Electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats

Abstract: Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10 weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60 Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6– C8 + and C6 + C8–) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6– Ref + and C8– Ref +). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60 Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.

Monzurul Alama, 1, Guillermo Garcia-Aliasa, 1, Benita Jina, Jonathan Keyesa, Hui Zhonga, Roland R. Roya, b, Yury Gerasimenkoa, c, d, Daniel C. Lue, V. Reggie Edgertona, b, f, g, ,
a Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States
b Brain Research Institute, University of California, Los Angeles, CA 90095, United States
c Pavlov Institute of Physiology, St. Petersburg 199034, Russia
d Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420006, Russia
e Departments of Neurosurgery, University of California, Los Angeles, CA 90095, United States
f Departments of Neurobiology, University of California, Los Angeles, CA 90095, United States
g Departments of Neuroscience, University of California, Los Angeles, CA 90095, United States

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