Dynamic Reorganization of Motor Networks During Recovery from Partial Spinal Cord Injury in Monkeys

2018 ◽  
Vol 29 (7) ◽  
pp. 3059-3073 ◽  
Author(s):  
Zenas C Chao ◽  
Masahiro Sawada ◽  
Tadashi Isa ◽  
Yukio Nishimura
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Time Course ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Motor Preparation ◽  
Compensatory Mechanism ◽  
Primate Model ◽  
Cord Injury

Abstract After spinal cord injury (SCI), the motor-related cortical areas can be a potential substrate for functional recovery in addition to the spinal cord. However, a dynamic description of how motor cortical circuits reorganize after SCI is lacking. Here, we captured the comprehensive dynamics of motor networks across SCI in a nonhuman primate model. Using electrocorticography over the sensorimotor areas in monkeys, we collected broadband neuronal signals during a reaching-and-grasping task at different stages of recovery of dexterous finger movements after a partial SCI at the cervical levels. We identified two distinct network dynamics: grasping-related intrahemispheric interactions from the contralesional premotor cortex (PM) to the contralesional primary motor cortex (M1) in the high-γ band (>70 Hz), and motor-preparation-related interhemispheric interactions from the contralesional to ipsilesional PM in the α and low-β bands (10–15 Hz). The strengths of these networks correlated to the time course of behavioral recovery. The grasping-related network showed enhanced activation immediately after the injury, but gradually returned to normal while the strength of the motor-preparation-related network gradually increased. Our findings suggest a cortical compensatory mechanism after SCI, where two interdependent motor networks redirect activity from the contralesional hemisphere to the other hemisphere to facilitate functional recovery.

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

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1368-1382 ◽  
Author(s):  
Hang Jin Jo ◽  
Monica A Perez
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Transcranial Magnetic Stimulation ◽  
Functional Recovery ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Lumbar Spinal Cord ◽  
Non Invasive ◽  
Cord Injury ◽  
Stimulation Of

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

scholarly journals Sensorimotor Cortical Activation in Patients With Cervical Spinal Cord Injury With Persisting Paralysis

2009 ◽  
Vol 24 (2) ◽  
pp. 136-140 ◽  
Author(s):  
Michael T. Jurkiewicz ◽  
David J. Mikulis ◽  
Michael G. Fehlings ◽  
Mary C. Verrier
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Time Course ◽  
Primary Motor Cortex ◽  
Cervical Spinal Cord ◽  
Motor Task ◽  
Cortical Activation ◽  
Healthy Individuals ◽  
Cord Injury ◽  
Over Time

Background. It is well documented that cortical sensorimotor representations are altered following nervous system pathology. However, little is known about these representations over time and, more specifically, in paralyzed individuals. Objective . To investigate the temporal changes in sensorimotor cortical activation in paralyzed individuals following spinal cord injury (SCI). Methods. Functional MRI (fMRI) was used to study 4 tetraplegic individuals repeatedly over the first year following traumatic SCI as well as 7 healthy individuals, 3 repeatedly. During fMRI, controls performed ankle movements, and patients attempted them. Standard clinical measures of SCI were used to assess movement ability. Results. Shortly after SCI, activation within the primary motor cortex (M1) was present at levels similar to those in controls. Extensive associated cortical sensorimotor activation, not seen in controls, was present. Over time, as paralysis persisted, activation in M1 was significantly reduced and progressively decreased in associated cortical sensorimotor areas. No session-specific dependence in M1 or associated sensorimotor cortical activation was found in healthy individuals. Conclusions. These findings provide the first report of the temporal evolution of cortical sensorimotor fMRI activation following traumatic SCI in humans who do not recover movement. Coupled with findings in patients who recover post-SCI, our results suggest an association between motor task—related fMRI activation and degree of motor function postinjury. Understanding the time course of plasticity and the relationship between cortical sensorimotor activation and motor ability following SCI could allow assessment of rehabilitation potential, monitoring of therapeutic efficacy, and improvement in therapeutic intervention along the course of recovery.

scholarly journals Optogenetic Neuronal Stimulation Promotes Functional Recovery After Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Wei-wei Deng ◽  
Guang-yan Wu ◽  
Ling-xia Min ◽  
Zhou Feng ◽  
Hui Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Primary Motor Cortex ◽  
Motor Evoked Potentials ◽  
Cell Types ◽  
Treatment Method ◽  
Cord Injury ◽  
Tissue Recovery

Although spinal cord injury (SCI) is the main cause of disability worldwide, there is still no definite and effective treatment method for this condition. Our previous clinical trials confirmed that the increased excitability of the motor cortex was related to the functional prognosis of patients with SCI. However, it remains unclear which cell types in the motor cortex lead to the later functional recovery. Herein, we applied optogenetic technology to selectively activate glutamate neurons in the primary motor cortex and explore whether activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI in rats and the preliminary neural mechanisms involved. Our results showed that the activation of glutamate neurons in the motor cortex could significantly improve the motor function scores in rats, effectively shorten the incubation period of motor evoked potentials and increase motor potentials’ amplitude. In addition, hematoxylin-eosin staining and nerve fiber staining at the injured site showed that accurate activation of the primary motor cortex could effectively promote tissue recovery and neurofilament growth (GAP-43, NF) at the injured site of the spinal cord, while the content of some growth-related proteins (BDNF, NGF) at the injured site increased. These results suggested that selective activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI and may be of great significance for understanding the neural cell mechanism underlying functional recovery induced by motor cortex stimulation.

scholarly journals Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury

2020 ◽  
Vol 11 ◽  
Author(s):  
Roxana Rodríguez-Barrera ◽  
Adrián Flores-Romero ◽  
Vinnitsa Buzoianu-Anguiano ◽  
Elisa Garcia ◽  
Karla Soria-Zavala ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Combination Strategy ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury

scholarly journals Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Exercise Group ◽  
Control Group ◽  
Epigenetic Changes ◽  
Cord Injury ◽  
The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

scholarly journals Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions

2021 ◽  
Vol 339 ◽  
pp. 113612
Author(s):  
Claudio Pizzolato ◽  
Mehmet A. Gunduz ◽  
Dinesh Palipana ◽  
Jingnan Wu ◽  
Gary Grant ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Therapeutic Targets ◽  
Non Invasive ◽  
Cord Injury
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