Network state dynamics underpin craving in a transdiagnostic population

Emerging fMRI brain dynamic methods present a unique opportunity to capture how brain region interactions across time give rise to evolving affective and motivational states. As the unfolding experience and regulation of affective states affect psychopathology and well-being, it is important to elucidate their underlying time-varying brain responses. Here, we developed a novel framework to identify network states specific to an affective state of interest and examine how their instantaneous engagement contributed to its experience. This framework investigated network state dynamics underlying craving, a clinically meaningful and changeable state. In a transdiagnostic sample of healthy controls and individuals diagnosed with or at risk for craving-related disorders (N=252), we utilized connectome-based predictive modeling (CPM) to identify craving-predictive edges. An edge-centric timeseries approach was leveraged to quantify the instantaneous engagement of the craving-positive and craving-negative networks during independent scan runs. Individuals with higher craving persisted longer in a craving-positive network state while dwelling less in a craving-negative network state. We replicated the latter results externally in an independent group of healthy controls and individuals with alcohol use disorder exposed to different stimuli during the scan (N=173). The associations between craving and network state dynamics can still be consistently observed even when craving-predictive edges were instead identified in the replication dataset. These robust findings suggest that variations in craving-specific network state recruitment underpin individual differences in craving. Our framework additionally presents a new avenue to explore how the moment-to-moment engagement of behaviorally meaningful network states supports our changing affective experiences. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by Yale Gruber Science Fellowship to J.Y.; Mind and Life Institute A-36649338 to K.A.G.; RL1-AA017539, R01 DA039136 to M.N.P.; R01-AA013892-15, P50-DA016556, UL1-DE019586, PL1-DA024859, R01-DK00039 to R.S.; K01-AA027832 to E.V.G; R01 MH121095 to D.S. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Yale University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data supporting findings of this study are available from the corresponding author upon reasonable request.