediately after training, patients in the associative group exhibited significantly larger amplitudes of muscular-evoked potentials, compared with pretraining measurements in response to transcranial magnetic stimulation. These changes persisted for at least 30 min and were not observed in the sham group. We demonstrate that motor-evoked potential amplitudes increased significantly following paired associative BCI training targeting upper limb muscles in patients with subacute stroke, which is in line with results from lower limb studies. NEW & NOTEWORTHY We have demonstrated that a single training session with an associative brain-computer interface increased corticospinal excitability in patients suffering from upper limb weakness following stroke. This is the first time such an effect is described in the upper limb, which paves the way for effect augmentation of existing upper limb rehabilitation protocols.

Background: Evaluation of the structural integrity and functional excitability of the corticospinal tract (CST) is likely to be important in predicting motor recovery after stroke. Previous reports are inconsistent regarding a possible link between CST structure and CST function in this setting. This study aims to investigate the structure‒function relationship of the CST at the acute phase of stroke (<7 days)., Methods: We enrolled 70 patients who had an acute ischaemic stroke with unilateral upper extremity (UE) weakness. They underwent a multimodal assessment including clinical severity (UE Fugl Meyer at day 7 and 3 months), MRI to evaluate the CST lesion load and transcranial magnetic stimulation to measure the maximum amplitude of motor evoked potential (MEP)., Results: A cross-sectional lesion load above 87% predicted the absence of MEPs with an accuracy of 80.4%. In MEP-positive patients, the CST structure/function relationship was bimodal with a switch from a linear relationship (rho=-0.600, 95% CI -0.873; -0.039, p<0.03) for small MEP amplitudes (<0.703 mV) to a non-linear relationship for higher MEP amplitudes (p=0.72). In MEP-positive patients, recovery correlated with initial severity. In patients with a positive MEP <0.703 mV but not in patients with an MEP ≥0.703 mV, MEP amplitude was an additional independent predictor of recovery. In MEP-negative patients, we failed to identify any factor predicting recovery., Conclusion: This large multimodal study on the structure/function of the CST and stroke recovery proposes a paradigm change for the MEP-positive patients phenotypes and refines the nature of the link between structural integrity and neurophysiological function, with implications for study design and prognostic information., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: There is limited information on brain perfusion single-photon emission computed tomography (SPECT) findings related to motor outcomes in patients with stroke. We aimed to investigate whether brain SPECT can be used to determine motor outcomes after corona radiata infarction., Methods: Eighty-nine patients were recruited in this study. Brain SPECT and diffusion tensor tractography (DTT) were conducted to evaluate the state of the corticospinal tract (CST) within 7-30 days of corona radiata infarct. Motor outcome was measured 6 months after infarct onset and was evaluated using the modified Brunnstrom classification (MBC) and functional ambulation category (FAC) for motor function of the upper and lower extremities, respectively. The presence of hypoperfusion on brain SPECT was evaluated in the frontal lobe, temporal lobe, parietal lobe, basal ganglia, thalamus, and cerebellum on both the ipsilesional and contralesional sides. Statistical analysis was performed using multivariate logistic regression, comparing patients in which CST was spared versus interrupted., Results: Hypoperfusion in the contralesional cerebellum was indicative of poor recovery in both the upper and lower extremities after corona radiata infarction when the CST was interrupted. Additionally, when the CST was preserved, hypoperfusion in the ipsilesional thalamus was indicative of poor recovery of the lower extremities., Conclusion: Brain SPECT evaluation was shown to be a useful tool for predicting motor outcomes in patients with corona radiata infarcts.

Purpose: Motor evoked potential (MEP) characteristics are potential biomarkers of whether rehabilitation interventions drive motor recovery after stroke. The test-retest reliability of Transcranial Magnetic Stimulation (TMS) measurements in sub-acute stroke remains unclear. This study aims to determine the test-retest reliability of upper limb MEP measures elicited by non-neuronavigated transcranial magnetic stimulation in sub-acute-stroke., Methods: In two identical data collection sessions, 1-3 days apart, TMS measures assessed: motor threshold (MT), amplitude, latency (MEP-L), silent period (SP), recruitment curve slope in the biceps brachii (BB), extensor carpi radialis (ECR), and abductor pollicis brevis (APB) muscles of paretic and non-paretic upper limbs. Test-retest reliability was calculated using the intra-class correlation coefficient (ICC) and 95% confidence intervals (CI). Acceptable reliability was set at a lower 95% CI of 0.70 or above. The limits of agreement (LOA) and smallest detectable change (SDC) were calculated., Results: 30 participants with sub-acute stroke were included (av 36 days post stroke) reliability was variable between poor to good for the different MEP characteristics. The SDC values differed across muscles and MEP characteristics in both paretic and less paretic limbs., Conclusions: The present findings indicate there is limited evidence for acceptable test-retest reliability of non-navigated TMS outcomes when using the appropriate 95% CI for ICC, SDC and LOA values., Clinical Trial Registration: Current Controlled Trials: ISCRT 19090862, http://www.controlled-trials.com.

