Deep brain stimulation rectifies the noisy cortex and irresponsive subthalamus to improve parkinsonian locomotor activities

Abstract

The success of deep brain stimulation (DBS) therapy indicates that Parkinson’s disease is a brain rhythm disorder. However, the manifestations of the erroneous rhythms corrected by DBS remain to be established. We found that augmentation of α rhythms and α coherence between the motor cortex (MC) and the subthalamic nucleus (STN) is characteristically prokinetic and is decreased in parkinsonian rats. In multi-unit recordings, movement is normally associated with increased changes in spatiotemporal activities rather than overall spike rates in MC. In parkinsonian rats, MC shows higher spike rates at rest but less spatiotemporal activity changes upon movement, and STN burst discharges are more prevalent, longer lasting, and less responsive to MC inputs. DBS at STN rectifies the foregoing pathological MC-STN oscillations and consequently locomotor deficits, yet overstimulation may cause behavioral restlessness. These results indicate that delicate electrophysiological considerations at both cortical and subcortical levels should be exercised for optimal DBS therapy.