Anatomical substrates and connectivity for bradykinesia motor features in Parkinson’s disease after subthalamic nucleus deep brain stimulation

Abstract

Parkinsonian bradykinesia is rated using a composite scale incorporating slowed frequency of repetitive movements, decrement amplitude, and arrhythmicity. Differential localization of these movement components within basal ganglia would drive the development of more personalized network-targeted symptomatic therapies. Using an optical motion sensor, amplitude and frequency of hand movements during a grasping task were evaluated with subthalamic nucleus deep brain Stimulation “on” or “off” in 15 patients with Parkinson’s disease. The severity of bradykinesia was assessed blindly using the Unified Parkinson’s Disease Rating Part III scale. Volumes of activated tissue of each subject were estimated where changes in amplitude and frequency were mapped to identify distinct anatomical substrates of each component in the subthalamic nucleus. Volumes of activated tissue were used to seed a normative functional connectome to generate connectivity maps associated with amplitude and frequency changes. Deep brain stimulation induced change in amplitude was negatively correlated with change in Unified Parkinson’s Disease Rating Part III scale for right (r = -0.65, p < 0.05) and left hand grasping scores (r = -0.63, p < 0.05). The change in frequency was negatively correlated with amplitude for both right (r = -0.63, p < 0.05) and left hand (r = -0.57, p < 0.05). The amplitude and frequency changes were represented as a spatial gradient with overlapping and non-overlapping regions spanning the anteromedial-posterolateral axis of the subthalamic nucleus. Whole-brain correlation maps between functional connectivity and motor changes were also inverted between amplitude and frequency changes. Deep brain stimulation associated changes in frequency and amplitude were topographically and distinctly represented both locally in subthalamic nucleus and in whole-brain functional connectivity.