title: Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control.
abstract: Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To test motor skill, rats were trained and tested to walk on a horizontal ladder with irregularly spaced rungs. Eight weeks after injury, produced by pyramidal tract transection, half of the rats received forelimb motor cortex stimulation of the intact hemisphere. Rats with injury and stimulation had significantly improved forelimb control compared with rats with injury alone and achieved a level of proficiency similar to uninjured rats. To test whether recovery of forelimb function was attributable to ipsilateral control, we selectively inactivated the stimulated motor cortex using the GABA agonist muscimol. The dose of muscimol we used produces strong contralateral but no ipsilateral impairments in naive rats. In rats with injury and stimulation, but not those with injury alone, inactivation caused worsening of forelimb function; the initial deficit was reinstated. These results demonstrate that electrical stimulation can promote recovery of motor function when applied late after injury and that motor control can be exerted from the ipsilateral motor cortex. These results suggest that the uninjured motor cortex could be targeted for brain stimulation in people with large unilateral CST lesions.
authors.affiliation: Brain and Mind Research Institute and Departments of Neurology and Pediatrics, Weill Cornell Medical College, New York, New York 10021, Burke Medical Research Institute, White Plains, New York 10605, Department of Physiology, Pharmacology, and Neuroscience, City College of the City University of New York, New York, New York 10031, and Departments of Neuroscience, Neurological Surgery, and Psychiatry, Columbia University, New York, New York 10032.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Carmel
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kimura
authors.forename: John H
authors.initials: JH
authors.lastname: Martin
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D009044:Motor Cortex / Q000503:physiopathology*; D011712:Pyramidal Tracts / Q000293:injuries / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*