Neuroimaging of Alcohol Use Disorder

酒精使用障碍的神经影像学

• 批准号: 10710499
• 负责人: Reza Momenan
• 金额: $ 71.23万
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 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/10710499
• 关键词: Abstinence; Adult; Affect; Age; Alcohol consumption; Alcohols; Amygdaloid structure; Anterior; Back; Behavior; Behavioral; Big Data; Biological; Biological Markers; Brain; Brain region; Cocaine; Cognitive; Collaborations; Country; Data; Data Analyses; Data Pooling; Diffusion Magnetic Resonance Imaging; Emotional; Female; Functional Magnetic Resonance Imaging; Genes; Genetic; Genetic Polymorphism; Graph; Heavy Drinking; Image; Individual; Individual Differences; Inferior frontal gyrus; Insula of Reil; Literature; Manuscripts; Medial; Meta-Analysis; Methamphetamine; Methamphetamine use disorder; Motor; National Institute of Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Neuroanatomy; Neurologic; Neurotransmitters; Nicotine; Parietal; Participant; Pathology; Patients; Pattern; Personality Traits; Persons; Phenotype; Psychometrics; Publishing; Questionnaires; Recovery; Recovery of Function; Relapse; Research; Research Personnel; Rest; Risk; Sample Size; Sex Differences; Signal Transduction; Site; Stimulant; Stress; Structure; Substance Use Disorder; Time; Treatment Efficacy; United States National Institutes of Health; Variant; Work; addiction; aging brain; alcohol effect; alcohol use disorder; anxious; base; behavior measurement; brain morphology; brain volume; chronic alcohol ingestion; cognitive function; cohort; computerized; design; disorder subtype; drinking; financial incentive; gray matter; imaging genetics; insight; instrument; male; morphometry; motivational processes; negative affect; neural; neural circuit; neuroimaging; response; sensory integration; stimulant dependence; underage drinking; white matter

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.

1. 短期戒酒期间酒精使用障碍患者的小脑恢复 这项研究的部分目的是确定酒精使用障碍患者在治疗 4 周后的大脑形态以及结构和静息状态功能连接恢复情况。我们已经开始对结构形态测量、白质扩散张量成像以及短期禁欲前后的静息态进行预处理。这项研究的数据仍在准备中，用于我们对短期禁欲期间结构和功能恢复的分析。 2. 综合酒精神经影像评估 本研究的目的是获得一套标准的评估，包括对所有 NIAAA 研究参与者的大脑行为、结构、功能和物质使用障碍神经回路的连接性（结构和功能），以便 a) 确定大脑结构和诱发反应的个体差异如何与广义特质人格和行为差异相关（通过心理测量问卷工具和行为测量进行评估）； b) 确定这些个体差异是否与控制神经递质活性的基因的遗传多态性具体相关。我们一直在独立或与其他 NIAAA 研究人员合作分析其中一些数据，以进一步了解酒精使用障碍的病理学。 从 2022 年开始，我们开始使用 7 特斯拉扫描仪收集 AUD 患者和健康对照的功能磁共振成像数据，执行七项计算机化任务，以评估与饮酒和酒精使用障碍相关的神经变化。这些任务是货币激励延迟任务、风险任务、停止信号任务、负面影响任务、预测错误任务、酒精接近避免任务和固定 N-Back 任务。这是一个正在进行的项目，旨在收集 500 多人的数据。目前，我们没有适当的样本量来为这些数据提供具有统计意义的见解。 一个。结构数据分析 我。成瘾 ENIGMA - 我们与国家药物滥用研究所神经影像研究部门的同行共同发起了 NIH-成瘾通过荟萃分析增强神经影像遗传学 (ENIGMA) 项目。该计划是 Addiction-ENIGMA 联盟的一部分，该联盟是一个大型、多地点的数据池计划，重点关注遗传学和大脑，已对 30 多个国家 100 多个实验室的数万名研究参与者进行了分析。我们继续与这个大数据联盟合作。结果，又出版了三份手稿。在第一项研究中，对患有酒精使用障碍的男性和女性患者的神经解剖学（区域脑容量）的性别差异进行了调查（Ottino-Gonzalez 等人，2021）。与健康对照组相比，酒精使用障碍患者的区域脑容量存在广泛差异。但只有特定的大脑区域（例如杏仁核）表现出性别差异。第二项研究利用结构协方差网络的图论分析来确定患有酒精使用障碍的成年人和酗酒青少年之间的大脑组织差异（Ottino-Gonzale 等人，2021）。在上一项研究中，研究了兴奋剂（尼古丁、可卡因和甲基苯丙胺）使用障碍患者微观结构的差异（Ottino-Gonzales 等人，2021）。结果表明，兴奋剂依赖与脑束内白质完整性紊乱有关，这与物质使用障碍的影响一致。事实证明，白质差异的多变量模式足以识别具有兴奋剂依赖性的个体，特别是可卡因和甲基苯丙胺。 二.大脑年龄 我们与 Elliot Stein 博士的神经影像研究分部 (NIDA) 合作，进行了一项大规模的大脑年龄研究，以确定饮酒对大脑生物年龄的影响。根据这项研究，大脑加速老化与基于两个大型队列之前 90 天饮酒量的估计终生饮酒量之间存在关联。这项工作于 2022 年完成（Angebrandt 等人，2022）。 b.功能性和结构性的结合 岛叶功能和结构连接——根据我们对岛叶区域的理解，长期饮酒可能会影响感觉运动、社会情感和认知功能的整合。本研究的目的是调查 AUD 患者前岛叶和后岛叶的变化。我们研究了 75 名酒精使用障碍参与者（女性 = 27）和 75 名年龄匹配的健康对照参与者（女性 = 39）的岛叶灰质体积、形态测量以及白质结构和静息状态功能连接。结果表明，AUD 患者的结构差异主要存在于前部区域，而前岛叶和后岛叶均存在功能连接差异。额叶、顶叶、枕叶、扣带回、小脑和颞叶脑区的连接性有所不同。这些结果与先前的研究一致，显示主要在前岛叶区域存在差异，它们也为现有文献做出了贡献，表明前岛叶与参与更高认知和情感任务的大脑区域的连接存在差异（Manuweera 等人，2022 年，出版中）。 3. 治疗 我们与 Mary Lee 博士合作，完成了一项研究的影像数据分析，该研究正在调查 pexacerfront 调节最近戒毒的 AUD 患者焦虑情绪和动机过程的能力。在对特里尔研究部分的分析中，我们发现 Pexacerfont 对压力下自我观察的神经反应没有影响。 看到自己处于压力下与处于压力下的未知他人相比，神经反应会激活前额脑区域，包括岛叶、额下回以及额内回、额上回。我们目前正在准备手稿，以提供我们发现的详细信息。