Understanding Altered Dynamics in Cocaine Use Disorder Through State Transitions Mediated by Artificial Perturbations

<b>Background/Objectives</b>: Cocaine use disorder (CUD) poses a worldwide health challenge, with severe consequences for brain function. However, the phase dynamics underlying CUD and the transitions between CUD and health remain poorly understood. <b>Methods</b>: Here, we used resting-state functional magnetic resonance imaging (fMRI) data from 43 CUD patients and 45 healthy controls (HCT). We performed empirical analysis to identify phase-coherence states and compared their probabilities of occurrence between conditions. To further explore the underlying mechanism, we employed computational modeling to replicate the observed state probabilities for each condition. These generated whole-brain models enabled us to simulate external perturbations and identify optimal brain regions mediating transitions between HCT and CUD. <b>Results</b>: We found that CUD was associated with a reduced occurrence probability of the state dominated by the default mode network (DMN). Perturbing the nucleus accumbens, thalamus, and specific regions within the default mode, limbic and frontoparietal networks drives transitions from HCT to CUD, while perturbing the hippocampus and specific regions within the visual, dorsal attention, and DMN facilitates a return from CUD to HCT. <b>Conclusions</b>: This study revealed altered DMN-related dynamics in CUD from the phase perspective and provides potential regions critical for state transitions. The results contribute to understanding the pathogenesis of CUD and the development of therapeutic stimulation strategies.