Aberrant functional brain network organization is associated with relapse during 1-year follow-up in alcohol-dependent patients

Alcohol dependence (AD) is a debilitating disease associated with high relapse rates even after long periods of abstinence. Thus, elucidating neurobiological substrates of relapse risk is fundamental for the development of novel targeted interventions that could promote long-lasting abstinence. In the present study, we analyzed resting-state functional magnetic resonance imaging (rsfMRI) data from a sample of recently detoxified AD patients ( n = 93) who were followed-up for 12 months after rsfMRI assessment. Specifically, we employed graph theoretic analyses to compare functional brain network topology and functional connectivity between future relapsers (REL, n = 59), future abstainers (ABS, n = 28) and age and gender matched controls (CON, n = 83). Our results suggest increased whole-brain network segregation, decreased global network integration and overall blunted connectivity strength in REL compared to CON. Conversely, we found evidence for a comparable network architecture in ABS relative to CON. At the nodal level, REL exhibited decreased integration and decoupling between multiple brain systems compared to CON, encompassing regions associated with higher-order executive functions, sensory and reward processing. Among AD patients, increased coupling between nodes implicated in reward valuation and salience attribution constitutes a particular risk factor for future relapse. Importantly, aberrant network organization in REL was consistently associated with shorter abstinence duration during follow-up, portending to a putative neural signature of relapse risk in AD. Future research should further evaluate the potential diagnostic value of the identified changes in network topology and functional connectivity for relapse prediction at the individual subject level.