Many athletes with recurrent ankle sprains complain of neurophysiological deficits related to chronic ankle instability (CAI). However, it remains unclear how changes in the corticospinal pathway affect the potential risk of subsequent ankle sprains. The purpose of this study was to investigate whether the corticospinal excitability (input-output properties) and silent period (SP) could be related to the risk of subsequent ankle sprains among athletes. Forty-three male collegiate basketball athletes were enrolled, and 82 ankles were finally sorted into four ankle groups based on symptoms (CAI, sub-CAI, copers, and normal). The neurophysiological data was recorded in both ankles using transcranial magnetic stimulation (TMS) as baseline assessments. Subsequently, we prospectively followed the occurrence of subsequent ankle sprain injuries for 24 months (SG, subsequent ankle sprain group; NSG, non-sprain group). In the baseline assessment, we confirmed that the threshold of the input-output properties in the CAI group was higher than those in the normal group. After the follow-up, 22 ankles sustained subsequent ankle sprains (SGs). We also found that SGs exhibited a significantly longer SP at the middle and high stimulus intensities of TMS compared to NSGs (60 ankles) (middle: p = 0.012, Cohen's d = 0.644, and high: p = 0.020, Cohen's d = 0.590). These findings suggest that a prolonged SP could be a crucial factor affecting subsequent ankle sprains in athletes. To prevent further recurrent sports injuries, neurophysiologic probes, particularly a longer SP, might be a potential assessment tool to return to the field., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest related to the research, authorship, or publication of this article. Ethical approval This study was approved by the Research Ethics Committee of Jobu University (No.17-B03) and Toyo University (TU2023-022) in accordance with the Declaration of Helsinki. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent for publication All the participants gave written informed consent for publication of the result of this study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

After corticospinal tract (CST) stroke, several motor deficits can emerge in the upper extremity (UE), including diminished muscle strength, motor control, and muscle individuation. Both the ipsilesional CST and contralesional corticoreticulospinal tract (CReST) innervate the paretic UE, but their relationship to motor behaviors after stroke remains uncertain. In this cross-sectional study of 14 chronic stroke and 27 healthy subjects, we examined two questions: whether the ipsilesional CST and contralesional CReST differentially relate to chronic motor behaviors in the paretic arm and hand and whether the severity of motor deficits differs by proximal versus distal location. In the paretic biceps and first dorsal interosseous muscles, we used transcranial magnetic stimulation to measure the projection strengths of the ipsilesional CST and contralesional CReST. We also used quantitative testing to measure strength, motor control, and muscle individuation in each muscle. We found that stroke subjects had muscle strength comparable to healthy subjects but poorer motor control and muscle individuation. In both paretic muscles, stronger ipsilesional CST projections related to better motor control, whereas stronger contralesional CReST projections related to better muscle strength. Stronger CST projections related to better individuation in the biceps alone. The severity of motor control and individuation deficits was comparable in the arm and hand. These findings suggest that the ipsilesional CST and contralesional CReST have specialized but complementary roles in motor behaviors of the paretic arm and hand. They also suggest that deficits in motor control and muscle individuation are not segmentally biased, underscoring the functional extent and efficacy of these pathways. NEW & NOTEWORTHY The corticospinal (CST) and corticoreticulospinal (CReST) tracts are two major descending motor pathways. We examined their relationships to motor behaviors in paretic arm and hand muscles in chronic stroke. Stronger ipsilesional CST projections related to better motor control, whereas stronger contralesional CReST projections related to better muscle strength. Stronger CST projections are also uniquely related to better biceps individuation. These findings support the notion of specialized but complementary contributions of these pathways to human motor function.

