Altered brain-state dynamics and associations with dependence severity and affective-somatic burden in cocaine use disorder

Cocaine use disorder (CUD) is characterized not only by impaired cognitive control but also by pronounced emotion dysregulation. Although resting-state brain dynamics have been linked to adaptive cognitive and emotional functioning, it remains unclear how these dynamics are altered in CUD and whether such alterations relate to dependence severity and affective-somatic symptom burden. We applied Hidden Markov modeling to resting-state fMRI from 58 individuals with CUD and 44 healthy controls to characterize large-scale brain-state dynamics. CUD was associated with reduced global switching, increased occupancy and persistence of a limbic-dominant state, reduced occupancy of a frontoparietal-ventral attention state, and prolonged persistence of a ventral attention-somatomotor state. Transition analyses further identified higher transition probabilities from default mode-dorsal attention and ventral attention-somatomotor configurations toward the limbic-dominant state. Limbic-state occupancy showed positive associations with dependence severity, emotion dysregulation, somatization, and anxiety. Meta-analytic decoding provided functional context for this state, while exploratory spatial comparisons with normative receptor and gene-expression atlases provided molecular context. Together, these findings identify altered resting-state temporal organization in CUD and suggest that limbic-state occupancy is a potential correlate of dependence severity and affective-somatic burden.