Subthalamic Electrophysiological Mapping of Gait Initiation Dynamics and Freezing in Parkinson's Disease

Objective: The objective of this study was to investigate the relationships among subthalamic nucleus (STN) activity, gait initiation (GI), and freezing of gait (FOG) in patients with Parkinson's disease (PD). Methods: We recorded GI and STN local field potentials (LFPs) via externalized cables in 38 patients with PD (35 reporting FOG in daily life), both OFF- and ON-dopamine (DOPA). GI was also recorded in 24 age-matched controls. GI scores related to pace, rhythm, and balance were derived from kinetics, and FOG was identified using kinematics. We compared GI performance related to FOG and DOPA, and GI-LFP relationships between posterior-sensorimotor versus central-associative STN regions. Results: DOPAOFF, 12 patients with PD had FOG observed (FOG-OBS, 263 episodes), occurring at a mean of 8 steps after GI, and 26 had no FOG observed (NOBS; FOG-NOBS). GI pace scores were worse in FOG-OBS than in FOG-NOBS patients with PD, even when not followed by FOG, with weaker association with alpha/low-beta activity in the posterior STN. Although rhythm/balance scores were similar between groups, their association with low-beta activity was stronger in FOG-OBS patients, with rhythm correlating more in the central STN and balance in the posterior STN. GI was worse preceding imminent FOG, with disrupted low-beta GI-LFP associations and emergent high-beta correlations with reversed spatial distribution (pace/rhythm-posterior STN, balance-central). Dopamine improved pace, rhythm, and FOG, and partially restored STN activity. Interpretation: Our results reveal 3 distinct GI patterns in patients with PD associated with absence, predisposition to, or imminent occurrence of FOG, with STN neuronal modulations differing dynamically between the posterior and central subregions. These markers could support developing adaptive DBS strategies tailored for episodic gait impairments. ANN NEUROL 2025.