Abstract: Pain-related motor adaptations may be enacted predictively at the mere threat of pain, before pain occurrence. Yet, in humans, the neurophysiological mechanisms underlying motor adaptations in anticipation of pain remain poorly understood. We tracked the evolution of changes in corticospinal excitability (CSE) as healthy adults learned to anticipate the occurrence of lateralized, muscle-specific pain to the upper limb. Using a Pavlovian threat conditioning task, different visual stimuli predicted pain to the right or left forearm (experiment 1) or hand (experiment 2). During stimuli presentation before pain occurrence, single-pulse transcranial magnetic stimulation was applied over the left primary motor cortex to probe CSE and elicit motor evoked potentials from target right forearm and hand muscles. The correlation between participants' trait anxiety and CSE was also assessed. Results showed that threat of pain triggered corticospinal inhibition specifically in the limb where pain was expected. In addition, corticospinal inhibition was modulated relative to the threatened muscle, with threat of pain to the forearm inhibiting the forearm and hand muscles, whereas threat of pain to the hand inhibited the hand muscle only. Finally, stronger corticospinal inhibition correlated with greater trait anxiety. These results advance the mechanistic understanding of pain processes showing that pain-related motor adaptations are enacted at the mere threat of pain, as sets of anticipatory, topographically organized motor changes that are associated with the expected pain and are shaped by individual anxiety levels. Including such anticipatory motor changes into models of pain may lead to new treatments for pain-related disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Nearly half of the amyotrophic lateral sclerosis (ALS) patients showed hyperintensity of the corticospinal tract (CST+), yet whether brain functional pattern differs between CST+and CST- patients remains obscure. In the current study, 19 ALS CST+, 41 ALS CST- patients and 37 healthy controls (HC) underwent resting state fMRI scans. We estimated local activity and connectivity patterns via the Amplitude of Low Frequency Fluctuations (ALFF) and the Network-Based Statistic (NBS) approaches respectively. The ALS CST+patients did not differ from the CST- patients in amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) score and disease duration. ALFF of the superior frontal gyrus (SFG) and the inferior frontal gyrus pars opercularis (OIFG) were highest in the HC and lowest in the ALS CST- patients, resulting in significant group differences (P FWE <0.05). NBS analysis revealed a frontal network consisting of connections between SFG, OIFG, orbital frontal gyrus, middle cingulate cortex and the basal ganglia, which exhibited HC>ALS CST+ > ALS CST- group differences (P FWE =0.037) as well. The ALFF of the OIFG was significantly correlated with ALSFRS-R (R=0.34, P=0.028) and mean connectivity of the frontal network was trend-wise significantly correlated with disease duration (R=-0.31, P=0.052) in the ALS CST- patients. However, these correlations were insignificant in ALS CST+patients (P values > 0.8). In conclusion, The ALS CST+patients exhibited different patterns of baseline functional activity and connectivity in the frontal cortex which may indicate a functional compensatory effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intracortical inhibitory/faciliatory measures are affected after stroke; however, the evidence is conflicting., Objective: This meta-analysis aimed to investigate the changes in motor threshold (MT), motor evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), and identify sources of study variability using a machine learning approach., Methods: We identified studies that objectively evaluated corticospinal excitability and intracortical inhibition/facilitation after stroke using transcranial magnetic stimulation. Pooled within- (ie, affected hemisphere [ AH ] vs unaffected hemisphere [ UH ]) and between-subjects (ie, AH and UH vs Control ) standardized mean differences were computed. Decision trees determined which factors accurately predicted studies that showed alterations in corticospinal excitability and intracortical inhibition/facilitation., Results: A total of 35 studies (625 stroke patients and 328 healthy controls) were included. MT was significantly increased and MEP was significantly decreased (ie, reduced excitability) in the AH when compared with the UH and Control ( P  < .01). SICI was increased (ie, reduced inhibition) for the AH when compared with the UH , and for the AH and UH when compared with Control ( P  < .001). ICF was significantly increased (ie, increased facilitation) in the AH when compared with UH ( P  = .016) and decreased in UH when compared with Control ( P  < 0.001). Decision trees indicated that demographic and methodological factors accurately predicted (73%-86%) studies that showed alterations in corticospinal and intracortical excitability measures., Conclusions: The findings indicate that stroke alters corticospinal and intracortical excitability measures. Alterations in SICI and ICF may reflect disinhibition of the motor cortex after stroke, which is contrary to the notion that stroke increases inhibition of the affected side., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: A teenager who suffered from left hemiparesis after traumatic brain injury underwent 18F-THK5351 PET 48, 286, and 810 days after the injury. The first scan showed slight uptake in the right corticospinal tract (CST), and the second scan showed intense uptake along the CST, which was significantly reduced in the third scan. The hemiparesis has improved between the first and second scans. 18F-THK5351 binds to monoamine oxidase B, which is expressed in reactive astrocytes (RAs). Recently, the beneficial role of RAs in plasticity and reconstruction after traumatic brain injury has been reported. 