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1.
Neurorehabil Neural Repair ; 38(6): 425-436, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38676561

ABSTRACT

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.


Subject(s)
Diffusion Tensor Imaging , Neuronal Plasticity , Pyramidal Tracts , Stroke Rehabilitation , Stroke , Humans , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/physiopathology , Pyramidal Tracts/pathology , Male , Female , Middle Aged , Neuronal Plasticity/physiology , Stroke Rehabilitation/methods , Aged , Stroke/physiopathology , Stroke/diagnostic imaging , Adult
2.
Clin Neurophysiol ; 161: 188-197, 2024 May.
Article in English | MEDLINE | ID: mdl-38520799

ABSTRACT

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.


Subject(s)
Neural Inhibition , Pyramidal Tracts , Spinal Cord Injuries , Transcranial Magnetic Stimulation , Upper Extremity , Humans , Female , Spinal Cord Injuries/physiopathology , Male , Adult , Middle Aged , Pyramidal Tracts/physiopathology , Upper Extremity/physiopathology , Transcranial Magnetic Stimulation/methods , Neural Inhibition/physiology , Muscle, Skeletal/physiopathology , Evoked Potentials, Motor/physiology , Cervical Cord/physiopathology , Cervical Cord/injuries , Young Adult , Cervical Vertebrae/physiopathology , Electromyography/methods
3.
J Neurol Sci ; 451: 120726, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37421883

ABSTRACT

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.


Subject(s)
Cerebellum , Cerebral Cortex , Crying , Laughter , Models, Neurological , Motor Neuron Disease , Pyramidal Tracts , Radiology , Aged , Female , Humans , Male , Middle Aged , Amyotrophic Lateral Sclerosis/complications , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/pathology , Amyotrophic Lateral Sclerosis/physiopathology , Cerebellum/diagnostic imaging , Cerebellum/pathology , Cerebellum/physiopathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Frontal Lobe/physiopathology , Magnetic Resonance Imaging , Medulla Oblongata/diagnostic imaging , Medulla Oblongata/pathology , Medulla Oblongata/physiopathology , Motor Cortex/diagnostic imaging , Motor Cortex/pathology , Motor Cortex/physiopathology , Motor Neuron Disease/complications , Motor Neuron Disease/diagnostic imaging , Motor Neuron Disease/pathology , Motor Neuron Disease/physiopathology , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/pathology , Pyramidal Tracts/physiopathology , Quality of Life , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology , Temporal Lobe/physiopathology
4.
Arch Phys Med Rehabil ; 103(1): 62-68, 2022 01.
Article in English | MEDLINE | ID: mdl-34371017

ABSTRACT

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


Subject(s)
Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/injuries , Recovery of Function , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/rehabilitation , Adult , Disability Evaluation , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Patient Discharge , Predictive Value of Tests , Pyramidal Tracts/physiopathology , Retrospective Studies , Spinal Cord Injuries/physiopathology
5.
J Neurophysiol ; 127(1): 56-85, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34731070

ABSTRACT

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


Subject(s)
Ataxia/physiopathology , Motor Cortex/physiopathology , Neuronal Plasticity/physiology , Pyramidal Tracts/physiopathology , Recovery of Function/physiology , Ventral Thalamic Nuclei/physiopathology , Walking/physiology , Animals , Behavior, Animal/physiology , Cats , Disease Models, Animal , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Ventral Thalamic Nuclei/drug effects , Ventral Thalamic Nuclei/pathology
6.
Behav Brain Res ; 416: 113533, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34453971

ABSTRACT

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.


Subject(s)
Behavior, Animal/physiology , Macaca , Nerve Regeneration/physiology , Pyramidal Tracts/physiopathology , Recovery of Function/physiology , Spinal Cord Injuries/physiopathology , Animals , Axons/physiology , Hand/innervation , Haplorhini , Male , Neuronal Plasticity , Sensorimotor Cortex/physiopathology
7.
Behav Brain Res ; 417: 113563, 2022 01 24.
Article in English | MEDLINE | ID: mdl-34499938

ABSTRACT

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.


