Decoding Dynamically Shifting States of Parkinson's Disease: Tremor, Bradykinesia, and Effective Motor Control

Parkinson's Disease (PD) is characterized by distinct motor phenomena that are expressed asynchronously. Understanding the neurophysiological correlates of these different motor states could facilitate monitoring of disease progression and allow improved assessments of therapeutic efficacy, as well as enable optimal closed-loop neuromodulation. We examined neural activity in the basal ganglia and cortex of subjects with PD during a quantitative motor task to decode tremor and bradykinesia - two cardinal motor signs of this disease - and relatively asymptomatic periods of behavior. Analysis of subcortical and cortical signals revealed that tremor and bradykinesia had distinct, nearly opposite neural signatures, while effective motor control displayed unique, differentiating features. The neurophysiological signatures of these motor states depended on the type of signal recorded as well as the location; cortical decoding accuracy generally outperformed subcortical decoding, while tremor and bradykinesia were better decoded from different portions of the subthalamic nucleus (STN). These results provide a roadmap to leverage real-time neurophysiology to understand and treat PD. ### Competing Interest Statement The authors have patents and patent applications broadly relevant to Parkinson's disease (but not directly based upon this work). WFA has received proprietary equipment and technical support for unrelated research through the Medtronic external research program.