18F-THK5351 uptake may represent axonal remodeling accompanied with RAs in the CST., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Stroke is one of the leading causes of disability worldwide. Stroke-in-evolution is an essential issue as it is often associated with a worse outcome. Central motor conduction time (CMCT) is the time required for neural impulses to travel through the central nervous system to the target muscles. CMCT prolongation indicates dysfunction of the corticospinal tract. This study aims to investigate the impact of CMCT on clinical features and MRI characteristics in patients with acute ischemic stroke. A total of 94 patients with suspected acute ischemic stroke, with an average age of 67.13 ± 10.73 years old and 69.15 % being male, were enrolled in this study. All patients underwent evaluation for stroke risk factors, medical record review, CMCT examination (with CMCT (+) indicating CMCT prolongation), cranial MRI examinations, and data analysis. Compared to CMCT (-), the number of CMCT (+) subjects was significantly higher in all groups except the "Ever Stroke" group. The CMCT (+) group exhibited significantly higher values of "NIHSS" and "mRS" compared to the CMCT (-) group. After ANCOVA adjustment, the number of CMCT (+) subjects remained significantly higher only in the radiologically classified "New Pyramidal Lesion on MRI" and clinically classified "Stroke-In-Evolution" groups. In conclusion, CMCT serves as both a diagnostic indicator of acute ischemic stroke with weakness accompanied by new pyramidal lesions on brain MRI, rather than weakness associated with old lesions on brain MRI, and as a predictive marker for stroke progression during hospitalization., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective. Finger dexterity, and finger individuation in particular, is crucial for human movement, and disruptions due to brain injury can significantly impact quality of life. Understanding the neurological mechanisms responsible for recovery is vital for effective neurorehabilitation. This study explores the role of two key pathways in finger individuation: the corticospinal (CS) tract from the primary motor cortex and premotor areas, and the subcortical reticulospinal (RS) tract from the brainstem. We aimed to investigate how the cortical-reticular network reorganizes to aid recovery of finger dexterity following lesions in these areas. Approach. To provide a potential biologically plausible answer to this question, we developed an artificial neural network (ANN) to model the interaction between a premotor planning layer, a cortical layer with excitatory and inhibitory CS outputs, and RS outputs controlling finger movements. The ANN was trained to simulate normal finger individuation and strength. A simulated stroke was then applied to the CS area, RS area, or both, and the recovery of finger dexterity was analyzed. Main results. In the intact model, the ANN demonstrated a near-linear relationship between the forces of instructed and uninstructed fingers, resembling human individuation patterns. Post-stroke simulations revealed that lesions in both CS and RS regions led to increased unintended force in uninstructed fingers, immediate weakening of instructed fingers, improved control during early recovery, and increased neural plasticity. Lesions in the CS region alone significantly impaired individuation, while RS lesions affected strength and to a lesser extent, individuation. The model also predicted the impact of stroke severity on finger individuation, highlighting the combined effects of CS and RS lesions. Significance. This model provides insights into the interactive role of cortical and subcortical regions in finger individuation. It suggests that recovery mechanisms involve reorganization of these networks, which may inform neurorehabilitation strategies., (Creative Commons Attribution license.)

Background: This study investigates the potential of transcranial magnetic stimulation (TMS) to enhance spinal cord axon regeneration by modulating corticospinal pathways and improving motor nerve function recovery in rats with spinal cord injury (SCI)., New Method: TMS is a non-invasive neuromodulation technique that generates a magnetic field to activate neurons in the brain, leading to depolarization and modulation of cortical activity. Initially utilized for brain physiology research, TMS has evolved into a diagnostic and prognostic tool in clinical settings, with increasing interest in its therapeutic applications. However, its potential for treating motor dysfunction in SCI has been underexplored., Results: The TMS intervention group exhibited significant improvements compared to the control group across behavioral assessments, neurophysiological measurements, pathological analysis, and immunological markers., Comparison With Existing Methods: Unlike most studies that focus on localized spinal cord injury or muscle treatments, this study leverages the non-invasive, painless, and highly penetrating nature of TMS to focus on the corticospinal tracts, exploring its therapeutic potential for SCI., Conclusions: TMS enhances motor function recovery in rats with SCI by restoring corticospinal pathway integrity and promoting axonal regeneration. These findings highlight TMS as a promising therapeutic option for SCI patients with currently limited treatment alternatives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Relapsing-Remitting Multiple Sclerosis manifests various motor symptoms including impairments in corticospinal tract integrity, whose symptoms can be assessed using transcranial magnetic stimulation. Several factors, such as exercise and interlimb coordination, can influence the plastic changes in corticospinal tract. Previous work in healthy and chronic stroke survivors showed