Abstract
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.
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Data availability
The datasets generated and/or analysed during the current study are not publicly available to protect patient confidentiality, but are available from the corresponding author on reasonable request.
Code availability
The custom code used for data processing and analysis in this study is openly available at the following GitHub repository: https://github.com/biomedical-signal-processing/sleep-homeostasis-dyskinesia.
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Acknowledgements
We thank the participants who devoted their time and efforts to take part in this study. This research was supported by the Synapsis Foundation (project ID 2021-PI06), the Parkinson Schweiz (project ID 2022-00736), and the Swiss National Science Foundation (project ID SNF 320030-228113) led by Salvatore Galati. The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.
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S.G., L.F. contributed to the conception and design of the study; L.F., G.L., N.L.P., L.A., M.V., and I.B. contributed to acquisition and analysis of the data; S.G., L.F., and G.L. contributed to drafting the manuscript and figures. We thank A.C., I.B., C.S., and A.K.-L. for their critical reading.
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Fiorillo, L., Lombardi, G., La Porta, N. et al. Altered wakeful theta activity characterizes levodopa-induced dyskinesia in Parkinson’s disease. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-026-01320-z
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DOI: https://doi.org/10.1038/s41531-026-01320-z
