Levodopa-related physiomarkers during deep brain stimulation in Parkinson’s disease

Adaptive deep brain stimulation (aDBS) can adjust stimulation to the (medication) state of patients with Parkinson’s disease using physiological biomarkers (physiomarkers), but whether a universal physiomarker frequency exists remains unknown. We quantified levodopa-induced spectral changes (2–100 Hz) during active DBS before and after levodopa intake in local field potential recordings from 52 PD patients (100 hemispheres). Using cluster-based permutation statistics, we assigned the frequency with the largest significant change as the personalized physiomarker. Alpha/low-beta (9–20 Hz) power reduction was the most common physiomarker (35% of hemispheres) followed by stimulation-entrained gamma (SEG, 62.5 Hz) power increases (19% of hemispheres). Strong levodopa responses, high levodopa doses, and lower stimulation amplitudes were mostly associated with alpha/low-beta physiomarkers, while higher stimulation amplitudes and average levodopa doses were associated with SEG physiomarkers. These findings argue against a single generalizable physiomarker frequency and support individualized selection based on patient-specific levodopa and stimulation profiles.