Subject(s)
Cervical Cord , Cortical Synchronization , Motor Cortex/physiopathology , Muscle Contraction/physiology , Muscle, Skeletal/innervation , Pyramidal Tracts/injuries , Adult , Cervical Cord/injuries , Cervical Cord/physiopathology , Electromyography , Female , Humans , Male , Movement , Pyramidal Tracts/physiopathology , Spinal Cord Injuries/physiopathology
8.
J Neurosci ; 41(50): 10247-10260, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34759029

ABSTRACT

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


Subject(s)
Nerve Regeneration/physiology , PTEN Phosphohydrolase/metabolism , Pyramidal Tracts/physiopathology , Spinal Cord Injuries/physiopathology , rho GTP-Binding Proteins/metabolism , Animals , Mice , Mice, Inbred C57BL , Mice, Knockout
9.
Int J Mol Sci ; 22(18)2021 Sep 19.
Article in English | MEDLINE | ID: mdl-34576288

ABSTRACT

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


Subject(s)
Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/physiopathology , Pyramidal Tracts/pathology , Pyramidal Tracts/physiopathology , Action Potentials , Animals , Blood Glucose/metabolism , Body Weight , Diabetes Mellitus, Experimental/blood , Male , Motor Neurons/pathology , Neural Conduction , Rats, Wistar , Spinal Cord/pathology , Streptozocin
10.
Neurorehabil Neural Repair ; 35(11): 1010-1019, 2021 11.
Article in English | MEDLINE | ID: mdl-34546138

ABSTRACT

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


Subject(s)
Corpus Callosum/pathology , Motor Activity/physiology , Pyramidal Tracts/pathology , Recovery of Function/physiology , Sensorimotor Cortex/pathology , Stroke/pathology , White Matter/pathology , Animals , Behavior, Animal/physiology , Corpus Callosum/diagnostic imaging , Corpus Callosum/physiopathology , Diffusion Tensor Imaging , Disease Models, Animal , Male , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Neural Pathways/physiopathology , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/physiopathology , Rats , Rats, Sprague-Dawley , Sensorimotor Cortex/diagnostic imaging , Sensorimotor Cortex/physiopathology
11.
Biomed Res Int ; 2021: 9956609, 2021.
Article in English | MEDLINE | ID: mdl-34527746

ABSTRACT

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


Subject(s)
Cerebral Peduncle/pathology , Hand/physiopathology , Motor Cortex/pathology , Pons/pathology , Psychomotor Disorders/pathology , Pyramidal Tracts/pathology , Schizencephaly/pathology , Adolescent , Adult , Brain Mapping , Cerebral Peduncle/diagnostic imaging , Cerebral Peduncle/physiopathology , Child , Child, Preschool , Diffusion Tensor Imaging/methods , Female , Hand Strength/physiology , Humans , Male , Middle Aged , Motor Cortex/diagnostic imaging , Motor Cortex/physiopathology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiopathology , Pons/diagnostic imaging , Pons/physiopathology , Psychomotor Disorders/diagnostic imaging , Psychomotor Disorders/physiopathology , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/physiopathology , Retrospective Studies , Schizencephaly/diagnostic imaging , Schizencephaly/physiopathology , Transcranial Magnetic Stimulation/methods
12.
Mol Neurobiol ; 58(11): 5494-5516, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34341881

ABSTRACT

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


Subject(s)
Neuronal Plasticity , Pyramidal Tracts/physiopathology , Spinal Cord Injuries/physiopathology , Animals , Brain-Computer Interfaces , Combined Modality Therapy , Electric Stimulation Therapy , Humans , Locomotion/physiology , Low-Level Light Therapy , Motor Cortex/physiopathology , Nerve Regeneration , Neuronal Outgrowth , Neuroprotective Agents/therapeutic use , Photochemotherapy , Quality of Life , Recovery of Function , Riluzole/therapeutic use , Spinal Cord/physiopathology , Spinal Cord Diseases/rehabilitation , Spinal Cord Injuries/therapy , Stem Cell Transplantation , Transcranial Direct Current Stimulation , Transcutaneous Electric Nerve Stimulation
13.
Neurorehabil Neural Repair ; 35(9): 812-822, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34219510

ABSTRACT

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


Subject(s)
Learning/physiology , Motor Cortex/physiopathology , Psychomotor Performance/physiology , Pyramidal Tracts/physiopathology , Stroke/physiopathology , Upper Extremity/physiopathology , Adult , Female , Humans , Male , Recovery of Function/physiology , Transcranial Magnetic Stimulation
14.
Clin Neurophysiol ; 132(9): 2211-2221, 2021 09.
Article in English | MEDLINE | ID: mdl-34311204

ABSTRACT

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


Subject(s)
Cerebral Palsy/diagnostic imaging , Gait , Pyramidal Tracts/diagnostic imaging , Brain/diagnostic imaging , Cerebral Palsy/physiopathology , Child , Diffusion Tensor Imaging , Female , Humans , Male , Postural Balance , Pyramidal Tracts/physiopathology
15.
Clin Neurol Neurosurg ; 206: 106715, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34088540

