Work

Levodopa Preferentially Reorganizes Dorsal Subthalamic Activity in Parkinson’s Disease

Year: 2026

Type: preprint

Abstract: Background Dopamine replacement reshapes subthalamic activity in Parkinson’s disease, but whether this response reflects anatomically organized network reconfiguration remains unclear. Objectives To determine whether levodopa preferentially reorganizes dorsal subthalamic spectral activity and cortico-subthalamic directionality. Methods Twelve participants undergoing bilateral subthalamic deep brain stimulation contributed 30 contacts (14 dorsal, 16 ventral). Recordings obtained OFF and ON medication underwent spectral parameterization and multiband state-space analysis. Simultaneous electroencephalography in six participants enabled assessment of directional cortico-subthalamic coupling using the phase slope index. Results Levodopa suppressed beta power more strongly dorsally than ventrally (−2.473 versus −0.120 dB; p=0.0438). Dorsal theta power increased, with a trend toward an increase after baseline normalization (p=0.07). Dorsal contacts exhibited greater theta–beta (+5.904 versus +1.610 dB; p=0.006) and gamma–beta (+2.516 versus +0.384 dB; p=0.0188) state-space shifts, principally driven by beta suppression. Gamma changes did not differ regionally. Concurrently, dorsal low-beta and beta interactions shifted toward cortical leading at selected electrodes, whereas ventral responses were less consistent. Conclusions Levodopa produces a topographically organized subthalamic response, combining preferential dorsal beta suppression with altered cortico-subthalamic directionality. These findings position contact anatomy as a key consideration in characterizing dopaminergic network responses and motivate clinical validation of spatially informed multiband biomarkers for adaptive stimulation.

Source: medRxiv

DOI: 10.64898/2026.10.13.26365259