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

Abstract

Adaptive deep brain stimulation (aDBS) can adjust stimulation to the (medication) state of patients with Parkinson’s disease using physiological biomarkers (physiomarkers), but whether individuals share a common physiomarker frequency remains unknown. We quantified levodopa-induced spectral changes (2–100 Hz) in local field potential recordings from the subthalamic nucleus during active DBS (median amplitude 2.0 mA, IQR: [1.6, 2.4]) in 52 PD patients (100 hemispheres). For each hemisphere we assigned the frequency with the largest significant change in spectral power before versus after levodopa intake (median dose 150 mg, IQR: [100, 200]) as the personalized physiomarker using cluster-based permutation tests. Overall, alpha/low-beta (9–20 Hz) power reduction was the most common (35% of physiomarkers) followed by stimulation-entrained gamma (SEG, 62.5 Hz) power increases (19%). Other physiomarkers were identified in theta (4–8 Hz, 8%), high beta (21-30 Hz, 9%), low gamma (31–59 Hz, 10%) or high gamma (66–100 Hz, 12%) bands, most of which increased in power after levodopa intake. Subsequent k-means clustering revealed lower stimulation amplitudes to be associated with alpha/low-beta physiomarkers, while higher stimulation amplitudes and longer disease duration were associated with SEG physiomarkers. These findings contradict the presence of a single generalizable physiomarker frequency and instead argue for individualized selection.