ABSTRACT

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


Subject(s)
Hemiplegia/surgery , Nerve Transfer/methods , Pyramidal Tracts , Spinal Nerves/transplantation , White Matter , Diffusion Tensor Imaging , Female , Humans , Middle Aged , Pyramidal Tracts/physiopathology , White Matter/physiopathology
16.
J Stroke Cerebrovasc Dis ; 30(8): 105889, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34062310

ABSTRACT

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


Subject(s)
Diffusion Tensor Imaging , Hemorrhagic Stroke/therapy , Ischemic Stroke/therapy , Motor Activity , Neurologic Examination , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/physiopathology , Stroke Rehabilitation , Adult , Aged , Evoked Potentials, Motor , Female , Functional Status , Hemorrhagic Stroke/diagnostic imaging , Hemorrhagic Stroke/physiopathology , Humans , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/physiopathology , Male , Middle Aged , Neural Conduction , Patient Admission , Patient Discharge , Predictive Value of Tests , Recovery of Function , Retrospective Studies , Transcranial Magnetic Stimulation , Treatment Outcome
17.
J Clin Neurophysiol ; 38(3): 166-170, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33958566

ABSTRACT

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


Subject(s)
Evoked Potentials, Motor/physiology , Multiple Sclerosis , Adult , Clinical Trials as Topic , Disease Progression , Electrophysiological Phenomena , Electrophysiology/methods , Humans , Male , Middle Aged , Multiple Sclerosis/diagnosis , Multiple Sclerosis/physiopathology , Pyramidal Tracts/physiopathology , Reproducibility of Results
18.
J Integr Neurosci ; 20(1): 119-123, 2021 Mar 30.
Article in English | MEDLINE | ID: mdl-33834698

ABSTRACT

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


Subject(s)
Ankle/physiopathology , Foot Orthoses , Gait Disorders, Neurologic/rehabilitation , Outcome Assessment, Health Care , Stroke Rehabilitation , Stroke/therapy , Transcranial Magnetic Stimulation , Adult , Aged , Evoked Potentials, Motor/physiology , Female , Gait Disorders, Neurologic/etiology , Humans , Male , Middle Aged , Muscle, Skeletal/physiopathology , Prognosis , Pyramidal Tracts/physiopathology , Stroke/complications
19.
J Clin Neurosci ; 86: 139-144, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33775318

ABSTRACT

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


Subject(s)
Motor Cortex/diagnostic imaging , Paresis/diagnostic imaging , Pyramidal Tracts/diagnostic imaging , Stroke/diagnostic imaging , Diffusion Tensor Imaging/methods , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Motor Cortex/physiopathology , Paresis/etiology , Paresis/physiopathology , Pyramidal Tracts/physiopathology , Recurrence , Stroke/complications , Stroke/physiopathology
20.
Clin Neurol Neurosurg ; 202: 106545, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33607530

ABSTRACT

OBJECTIVES: Isolated dysarthria caused by stroke is a rare condition and generally seen in infratentorial lesions, especially in cerebellar lesions. Isolated dysarthria associated with supratentorial ischemic lesions are also very rare and, these conditions were shown in only a few cases. In this study, six patients characterized by IHP due to supratentorial ischemic lesions are presented. PATIENTS AND METHODS: Physical examinations of patients were done by two different neurologists. The risk factors for stroke were determined. Localisations of lesions were identified by using magnetic resonance images(MRI). Corticolingual tract affection without sensorial and other corticospinal tract involvement was confirmed using Somatosensory evoked potentials(SEPs) and Transcranial Magnetic Stimulation(TMS). RESULTS: Unilateral lingual paresis was detected in all of the patients. The lesions were demonstrated on MRI slices. All lesions were on the same localization. The affection of the corticolingual tract without any other motor and sensory tract involvement was proven electrophysiologically. CONCLUSION: Corticospinal and corticobulbar fibers are very close to each other. Therefore common involvement is expected in cerebrovascular diseases. However, six patients with IHP caused by supratentorial ischemic lesions were reported in this study. Thus, a possible map of the corticolingual tract was drawn.


Subject(s)
Dysarthria/physiopathology , Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Hypoglossal Nerve Diseases/physiopathology , Ischemic Stroke/diagnostic imaging , Paresis/physiopathology , Pyramidal Tracts/physiopathology , Aged , Dysarthria/etiology , Humans , Hypoglossal Nerve Diseases/etiology , Ischemic Stroke/complications , Magnetic Resonance Imaging , Male , Middle Aged , Paresis/etiology , Transcranial Magnetic Stimulation
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