Neuroimaging of Alcohol Use Disorder

National Institute On Alcohol Abuse And Alcoholism

Investigators

Linked publications, trials & patents

Abstract

1. Cerebellar recovery of alcohol use disorder patients during short term abstinence This study was in part designed to determine the brain morphological as well as structural- and resting state functional-connectivity recovery in patients with alcohol use disorder after a 4 week treatment. We have started preprocessing of the structural morphometry, white matter diffusion tensor imaging, and resting state pre- and post- short term abstinence. The data from this study are still in the pipeline for our analyses of structural and functional recovery during short-term abstinence. 2. Omnibus Alcohol Neuroimaging Assessments The purpose of this study is to obtain a standard set of assessments, including brain behavioral, structural, functional, and connectivity (structural and functional) of the neurocircuitry of substance use disorders, on all NIAAA research participants to a) to determine how individual differences in brain structure and evoked responses relate to generalized trait personality and behavior differences (as assessed by psychometric questionnaire instruments and behavioral measures); and b) to determine whether these individual differences relate specifically to genetic polymorphisms in genes governing neurotransmitter activity. We have been analyzing some of this data independently or in collaborative work with other NIAAA investigators in further understanding the pathology of alcohol use disorder. Beginning in 2022 we have started collecting fMRI data on AUD patients and healthy controls using a 7 Tesla scanner on seven computerized tasks to assess the neurological changes related to drinking and alcohol use disorder. These tasks are the Monetary Incentive Delay Task, Risk Task, Stop Signal Task, Negative Affect Task, Prediction Error Task, Alcohol Approach-Avoidance Task, and Fixed N-Back Task. This is an ongoing project aiming at collecting data from more than 500 individuals. At the present time we do not have the appropriate sample size to provide statistically meaningful insight to this data. a. Structural Data Analysis i. Addiction ENIGMA - Jointly, with our counterparts at the National Institute on Drug Abuse's Neuroimaging Research Branch, we initiated the NIH-Addiction Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA). This initiative is part of the Addiction-ENIGMA consortium, a large, multi-site, data-pooling initiative focused on genetics and the brain that has analyzed tens of thousands of study participants at more than 100 labs in over 30 countries. We continued our collaboration with this big data consortium. As a result, three additional manuscripts were published. In the first study, sex differences in neuroanatomy (regional brain volume) of male and female patients with alcohol use disorder were investigated (Ottino-Gonzalez et al., 2021). Widespread differences were found in regional brain volumes of individuals with alcohol use disorder in comparison to healthy controls. But there were only select brain regions (such as amygdala) which demonstrated sex differences. The second study utilized graph theoretic analysis of structural covariance networks to determine the brain organizational differences between adults with alcohol use disorder and heavy drinking adolescents (Ottino-Gonzale et al., 2021). In the last study, the differences in microstructure of those with stimulant (nicotine, cocaine and methamphetamine) use disorder were investigated (Ottino-Gonzales et al., 2021). The results showed stimulant dependence was related to white matter integrity disturbances within tracts consistent with effects of substance use disorders. The multivariate pattern of white matter differences proved sufficient to identify individuals with stimulant dependence, particularly for cocaine and methamphetamine. ii. Brain Age In collaboration with Dr. Elliot Stein's Neuroimaging Research Branch (NIDA), we conducted a large scale brain age study to determine the effect of alcohol use on biological brain age. According to this study, there was an association between accelerated brain aging and the estimated lifetime alcohol use based on the previous 90-day alcohol consumption in two large cohorts. This work was completed in 2022 (Angebrandt et al., 2022). b. Combined Functional and Structural Connectivity Insular functional and structural connectivity - Based on our understanding of insular regions, chronic alcohol use may affect the integration of sensory-motor, socio-emotional and cognitive function. The purpose of this study was to investigate the variations in both the anterior and posterior insula in persons with AUD. We investigated insula gray matter volume, morphometry, as well as white matter structural and resting state functional connectivity in 75 participants with alcohol use disorder (Females = 27) and 75 age-matched healthy control participants (Females = 39). Results indicated structural differences mostly in the anterior regions, while functional connectivity differences were observed in both the anterior and posterior insula in those with AUD. Differing connectivity was observed with frontal, parietal, occipital, cingulate, cerebellar and temporal brain regions. These results align with prior studies showing differences primarily in anterior insular regions, they also contribute to the existing literature suggesting differences in anterior insular connectivity with brain regions shown to be engaged in higher cognitive and emotional tasks (Manuweera, et. al, 2022, in press). 3. Treatment In collaboration with Dr. Mary Lee, we completed analyzing imaging data from a study that was investigating the ability of pexacerfront to modulate emotional and motivational processes in anxious, recently detoxified AUD patients. In this analysis of the Trier portion of the study we found that Pexacerfont had no effect on the neural response to self-observation under stress. The neural response to viewing oneself under stress vs an unknown other under stress activated prefrontal brain regions including insula, inferior frontal gyrus as well as medial, superior frontal gyri. We are currently preparing the manuscript to provide details of our findings.