Investigating premotor corticospinal excitability in fast and slow voluntary contractions of the elbow flexors.

Corticospinal excitability (CSE) increases prior to a voluntary contraction; however, the relative contributions of premotor cortical and spinal mechanisms are poorly understood. It is unknown whether the intended voluntary contractile rate affects CSE. Eighteen young, healthy participants (nine females) completed isometric elbow flexion contractions targeting 50% maximal voluntary contraction (MVC) torque, at either fast (fast as possible) or slow (25% MVC/s) contractile rates. Participants were cued to contract with warning (red) and "GO" (green) visual signals. Magnetic and electric stimulations were applied to elicit motor evoked potentials (MEPs), cervicomedullary evoked potentials (CMEPs), and M-waves, in the surface electromyogram (EMG) recorded over the biceps brachii. MEPs and CMEPs were collected at 0, 25, 50 and 75% premotor reaction time (RT - defined as the time between the "GO" cue and onset of biceps brachii EMG) and compared to a resting baseline. MEP amplitude was greater than baseline at 75% RT (p=0.009), and CMEP amplitude was significantly increased at all RT points relative to baseline (p≤0.001). However, there were no differences in MEP and CMEP amplitudes when compared between fast and slow conditions (p≥0.097). Normalized to the CMEP, there was no difference in MEP amplitude from baseline in either contractile condition (p≥0.264). These results indicate that increased premotor CSE is a spinally-mediated response. Furthermore, premotor CSE is not influenced by the intended voluntary contractile rate. CMEP amplitudes were larger for females than males within the premotor RT period (p=0.038), demonstrating that premotor spinal excitability responses may be influenced by sex.

Explainable artificial intelligence on safe balance and its major determinants in stroke patients.

This study develops explainable artificial intelligence for predicting safe balance using hospital data, including clinical, neurophysiological, and diffusion tensor imaging properties. Retrospective data from 92 first-time stroke patients from January 2016 to June 2023 was analysed. The dependent variables were independent mobility scores, i.e., Berg Balance Scales with 0 (45 or below) vs. 1 (above 45) measured after three and six months, respectively. Twenty-nine predictors were included. Random forest variable importance was employed for identifying significant predictors of the Berg Balance Scale and testing its associations with the predictors, including Berg Balance Scale after one month and corticospinal tract diffusion tensor imaging properties. Shapley Additive Explanation values were calculated to analyse the directions of these associations. The random forest registered a higher or similar area under the curve compared to logistic regression, i.e., 91% vs. 87% (Berg Balance Scale after three months), 92% vs. 92% (Berg Balance Scale after six months). Based on random forest variable importance values and rankings: (1) Berg Balance Scale after three months has strong associations with Berg Balance Scale after one month, Fugl-Meyer assessment scale, ipsilesional corticospinal tract fractional anisotropy, fractional anisotropy laterality index and age; (2) Berg Balance Scale after six months has strong relationships with Fugl-Meyer assessment scale, Berg Balance Scale after one month, ankle plantar flexion muscle strength, knee extension muscle strength and hip flexion muscle strength. These associations were positive in the SHAP summary plots. Including Berg Balance Scale after one month, Fugl-Meyer assessment scale or ipsilesional corticospinal tract fractional anisotropy in the random forest will increase the probability of Berg Balance Scale after three months being above 45 by 0.11, 0.08, or 0.08. In conclusion, safe balance after stroke strongly correlates with its initial motor function, Fugl-Meyer assessment scale, and ipsilesional corticospinal tract fractional anisotropy. Diffusion tensor imaging information aids in developing explainable artificial intelligence for predicting safe balance after stroke.

Advanced tractography-guided laser ablation of a perirolandic long-term epilepsy-associated tumor: illustrative case.

