Effects of Subdural Monopolar Cortical Stimulation Paired With Rehabilitative Training on Behavioral and Neurophysiological Recovery After Cortical Ischemic Stroke in Adult Squirrel Monkeys.

BACKGROUND: Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enhancing poststroke functional recovery in rats, but human clinical trials have had mixed outcomes.
OBJECTIVE: To assess the efficacy of CS/RT versus RT in a nonhuman primate model of cortical ischemic stroke.
METHODS: Squirrel monkeys learned a pellet retrieval task, then received an infarct to the distal forelimb (DFL) representation of primary motor cortex. A subdural monopolar electrode was implanted over the spared DFL representation in dorsal premotor cortex (PMD). Seven weeks postinfarct, monkeys underwent 4 to 6 weeks of RT (n = 8) or CS/RT (n = 7; 100 Hz, cathodal current) therapy. Behavioral performance was assessed before and after infarct, prior to therapy, and 1 and 12 weeks posttherapy (follow-up). The primary outcome measure was motor performance at 1 week posttherapy. Secondary outcomes included follow-up performance at 12 weeks and treatment-related changes in neurophysiological maps of spared DFL representations.
RESULTS: While postinfarct performance deficits were found in all monkeys, both groups demonstrated similar recovery profiles, with no difference in motor recovery between the RT and CS/RT groups. Posttherapy, PMD DFL area was significantly expanded in the RT group but not the CS/RT group. A significant relationship was found between motor recovery and DFL expansion in premotor cortex.
CONCLUSIONS: Results suggest that the specific parameters utilized here were not optimal for promoting behavioral recovery in nonhuman primates. Though CS/RT has consistently shown efficacy in rat stroke models, the present finding has cautionary implications for translation of CS/RT therapy to clinical populations.