Contrasting Effects of Deep Brain Stimulation and Intravenous Levodopa on Local Field Potentials

BACKGROUND/OBJECTIVE: Within-patient comparison of intravenous levodopa and subthalamic nucleus deep brain stimulation effects on neural oscillations and motor function in Parkinson's disease (PD). METHODS: Twelve patients with advanced PD and bilaterally implanted subthalamic electrodes underwent five treatment conditions: medication off/stimulation off, placebo infusion, medication on/stimulation off, medication off/stimulation on, and medication on/stimulation on. For each condition, bilateral local field potentials were recorded, and motor function was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III. RESULTS: Both levodopa and stimulation improved motor scores (p < 0.01) and reduced low β activity (13-20 Hz). High β activity (21-30 Hz) decreased only during stimulation (p < 0.01). Finely tuned γ (FTG) oscillations (60-90 Hz) appeared most often during combined therapy (68.2%), with peak frequencies entrained to half the stimulation frequency in 93.3% of electrodes, except under 180 Hz stimulation. During intravenous levodopa infusion, FTG emerged with a median latency of 14.3 minutes, frequently before peak plasma levels, and declined in frequency over time. Changes in FTG power correlated with motor improvement (p < 0.05), whereas placebo had no effect. CONCLUSIONS: Levodopa and stimulation exert distinct but complementary effects on oscillatory activity. FTG, rather than β power alone, reflected therapeutic state and was associated with motor improvement without dyskinesia. These findings highlight FTG as a potential biomarker for adaptive stimulation systems in PD. © 2026 International Parkinson and Movement Disorder Society.