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.
Show abstract
Although dopaminergic therapies in Parkinson's 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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