that the greatest improvement in corticospinal plasticity occurred during in-phase bilateral exercises of the upper limbs. Altered corticospinal plasticity due to bilateral lesions in the central nervous system is common after Multiple Sclerosis, yet the effect of in-phase bilateral exercise on the bilateral corticospinal plasticity in this cohort remains unclear. Our aim was to investigate the effects of in-phase bilateral exercises on central motor conduction time, motor evoked potential amplitude and latency, motor threshold and clinical measures in people with Relapsing-Remitting Multiple Sclerosis., Methods: Five people were randomized and recruited in this single case concurrent multiple baseline design study. The intervention protocol lasted for 12 consecutive weeks (30-60 minutes /session x 3 sessions / week) and included in-phase bilateral upper limb movements, adapted to different sports activities and to functional motor training. To define the functional relation between the intervention and the results, we conducted a visual analysis. If a potential sizeable effect was observed, we subsequently performed a statistical analysis., Results: Results demonstrated bilateral reduction of the motor threshold alongside with improvement of all clinical measures, but not in any other corticospinal plasticity measures., Conclusion: Our preliminary findings suggest that in-phase bilateral exercise affects motor threshold in people with Relapsing-Remitting Multiple Sclerosis. Therefore, this measure could potentially serve as a proxy for detecting corticospinal plasticity in this cohort. However, future studies with larger sample sizes should validate and potentially establish the effect of in-phase bilateral exercise on the corticospinal plasticity and clinical measures in this cohort., Trial Registration: Clinical trial registration: ClinicalTrials.gov NCT05367947., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sokratous et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Objectives: Clinical factors are not sufficient to fix a prognosis of recovery after stroke. Pyramidal tract or alternate motor fiber (aMF: reticulo-, rubrospinal pathways and transcallosal fibers) integrity and remodeling processes assessable by diffusion tensor MRI (DTI) and voxel-based morphometry (VBM) may be of interest. The primary objective was to study longitudinal cortical brain changes using VBM and longitudinal corticospinal tract changes using DTI during the first 4 months after lacunar cerebral infarction. The second objective was to determine which changes were correlated to clinical improvement., Methods: Twenty-one patients with deep brain ischemic infarct with pure motor deficit (NIHSS score ≥ 2) were recruited at Purpan Hospital and included. Motor deficit was measured [Nine peg hole test (NPHT), dynamometer (DYN), Hand-Tapping Test (HTT)], and a 3T MRI scan (VBM and DTI) was performed during the acute and subacute phases., Results: White matter changes: corticospinal fractional anisotropy (FA CST ) was significantly reduced at follow-up (approximately 4 months) on the lesion side. FAr (FA ratio in affected/unaffected hemispheres) in the corona radiata was correlated to the motor performance at the NPHT, DYN, and HTT at follow-up. The presence of aMFs was not associated with the extent of recovery. Grey matter changes: VBM showed significant increased cortical thickness in the ipsilesional premotor cortex at follow-up. VBM changes in the anterior cingulum positively correlated with improvement in motor measures between baseline and follow-up., Discussion: To our knowledge, this study is original because is a longitudinal study combining VBM and DTI during the first 4 months after stroke in a series of patients selected on pure motor deficit. Our data would suggest that good recovery relies on spared CST fibers, probably from the premotor cortex, rather than on the aMF in this group with mild motor deficit. The present study suggests that VBM and FA CST could provide reliable biomarkers of post-stroke atrophy, reorganization, plasticity and recovery., Gov Identifier: NCT01862172, registered May 24, 2013., (© 2024. The Author(s).)

Objectives: Neuroimaging studies of dyskinetic cerebral palsy (CP) are scarce and the neuropathological underpinnings are not fully understood. We delineated the corticospinal tract (CST) and cortico-striatal-thalamocortical (CSTC) pathways with probabilistic tractography to assess their (1) integrity and (2) association with motor functioning in people with dyskinetic CP., Methods: Diffusion weighted magnetic resonance images were obtained for 33 individuals with dyskinetic CP and 33 controls. Fractional anisotropy (FA) and mean diffusivity (MD) for the CST and the CSTC pathways were compared between groups. Correlation analyses were performed between tensor metric values and motor function scores of participants with dyskinetic CP as assessed by the Gross Motor Function Classification System (GMFCS), the Bimanual Fine Motor Function (BFMF), and the Manual Ability Classification System (MACS)., Results: White matter integrity in both the CST and the CSTC pathways was reduced in people with dyskinetic CP. The GMFCS, MACS and, less commonly, the BFMF were associated with FA and, particularly, MD in most portions of these pathways., Interpretation: The present study advances our understanding of the involvement of white matter microstructure in sensorimotor pathways and its relationship with motor impairment in people with dyskinetic CP. Our results are consistent with well-described relationships between upper limb function and white matter integrity in the CST and CSTC pathways in other forms of CP. This knowledge may ultimately help prognosis and therapeutic programmes., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: Parkinson's disease (PD) patients exhibit changes in mechanisms underlying movement preparation, particularly the suppression of corticospinal excitability - termed "preparatory suppression" - which is thought to facilitate movement execution in healthy individuals. