Shared and Distinct Dynamic Brain Activity and Functional Connectivity Variability in Patients with Isolated Craniocervical Dystonia

Abstract Isolated craniocervical dystonia is a hyperkinetic movement disorder with motor and non-motor features, yet the temporal dynamics of its brain activity remain underexplored. Using resting-state Functional MRI from 201 isolated craniocervical dystonia patients (102 blepharospasm, 43 blepharospasm–oromandibular dystonia, and 56 cervical dystonia) and 160 healthy controls, we applied a sliding-window approach to evaluate dynamic functional metrics and dynamic functional connectivity patterns. Isolated craniocervical dystonia patients showed widespread abnormalities in dynamic regional activity involving the cerebellum, primary motor cortex, and visual cortex, which were consistent with instability in neural activity or coordination. Subnetwork analyses indicated significant alterations—particularly increased dynamic functional connectivity variability in cerebello-cortical and cortico-cortical circuits—in isolated craniocervical dystonia and blepharospasm as compared to healthy controls. Clustering of time-resolved connectivity revealed two recurring brain states: a strongly connected State 1 and a weakly connected State 2. Compared to healthy controls, isolated craniocervical dystonia, blepharospasm, blepharospasm–oromandibular dystonia, and cervical dystonia groups spent proportionally more time in State 2 and exhibited fewer state transitions, suggesting reduced network flexibility and a bias toward hypo-connected configurations. Together, these findings demonstrated shared and subtype-specific disruptions in the dynamics of spontaneous activity and interregional coupling in isolated craniocervical dystonia, implicating alterations of cerebello-cortical and sensorimotor-visual systems in its pathophysiology and highlighting temporal instability and diminished switching as potential disease signatures.