Sex Differences in the Effects of Alcohol Use Disorder on Brain Circuitry using Existing Data

使用现有数据研究酒精使用障碍对大脑回路影响的性别差异

• 批准号: 9321385
• 负责人: LISA D NICKERSON
• 金额: $ 19.42万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321385
• 关键词: Abstinence; Acute; Adult; Affective; Age; Alcohol abuse; Alcohol dependence; Alcoholic Intoxication; Alcoholics Anonymous; Alcohols; Area; Behavior; Behavioral; Brain; Brain Injuries; Brain imaging; Chronic; Clinical; Data; Data Analyses; Drug Use Disorder; Drug usage; Emotional Intelligence; Emotions; Equilibrium; Family; Family history of; Female; Functional Magnetic Resonance Imaging; Funding; Future; Human; Impaired cognition; Impairment; Individual; Intoxication; Link; Magnetic Resonance Imaging; Maps; Measurement; Measures; Menstrual cycle; Mind; Modality; Modeling; Nature; Neurobiology; Oral; Pattern; Perception; Perfusion; Pilot Projects; Population; Population Characteristics; Prefrontal Cortex; Psychophysiology; Recording of previous events; Reporting; Research; Rest; Rewards; Sample Size; Severities; Sex Characteristics; Smoking Status; Structure; Techniques; United States National Institutes of Health; Withdrawal; Woman; Work; alcohol effect; alcohol misuse; alcohol sensitivity; alcohol use disorder; binge drinking; brain circuitry; connectome; executive function; gray matter; improved; insight; interest; male; men; network dysfunction; neural correlate; neuroimaging; neurotoxic; programs; psychiatric symptom; relapse risk; repaired; secondary analysis; sex; sexual dimorphism; social; social cognition; theories; white matter

Social cognition difficulties in individuals with alcohol use disorders (AUD), including emotion perception deficits and deficits in theory of mind (ToM) processing, are more severe with greater alcohol misuse and persist despite extended abstinence. ToM is a key aspect of social cognition that refers to the ability to understand the intentions (cognitive ToM) and emotions (affective ToM) of self and others. Research suggests that females generally outperform males on measures of social cognition. However research on the neural correlates of ToM processing in AUD is scant and there are no studies of sex differences in individuals with AUD. The prefrontal cortex (PFC) is a key region of the “default mode network” (DMN) that is engaged during ToM processing and, notably it is especially vulnerable to the neurotoxic effects of alcohol. Thus the DMN may be implicated in social cognition difficulties in individuals with AUD. Given evidence of sexual dimorphism in brain structure, sex differences in resting and task functional magnetic resonance imaging (FMRI) brain activation, and of a “telescoping” effect on brain damage in women (women have more damage with less alcohol misuse than men), there is a strong rationale for the presence of sex differences in the damage from alcohol misuse to PFC and in ToM processing. We propose to conduct secondary analyses of existing data collected from the Human Connectome Project (HCP), with behavioral, clinical, demographic, and drug use data and resting FMRI, social cognition and emotion processing task FMRI, and structural MRI data of interest for this project, to investigate sex differences in the structure and function of ToM-related brain circuits in individuals with AUD. The HCP is an NIH-funded initiative to comprehensively map human brain circuits and their relationships to behavior in 1200 adults. Data from 500 subjects have been released to date. From those, we have identified 35 females and 35 males with AUD and 70 carefully matched healthy subjects (35M/35F), whose data will be used for this study. In addition, we will include new subjects identified from the next two HCP releases, which may more than double our final sample size to ~300-350 subjects. Our specific aims are: 1) Use resting FMRI data to investigate DMN function and the relationships between DMN function, social cognition measures, sex and AUD, 2) Use task FMRI to investigate the connections between DMN and other key ToM brain circuits, sex, and AUD, and 3) Apply data fusion analysis to all MRI measurements combined together to identify “features” of combined structure/function that will be uniquely related to AUD and sex.

酒精使用障碍的人的社会认知困难（AUD），包括情绪感知 缺陷和定义的思想（汤姆）处理，由于滥用酒精而更加严重，并且 持续的目的地延长禁欲。汤姆是社会认知的关键方面，是指 了解自我和他人的意图（认知汤姆）和情感（情感汤姆）。研究建议 在社会认知措施上，女性通常比男性表现优于男性。但是关于神经的研究 AUD中的TOM处理的相关性很少，并且没有研究 奥德前额叶皮层（PFC）是“默认模式网络”（DMN）的关键区域，该区域在 Tom加工，尤其是它特别容易受到酒精的神经毒性作用。 DMN可以 在有AUD的个体中，与社会认知难度有关。给出了性二态性的证据 大脑结构，休息和任务功能磁共振成像（fMRI）大脑的性别差异 激活以及对女性脑损伤的“伸缩性”影响（女性损害更多，而较少 滥用酗酒），对于在损害中存在性别差异的有力理由 滥用PFC和TOM加工。我们建议对现有数据进行次要分析 从人类连接项目（HCP）中收集，并具有行为，临床，人口统计学和吸毒 数据和休息fMRI，社会认知和情感处理任务fMRI以及感兴趣的结构MRI数据 对于这个项目，研究与TOM相关脑电路的结构和功能的性别差异 有声音的人。 HCP是一项由NIH资助的计划，旨在全面绘制人脑电路和 他们与1200名成年人的行为关系。迄今为止，来自500名受试者的数据已发布。从这些， 我们已经确定了35名女性和35位男性，有70名精心匹配的健康受试者（35m/35f）， 其数据将用于本研究。此外，我们将包括从接下来的两个中确定的新主题 HCP发布，我们的最终样本量将其两倍多于〜300-350受试者。我们的具体目的是： 1）使用静止的fMRI数据研究DMN功能以及DMN功能，社交功能之间的关系 认知措施，性别和AUD，2）使用fMRI的任务来研究DMN与其他人之间的联系 关键的Tom脑电路，性别和AUD，以及3）将数据融合分析应用于所有MRI测量合并 共同确定将与AUD和性别唯一相关的组合结构/功能的“特征”。