Rationale Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cuereactivity. Objectives In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cuereactivity with a hybrid imaging task. Methods Out of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cuereactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. Results The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. Conclusions Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

BackgroundAlcohol Use Disorder is a highly prevalent mental disorder which puts a severe burden on individuals, families, and society. The treatment of Alcohol Use Disorder is challenging and novel and innovative treatment approaches are needed to expand treatment options. A promising neuroscience-based intervention method that allows targeting cortical as well as subcortical brain processes is real-time functional magnetic resonance imaging neurofeedback. However, the efficacy of this technique as an add-on treatment of Alcohol Use Disorder in a clinical setting is hitherto unclear and will be assessed in the Systems Biology of Alcohol Addiction (SyBil-AA) neurofeedback study.MethodsN = 100 patients with Alcohol Use Disorder will be randomized to 5 parallel groups in a single-blind fashion and receive real-time functional magnetic resonance imaging neurofeedback while they are presented pictures of alcoholic beverages. The groups will either downregulate the ventral striatum, upregulate the right inferior frontal gyrus, negatively modulate the connectivity between these regions, upregulate, or downregulate the auditory cortex as a control region. After receiving 3 sessions of neurofeedback training within a maximum of 2 weeks, participants will be followed up monthly for a period of 3 months and relapse rates will be assessed as the primary outcome measure.DiscussionThe results of this study will provide insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback training in the treatment of Alcohol Use Disorder as well as in the involved brain systems. This might help to identify predictors of successful neurofeedback treatment which could potentially be useful in developing personalized treatment approaches.Trial registrationThe study was retrospectively registered in the German Clinical Trials Register (trial identifier: DRKS00010253; WHO Universal Trial Number (UTN): U1111–1181-4218) on May 10th, 2016.