Insula Sensitivity to Unfairness in Alcohol Use Disorder.

AIMS: Social decision making has recently been evaluated in alcohol use disorder (AUD) using the ultimatum game (UG) task, suggesting a possible deficit in aversive emotion regulation elicited by the unfairness during this task. Despite the relevance to relapse of this possible faulty regulation, the brain correlates of the UG in AUD are unknown. METHODS: In total, 23 AUD and 27 healthy controls (HC) played three consecutive fMRI runs of the UG, while behavioral and brain responses were recorded. RESULTS: Overall, acceptance rate of unfair offers did not differ between groups, but there was a difference in the rate of behavioral change across runs. We found significant anterior insula (aINS) activation in both groups for both fair and unfair conditions, but only HC showed a trend towards increased activation during unfair vs. fair offers. There were not overall whole-brain between-group significant differences. We found a trend of signal attenuation, instead of an increase, in the aINS for AUD when compared to HC during the third run, which is consistent with our recent findings of selective insula atrophy in AUD. CONCLUSION: We found differential group temporal dynamics of behavioral response in the UG. The HC group had a low acceptance rate for unfair offers in the first two runs that increased markedly for the third run; whereas the AUD group was consistent in their rejection of unfair offers across the three runs. We found a strong significant decrease in neural response across runs for both groups. SHORT SUMMARY: This fMRI study of UG in alcohol use disorder found behavioral group differences in acceptance rate across runs, which together with significant BOLD-signal decrease across runs in UG-related regions in both groups, highlights the impairment of strategy in AUD and the effect of repetitive exposure to unfairness in this task.

Glucose utilization in the medial prefrontal cortex correlates with serotonin turnover rate and clinical depression in alcoholics.

We measured the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), regional cerebral glucose uptake (rCMRglc) as assessed with positron emission tomography in the medial prefrontal cortex (PFC) and severity of clinical depression (Beck's Depression Inventory, BDI) in detoxified male alcoholics and age-matched healthy men. In alcoholics, the severity of clinical depression was negatively correlated with rCMRglc in the medial PFC and positively with CSF 5-HIAA concentrations. A voxel-based analysis showed that the strongest correlation between CSF 5-HIAA levels and rCMRglc was found in alcoholics in the left orbitofrontal and medial PFC (BA10 and BA11); no significant correlations were observed among healthy control subjects. This pilot study indicates that a dysfunction of medial PFC may interact with central serotonin turnover and negative mood states during early abstinence.

A select group of perpetrators of domestic violence: evidence of decreased metabolism in the right hypothalamus and reduced relationships between cortical/subcortical brain structures in position emission tomography.

In an earlier study, we reported that some perpetrators of domestic violence evidenced exaggerated fear-related responses to the panicogenic agent sodium lactate. In the current study, we employed positron emission tomography (PET) to investigate our hypothesis that there are differences in the neural structures and/or pathways that mediate and control the expression of fear-induced aggression in perpetrators of domestic violence. Regional cerebral glucose metabolism was measured in eight male perpetrators of domestic violence who fulfilled DSM-III-R criteria for alcohol dependence (DV-ALC), 11 male participants who fulfilled DSM-III-R criteria for alcohol dependence and had no history of interpersonal aggression (ALC) and 10 healthy male participants who did not fulfill criteria for any DSM-III-R axis I diagnosis and had no history of interpersonal aggression (HCS). DV-ALC had a significantly lower mean glucose uptake in the right hypothalamus compared to ALC and HCS. Correlations were performed between measures of glucose utilization in the brain structures involved in fear-induced aggression. The comparison of DV-ALC to HCS and to ALC differed in six and seven comparisons, respectively, involving various cortical and subcortical structures. HCS and ALC differed between the left thalamus and the left posterior orbitofrontal cortex. These PET findings show that some perpetrators of domestic violence differ from control participants in showing lower metabolism in the right hypothalamus and decreased correlations between cortical and subcortical brain structures. A possible psychological covariate of these changes in regional activity might be fear-induced aggression, but this hypothesis should be examined in larger study groups that undergo provocation during imaging.

Effects of alcohol dependence on cortical thickness as determined by magnetic resonance imaging.

Alterations of brain structures have been seen in patients suffering from drug abuse or mental disorders like schizophrenia. Similar changes in volume of brain structures have been observed in both alcoholic men and women. We examined the thickness of gray matter in the cerebral cortex in control men and women (n=69, 47 men) and alcohol-dependent subjects (n=130, 83 men) to test the hypothesis that alcoholic inpatients would have more cortical damage than controls. We also hypothesized that alcoholic women would be more affected than alcoholic men. Alcoholic participants with a history of schizophrenia, psychotic, or bipolar disorder were excluded from the study. Volumetric structural magnetic resonance images were collected, 3D surfaces were created using Freesurfer, and statistical testing for cortical thickness differences was carried out using AFNI/SUMA. Covarying for age and years of education, we confirmed significant differences between alcoholics and healthy controls in cortical thickness in both the left and right hemispheres. Significant differences in cortical thickness between control men and women were also observed. These differences may reflect sexual dimorphisms in the human brain, a genetic predisposition to alcoholism and comorbid drug use, and the extent of gray matter damage in alcoholism and substance use.