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

酒精使用障碍（AUD）患者的社会认知困难，包括情绪感知 心理理论（ToM）处理的缺陷和缺陷，随着酒精滥用的增加而更加严重， 尽管长期禁欲，但仍然存在。心理理论是社会认知的一个关键方面，指的是 理解自我和他人的意图（认知心理理论）和情感（情感心理理论）。研究表明 女性在社会认知方面的表现通常优于男性。然而，对神经系统的研究 AUD中ToM加工的相关性很少，也没有研究个体中的性别差异。 澳元。前额叶皮层（PFC）是“默认模式网络”（DMN）的关键区域， 心理理论加工，特别是它特别容易受到酒精的神经毒性作用。因此，DMN可以 与AUD患者的社会认知困难有关。鉴于两性异形的证据 静息和任务功能磁共振成像（FMRI）脑结构、性别差异 激活，以及对女性脑损伤的“伸缩”效应（女性有更多的损害， 酒精滥用比男性），有一个强有力的理由存在性别差异的损害， 在PFC和ToM处理中滥用酒精。我们建议对现有数据进行二次分析 从人类连接组项目（HCP）收集，包括行为，临床，人口统计学和药物使用 数据和静息功能磁共振成像，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成像数据 在这个项目中，为了研究与ToM相关的脑回路的结构和功能的性别差异， 个人AUD HCP是NIH资助的一项计划，旨在全面绘制人类大脑回路， 1200名成年人的行为。迄今为止，已公布了500名受试者的数据。从这些， 我们已经确定了35名患有AUD的女性和35名男性以及70名仔细匹配的健康受试者（35 M/35 F）， 他们的数据将用于本研究。此外，我们还将纳入从下两个 HCP发布，这可能使我们的最终样本量增加一倍以上，达到约300-350例受试者。我们的具体目标是： 1)利用静息状态下的功能磁共振成像数据研究DMN的功能以及DMN功能、社会功能和认知功能之间的关系。 （2）采用任务功能磁共振成像（fMRI）研究DMN与其他认知功能之间的关系。 关键的ToM脑回路、性别和AUD，以及3）将数据融合分析应用于所有组合的MRI测量 一起鉴定与AUD和性别唯一相关的组合结构/功能的“特征”。

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.