Relapse rates in psychosocially-based treatment programs for alcohol use disorder (AUD) remain high. Novel brain-based interventions are needed to improve outcomes. Interventions that target the underlying neural networks associated with relapse hold significant promise in reducing this critical public health problem. My resting-state functional connectivity (RSFC) data showed that individuals with AUD (i) who have achieved long- term abstinence have higher prefrontal-striatal RSFC, and (ii) who subsequently relapse show low prefrontal- striatal RSFC during early abstinence. I am interested in investigating whether prefrontal-striatal RSFC can be modified during early abstinence as a form of treatment to prevent subsequent relapse. We have evidence that transcranial direct current stimulation (tDCS) interventions paired with cognitive training can significantly increase brain RSFC and modify behavior. We will conduct a double-blind randomized trial including 75 participants receiving treatment for AUD to determine whether a tDCS intervention combined with cognitive training can increase prefrontal-striatal RSFC and reduce amount of alcohol use during a follow-up period. We will also investigate whether RSFC changes are related to clinical outcomes. The central hypothesis is that active-tDCS combined with cognitive training will increase prefrontal-striatal RSFC and reduce amount of alcohol use during a 6-month follow-up period. This research proposal will address the following specific aims: SA1. Compare the effect of active- vs. sham-tDCS intervention on RSFC. Hypothesis: Active-tDCS, compared to sham-tDCS will produce greatest increase in prefrontal-striatal RSFC. SA2. Determine whether RSFC changes during early abstinence affect alcohol use during a follow-up period (FC changes independent of tDCS intervention). Hypothesis: Degree of prefrontal-striatal FC increases will correspond to reduction in alcohol use 6-months after intervention. SA3. Compare the effects of active- vs. sham-tDCS intervention on abstinence over 6-month follow-up period. Hypothesis: Active-tDCS, compared to sham tDCS will produce lower alcohol use 6-months after intervention. Findings will provide crucial evidence supporting the therapeutic use of customized brain-based interventions targeting underlying neural mechanisms to support alcohol abstinence. T his research will provide preliminary data for a properly powered clinical trial, a future R01 application with larger sample sizes and more neuroimaging time points to inform validated new interventions. Combined with my career development plan and strong mentoring team, this K award will foster my successful transition to independence as an investigator with the knowledge and skills to lead a team that converges neuroimaging findings with novel treatment interventions to improve outcomes in substance use disorders.

Public Health Relevance

Given? ?high? ?relapse? ?rates,? ?it? ?is? ?crucial? ?to? ?investigate? ?how? ?treatment? ?for? ?alcohol? ?use? ?disorders? ?can? ?be? ?improved. The? ?overarching? ?goal? ?of? ?this? ?proposal? ?is? ?to? ?integrate? ?brain? ?stimulation,? ?cognitive? ?training,? ?and? ?neuroimaging techniques? ?to? ?investigate? ?whether? ?brain? ?networks? ?associated? ?with? ?subsequent? ?relapse? ?can? ?be? ?modified? ?to support? ?abstinence.? ?This? ?research? ?proposal? ?is? ?the? ?first? ?study? ?to? ?examine? ?whether? ?the? ?combined? ?effect? ?of? ?brain stimulation? ?plus? ?cognitive? ?training? ?can? ?affect? ?brain? ?networks? ?during? ?early? ?abstinence? ?in? ?individuals? ?with? ?alcohol use? ?disorder,? ?providing? ?critical? ?information? ?to? ?guide? ?future? ?research? ?and? ?treatment? ?development.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Scientist Development Award - Research & Training (K01)
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National Institute on Alcohol Abuse and Alcoholism Initial Review Group (AA)
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Matochik, John A
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University of Minnesota Twin Cities
Schools of Medicine
United States
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