Alcohol-specific inhibition training in patients with alcohol use disorder: a multi-centre, double-blind randomized clinical trial examining drinking outcome and working mechanisms.

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; ß = 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; ß = -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.

Right Inferior Frontal Activation During Alcohol-Specific Inhibition Increases With Craving and Predicts Drinking Outcome in Alcohol Use Disorder.

Alcohol use disorder (AUD) is characterized by enhanced cue-reactivity and the opposing control processes being insufficient. The ability to inhibit reactions to alcohol-related cues, alcohol-specific inhibition, is thus crucial to AUD; and trainings strengthening this ability might increase treatment outcome. The present study investigated whether neurophysiological correlates of alcohol-specific inhibition (I) vary with craving, (II) predict drinking outcome in AUD and (III) are modulated by alcohol-specific inhibition training. A total of 45 recently abstinent patients with AUD and 25 controls participated in this study. All participants underwent functional magnetic resonance imaging (fMRI) during a Go-NoGo task with alcohol-related as well as neutral conditions. Patients with AUD additionally participated in a double-blind RCT, where they were randomized to either an alcohol-specific inhibition training or an active control condition (non-specific inhibition training). After the training, patients participated in a second fMRI measurement where the Go-NoGo task was repeated. Percentage of days abstinent was assessed as drinking outcome 3 months after discharge from residential treatment. Whole brain analyses indicated that in the right inferior frontal gyrus (rIFG), activation related to alcohol-specific inhibition varied with craving and predicted drinking outcome at 3-months follow-up. This neurophysiological correlate of alcohol-specific inhibition was however not modulated by the training version. Our results suggest that enhanced rIFG activation during alcohol-specific (compared to neutral) inhibition (I) is needed to inhibit responses when craving is high and (II) fosters sustained abstinence in patients with AUD. As alcohol-specific rIFG activation was not affected by the training, future research might investigate whether potential training effects on neurophysiology are better detectable with other methodological approaches.

Reduced structural connectivity of the amygdala is associated with childhood trauma in adult patients with alcohol use disorder.

Childhood trauma (CT) is frequent in patients with alcohol use disorder (AUD) and may impact on adult drinking behaviour and treatment outcome. This study aimed to investigate the structural correlates of CT in AUD, focusing on the amygdala, which plays a crucial role in the neurobiology of trauma. We hypothesized reduced amygdala volume and reduced structural connectivity as quantified by fractional anisotropy (FA) and by number of streamlines in those AUD patients with a history of moderate to severe CT (AUD-CT). T1-weighted MP2RAGE and diffusion-weighted imaging (DWI) 3-Tesla MRI-scans were acquired in 41 recently abstinent patients with AUD. We compared bilateral amygdala volume and structural connectivity (FA and number of streamlines) of pathways emanating from the amygdala between AUD-CT (n = 20) and AUD without CT (AUD-NT, n = 21) using a mixed model multivariate analysis of variance (MANCOVA) controlling for age and gender. AUD-CT displayed reduced FA and reduced number of streamlines of amygdalar tracts. There were no differences regarding amygdala volume. The severity of physical abuse, a subscale of the childhood trauma questionnaire, was negatively correlated with FA and with number of streamlines. AUD-CT and AUD-NT differ regarding structural connectivity of pathways projecting to and from the amygdala, but not regarding amygdala volume. Those alterations of structural connectivity in AUD-CT may represent a distinguishable neurobiological subtype of AUD, which might be associated with the complex clinical picture and poorer outcome that patients with CT and AUD often present.

Neurophysiological correlates of alcohol-specific inhibition in alcohol use disorder and its association with craving and relapse.

OBJECTIVE: This study investigates neurophysiological correlates of general and alcohol-specific inhibitory control in patients with Alcohol Use Disorder (AUD), focusing on its association with individual craving levels and with relapse at three-month follow-up. METHODS: 59 abstinent AUD patients and 20 healthy controls performed a Go/NoGo task incorporating alcohol-related and neutral stimuli during 64-channel electroencephalography (EEG) recording, yielding four event-related potentials (ERP) per participant (NoGo-Alcohol, Go-Alcohol, NoGo-Neutral, Go-Neutral). Whole-scalp randomization-based statistics assessed effects of the factors group (patients/controls or relapsers/abstainers), craving level, response type (NoGo/Go) and picture type (alcohol/neutral) on topography and signal strength of the ERP components N2 and P3. RESULTS: No differences on group level were observed between patients and controls. However, analyses incorporating individual craving indicated that the topographic difference between alcohol-related and neutral NoGo-N2 components increased with craving. Moreover, topographic differences in the alcohol-related and neutral NoGo-P3 component allowed for differentiation between relapsers and abstainers. CONCLUSIONS: In alcohol-related contexts, the response inhibition conflict reflected in the NoGo-N2 seems enhanced in patients with high craving. The inhibition-sensitive NoGo-P3 varies in relapsers but not in abstainers between neutral and alcohol-related contexts. SIGNIFICANCE: In AUD patients, neurophysiological correlates of inhibition vary with alcohol-related contexts and craving, and might be indicative of relapse risk.

Learning to resist the urge: a double-blind, randomized controlled trial investigating alcohol-specific inhibition training in abstinent patients with alcohol use disorder.

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.

Alcohol-Specific Computerized Interventions to Alter Cognitive Biases: A Systematic Review of Effects on Experimental Tasks, Drinking Behavior, and Neuronal Activation.

Background: In patients with alcohol use disorder, novel interventions to increase abstinence have attracted growing attention. Interventions aimed at modifying cognitive biases linked to alcohol use [i.e. cognitive bias modification (CBM)] may serve as an add-on to standard therapy. This systematic review thoroughly aggregates existing data on the effects of three alcohol-specific computerized interventions, namely attentional bias modification (AtBM), approach bias modification (ApBM), and inhibition training (IT). In doing so, each CBM's effects on experimental tasks assessing the relevant biases, drinking behavior, and neurophysiology are summarized. Also, the influence of drinking behavior severity and motivation to change drinking behavior are discussed. Methods: A literature search was conducted in four databases for original research articles published between 2000 and May 2019. Studies were eligible if investigating the effects of alcohol-specific computerized interventions (AtBM, ApBM, IT) on drinking behavior, bias change, and/or neurophysiology. Forty eligible articles were classified as being either a non-clinical experimental lab study (ELS) or clinical randomized-controlled trial (RCT) and summarized. Results: While AtBM seems to influence attentional bias, its effects on drinking behavior are inconsistent. As for ApBM, the best effects on drinking behavior are obtained in clinical samples. Effects of ApBM on approach bias are mixed. Interestingly, those clinical RCTs which investigated ApBM effects on bias change as well as on drinking outcome, reported consistent effects in both measures (i.e. either effects on bias and drinking or no effects). Studies on IT are limited to non-clinical samples and show inconsistent effects on drinking behavior. Considering ITs effects on implicit semantic associations, most studies do not support the conceptualization of IT as a form of memory bias modification, while reports on IT's effects on inhibitory control are still incomplete. Conclusions about the overall influence of drinking behavior severity are hampered by the non-uniform use of sample descriptions. Conclusions: In clinical samples, ApBM has shown more consistent beneficial effects, while evidence on AtBM is more inconsistent, and data on IT still lacks important information. Conclusions about the influence of drinking behavior severity would be facilitated by a uniform use of clearly defined sample descriptions.