Brain Functional Connectivity in Alcohol Use Disorder
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Study type: Observational

Summary: 
      Due to the relapsing nature of alcoholism, excessive alcohol consumption represents a
      significant cost to US society ($249 billion in 20101). About 64% of those entering treatment
      will relapse within one year. 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
      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. 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. 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
      craving6 and executive function7 add value to prediction models. Findings from this proposal
      will provide insight into the neurobiology of relapse vulnerability that will inform new
      treatment strategies needed to improve treatment outcome.
    

Detailed description: 
      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:

      SA 1: To evaluate prediction accuracy of FC measures in individuals with alcohol use disorder
      (AUD) during early (2-3 weeks) abstinence. To evaluate whether non-imaging measures (e.g.
      craving, executive function) add value to FC prediction models we will test prediction models
      using (i) only imaging variables (FC during task and rest fMRI), (ii) only non-imaging
      variables, and (iii) a combination of imaging and non-imaging variables as predictors of time
      to relapse. Hypothesis: Based on compensatory mechanisms hypothesis, we expect that
      subsequent abstainers will have stronger NAcc-DLPFC FC when compared to subsequent relapsers
      and controls. Pilot data suggests that a combination of imaging and non-imaging variables
      will have high prediction accuracy. SA 2. To expand our examination of NAcc-DLPFC FC beyond
      resting state we will use the Reversal Learning (RL) task, which involves executive
      functioning and reward processing. Hypothesis: Pilot data suggests that subsequent abstainers
      will show higher task-related NAcc FC than relapsers and controls. Exploratory Aim: We will
      explore whether the strength of resting NAcc-DLPFC FC changes after performing the RL task.
      We will collect rest fMRI data before and after RL task performance in the scanner.
      Hypothesis: Based on previous findings of increased task-evoked activity in these regions, we
      hypothesize that patients will show increased resting NAcc-DLPFC FC after performing the RL
      task.

      SIGNIFICANCE:

      Addiction treatment outcomes are poor. Alcohol use disorder (AUD) in the U.S. remains an
      important public health problem with an estimated total annual cost to society of $249.5
      billion. The chronic and relapsing nature of AUD is a major obstacle to successful recovery.
      We lack tools to subtype in alcohol use disorder (AUD). Subtyping in clinical populations can
      be an effective approach to model targeted interventions. For example, targeted treatment for
      breast cancer patients based on individual tumor estrogen receptor typing (biomarker) has
      improved outcomes from a 25 to 77% survival rate; there has not been a similar improvement in
      outcome for AUD treatment. We need to identify biomarkers in AUD that predict relapse and
      guide the development and selection of treatment based on subtypes to increase the chances of
      achieving long-term abstinence.
    

Intervention name(s): MRI: Brain Imaging data collection
Intervention type(s): Device
Intervention description(s): This study has no intervention, it is observational. We will collect brain imaging data and behavioral assessments.
Observational model: Case-Control
Time perspective: Other
Sampling method: Probability Sample
Study population: 
        Individuals with alcohol use disorder will be only recruited from the Lodging Plus
        treatment program at Fairview Riverside in Minneapolis, MN Healthy volunteers will be
        recruited through community advertisements in Minneapolis, MN
      
Keywords: fMRI; brain networks; biomarker; relapse; alcohol