BACKGROUND: Microsurgical resection of drug-resistant epilepsy-associated perirolandic lesions can lead to postoperative motor impairment. Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRgLITT) has emerged as a less invasive alternative, offering reduced surgical risks and improved neurological outcomes. Electrophysiological tools routinely used for motor mapping in resective microsurgery are incompatible with intraoperative MRI. The utilization of advanced neuroimaging adjuncts for eloquent brain mapping during MRgLITT is imperative. The authors present the case of a 17-year-old athlete who underwent MRgLITT for a perirolandic long-term epilepsy-associated tumor (LEAT). They performed probabilistic multi-tissue constrained spherical deconvolution (MT-CSD) tractography to delineate the corticospinal tract (CST) for presurgical planning and intraoperative image guidance. The CST tractography was integrated into neuronavigation and MRgLITT workstation software to guide the ablation while monitoring the CST throughout the procedure. OBSERVATIONS: The integration of CST tractography into neuronavigation workstation planning and laser ablation workstation thermoablation is feasible and practical, facilitating complete ablation of a deep-seated perirolandic LEAT while preserving motor function. LESSONS: Probabilistic MT-CSD tractography enhanced MRgLITT planning as well as intraprocedural CST visualization and preservation, leading to a favorable functional outcome. The limitations of tractography and the predictability of thermal output distribution compared to the gold standard of microsurgical resection merit further discussion. https://thejns.org/doi/10.3171/CASE24139.

The relationship between corticospinal excitability and structural integrity in stroke patients.

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.

Combined biomaterial scaffold and neuromodulation strategy to promote tissue repair and corticospinal connectivity after spinal cord injury in a rodent model.

Spinal cord injury (SCI) damages the trauma site, leading to progressive and secondary structural defects rostral and caudal to the injury. Interruption of ascending and descending pathways produce motor, sensory, and autonomic impairments, driving the need for effective therapies. In this study, we address lesion site repair and promoting descending projections using a combined biomaterial-neuromodulation strategy in a rat model of cervical contusion SCI. To promote tissue repair, we used Chitosan fragmented physical hydrogel suspension (Cfphs), a biomaterial formulation optimized to mitigate inflammation and support tissue remodeling. To promote descending projections, we targeted the corticospinal motor system with dual motor cortex-trans-spinal direct current neuromodulation to promote spared corticospinal tract (CST) axon sprouting rostral and caudal to SCI. Cfphs, injected into the lesion site acutely, was followed by 10 days of daily neuromodulation. Analysis was made at the chronic phase, 8-weeks post-SCI. Compared with SCI only, Cfphs alone or in combination with neuromodulation prevented cavity formation, by promoting tissue remodeling at the injury site, abrogated astrogliosis surrounding the newly formed tissue, and enabled limited CST axon growth into the remodeled injury site. Cfphs alone significantly reduced CST axon dieback and was accompanied by preserving more CST axon gray matter projections rostral to SCI. Cfphs + neuromodulation produced sprouting rostral and caudal to injury. Our findings show that our novel biomaterial-neuromodulation combinatorial strategy achieves significant injury site tissue remodeling and promoted CST projections rostral and caudal to SCI.

Effects of transcranial magnetic stimulation on axonal regeneration in the corticospinal tract of female rats with spinal cord injury.

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.

Timing of diffusion tensor imaging in the management of a ruptured pediatric arteriovenous malformation: illustrative case.

BACKGROUND: Diffusion tensor imaging (DTI) can characterize eloquent white matter tracts affected by brain arteriovenous malformations (AVMs). However, DTI interpretation can be difficult in ruptured cases due to the presence of blood products. The authors present the case of a ruptured pediatric AVM in the corticospinal tract (CST) and discuss how DTI at different time points informed the treatment. OBSERVATIONS: A 9-year-old female presented with a sudden headache and left hemiparesis. She was found to have a Spetzler-Martin grade III, Supplementary grade I AVM in the right caudate and centrum semiovale, with obliteration and corresponding reduced fractional anisotropy (FA), fiber density (FD), and tract count (TC) of the adjacent CST on DTI. The patient remained stable and was scheduled for elective resection following a 6-week period to facilitate hematoma resorption. After 6 weeks, repeat DTI showed part of the nidus within intact CST fibers with concordant improvement in FA, FD, and TC. Considering the nidus location, CST integrity, and motor function recovery, surgery was deferred in favor of stereotactic radiosurgery. LESSONS: In ruptured AVMs, DTI may initially create an incomplete picture and false assumptions about white matter tract integrity. DTI should be repeated if delayed treatment is appropriate to ensure informed decision-making and prevent avoidable permanent neurological deficits. https://thejns.org/doi/10.3171/CASE24225.

