Subthalamic Nucleus Activity during Cognitive Load and Gait Dysfunction in Parkinson's Disease.

Abstract

Gait freezing is a common, disabling symptom of Parkinson's disease characterized by sudden motor arrest during walking. Adaptive deep brain stimulation devices that detect freezing and deliver real-time, symptom-specific stimulation are a potential treatment strategy. Real-time alterations in subthalamic nucleus firing patterns have been demonstrated with lower limb freezing, however, whether similar abnormal signatures occur with freezing provoked by cognitive load, is unknown. We obtained subthalamic nucleus microelectrode recordings from eight Parkinson's disease patients performing a validated virtual reality gait task, requiring responses to on-screen cognitive cues while maintaining motor output. Signal analysis during 15 trials containing freezing or significant motor output slowing precipitated by dual-tasking demonstrated reduced θ frequency (3-8 Hz) firing compared to 18 unaffected trials. These preliminary results reveal a potential neurobiological basis for the interplay between cognitive factors and gait disturbances including freezing in Parkinson's disease, informing development of adaptive deep brain stimulation protocols. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.