Neuroimaging of Alcohol Addiction

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1. Structural Data Analysis Addiction ENIGMA. Jointly, with our counterparts at the National Institute on Drug Abuses Neuroimaging Research Branch of Dr. Elliot Stein, 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, two additional manuscripts were published. As part of this collaborations two studies were conducted. These studies investigated the effect of substance dependence on subcortical morphometry (Chye et al., 2019) and the structural brain differences caused by substance use disorders in comparison to other psychiatric conditions (Navarri et al. 2020) 2. Cerebellar recovery of alcohol dependent patients during short term abstinence We are continuing our work that started as a collaboration with Dr. George Fein of Neurobehavioral Research (NRI) in a funded U01 grant to develop and apply a 30-parcel active appearance model of the cerebellum on prospective motion tracking and corrected structural MRIs. We are currently finalizing our analyses structural and functional brain recovery of short-term abstinence and treatment. The methodology to parcellate cerebellum was tested and re-tested to demonstrate the validity of the algorithm developed in conjunction with this study. The result of application of this algorithm on adolescents with histories of prenatal alcohol exposure and non-exposed controls were compared. (Price, Momenan, and Fein 2020) 3. 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) information, 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 addiction. This in turn might enable us to have identified and established an Addictions Neuroimaging Assessment (ANiA) (Voon et al. 2020). Create a standardized neuroimaging assessment to provide AUD subtyping phenotypes using information from: o Resting state and task driven functional connectivity; o Neurocircuitries associated with AD domains; o Gray and white matter structural integrity of the human brain in various stages of this heterogeneous disease. o Develop a big data system that enables the use of ANA and ANiA assessments and phenotypic data. o Determine the neural correlates (i.e. networks) associated with the domains and neuroclinical measures of alcohol use disorders. o Utilize innovative approaches such as machine learning to assist in individualized patient treatment, treatment efficacy, and relapse prediction. The following is an example of such analyses. a. Negative Affects in Anxious Patients with Alcohol Use Disorder. Studies have shown association between substance use disorders and mood and anxiety disorders. Compared to neutral faces, amygdala preferentially responds to fearful faces in contrast to neutral faces and habituates rapidly. Anxiety prone individuals have shown greater bilateral amygdala and insula activity to negative emotional faces. The amygdala response to emotional faces in patients with AUD has been somewhat contradictory. Some studies, including our own lab, have shown that anxious patients with AUD show a blunted response to emotional stimuli during fMRI in anterior cingulate cortex, amygdala, and hippocampus. While, others have characterized patients with AUD as having a greater tendency to experience negative emotion and impulsivity and a lack of social constraint. In this preliminary study we have examined the association between an alcohol use severity, anxiety score, and alterations in brain activation during exposure to negative facial emotion stimuli. Our initial results indicate a stronger association between STAI-T anxiety score and alcohol use severity as measured by AUDIT score in participants with both AUD and anxiety symptoms in comparison to control subjects and AUD participants without anxiety. The neuroimaging data suggests patients with AUD and anxiety symptoms show hypersensitivity to negative affects as demonstrated by response to angry facial expression stimuli. The hyperactivation of caudate might point to increased valuation of this type of emotions. On the other hand, the hypoactivation of anterior cingulate gyrus may suggest an inability of anxious AUD participants to normalize their response to fearful stimuli. The hyperactivity of AUD in left precuneus demonstrates the potential attention bias across AUD to negative affect. (MacIlvane et al., under review) 4. Treatment. In collaboration with Dr. Leggio s CPN investigators, we continued analyzing the effects of pexacerfront, to evaluate a selective CRH1 antagonist brain penetrant for its ability to modulate emotional and motivational processes in anxious, recently detoxified AUD patients, we conducted an fMRI study of the Trier portion of this study. The analysis for this portion of the study was performed on 20 subjects on placebo and 19 subjects on active compound. In particular, random alternating blocks, consisting of SELF- and OTHER-video perfuming the Trier task were presented. We have completed this analysis and currently interpreting the outcomes for drug effect and stress effects on brain activations.