Effects of Motor Learning on Corticospinal Tract Excitability During Motor Imagery.

We aimed to examine the effects of motor performance improvements produced by practice on corticospinal tract excitability during motor imagery (MI) of identical movements. Participants performed a motor task with no guidelines displayed on the monitor (performance test); the participants only imagined performing the task without performing the movement (MI test), and the participants performed the power output and then adjusted it (exercise). The output force conditions were 20, 40, and 60% of the maximum voluntary contraction, and the objective was for 21 participants to learn each output force condition. The outcome of the performance test was calculated as the difference between the actual motor output and the target. During the MI test, we applied a single transcranial magnetic stimulation during imagery, assessed the corticospinal tract excitability of the right first dorsal interosseous by motor-evoked potential (MEP) amplitude, and recorded the vividness of the MI in each trial. We evaluated performance and MI before practice (Pre-test), after 150 practice sessions (Post-test 1), and after another 150 practice sessions (Post-test 2). The MEP amplitude was significantly reduced at Post-test 2 compared to Pre-test. The vividness of the MI improved with practice. Corticospinal tract excitability during MI decreased as motor performance improved. Thus, actual motor practice was also reflected in the MI of the exercise. Performance improvement was accompanied by a decrease in redundant activity, enhancing the efficiency and appropriateness of the exercise.

Alpha and beta/low-gamma frequency bands may have distinct neural origin and function during post-stroke walking.

Plantarflexors provide propulsion during walking and receive input from both corticospinal and corticoreticulospinal tracts, which exhibit some frequency-specificity that allows potential differentiation of each tract's descending drive. Given that stroke may differentially affect each tract and impair the function of plantarflexors during walking; here, we examined this frequency-specificity and its relation to walking-specific measures during post-stroke walking. Fourteen individuals with chronic stroke walked on an instrumented treadmill at self-selected and fast walking speed (SSWS and FWS, respectively) while surface electromyography (sEMG) from soleus (SOL), lateral gastrocnemius (LG), and medial gastrocnemius (MG) and ground reaction forces (GRF) were collected. We calculated the intermuscular coherences (IMC; alpha, beta, and low-gamma bands between SOL-LG, SOL-MG, LG-MG) and propulsive impulse using sEMG and GRF, respectively. We examined the interlimb and intralimb IMC comparisons and their relationships with propulsive impulse and walking speed. Interlimb IMC comparisons revealed that beta LG-MG (SSWS) and low-gamma SOL-LG (FWS) IMCs were degraded on the paretic side. Intralimb IMC comparisons revealed that only alpha IMCs (both speeds) exhibited a statistically significant difference to random coherence. Further, alpha LG-MG IMC was positively correlated with propulsive impulse in the paretic limb (SSWS). Alpha and beta/low-gamma bands may have a differential functional role, which may be related to the frequency-specificity of the underlying descending drives. The persistence of alpha band in plantarflexors and its strong positive relationship with propulsive impulse suggests relative alteration of corticoreticulospinal tract after stroke. These findings imply the presence of frequency-specific descending drives to walking-specific muscles in chronic stroke.

Brain-Hand Function Relationships Based on Level of Grasp Function in Chronic Left-Hemisphere Stroke.

