Abstract
BACKGROUND: Deep brain stimulation (DBS) targeting the dentato-thalamo-cortical (DTC) pathway at its origin in the lateral cerebellar nucleus (LCN) has been shown to enhance motor recovery in a rodent model of cortical ischemia. LCN DBS also yielded frequency-specific changes in motor cortex excitability in the normal brain, indexed by motor evoked potential (MEP) amplitude. OBJECTIVE: To investigate the effect of cortical stroke on cortical motor excitability in a rodent ischemia model and to measure the effects of LCN DBS on post-ischemia excitability as a function of stimulation parameters. METHODS: Adult Sprague-Dawley rats were divided into two groups: naïve and stroke, with cortical ischemia induced through multiple, unilateral endothelin-1 injections. All animals were implanted with a bipolar electrode in the LCN opposite the affected hemisphere. MEPs were elicited from the affected hemisphere using intracortical microstimulation (ICMS) techniques. Multiple LCN DBS parameters were examined, including isochronal stimulation at 20, 30, 50, and 100 Hz as well as a novel burst stimulation pattern. RESULTS: ICMS-evoked MEPs were reduced in stroke (n = 10) relative to naïve (n = 12) animals. However, both groups showed frequency-dependent augmentation of cortical excitability in response to LCN DBS. In the naïve group, LCN DBS increased MEPs by 22-58%, while in the stroke group, MEPs were enhanced by 9-41% compared to OFF-DBS conditions. CONCLUSIONS: Activation of the DTC pathway increases cortical excitability in both naïve and post-stroke animals. These effects may underlie, at least partially, functional reorganization and therapeutic benefits associated with chronic LCN DBS in post-stroke animals.