Departure from OFF-State Microstate Dynamics Tracks Levodopa Response in Parkinson's Disease

Demuru, M.; Angiolelli, M.; Troisi Lopez, E.; De Luca, M.; Gallo, E.; Tafuri, D.; Depannemaecker, D.; Granata, C.; Sorrentino, G.; Sorrentino, P.

doi:10.64898/2026.08.03.742400

bioRxiv · 10.64898/2026.08.03.742400

Departure from OFF-State Microstate Dynamics Tracks Levodopa Response in Parkinson's Disease

Demuru, M.·Angiolelli, M.·Troisi Lopez, E.·De Luca, M.·Gallo, E.·Tafuri, D.·Depannemaecker, D.·Granata, C.·Sorrentino, G.·Sorrentino, P.

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Abstract

Although dopaminergic therapies in Parkinsons disease primarily restore dopamine within nigrostriatal circuits, symptoms are better indexed by whole-brain dynamics than by local activity. In this manuscript, we hypothesize that L-Dopa therapy affects whole-brain dynamics alike, which in turn relate to clinical improvement. To test this hypothesis, we conducted a repeated-measures, source-reconstructed MEG study in 13 bradykinetic-dominant PD patients, recording resting-state cortical activity OFF medication and [~]1 hour after levodopa administration (ON). We characterize brain dynamics using a microstate framework, in which transition probabilities between microstates are used to contrast pathological OFF-state dynamics with those in the ON-state. Microstate dynamics were stable within medication states but reconfigured by L-Dopa, with greater departures from the OFF-state pattern associated, at the individual level, with larger clinical improvements. Our results suggest that individualized changes in microstate dynamics may serve as a neurophysiological marker of dopaminergic responsiveness.

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Demuru, M., Angiolelli, M., Troisi Lopez, E., De Luca, M., Gallo, E., Tafuri, D., Depannemaecker, D., Granata, C., Sorrentino, G., Sorrentino, P.. 2026-08-06. Departure from OFF-State Microstate Dynamics Tracks Levodopa Response in Parkinson's Disease. https://doi.org/10.64898/2026.08.03.742400

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