BACKGROUND AND OBJECTIVE: The biomarkers of hand function may differ based on level of motor impairment after stroke. The objective of this study was to determine the relationship between resting state functional connectivity (RsFC) and unimanual contralesional hand function after stroke and whether brain-behavior relationships differ based on level of grasp function. METHODS: Sixty-two individuals with chronic, left-hemisphere stroke were separated into three functional levels based on Box and Blocks Test performance with the contralesional hand: Low (moved 0 blocks), Moderate (moved >0% but <90% of blocks relative to the ipsilesional hand), and High (moved ≥90% of blocks relative to the ipsilesional hand). RESULTS: RsFC in the ipsilesional and interhemispheric motor networks was reduced in the Low group compared to the Moderate and High groups. While interhemispheric RsFC correlated with hand function (grip strength and Stroke Impact Scale Hand) across the sample, contralesional RsFC correlated with hand function in the Low group and no measures of connectivity correlated with hand function in the Moderate and High groups. Linear regression modeling found that contralesional RsFC significantly predicted hand function in the Low group, while no measure correlated with hand function in the High group. Corticospinal tract integrity was the only predictor of hand function for the Moderate group and in an analysis across the entire sample. CONCLUSIONS: Differences in brain-hand function relationships based on level of motor impairment may have implications for predictive models of treatment response and the development of intervention protocols aimed at improving hand function after stroke.

Prediction of Motor Recovery Using Diffusion Tensor Imaging and Regional Cerebral Blood Flow in Postoperative Brain Tumors.

OBJECTIVE: To determine whether diffusion tensor image (DTI) parameters and regional cerebral blood flow (rCBF) serve to preoperatively predict postoperative motor outcomes in patients with brain tumors. METHODS: We included 81 patients with brain tumors who underwent surgical treatment. Motor function was assessed using the manual muscle test in the upper and lower limbs at admission and discharge. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and their ratios (rFA, rMD, rAD, and rRD) were measured at the corona radiata, internal capsule, and cerebral peduncle of the corticospinal tract (CST). In addition, DTI and single photon emission computed tomography (SPECT) were synthesized to measure rCBF at the CST. RESULT: Both DTI parameters and rCBF at the CST in the preoperative motor weakness group significantly differed from those of the preoperative normal function group. rFA at the cerebral peduncle and the internal capsule was considerably higher in those showing postoperative motor recovery than in those postoperative unchanged or with deteriorated motor function (P < 0.05). Moreover, there was significantly lower rMD and rRD at the internal capsule in the motor recovery group (P < 0.05, P < 0.01). Furthermore, rCBF was higher at all the cerebral peduncle, internal capsule, and corona radiate in the motor recovery group than in the unchanged and deteriorated motor function group (P < 0.05, P < 0.01, P < 0.01). CONCLUSION: The analysis of DTI parameters and rCBF is useful in predicting postoperative motor outcomes in patients with brain tumors.

A rare case of ispilateral hemiparesis in a patient with uncrossed pyramidal tract shown by tractography.

This article presents a unique case of ipsilateral hemiparesis in a 66-year-old individual, contrary to the conventional understanding of supratentorial strokes causing contralateral neurological deficits. The patient exhibited persistent weakness and sensory abnormalities on the left side of the body following a left occipital infarct. Neuroimaging revealed a chronic stroke in the left occipital lobe, with diffusion tensor imaging demonstrating uncrossed pyramidal tracts at the level of the medulla. The discussion encompasses the anatomical basis of corticospinal tract crossing, historical perspectives, and previous documented cases of ipsilateral strokes. The rarity of complete uncrossed corticospinal tracts without underlying congenital abnormalities or genetic disorders is highlighted. The study underscores the importance of considering such atypical presentations in stroke evaluations and the role of advanced imaging techniques in confirming diagnosis and understanding underlying mechanisms.

