Beyond beta rhythms: subthalamic aperiodic broadband power scales with Parkinson's disease severity–a cross-sectional multicentre study
Moritz Gerster, Gunnar Waterstraat, Thomas S. Binns, Natasha Darcy, Christoph Wiest, Richard M. Köhler, Jonathan Vanhoecke, Timothy O. West, Matthias Sure, Dmitry Todorov, Lukasz Radzinski, Jeroen Habets, Johannes L. Busch, Lucia K. Feldmann, Patricia Krause, Katharina Faust, Gerd‐Helge Schneider, Keyoumars Ashkan, Erlick Pereira, Harith Akram, Ludvic Zrinzo, Benjamin Blankertz, Arno Villringer, Huiling Tan, Jan V. Hirschmann, Andrea A. Kühn, Esther Florin, Alfons Schnitzler, Ashwini Oswal, Vladimir Litvak, Wolf‐Julian Neumann, Gabriel Curio, Vadim V. Nikulin
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 ( r Offset = − 0.32 , p = 4 e − 4 ; r L γ = − 0.21 , p = 0.021 ), whereas low beta oscillations were positively correlated ( r L β = 0.24 , p = 0.010 ). Combining offset, low beta, and low gamma power ( r Lin . reg . ( Offset , L β , L γ ) = 0.47 , p = 1 e − 4 ) explained significantly more variance in symptom severity than low beta alone ( J -test: p = 2 e − 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. Funding This work was supported by Deutsche Forschungsgemeinschaft (German Research Foundation) Project ID 424778381 TRR 295 "ReTune". H.A. is supported by NIHR UCLH BRC. This work was supported by an MRC Clinician Scientist Fellowship (MR/W024810/1) held by A.O. W.-J.N. received funding from the European Union (ERC, ReinforceBG, project 101077060). E.F. received funding from the Volkswagen foundation (Lichtenberg program 89387). G.W. and L.R. received funding from Deutsche Forschungsgemeinschaft Project ID 511192033.