Gerster M, Waterstraat G, Binns TS, Darcy N, Wiest C, Köhler RM, Vanhoecke J, West TO, Sure M, Todorov D, Radzinski L, Habets J, Busch JL, Feldmann LK, Krause P, Faust K, Schneider GH, Ashkan K, Pereira E, Akram H, Zrinzo L, Blankertz B, Villringer A, Tan H, Hirschmann J, Kühn AA, Florin E, Schnitzler A, Oswal A, Litvak V, Neumann WJ, Curio G, Nikulin V
EBioMedicine. 2025 Nov 4: 105988. doi: 10.1016/j.ebiom.2025.105988. Online ahead of print.
Abstract
Background: Parkinson’s disease is linked to increased beta rhythms (13–30 Hz) in the subthalamic nucleus, which correlate with motor symptoms. However, findings across studies are inconsistent. Furthermore, the contribution of other frequencies to symptom severity remains underexplored.
Methods: We analysed subthalamic local field potentials from 119 patients with Parkinson’s disease (31 female; mean age 60 ± 9 years) across five independent datasets. Power spectra were parametrised and studied in relation to Levodopa administration and the severity of motor symptoms.
Findings: Our findings suggest that small sample sizes contributed to the variable correlations between beta power and motor symptoms reported in previous studies. Here, we demonstrate that more than 100 patients are required for stable replication. Aperiodic offset and low gamma (30-45 Hz) oscillations were negatively correlated with motor deficits (rOffset=-0.32, p=4e-4; rLγ=-0.21, p=0.021), whereas low beta oscillations were positively correlated (rLβ=0.24, p=0.010). Combining offset, low beta, and low gamma power (rLin.reg.(Offset,Lβ,Lγ)=0.47, p=1e-4) explained significantly more variance in symptom severity than low beta alone (J-test: p=2e-5). Interhemispheric within-patient analyses showed that, unlike beta oscillations, aperiodic broadband power (2-60 Hz)-likely reflecting spiking activity-was increased in the more affected hemisphere (Levodopa off-state: p=0.015; on-state: p=0.005).
Interpretation: Spectral features beyond conventional beta rhythms are critical to understanding Parkinson’s pathophysiology. Aperiodic broadband power shows potential as a new biomarker for adaptive deep brain stimulation, providing important insights into the relationship between subthalamic hyperactivity and motor symptoms in Parkinson’s disease.