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

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

Contribution of changes in the spinal cord and brain to the onset and progression of hand clumsiness symptoms in cervical spondylotic myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) stands as the most prevalent form of spinal cord injury, frequently prompting various changes in both the brain and spinal cord. However, the precise nature of these changes within the brains and spinal cords of CSM patients experiencing hand clumsiness (HCL) symptoms has remained elusive. The authors aimed to scrutinize these alterations and explore potential links between these changes and the onset of HCL symptoms. METHODS: Using the modified Japanese Orthopaedic Association (mJOA) scale, the authors classified CSM patients into two groups: those without HCL and those with HCL. The authors performed voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (FC) evaluations in the brain. Additionally, they used the Spinal Cord Toolbox to calculate the fractional anisotropy (FA) of spinal cord tracts. The analysis also encompassed an examination of the correlation of these measures with improvements in mJOA scores. RESULTS: Significant disparities in zALFF values surfaced in the right calcarine, right cuneus, right precuneus, right middle occipital gyrus (MOG), right superior occipital gyrus (SOG), and right superior parietal gyrus (SPG) between healthy controls (HC), patients without HCL, and patients with HCL, primarily within the visual cortex. In the patient group, patients with HCL displayed reduced FC between the right calcarine, right MOG, right SOG, right SPG, right SFG, bilateral MFG, and left median cingulate and paracingulate gyri when compared with patients without HCL. Moreover, significant differences in FA values of the corticospinal tract (CST) and reticulospinal tract (REST) at the C2 level emerged among HC, patients without HCL, and patients with HCL. Notably, zALFF, FC, and FA values in specific brain regions and spinal cord tracts exhibited correlations with mJOA upper-extremity scores. Additionally, FA values of the CST and REST correlated with zALFF values in the right calcarine, right MOG, right SOG, and right SPG. CONCLUSIONS: Alterations within brain regions associated with the visual cortex, the fronto-parietal-occipital attention network, and spinal cord pathways appear to play a substantial role in the emergence and progression of HCL symptoms. Furthermore, the existence of a potential connection between the spinal cord and the brain suggests that this link might be related to the clinical symptoms of CSM.

Evidence for reticulospinal plasticity underlying motor recovery in Brown-Séquard-plus Syndrome: a case report.

Brown-Séquard Syndrome (BSS) is a rare neurological condition caused by a unilateral spinal cord injury (SCI). Upon initial ipsilesional hemiplegia, patients with BSS typically show substantial functional recovery over time. Preclinical studies on experimental BSS demonstrated that spontaneous neuroplasticity in descending motor systems is a key mechanism promoting functional recovery. The reticulospinal (RS) system is one of the main descending motor systems showing a remarkably high ability for neuroplastic adaptations after incomplete SCI. In humans, little is known about the contribution of RS plasticity to functional restoration after SCI. Here, we investigated RS motor drive to different muscles in a subject with Brown-Séquard-plus Syndrome (BSPS) five months post-injury using the StartReact paradigm. RS drive was compared between ipsi- and contralesional muscles, and associated with measures of functional recovery. Additionally, corticospinal (CS) drive was investigated using transcranial magnetic stimulation (TMS) in a subset of muscles. The biceps brachii showed a substantial enhancement of RS drive on the ipsi- vs. contralesional side, whereas no signs of CS plasticity were found ipsilesionally. This finding implies that motor recovery of ipsilesional elbow flexion is primarily driven by the RS system. Results were inversed for the ipsilesional tibialis anterior, where RS drive was not augmented, but motor-evoked potentials recovered over six months post-injury, suggesting that CS plasticity contributed to improvements in ankle dorsiflexion. Our findings indicate that the role of RS and CS plasticity in motor recovery differs between muscles, with CS plasticity being essential for the restoration of distal extremity motor function, and RS plasticity being important for the functional recovery of proximal flexor muscles after SCI in humans.

Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice.

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice. To prove direct effect of Nurr1 on CST integrity, we examined the effect of Nurr1 overexpression in neurons of the primary motor cortex on pathological consequences of ICH in mice. ICH was induced by intrastriatal injection of collagenase type VII, where hematoma invaded into IC. Neuron-specific overexpression of Nurr1 was induced by microinjection of synapsin I promoter-driven adeno-associated virus (AAV) vector into the primary motor cortex. Nurr1 overexpression significantly alleviated motor dysfunction but showed only modest effect on sensorimotor dysfunction after ICH. Nurr1 overexpression also preserved axonal structures in IC, while having no effect on hematoma-associated inflammatory events, oxidative stress, and neuronal death in the striatum after ICH. Immunostaining revealed that Nurr1 overexpression increased the expression of Ret tyrosine kinase and phosphorylation of Akt and ERK1/2 in neurons in the motor cortex. Moreover, administration of Nurr1 ligands 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane or amodiaquine increased phosphorylation levels of Akt and ERK1/2 as well as expression of glial cell line-derived neurotrophic factor and Ret genes in the cerebral cortex. These results suggest that the therapeutic effect of Nurr1 on striatal ICH is attributable to the preservation of CST by acting on cortical neurons.

