Altered wakeful theta activity characterizes levodopa-induced dyskinesia in Parkinson’s disease

Slow-wave activity during sleep facilitates synaptic downscaling, while theta activity during wakefulness reflects synaptic upscaling, and both processes may be altered in levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). We compared actigraphy and high-density EEG in 12 healthy volunteers and three PD cohorts: early stage (EPD, n = 12), advanced non-dyskinetic (ADV, n = 13), and advanced dyskinetic (DYS, n = 11). Participants completed one week of actigraphy monitoring, followed by two resting-state EEG recordings conducted separately in the morning and evening. Wake-theta activity was analyzed using both linear and linear mixed-effects models, adjusted for age/sex, plus cluster-based non-parametric statistics, then related to clinical variables, and actigraphy-derived sleep metrics via partial correlations. Dyskinetic patients showed marked sleep disruption, elevated morning theta compared with controls (p = 0.006, d = 1.54) and EPD (p = 0.03, d = 0.85), along with a significantly reduced diurnal theta build-up compared with controls (p = 0.009, d = 1.57). EPD and ADV groups showed preserved diurnal increases. In dyskinetic patients, a higher levodopa equivalent daily dose (LEDD) was correlated with higher morning theta (ρ = 0.70, p = 0.023, pFDR=0.046) and smaller diurnal theta increases (ρ = -0.77, p = 0.009, pFDR=0.046). Relationships between theta and actigraphy-derived sleep metrics were weaker and inconsistent across groups. These findings suggest a dyskinesia-specific profile of impaired wake-related theta homeostasis, motivating longitudinal studies combining polysomnography and waking EEG.