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) being an attractive treatment for advanced PD, we aimed to study the potential contribution of this nucleus to PD-related changes in such corticospinal dynamics., Methods: On two consecutive days, we applied single-pulse transcranial magnetic stimulation to the primary motor cortex of 20 advanced PD patients treated with bilateral STN-DBS (ON vs. OFF), as well as 20 healthy control subjects. Motor-evoked potentials (MEPs) were elicited at rest or during movement preparation in an instructed-delay choice reaction time task including left- or right-hand responses. Preparatory suppression was assessed by expressing MEPs during movement preparation relative to rest., Results: PD patients exhibited a deficit in preparatory suppression when it was probed on the responding hand side, particularly when this corresponded to their most-affected hand, regardless of their STN-DBS status., Conclusions: Advanced PD patients displayed a reduction in preparatory suppression which was not restored by STN-DBS., Significance: The current findings confirm that PD patients lack preparatory suppression, as previously reported. Yet, the fact that this deficit was not responsive to STN-DBS calls for future studies on the neural source of this regulatory mechanism during movement preparation., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The corticospinal tract (CST) is considered the most important motor output pathway comprising fibers from the primary motor cortex (M1) and various premotor areas. Damage to its descending fibers after stroke commonly leads to motor impairment. While premotor areas are thought to critically support motor recovery after stroke, the functional role of their corticospinal output for different aspects of post-stroke motor control remains poorly understood., Methods: We assessed the differential role of CST fibers originating from premotor areas and M1 in the control of basal (single-joint muscle synergies and strength) and complex motor control (involving inter-joint coordination and visuomotor integration) using a novel diffusion imaging approach in chronic stroke patients., Results: While M1 sub-tract anisotropy was positively correlated with basal and complex motor skills, anisotropy of PMd, PMv, and SMA sub-tracts was exclusively associated with complex motor tasks. Interestingly, patients featuring persistent motor deficits showed an additional positive association between premotor sub-tract integrity and basal motor control., Interpretation: While descending M1 output seems to be a prerequisite for any form of upper limb movements, complex motor skills critically depend on output from premotor areas after stroke. The additional involvement of premotor tracts in basal motor control in patients with persistent deficits emphasizes their compensatory capacity in post-stroke motor control. In summary, our findings highlight the pivotal role of descending corticospinal output from premotor areas for motor control after stroke, which thus serve as prime candidates for future interventions to amplify motor recovery., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Children with spastic cerebral palsy (CP) have damage to the corticospinal tracts that are responsible for selective motor control (SMC). Force, velocity and timing of joint movement are related biomechanical features controlled by the corticospinal tracts (CSTs) that are important for skilled movement., Research Question: Does SMC influence knee joint biomechanics in spastic CP?, Methods: In this prospective study, relationships between SMC and knee biomechanics (peak torque, total work, average power) across a range of velocities (0-300 deg/s) were assessed using an isokinetic dynamometer in 23 children with spastic CP. SMC was assessed using Selective Control Assessment of the Lower Extremity (SCALE). Logistic and linear regression models were used to evaluate relationships between SCALE and biomechanical measures., Results: The ability to produce knee torque diminished with increasing velocity for both Low (0-4 points) and High (5-10 points) SCALE limb score groups (p < 0.01). More knees in the High group produced extension torque at 300 deg/s (p < 0.05) and flexion torque at 30, 90,180, 240 and 300 deg/s (p < 0.05). The ability to produce torque markedly decreased above 180 deg/s for Low group flexion. For knees that produced torque, significant positive correlations between SCALE limb scores and joint torque (0 and 120 deg/s), work (120 deg/s) and power (120 deg/s) were found (p < 0.05). Greater knee torque, work and power for the High group was found for the extensors at most velocities and the flexors for up to 120 deg/s (p < 0.05). Few Low group participants generated knee flexor torque above 120 deg/s limiting comparisons., Significance: Biomechanical impairments found for children with low SMC are concerning as skilled movements during gait, play and sport activities occur at high velocities. Differences in SMC should be considered when designing individualized assessments and interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Chronic low back pain (CLBP) impacts on spine movement. Altered sensorimotor integration can be involved. Afferents from the lumbo-pelvic area might be processed differently in CLBP and impact on descending motor control. This study aimed to determine whether afferents influence the corticomotor control of paravertebral muscles in CLBP. Fourteen individuals with CLBP (11 females) and 13 pain-free controls (8 females) were tested with transcranial magnetic stimulation (TMS) to measure the motor-evoked potential [MEP] amplitude of paravertebral muscles. Noxious