Dynamic depletion of a cortico–basal ganglia–cerebellar network state is associated with dopaminergic treatment resistance in Parkinson’s disease

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Abstract Parkinson’s disease (PD) involves widespread brain network dysfunction, yet the neural mechanisms underlying the highly heterogeneous clinical response to dopaminergic therapy remain poorly understood. To address this gap, we applied whole-brain Co-activation Pattern (CAP) analysis to resting-state fMRI data from healthy controls and a longitudinal cohort of PD patients evaluated in both OFF- and ON-medication states. Our findings suggest that PD is characterized by a pathologically shifted dynamic state repertoire. Crucially, we identified a specific cortico–basal ganglia–cerebellar integrative state (CAP-2) that may represent a treatment-sensitive network configuration. Following levodopa administration, clinical responders adaptively maintain this network configuration. Conversely, non-responders exhibit a marked depletion of CAP-2 dynamics, consistent with a failure of adaptive network reconfiguration, characterized by the marked reduction of CAP-2 occurrences (counts) and abnormally rigid state transition dynamics. Furthermore, integrating these CAP-2 transition features into classification models provided proof-of-concept evidence that this cortico–basal ganglia–cerebellar network configuration captures mechanistic information underlying treatment heterogeneity. These findings underscore that dopaminergic response depends on adaptive macroscopic reconfiguration, positioning the dynamic depletion of CAP-2 as a proof-of-concept exploratory target for understanding treatment heterogeneity in PD.

Related topics