Functional & Structural Connectivity in Alcohol Use Disorder

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1. fMRI Network Analysis and Resting State Studies a. Resting state Connectivity and alcohol use disorder domains. Withdrawal/negative affect is one of the biological neurocircuitries implicated in the cycle of addiction model (Koob et al. 2010). Previous studies have indicated that amygdala connectivity and negative affect play a role in the cycle of addiction. Also, neuroticism (pessimism, nervousness, and anxiousness), which shares similar qualities with negative affect, is related to amygdala connectivity. The purpose of this study was to investigate the effect of neuroticism on the relationship between alcohol use severity and amygdala connectivity. We used the Alcohol Use Disorders Identification Test (AUDIT) to quantify alcohol use severity and the Revised NEO Personality Assessment (NEO PI-R) to quantify levels of neuroticism. The whole brain analysis showed a positive relationship between right amygdala-right temporal fusiform gyrus connectivity and AUDIT scores and a negative relationship between left amygdala-left temporal parietal junction (TPJ) connectivity and NEO neuroticism scores. The indirect effect of neuroticism was significant for the latent variable model of left amygdala connectivity with the nucleus accumbens (NAcc), posterior insula, and dorsal anterior cingulate(dACC). These results suggest that personality plays an important role in the cycle of addiction (Dean et al., 2020). b. Resting State Connectivity under acute alcohol administration. Studies conducted by Dr. Lovinger's Laboratory for Integrative Neuroscience have demonstrated a selective acute ethanol effect on external globus palidus (GPe) neurons that have a specific connectivity with the dorsal striatum (Abrahao et al.,_2016). Based on this finding and the known role of the basal ganglia in habitual, inhibitory control, and compulsive behaviors seen in addiction, we investigated the functional resting-state connectivity changes of the GPe and basal ganglia. In fact, studies in rodents have revealed that alcohol can change GPe activity by decreasing neuronal firing rates, suggesting that the GPe may have a central role in explaining impulsive behaviors and failures of inhibition that occur during binge drinking. In this study, twenty-five healthy volunteers underwent intravenous alcohol infusion to achieve a blood alcohol level of 0.08 g/dl, which is equivalent to a binge drinking episode. The resting state functional magnetic resonance imaging scan was collected prior to the infusion and at binge-level exposure. Functional connectivity analysis was used to investigate the association between alcohol-induced changes in GPe connectivity, drinking behaviors, and impulsivity traits. We found that individuals with greater number of drinks or heavy drinking days in the recent past had greater alcohol induced deficits in GPe connectivity, particularly to the striatum. Our data also indicated an association between impulsivity and alcohol-induced deficits in GPefrontal/precentral connectivity. Moreover, alcohol induced changes in GPe-amygdala circuitry suggested greater vulnerabilities to stress-related drinking in some individuals. Taken together, these findings suggest that alcohol may interact with impulsive personality traits and drinking patterns to drive alterations in GPe circuitry associated with behavioral inhibition, possibly indicating a neural mechanism by which binge drinking could lead to impulsive behaviors. (Fede et al., 2020) 2. Structural Connectivity The damage associated with chronic alcohol use on the brains white matter has been demonstrated by previous diffusion tensor imaging (DTI) research. However, there is conflicting evidence as to whether the severity of damage is influenced by an individuals biological sex. The purpose of the present study was to investigate the prevalence of sex differences in the white matter microstructure of the brains of individuals with alcohol use disorder (AUD) and healthy controls. One hundred participants with AUD (38 female) in the NIAAAs inpatient treatment program and 98 healthy control participants (52 female) underwent a diffusion weighted scan. Images collected were processed for each subject individually and voxelwise tract-based spatial statistics (TBSS) analysis was conducted to measure differences in the DTI measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) between groups. Our analyses testing for differences in group and sex revealed widespread differences between subjects with AUD and control subjects, but no interaction between group and sex. Additionally, clusters of significant group differences correlated significantly with age and heavy drinking years. Further analyses revealed that in this sample, age impacted DTI measures to a greater extent than alcohol use variables. These results bolster recent findings of similar alcohol-related microstructural damage in men and women with AUD but contradict earlier research of sex-specific structural damage.(Kisner et al., manuscript in preparation)