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.