权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Neuroimaging of Alcohol Use Disorder

酒精使用障碍的神经影像学

基本信息

批准号：
10927714
负责人：
Reza Momenan
金额：
$ 107.44万
依托单位：
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10927714
关键词：
Abstinence Adult Affect Alcohol consumption Amygdaloid structure Anxiety Appearance Attention Bayesian Modeling Behavior Behavioral Biological Markers Body mass index Brain Brain region COVID-19 CRF receptor type 1 Categories Cerebellum Childhood Clinical Research Collaborations Complex Corticotropin-Releasing Hormone Receptors Data Data Analyses Development Disease Emotions Equilibrium Functional Magnetic Resonance Imaging Functional disorder Gender Goals Impulsivity Individual Inferior frontal gyrus Insula of Reil Laboratories Left Link Manuscripts Medial Medical center Metabolism Methodology Motor Neurobiology Obesity Outcome Participant Patients Pattern Phase Phenotype Play Population Intervention Pre-Clinical Model Prediction of Response to Therapy Predisposition Preparation Probability Process Publishing Recording of previous events Recovery Relapse Reproducibility Rest Risk Risk Factors Role Sample Size Sampling Science Sensory Shapes Stress Substance Use Disorder Testing Time Tissues Trauma Treatment Efficacy United States Department of Veterans Affairs Up-Regulation Visual Woman Work addiction alcohol effect alcohol misuse alcohol use disorder antagonist cognitive function comorbidity design discounting disorder subtype drinking drug misuse early life stress executive function experience gender difference gray matter hypothalamic-pituitary-adrenal axis improved large scale data men neural neural circuit neuroimaging neuromechanism nicotine use nicotine user non-smoker opioid use disorder personalized approach personalized medicine preclinical study response sex somatosensory trait trend white matter working group

项目摘要

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).

性别特异性结构差异-本研究是与Addiction-ENIGMA联盟合作，使用全脑、基于体素的多组织大分析方法，研究性别间酒精使用障碍（AUD）的神经生物学相关性（灰质和白质）。在顶枕和中扣带灰质（GM）体积中发现了按性别划分的群体效应，男性比女性更容易受到AUD的影响，而在额小脑GM和白质（WM）体积中，女性比男性更容易受到酒精使用障碍的影响。研究显示，男性每月标准饮酒量与小脑部分GM体积呈正相关，而女性则没有。AUD个体共有的和特定的性别差异表明，需要关注包括AUD在内的物质使用障碍的个性化方法（Maggioni, et al. 2022）。