Behavioral impulsivity mediates the relationship between decreased frontal gray matter volume and harmful alcohol drinking: A voxel-based morphometry study.

Alcohol use disorder (AUD) with harmful drinking patterns is on the one hand characterized by impulsive behavior and is on the other hand known to involve structural brain alterations with lower gray matter volume (GMV), especially in the prefrontal cortex (PFC). So far it is unclear whether frontal brain volumes are associated to harmful alcohol drinking and impulsivity, while controlling simultaneously for a wide array of important confounding factors, which are related to alcohol consumption. We used voxel-based morphometry in 99 adults ranging within a continuum of normal to harmful drinking behavior and alcohol dependence, measured by the 'Alcohol Use Disorders Identification Test', to examine whether the severity of harmful drinking is correlated with structural markers, in particular in the PFC and whether such markers are linked to self-reported impulsivity. We included alcohol and nicotine lifetime exposure, age, education, and BMI as covariates to control that GMV decreases were not related to those factors. Harmful drinking was associated with lower GMV in the right frontal pole, left inferior frontal gyrus, and bilateral inferior parietal lobe. GMV loss in the PFC regions was correlated with increased impulsivity. Follow-up mediation analyses showed that the relationship between GMV in the frontal pole and harmful drinking was mediated by impulsivity. Our findings show that PFC reductions are associated with harmful drinking and impulsivity. Our data suggest that reduced frontal pole GM, independent of a number of alcohol drinking associated covariates, e.g. lifetime alcohol consumption, is related to impaired top-down control of alcohol drinking behavior.

To drink or not to drink: Harmful drinking is associated with hyperactivation of reward areas rather than hypoactivation of control areas in men.

BACKGROUND: The maintenance of harmful alcohol use can be considered a reiterated decision in favour of alcohol in concrete drinking occasions. These decisions are often made despite an intention to quit or reduce alcohol consumption. We tested if a hyperactive reward system and/or an impaired cognitive control system contribute to such unfavourable decision-making. METHODS: In this fMRI study, men with modest to harmful drinking behaviour, which was measured using the Alcohol Use Disorders Identification Test (AUDIT), repeatedly made decisions between alcoholic and nonalcoholic drinks. Based on prior individual ratings, decision pairs were created with an alcoholic decision option considered more desirable but less beneficial by the participant. By correlating AUDIT scores with brain activation during decision-making, we determined areas explicitly related to pro-alcohol decisions in men with greater drinking severity. RESULTS: Thirty-eight men participated in our study. Behaviourally, we found a positive correlation between AUDIT scores and the number of decisions for desired alcoholic drinks compared with beneficial nonalcoholic drinks. The fMRI results show that AUDIT scores were positively associated with activation in areas associated with reward and motivation processing (i.e., ventral striatum, amygdala, medial prefrontal cortex) during decisions favouring a desired, nonbeneficial alcoholic drink. Conversely, we did not find hypoactivation in areas associated with self-control (dorsolateral prefrontal cortex). These effects were not present when participants chose a desired, nonbenefical, nonalcoholic drink. LIMITATIONS: The men participating in our study had to be abstinent and would potentially consume an alcoholic drink at the end of the experiment. Hence, we did not define manifest alcohol dependence as an inclusion criterion and instead focused on less severely affected individuals. CONCLUSION: Our results indicate that with growing drinking severity, decisions for alcoholic drinks are associated with increasing activity in reward-associated neural systems, rather than decreasing activity in self-control-associated systems.

Decreased gray matter volume in inferior frontal gyrus is related to stop-signal task performance in alcohol-dependent patients.