and non-noxious electrical stimulation, and magnetic stimulation in the lumbo-sacral area were used as afferent stimuli and triggered 20 to 200 ms prior to TMS. EMG modulation elicited by afferent stimulation alone was measured to control net motoneuron excitability. MEP/EMG ratio was used as a measure of corticospinal excitability with control of net motoneuron excitability. MEP/EMG ratio was larger at 60, 80 and 100-ms intervals in CLBP compared to controls, and afferent stimulations alone reduced EMG amplitude greater in CLBP than controls at 100 ms. Our results suggest alteration in sensorimotor integration in CLBP highlighted by a greater facilitation of the descending corticospinal input to paravertebral muscles. Our results can help to optimise interventions by better targeting mechanisms., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Mobility impairment is common in multiple sclerosis (MS); however, agility has received less attention. Agility requires strength and neuromuscular coordination to elicit controlled propulsive rapid whole-body movement. Grip strength is a common method to assess whole body force production, but also reflects neuromuscular integrity and global brain health. Impaired agility may be linked to loss of neuromuscular integrity (reflected by grip strength or corticospinal excitability)., Objectives: We aimed to determine whether grip strength would be associated with agility and transcranial magnetic stimulation (TMS)-based indices of corticospinal excitability and inhibition in persons with MS having low disability. We hypothesized that low grip strength would predict impaired agility and reflect low corticospinal excitability., Methods: We recruited 34 persons with relapsing MS (27 females; median [range] age 45.5 [21.0-65.0] years) and mild disability (median [range] Expanded Disability Status Scale 2.0 [0-3.0]), as well as a convenience sample of age- and sex-matched apparently healthy controls. Agility was tested by measuring hop length during bipedal hopping on an instrumented walkway. Grip strength was measured using a calibrated dynamometer. Corticospinal excitability and inhibition were examined using TMS-based motor evoked potential (MEP) and corticospinal silent period (CSP) recruitment curves, respectively., Results: MS participants had significantly lower grip strength than controls independent of sex. Females with and without MS had weaker grip strength than males. There were no statistically significant sex or group differences in agility. After controlling for sex, weaker grip strength was associated with shorter hop length in controls only (r = 0.645, p < .05). Grip strength did not significantly predict agility in persons with MS, nor was grip strength predicted by corticospinal excitability or inhibition., Conclusions: In persons with MS having low disability, grip strength (normalized to body mass) was reduced despite having intact agility and walking performance. Grip strength was not associated with corticospinal excitability or inhibition, suggesting peripheral neuromuscular function, low physical activity or fitness, or other psychosocial factors may be related to weakness. Low grip strength is a putative indicator of early neuromuscular aging in persons with MS having mild disability and normal mobility., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

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.

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., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

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.

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.

Acute intermittent hypoxia (AIH) can induce sustained facilitation of motor output in people with spinal cord injury (SCI). Most studies of corticospinal tract excitability in humans have used 9% fraction inspired oxygen ([Formula: see text]) AIH (AIH-9%), with inconsistent outcomes. We investigated the effect of single sessions of 9% [Formula: see text] and 12% [Formula: see text] AIH (AIH-12%) on corticospinal excitability of a hand and leg muscle in able-bodied adults. Ten naïve participants completed three sessions on separate days comprising 15 epochs of 1 min of AIH-9%, AIH-12%, or sham (SHAM-21%) followed by 1 min of room air (21% [Formula: see text]) in a randomized crossover design. Motor-evoked potentials (MEPs; n = 30, ∼1 mV) elicited at rest by transcranial magnetic stimulation and maximal M-waves (M max ) evoked by peripheral nerve stimulation were measured from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles at baseline and at ∼0, 20, 40, and 60 min post intervention. AIH-9% induced the greatest reduction in peripheral oxygen saturation (to 85% vs. 93% and 100% in AIH-12% and SHAM-21%, respectively; P < 0.001) and the greatest increase in ventilation [by 22% vs. 12% and -3% in AIH-9%, AIH-12%, and SHAM-21%, respectively ( P < 0.001)]. There was no difference in MEP amplitudes (%M max ) after any of the three conditions (AIH-9%, AIH-12%, SHAM-21%) for both the FDI ( P = 0.399) and TA ( P = 0.582). Despite greater cardiorespiratory changes during AIH-9%, there was no evidence of corticospinal facilitation (tested with MEPs) in this study. Further studies could explore variability in response to AIH between individuals and other methods to measure motor facilitation in people with and without spinal cord injuries. NEW & NOTEWORTHY This is the first study that tests whether acute intermittent hypoxia (AIH) induces motor output facilitation in humans after two different doses of AIH (9% and 12% [Formula: see text]) and the reproducibility of participant responses after a repeat AIH intervention at 9% AIH. There was no motor output facilitation in response to either dose of AIH. The results question the effectiveness of a single 30-min session of AIH in inducing motor output facilitation, tested in this way.

