Subthalamic neuromodulation improves short-term motor learning in Parkinson’s disease

Abstract

Abstract The basal ganglia and cerebellum are implicated in both motor learning and Parkinson’s disease. Deep brain stimulation (DBS) is an established treatment for advanced Parkinson’s disease that leads to motor and non-motor effects by modulating specific neural pathways. Recently, a disynaptic projection from the subthalamic nucleus (STN) to cerebellar hemispheres was discovered. To investigate the functional significance of this pathway in motor learning, short-term improvement in motor execution in 20 patients with Parkinson’s disease on and off STN-DBS and 20 age-matched healthy controls was studied in a visuomotor task combined with whole-brain connectomics. Motor learning was impaired in Parkinson’s disease off stimulation but was partially restored through DBS. Connectivity between active DBS contacts and a distributed network of brain regions correlated with improvement in motor learning. Region of interest analysis revealed connectivity from active contact to cerebellar hemisphere ipsilateral to hand movement as the strongest predictor for change in motor learning. Peak predictive voxels in the cerebellum localized to Crus II of lobule VII, which also showed higher STN than motor cortex connectivity, suggestive of a connection surpassing motor cortex. Our findings provide new insight into the circuit nature of Parkinson’s disease and the distributed network effects of DBS in motor learning.