title: 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 10weeks 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 60Hz) 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 60Hz. 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.
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Monzurul
authors.initials: M
authors.lastname: Alam
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Alias
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Benita
authors.initials: B
authors.lastname: Jin
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Keyes
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States; Brain Research Institute, University of California, Los Angeles, CA 90095, United States.
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States; Pavlov Institute of Physiology, St. Petersburg 199034, Russia; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420006, Russia.
authors.forename: Yury
authors.initials: Y
authors.lastname: Gerasimenko
authors.affiliation: Departments of Neurosurgery, University of California, Los Angeles, CA 90095, United States.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Lu
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States; Brain Research Institute, University of California, Los Angeles, CA 90095, United States; Departments of Neurobiology, University of California, Los Angeles, CA 90095, United States; Departments of Neuroscience, University of California, Los Angeles, CA 90095, United States. Electronic address: vre@ucla.edu.
authors.forename: V Reggie
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002574:Cervical Vertebrae / Q000502:physiology*; D004195:Disease Models, Animal; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D005552:Forelimb / Q000503:physiopathology*; D018737:Hand Strength / Q000502:physiology; D016059:Range of Motion, Articular / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000628:therapy; D062187:Spinal Cord Stimulation / Q000379:methods*
keywords: Cervical spinal cord injury; Corticospinal tract; Epidural electrical stimulation; Motor-evoked potentials; Reaching and grasping