Background: Upper limb motor impairment commonly occurs after stroke, impairing quality of life. Brain network reorganization likely differs between subgroups with differing impairment severity. This study explored differences in functional connectivity (FC) and corticospinal tract (CST) integrity between patients with mild/moderate versus severe hemiplegia poststroke to clarify the neural correlates underlying motor deficits., Method: Sixty chronic stroke patients with upper limb motor impairment were categorized into mild/moderate and severe groups based on Fugl-Meyer scores. Resting-state FC was assessed using functional near-infrared spectroscopy (fNIRS) to compare connectivity patterns between groups across motor regions. CST integrity was evaluated by inducing motor evoked potentials (MEP) via transcranial magnetic stimulation., Results: Compared to the mild/moderate group, the severe group exhibited heightened premotor cortex-primary motor cortex (PMC-M1) connectivity (t = 4.56, p < 0.01). Absence of MEP was also more frequent in the severe group (χ 2  = 12.31, p = 0.01). Bayesian models effectively distinguished subgroups and identified the PMC-M1 connection as highly contributory (accuracy = 91.30%, area under the receiver operating characteristic curve [AUC] = 0.86)., Conclusion: Distinct patterns of connectivity and corticospinal integrity exist between stroke subgroups with differing impairments. Strengthened connectivity potentially indicates recruitment of additional motor resources to compensate for damage. These findings elucidate the neural correlates underlying motor deficits poststroke and could guide personalized, network-based therapies targeting predictive biomarkers to improve rehabilitation outcomes., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Context: Individuals with shoulder impingement syndrome (SIS) exhibit changes in corticospinal excitability, scapular kinematics, and scapular muscle-activation patterns. To restore the scapular kinematics and muscle-activation patterns in individuals with SIS, treatment protocols usually include scapula-focused exercises, such as scapular-orientation and strength training., Objective: To investigate whether scapular-orientation and strength training can reverse the altered corticospinal excitability of recreational overhead athletes with SIS., Design: Randomized controlled clinical trial., Setting: University laboratory., Patients or Other Participants: Forty-one recreational overhead athletes with SIS: 20 in the scapular-orientation group (age = 26.45 ± 4.13 years, height = 171.85 ± 7.88 cm, mass = 66.70 ± 10.68 kg) and 21 in the strengthening group (age = 26.43 ± 5.55 years, height = 171.62 ± 5.87 cm, mass = 68.67 ± 10.18 kg)., Intervention(s): Both groups performed a 30-minute training protocol consisting of 3 exercises to strengthen the lower trapezius (LT) and serratus anterior muscles without overactivating the upper trapezius muscles. Participants in the scapular-orientation group were instructed to consciously activate their scapular muscles with electromyographic biofeedback and cues, whereas the strengthening group did not receive biofeedback or cues for scapular motion., Main Outcome Measure(s): Corticospinal excitability was assessed using transcranial magnetic stimulation. Scapular kinematics and muscle activation during arm elevation were also measured., Results: After training, both groups demonstrated an increase in motor-evoked potentials in the LT (P = .004) and increases in scapular upward rotation (P = .03), LT activation (P < .001), and serratus anterior activation (P < .001) during arm elevation. Moreover, the scapular-orientation group showed higher LT activation levels during arm elevation after training than the strengthening group (P = .03)., Conclusions: With or without biofeedback and cues, scapula-focused exercises improved scapular control and increased corticospinal excitability. Adding biofeedback and cues for scapular control during exercise helped facilitate greater LT activation, so feedback and cues are recommended during scapula-focused training., (© by the National Athletic Trainers' Association, Inc.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Conflicts of Interest The authors report no potential conflict of interests., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors have no financial or non-financial interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: A new paradigm for Transcranial Magnetic Stimulation (TMS), referred to as prolonged continuous theta burst stimulation (pcTBS), has recently received attention in the literature because of its advantages over high frequency repetitive TMS (HF-rTMS). Clinical advantages include less time per intervention session and the effects appear to be more robust and reproducible than HF-rTMS to modulate cortical excitability. HF-rTMS targeted at the primary motor cortex (M1) has demonstrated analgesic effects in patients with neuropathic pain but their mechanisms of action are unclear and pcTBS has been studied in healthy subjects only. This study examined the neural mechanisms that have been proposed to play a role in explaining the effects of pcTBS targeted at the M1 and DLPFC brain regions in neuropathic pain (NP) patients with Type 2 diabetes., Methods: Forty-two patients with painful diabetic neuropathy were randomized to receive a single session of pcTBS targeted at the left M1 or left DLPFC. pcTBS stimulation consisted of 1,200 pulses delivered in 1 min and 44 s with a 35-45 min gap between sham and active pcTBS stimulation. Both the activity of the descending pain system which was examined using conditioned pain modulation and the activity of the ascending pain system which was assessed using temporal summation of pain were recorded using a handheld pressure algometer by measuring pressure pain thresholds. The amplitude of the motor evoked potential (MEP) was used to measure motor corticospinal excitability and GABA activity was assessed using short (SICI) and long intracortical inhibition (LICI). All these measurements were performed at baseline and post-pcTBS stimulation., Results: Following a single session of pcTBS targeted at M1 and DLPFC, there was no change in BPI-DN scores and on the activity of the descending (measured using conditioned pain modulation) and ascending pain systems (measured using temporal summation of pain) compared to baseline but there was a significant improvement of >13% in perception of acute pain intensity, increased motor corticospinal excitability (measured using MEP amplitude) and intracortical inhibition (measured using SICI and LICI)., Conclusion: In patients with NP, a single session of pcTBS targeted at the M1 and DLPFC modulated the neurophysiological mechanisms related to motor corticospinal excitability and neurochemical mechanisms linked to GABA activity, but it did not modulate the activity of the ascending and descending endogenous modulatory systems. In addition, although BPI-DN scores did not change, there was a 13% improvement in self-reported perception of acute pain intensity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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 (β=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 (β=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 (β=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., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)