Neuroimaging of Alcohol Use Disorder

National Institute On Alcohol Abuse And Alcoholism

Investigators

Linked publications, trials & patents

Abstract

SEX SPECIFIC STRUCTURAL DIFFERENCES - This study is a collaboration with the Addiction-ENIGMA consortium, to investigate the neurobiological correlates (gray matter and white matter) of alcohol use disorder (AUD) between sexes using a whole-brain, voxel-based, multi-tissue mega-analytic approach. The group-by-gender effects were found in parieto-occipital and mid cingulate gray matter (GM) volumes, which were more affected by AUD in men compared to women, and in frontocerebellar GM and white matter (WM) volumes, which were more affected by alcohol use disorder in women compared to men. AUD men but not women showed a positive association between number of monthly standard drinks and GM volume in a portion of the cerebellum. The shared and specific to gender differences in AUD individuals indicate the need for attention to personalized approaches in substance use disorders, including AUD (Maggioni, et al. 2022). RESTING STATE: ASSOCIATION WITH ALCOHOL MISUSE RISK LEVEL - This study is a collaborative effort between CNIRC and a COVID-19 related study (Co-PIs Drs. Diazgranados and Ramchandani). Alcohol misuse levels (AMLs) capturing hazardous alcohol consumption were derived from the first three questions of the Alcohol Use Disorder Identification Test. Differences between AML scores across pairs of timepoints were then categorized. Our results showed association between connectivity of regions implicated in addiction neurocircuitry and alcohol consumption changes. The overlap of the observed connectivity patterns with prior studies on AUD suggests that these connectivity effects may reflect trait-like features underlying predisposition to addiction-related behaviors. The manuscript for this study is in preparation. DYNAMIC RESTING STATE While static functional connectivity in alcohol use disorder has been studied by our own group and others, potential dynamic effects of drug misuse on brain networks at rest are less explored. In collaboration with Dr. Volkow's Laboratory of Neuroimaging, we investigated brain state dynamics in individuals with opioid use disorder (OUD) and AUD and the effects of nicotine use, a common comorbidity of these disorders, on such dynamics. Resting-state fMRI data of healthy controls and individuals with OUD and AUD were included in these analyses. In this study non-smoker OUD and AUD individuals displayed similar changes in brain state dynamics which included decreased fractional occupancy or dwell time in default mode network (DMN)-dominated brain states and increased appearance rate in visual network (VIS)-dominated brain states and their related brain state transition probabilities. In contrast, nicotine users demonstrated opposite effects that included lowering VIS-dominated and increasing DMN-dominated brain states in both disorders. These outcomes once again point to the need for personalized treatment approach based on the disease dynamics and their comorbidities. The manuscript for this study is under review. BRAIN RECOVERY DURING SHORT TERM ABSTINENCE - This study was in part designed to determine the brain recovery in patients with AUD after a 4 week treatment. The early abstinence period is a crucial phase in which patients may find a new equilibrium and start recovery. In this study we focused on three networks: the frontoparietal networks (left and right FPN) and default mode network (DMN). In contrast to the controls, the AUD patients showed a trend towards a decrease in within left FPN connectivity. This decrease in left FPN connectivity may reflect an initially upregulated FPN recovery process to a lower resting-state connectivity level during subsequent weeks of abstinence. The AUD patients also showed trends for a positive association between the change in left FPN connectivity and trait anxiety, and a negative association between the change in left FPN connectivity and delay discounting. This suggests that the FPN might be involved in top-down control of anxiety and impulsivity, which are important risk factors for relapse. Details of this study are published (van Oort et al. 2023). FUNCTIONAL CONNECTIVITY: TRAUMA TIMING LOAD - Timing and type of trauma have been shown to impact on the development, function and connectivity of brain circuits implicated in emotion processing, top-down inhibitory control, and cognitive functions. Dysfunctions in these processes and their underlying brain circuits are commonly observed in patients with AUD. The goal of this study is to investigate whether timing of trauma (childhood vs. adulthood) differentially affects the behavioral and circuit-level phenotype of individuals with AUD. Our preliminary data analysis indicates that the effect of alcohol use disorder is far more impressive than that of trauma on alteration of resting state connectivity in regions associated with traumatic experiences. We are in the process of preparing a manuscript for these results. FUNCTIONAL CONNECTIVITY: EARLY LIFE STRESS AND BMI ASSOCIATION - In collaborative work with Dr. Paule Joseph's Section of Sensory Science and Metabolism, we examined the effects of Early life stress (ELS) on brain functional connectivity in individuals with AUD, considering varying body mass index (BMI) levels. We identified a negative correlation between salience network seeds and brain regions involved with somatosensory processing, motor coordination, and executive control. The findings in this study highlight the role played by ELS-induced alterations in SN seed connectivity, influenced by BMI, in shaping the complex neurobiology of AUD. Understanding neural mechanisms linking obesity and AUD with ELS history can guide targeted interventions for this population. The manuscript for this study has been submitted and is currently in review. TREATMENT - In preclinical models of alcohol use disorder, the corticotropin-releasing factor receptor is upregulated, particularly in the extended amygdala. This upregulation is thought to play a role in stress-induced relapse to drinking by a mechanism that is independent of the hypothalamic-pituitary-adrenal axis. As part of a clinical study with pexacerfont, a CRF1 receptor antagonist which has anti-anxiety effects in preclinical studies, we examined the neural responses to viewing oneself and an unknown other under stress. In this study which was conducted in collaboration with Dr. Mary Lee of the Veteran Affairs Medical Center, we found that viewing oneself under stress versus an unknown other under stress activated prefrontal brain regions including insula, inferior frontal gyrus as well as medial, superior frontal gyri. Potential applications of this task to probe neurocircuitry that is disrupted in addiction is discussed in the manuscript (Lee et al. 2022). NEUROIMAGING METHODOLOGY AND ANALYSIS - Although in recent years a general tendency has been developed to conduct large scale data analysis via collaborations and consortia, there still are many studies with small sample sizes that can be very informative. However the growing concerns about reliability and reproducibility of such data has been a major obstacle. In this study conducted in collaboration with the ENIGMA addiction working group, a hierarchical Bayesian model was proposed to adjust the magnitude of single-study effect sizes while incorporating a tailored estimation of sampling variance. The magnitude of adjustment was negatively correlated with the sample size and positively correlated with empirically estimated sampling variance, suggesting studies with smaller samples and larger sampling variance tended to have greater adjustments. This work demonstrated the ability to improve the effect size estimation of individual smaller studies (Cao et al., 2022).