Anatomical Substrates and Connectivity for Parkinson’s Disease Bradykinesia Components after STN-DBS

Abstract

Background: 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. Methods: Using an optical motion sensor, amplitude and frequency of hand movements during grasping task were evaluated with subthalamic nucleus (STN)-Deep Brain Stimulation (DBS) "on" or "off" in 15 patients with Parkinson's disease (PD). The severity of bradykinesia was assessed blindly using the MDS-UPDRS Part-III scale. Volumes of activated tissue (VAT) of each subject were estimated where changes in amplitude and frequency were mapped to identify distinct anatomical substrates of each component in the STN. VATs were used to seed a normative functional connectome to generate connectivity maps associated with amplitude and frequency changes. Results: STN-DBS-induced change in amplitude was negatively correlated with change in MDS-UPDRS-III 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 dorsolateral-ventromedial axis of the STN. Whole-brain correlation maps between functional connectivity and motor changes were also inverted between amplitude and frequency changes. Conclusion: DBS-associated changes in frequency and amplitude were topographically and distinctly represented both locally in STN and in whole-brain functional connectivity.