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

Abstract

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.

Keywords: Go-NoGo; alcohol use disorder (AUD); craving; drinking outcome; fMRI; inferior frontal gyrus (IFG); inhibition; inhibition training.

Figure 1

Study design of the GNG-fMRI sub-study within the INTRA project. Dashed box contours indicate data that is shown in Supplementary Material. Alc-IT, alcohol-specific inhibition training; AUD, alcohol use disorder; GNG, Go-NoGo task; HC, healthy controls; MRI, magnetic resonance imaging; N, sample size.

Figure 2

Schematic illustration of the GNG event-related fMRI task. The stimuli are either an alcoholic bottle with a glass (ALC) or a neutral (i.e., water) bottle with a glass (NEU). This is an example of the beer set, whereas depending on the participant's preference, also wine or spirits sets were available. Participants were instructed to press a button whenever a stimulus appeared (Go), unless the exact same stimulus was shown twice successively (NoGo).

Figure 3

Visualization of the relationship of rIFG beta-values and log10-transformed OCDSimp scores, stratified for stimulus type. The graph confirms that craving has a positive relationship with inhibition activation during alcohol-related inhibition only.

Figure 4

Boxplots indicating beta-value differences of response type (NoGo in red, Go in green), stimulus type, pre- and post-training, and training type. Black lines connecting black dots highlight mean-differences in inhibition activation.

Figure 5

The red dot indicates the region in the right inferior frontal gyrus, where a higher activation during alcohol-related inhibition is predictive for higher craving. The cyan dot indicates the region in the right inferior frontal gyrus, where a higher activation during alcohol-specific inhibition is predictive for a better drinking outcome. The anatomical brain render used for this illustration is based on the mean normalized gray matter image of all participants included in this study. All three views were cut from the surface to the localization of the cyan ROI. Since the red ROI is on the same pane as the cyan ROI only in the lateral view, the red ROI should be viewed as “hovering in the air” in the superior and frontal views. A, anterior; I, inferior; L, left; P, posterior; R, right; ROI, region of interest; S, superior.