Effects of tDCS Paired with Cognitive Training on Brain Networks associated with Alcohol Use Disorder in Veterans

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Alcohol misuse is an epidemic among Veterans in the United States. Nearly 1/3 of Veterans have a lifetime history of Alcohol Use Disorder (AUD). Across Veteran and civilian populations, about 60% of those entering treatment will relapse within one year. Paradoxically, chronic alcohol use is associated with cognitive impairments and changes in their underlying neural circuitry, that interfere with adaptive behavior needed for successful recovery. However, these cognitive impairments and their underlying neural substrates are promising new targets for interventions that can reduce relapse rates. Evidence suggests that cognitive training can improve cognition in individuals with AUD, strengthen neural networks mediating cognition, and improve treatment outcome. However, cognitive training is effort intensive, has small effect sizes, and may have limited durability. Evidence suggests that addiction is mediated by a dysfunctional cortico-striatal neurocircuitry characterized by excess striatal activity (driving substance use) coupled with hypoactive prefrontal cortex (impaired cognitive control)​.​ Resting-state functional connectivity (RSFC) data has identified a promising circuit-based target for the treatment of addiction. Individuals who have achieved long-term abstinence from alcohol (~7 years of abstinence) have higher RSFC in prefrontally-mediated networks (e.g. prefrontal-striatal, prefrontal-parietal, prefrontal-insular, prefrontal-thalamic networks) th​an controls or those with short-term abstinence (6-10 weeks of abstinence). Moreover, lower prefrontal RSFC during short-term abstinence can predict subsequent relapse. The ​primary objective​ of this study is to investigate the use of a novel neuroplasticity based intervention that combines ​cognitive training​ and ​transcranial direct current stimulation ​(tDCS) neuromodulation​ to enhance frontal-striatal RSFC and cognition, with the goal to improve treatment outcomes and increase abstinence in Veterans with AUD. This research proposal will address the following ​Specific Aims (SAs)​: ​SA1) ​Compare brain network changes between active tDCS vs. sham tDCS (placebo) groups, ​when both groups receive cognitive training​. RSFC changes will be measured with functional magnetic resonance imaging data collected pre- and post-intervention. ​Hypothesis:​ ​Active tDCS, compared to sham tDCS will produce a significantly greater increase in prefrontal-striatal RSFC. ​SA2) ​Evaluate cognitive changes between active tDCS vs. sham tDCS (placebo) groups. ​Hypothesis:​ ​Active tDCS, compared to sham tDCS, will produce a significantly greater improvement in cognitive performance measures. ​SA3) ​Compare the effects of active tDCS vs. sham tDCS on drinking behavior over a 2 month follow-up period.​ ​Our primary outcome will be to compare binge drinking days per week​ w​ ithin the 2 months after the intervention between AUD participants who receive active tDCS vs. sham. ​Hypothesis:​ ​Active tDCS, compared to sham tDCS, will produce significantly fewer binge drinking days per week​ i​ n the 2 months following the intervention. Cognitive impairment and its underlying neural mechanisms affect alcohol addiction​ treatment outcomes​. We propose the first study to examine how tDCS-augmented cognitive training affects cognition and its related brain circuitry in alcohol use disorder in Veterans, which will provide critical information to guide future research and treatment development.