Theta-Gamma Decoupling - A neurophysiological marker of impaired reward processing in Parkinson's disease.

Abstract

Individuals with Parkinson's disease (PD) exhibit altered reward processing, reflected by a decreased amplitude of an event-related potential (ERP) marker called reward positivity (RewP). Most studies have used RewP to investigate reward behavior due to the high temporal resolution of EEG and its high sensitivity. However, traditional single-electrode ERP analyses often overlook the intricate dynamics of non-phase-locked oscillatory activity and the complex interactions within these neural oscillatory patterns. Studying oscillatory activity is crucial as it provides mechanistic insights into the functional, spatial, and temporal aspects of neuronal processing. To address this gap, we employed a data-driven approach to identify EEG-based markers associated with PD reward processing deficits. Using an openly available 64-channel EEG dataset of 28 age- and sex-matched PD and control participants during a reinforcement learning task, we conducted a comprehensive secondary analysis. First, we employed a cluster-based permutation method to extract ERP markers, finding a consistent decrease in reward positivity in PD, regardless of medication status. Additionally, through region of interest (ROI) analysis on time-frequency data, we identified specific oscillatory patterns during reward processing. PD patients exhibited attenuated theta power and increased gamma power compared to healthy controls (HC). Notably, within the PD group, those off medication showed anterior localization of high gamma power, while those on medication displayed higher posterior gamma power. Building upon these findings, we explored phase-amplitude coupling between theta phase and gamma amplitude measured by the modulation index. We observed a trend of decreased theta-gamma coupling in PD patients, with statistically significant differences between on and off medication conditions. These results highlight the potential role of theta-gamma coupling as a neuromodulatory target for improving goal-oriented behavior in PD. Our correlation analyses suggest that high gamma power is linked to longer disease duration, while reduced reward positivity and low theta-gamma coupling may serve as markers of the dopaminergic impact on reward processing. Thus, our study unveils the intricate time-frequency dynamics underlying reward processing deficits in PD, emphasizing the utility of a data-driven approach to elucidate neural mechanisms and to identify potential therapeutic targets.