Impairment in inhibitory control has been proposed to contribute to habitual alcohol use, abuse and eventually dependence. Moreover, alcohol-dependent (AD) patients have shown a loss of gray matter volume (GMV) in the brain, specifically in prefrontal regions associated with executive functions, including response inhibition. To date, no study has evaluated whether this prefrontal GMV reduction is related to response inhibition in alcohol dependence. To address this issue, we acquired high-resolution T1-weighted magnetic resonance mages from recently detoxified AD patients (n = 22) and healthy controls (HC; n = 21). Differences in local GMV between groups were assessed by means of voxel-based morphometry (VBM). Moreover, within the AD group, mean local GMV reductions were extracted and correlated with behavioral performance on the stop-signal task. We found a significantly decrease in GMV in the left inferior frontal gyrus (IFG) in AD patients compared with HC subjects. Further, mean local GMV in this area correlated positively with reaction times on go trials during the stop-signal task in AD patients. Our findings suggest that GMV losses in the IFG in AD patients are related to faster go responses on the stop-signal task.

Effects of cognitive bias modification training on neural alcohol cue reactivity in alcohol dependence.

OBJECTIVE: In alcohol-dependent patients, alcohol cues evoke increased activation in mesolimbic brain areas, such as the nucleus accumbens and the amygdala. Moreover, patients show an alcohol approach bias, a tendency to more quickly approach than avoid alcohol cues. Cognitive bias modification training, which aims to retrain approach biases, has been shown to reduce alcohol craving and relapse rates. The authors investigated effects of this training on cue reactivity in alcohol-dependent patients. METHOD: In a double-blind randomized design, 32 abstinent alcohol-dependent patients received either bias modification training or sham training. Both trainings consisted of six sessions of the joystick approach-avoidance task; the bias modification training entailed pushing away 90% of alcohol cues and 10% of soft drink cues, whereas this ratio was 50/50 in the sham training. Alcohol cue reactivity was measured with functional MRI before and after training. RESULTS: Before training, alcohol cue-evoked activation was observed in the amygdala bilaterally, as well as in the right nucleus accumbens, although here it fell short of significance. Activation in the amygdala correlated with craving and arousal ratings of alcohol stimuli; correlations in the nucleus accumbens again fell short of significance. After training, the bias modification group showed greater reductions in cue-evoked activation in the amygdala bilaterally and in behavioral arousal ratings of alcohol pictures, compared with the sham training group. Decreases in right amygdala activity correlated with decreases in craving in the bias modification but not the sham training group. CONCLUSIONS: These findings provide evidence that cognitive bias modification affects alcohol cue-induced mesolimbic brain activity. Reductions in neural reactivity may be a key underlying mechanism of the therapeutic effectiveness of this training.

Neural correlates of alcohol-approach bias in alcohol addiction: the spirit is willing but the flesh is weak for spirits.

Behavioral studies have shown an alcohol-approach bias in alcohol-dependent patients: the automatic tendency to faster approach than avoid alcohol compared with neutral cues, which has been associated with craving and relapse. Although this is a well-studied psychological phenomenon, little is known about the brain processes underlying automatic action tendencies in addiction. We examined 20 alcohol-dependent patients and 17 healthy controls with functional magnetic resonance imaging (fMRI), while performing an implicit approach-avoidance task. Participants pushed and pulled pictorial cues of alcohol and soft-drink beverages, according to a content-irrelevant feature of the cue (landscape/portrait). The critical fMRI contrast regarding the alcohol-approach bias was defined as (approach alcohol>avoid alcohol)>(approach soft drink>avoid soft drink). This was reversed for the avoid-alcohol contrast: (avoid alcohol>approach alcohol)>(avoid soft drink>approach soft drink). In comparison with healthy controls, alcohol-dependent patients had stronger behavioral approach tendencies for alcohol cues than for soft-drink cues. In the approach, alcohol fMRI contrast patients showed larger blood-oxygen-level-dependent responses in the nucleus accumbens and medial prefrontal cortex, regions involved in reward and motivational processing. In alcohol-dependent patients, alcohol-craving scores were positively correlated with activity in the amygdala for the approach-alcohol contrast. The dorsolateral prefrontal cortex was not activated in the avoid-alcohol contrast in patients vs controls. Our data suggest that brain regions that have a key role in reward and motivation are associated with the automatic alcohol-approach bias in alcohol-dependent patients.