Motor cortex stimulation ameliorates parkinsonian locomotor deficits: effectual and mechanistic differences from subthalamic modulation

Abstract

Subthalamic deep brain stimulation (STN DBS) has been a therapeutic choice for Parkinson’s disease (PD). We found that epidural motor cortex stimulation (MCS) with sustained positive (hyperpolarizing) currents could also consistently ameliorate the locomotor deficits in parkinsonian animals, rectifying the pathological paucity in both discharging unit varieties and movement-dependent spatiotemporal activity pattern changes in motor cortex (MC). Mechanistically, MCS hyperpolarizes both glutamatergic pyramidal neurons (PN) and GABAergic interneurons (IN) and consequently partly relieves PN from IN’s control. MC discharging units are thus enlarged with enhanced PN burst discharges against a relatively silenced background, presumably compensating for the hypoactive striatal selection to restore the MC activity changes upon movement. Behaviorally, MCS retains interim short pauses like normal locomotor behaviors, in contrast to the propensity of abnormal “restlessness” with STN DBS. Individually designed MCS, alone or in combination with STN DBS and dopaminergic therapy, may provide an optimal therapeutic approach for PD.