Brain Functional Connectivity During Early Recovery in Alcohol Use Disorder as a Marker for Relapse

BACKGROUND:

Due to the relapsing nature of alcoholism, excessive alcohol consumption represents a significant cost to US society ($249 billion in 2010). About 64% of those entering treatment will relapse within one year. Development of new and improved treatments that could be personalized to maximize the chance of maintaining abstinence in the first year will require advancement in understanding the behavioral and neural mechanisms underlying vulnerability to relapse during early abstinence. New interventions targeting the underlying brain biomarkers of relapse vulnerability hold significant promise in reducing this critical public health problem. Using resting functional magnetic resonance imaging (fMRI) we have identified brain biomarkers that support long-term abstinence and brain biomarkers that predict relapse. Our cross-sectional and longitudinal findings provide evidence that higher functional connectivity (FC), particularly between nucleus accumbens (NAcc) and dorsolateral prefrontal cortex (DLPFC) is a potential brain biomarker that supports abstinence. Resting NAcc-DLPFC FC is graded depending on abstinence length, with higher FC in long-term abstinent alcoholics (7 years of abstinence) than controls and intermediate FC in short-term abstinent alcoholics (11 weeks of abstinence). Further, lower NAcc-DLPFC FC at 11-weeks of abstinence can be a predictor of subsequent relapse (with 74% accuracy). Our data point to specific brain biomarkers that index higher relapse vulnerability at 11 weeks of abstinence. Many individuals, however, have already relapsed by this time and were not included in the studies above. It is unknown whether these biomarkers can be identified earlier during the recovery period. We need to investigate whether this biomarker of relapse vulnerability can be identified during earlier stages of abstinence. Earlier identification of this biomarker will give valuable information for timely targeted interventions (e.g. closer monitoring, longer stay in treatment program, neuromodulation), increasing the chances of maintaining abstinence.

PURPOSE OF THE STUDY:

Our long-term goal is to use identified brain and behavioral biomarkers to facilitate the development of new, personalized treatments that will support enduring abstinence in addiction. The overall objective of this study is to identify biomarkers of relapse during early abstinence (2-3 weeks of abstinence). A secondary objective is to evaluate whether non-imaging measures such as craving and executive function add value to prediction models. Findings from this study will provide insight into the neurobiology of relapse vulnerability that will inform new treatment strategies needed to improve treatment outcome.

SPECIFIC AIMS: