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This study aimed to investigate structural and functional alterations of the reward system and the neurobiology of craving in alcohol use disorder (AUD). We hypothesized reduced volume of the nucleus accumbens (NAcc), reduced structural connectivity of the segment of the supero-lateral medial forebrain bundle connecting the orbitofrontal cortex (OFC) with the NAcc (OFC-NAcc), and reduced resting-state OFC-NAcc functional connectivity (FC). Furthermore, we hypothesized that craving is related to an increase of OFC-NAcc FC. Thirty-nine recently abstinent patients with AUD and 18 healthy controls (HC) underwent structural (T1w-MP2RAGE, diffusion-weighted imaging (DWI)) and functional (resting-state fMRI) MRI-scans. Gray matter volume of the NAcc, white matter microstructure (fractional anisotropy (FA)) and macrostructure (tract length) of the OFC-NAcc connection and OFC-NAcc FC were compared between AUD and HC using a mixed model MANCOVA controlling for age and gender. Craving was assessed using the thoughts subscale of the obsessive-compulsive drinking scale (OCDS) scale and was correlated with OFC-NAcc FC. There was a significant main effect of group. Results were driven by a volume reduction of bilateral NAcc, reduced FA in the left hemisphere, and reduced tract length of bilateral OFC-NAcc connections in AUD patients. OFC-NAcc FC did not differ between groups. Craving was associated with increased bilateral OFC-NAcc FC. In conclusion, reduced volume of the NAcc and reduced FA and tract length of the OFC-NAcc network suggest structural alterations of the reward network in AUD. Increased OFC-NAcc FC is associated with craving in AUD, and may contribute to situational alcohol-seeking behavior in AUD.

Background Alcohol use disorder (AUD) leads to a significant individual and societal burden. To achieve higher therapy success rates, therapeutic interventions still need to be improved. Most current neuroscientific conceptualizations of AUD focus on the imbalance between an enhanced automatic reaction to alcohol cues and impaired inhibition. Complementary to traditional relapse prevention strategies, novel computerized training interventions aim to directly alter these processes. This study tests a computerized alcohol-specific inhibition training in a large clinical sample and investigates its effects on behavioral, experimental and neurophysiological outcomes. It also analyzes whether variations in inhibition difficulty and/or endogenous cortisol levels during training impact these effects. Methods This is a double-blind, randomized controlled trial (RCT) with 246 inpatients with AUD participating. After baseline assessment, participants are randomly assigned to one of three computerized Go-NoGo-based inhibition training interventions (two alcohol-specific versions with different Go/NoGo ratios, or neutral control training) and one of two intervention times (morning/afternoon), resulting in six study arms. All patients perform six training sessions within 2 weeks. Endogenous cortisol is measured in 80 patients before and after the first training session. Inhibitory control and implicit associations towards alcohol are assessed pre and post training, at which point electroencephalography (EEG) is additionally measured in 60 patients. Patients’ alcohol consumption and relevant psychological constructs (e.g., craving, self-efficacy, treatment motivation) are measured at discharge and at 3-, 6- and 12-month follow-ups. Fifty healthy participants are assessed (20 with EEG) at one time point as a healthy control group. Discussion This study investigates the effects of a computerized, alcohol-specific inhibition training for the first time in patients with AUD. Results should give insight into the effectiveness of this potential add-on to standard AUD treatment, including proximal and distal measures and effects on behavioral, experimental and neurophysiological measures. Information about working mechanisms and potential optimizations of this training are gathered through variations regarding difficulty of inhibition training and training time. This study may thus contribute to a deepened understanding of AUD and the improvement of its evidence-based treatment. Trial registration ClinicalTrials.gov, ID: NCT02968537 . Registered on 18 November 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3505-2) contains supplementary material, which is available to authorized users.

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Aims For the first time, to our knowledge, in a clinical sample with alcohol use disorder (AUD), this study compared the effects of two versions of alcohol‐specific inhibition training (Alc‐IT) on drinking outcomes and on experimental parameters assessing two possible working mechanisms: stimulus devaluation and inhibitory enhancement. Design Multi‐centre, double‐blind, three‐arm clinical RCT with 3‐, 6‐ and 12‐month follow‐up comparing standard Alc‐IT, improved Alc‐IT and an active control condition. Setting Three specialized AUD treatment centres in Switzerland. Participants A total of 242 detoxified, recently abstinent patients with severe AUD (18–60 years; 29.8% female). Intervention and Comparator Both interventions [standard Alc‐IT (n = 84) and improved Alc‐IT (n = 79)] and the comparator [unspecific inhibition training (n = 79)] consisted of six sessions of a modified inhibitory task (Go/NoGo task) with alcohol‐related and neutral stimuli. Both versions of Alc‐IT required response inhibition in alcohol‐related trials but differed in Go/NoGo ratios (standard: 50/50; improved: 75/25), with improved Alc‐IT posing higher inhibitory demands. The control condition, an unspecific inhibition training, featured alcohol‐related pictures in Go as well as NoGo trials. Measurements The primary outcome, percentage of days abstinent, was assessed at 3‐month follow‐up with a time‐line follow‐back interview. Findings The group receiving improved Alc‐IT showed a significantly higher percentage of days abstinent at 3‐month follow‐up compared with the control group [γcontrol = 74.30; γimproved = 85.78; β = 11.48, 95% confidence interval (CI) = 2.57, 20.40, P = 0.012, adjusted r2 = 0.062], while for standard Alc‐IT no effect significantly different from zero was detected (γstandard = 70.95; β = −3.35, 95% CI = −12.20, 5.50, P = 0.457, adjusted r2 = −0.04). Conclusions Alcohol‐specific inhibition training with high inhibitory demands increased days abstinent at 3‐month follow‐up in patients with severe alcohol use disorder. Such an improved, inhibitory‐demanding, alcohol‐specific inhibition training outperformed the standard version of alcohol‐specific inhibition training, suggesting an inhibitory working mechanism.