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.

酒精使用障碍患者的社会认知障碍，包括情绪知觉 心理理论(TOM)加工中的缺陷和缺陷，随着酒精滥用和 即使长期禁欲，也要坚持下去。TOM是社会认知的一个关键方面，指的是 了解自己和他人的意图(认知的汤姆)和情感(情感的汤姆)。研究表明 女性在社会认知方面的表现通常要好于男性。然而，对神经的研究 AUD患者TOM加工的相关性很少，也没有关于患有AUD的个体的性别差异的研究 澳元。前额叶皮质(PFC)是“默认模式网络”(DMN)的一个关键区域 汤姆加工，值得注意的是，它特别容易受到酒精的神经毒性影响。因此，DMN可以 与AUD患者的社会认知障碍有牵连。给出了性别二态的证据 静息和任务脑功能磁共振成像的脑结构、性别差异 激活，以及对女性大脑损伤的“伸缩”效应(女性损伤越多，损伤越少 酒精滥用比男性多)，有充分的理由说明存在性别差异所造成的损害 酒精误用到PFC和TOM加工中。我们建议对现有数据进行二次分析 收集自人类连接组项目(HCP)，包括行为、临床、人口统计学和药物使用情况 数据和静态功能磁共振成像、社会认知和情绪处理任务功能磁共振成像以及感兴趣的结构磁共振数据 在这个项目中，研究性别差异在与心理理论相关的大脑回路的结构和功能。 患有澳门氏症的个人。HCP是由美国国立卫生研究院资助的一项倡议，旨在全面绘制人类大脑回路和 他们与1200名成年人的行为之间的关系。到目前为止，已经公布了500名受试者的数据。从这些方面来看， 我们已经确定了35名女性和35名男性AUD和70名精心匹配的健康受试者(35M/35F)， 谁的数据将被用于这项研究。此外，我们将包括在接下来的两个主题中确定的新主题 HCP发布，这可能会使我们的最终样本量增加一倍以上，达到约300-350名受试者。我们的具体目标是： 1)利用静息fMRI数据研究DMN功能及其与社会功能的关系 2)使用任务功能磁共振研究DMN与其他因素之间的联系 关键的Tom大脑回路、性别和AUD，以及3)将数据融合分析应用于所有MRI测量组合 共同确定将与澳元和性别唯一相关的组合结构/功能的“特征”。