Selenoprotein I is indispensable for ether lipid homeostasis and proper myelination.

Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations in genes affecting plasmenyl-PE metabolism have been implicated in hereditary spastic paraplegia, including SELENOI. Herein, we developed a mouse model of nervous system-restricted SELENOI deficiency that circumvents embryonic lethality caused by constitutive deletion and recapitulates phenotypic features of hereditary spastic paraplegia. Resulting mice exhibited pronounced alterations in brain lipid composition, which coincided with motor deficits and neuropathology including hypomyelination, elevated reactive gliosis, and microcephaly. Further studies revealed increased lipid peroxidation in oligodendrocyte lineage cells and disrupted oligodendrocyte maturation both in vivo and in vitro. Altogether, these findings detail a critical role for SELENOI-derived plasmenyl-PE in myelination that is of paramount importance for neurodevelopment.

Hypothermia protects the integrity of corticospinal tracts and alleviates mitochondria injury after intracerebral hemorrhage in mice.

Disruption of corticospinal tracts (CST) is a leading factor for motor impairments following intracerebral hemorrhage (ICH) in the striatum. Previous studies have shown that therapeutic hypothermia (HT) improves outcomes of ICH patients. However, whether HT has a direct protection effect on the CST integrity and the underlying mechanisms remain largely unknown. In this study, we employed a chemogenetics approach to selectively activate bilateral warm-sensitive neurons in the preoptic areas to induce a hypothermia-like state. We then assessed effects of HT treatment on the integrity of CST and motor functional recovery after ICH. Our results showed that HT treatment significantly alleviated axonal degeneration around the hematoma and the CST axons at remote midbrain region, ultimately promoted skilled motor function recovery. Anterograde and retrograde tracing revealed that HT treatment protected the integrity of the CST over an extended period. Mechanistically, HT treatment prevented mitochondrial swelling in degenerated axons around the hematoma, alleviated mitochondrial impairment by reducing mitochondrial ROS accumulation and improving mitochondrial membrane potential in primarily cultured cortical neurons with oxyhemoglobin treatment. Serving as a proof of principle, our study provided novel insights into the application of HT to improve functional recovery after ICH.

Structural changes in corticospinal tract profiling via multishell diffusion models and their relation to overall survival in glioblastoma.

PURPOSE: Advanced MR fiber tracking imaging reflects fiber bundle invasion by glioblastoma, particularly of the corticospinal tract (CST), which is more susceptible as the largest downstream fiber tracts. We aimed to investigate whether CST features can predict the overall survival of glioblastoma. METHODS: In this prospective secondary analysis, 40 participants (mean age, 58 years; 16 male) pathologically diagnosed with glioblastoma were enrolled. Diffusion spectrum MRI was used for CST reconstruction. Fifty morphological and diffusion indicators (DTI, DKI, NODDI, MAP and Q-space) were used to characterize the CST. Optimal parameters capturing fiber bundle damage were obtained through various grouping methods. Eventually, the correlation with overall survival was determined by the hazard ratios (HRs) from various Cox proportional hazard model combinations. RESULTS: Only intracellular volume fraction (ICVF) and non-Gaussianity (NG) values on the affected tumor level were significant in all four groups or stratified comparisons (all P < .05). During the median follow-up 698 days, only the ICVF on the affected tumor level was independently associated with overall survival, even after adjusting for all classic prognostic factors (HR [95 % CI]: 0.611 [0.403, 0.927], P = .021). Moreover, stratification by the ICVF on the affected tumor level successfully predicted risk (P < .01) and improved the C-index of the multivariate model (from 0.695 to 0.736). CONCLUSIONS: This study demonstrates a relationship between NODDI-derived CST features, ICVF on the affected tumor level, and overall survival in glioblastoma. Independent of classical prognostic factors for glioblastoma, a lower ICVF on the affected tumor level might predict a lower overall survival.

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

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