Multimodal Imaging of Cognitive Control in Individuals with a Family History of Alcoholism

项目摘要/摘要 有酗酒家族史(FHP)是酒精使用发展的公认危险因素 精神障碍(澳大利亚)。此漏洞是多方面的，因为它与几个单独的风险因素相关，例如 认知控制受损，对酒精的反应(LR)水平低。认知控制是一种 行政职能的基本方面，使个人能够灵活应对不断变化的环境 通过将过去的经验与当前的目标导向行为相结合来满足需求。神经成像证据表明 这种有效的认知控制依赖于外侧和内侧前额叶皮质(PFC)的激活和 区域之间的功能互联互通。虽然有限，但来自神经生理学和 血流动力学方法显示FHP的神经激活模式和功能连接性的变化 个人。认知控制受损与AUD的发展密切相关，这主要是由于认知控制能力减退 对酒精消费的监管。除了认知控制缺陷外，FHP还表现出对主观的低似然比 酒精的影响，需要更多的剂量才能感觉到与没有家族史的人相似的影响。 重要的是，急性酒精中毒选择性地减弱外侧和内侧PFC的激活，这可能 导致冲动饮酒超过预期。然而，很少有研究研究这种影响是如何 酒精对辅助认知控制的神经回路的影响受到FHP的影响。因此，总的目标是 这项建议是为了表征认知控制的神经指标及其对酒精影响的敏感性， 以及基础网络的功能连接性，在FHP个体与匹配组进行比较 没有酗酒家族史的个人。拟议的项目将使用多模式成像方法 主要目的有两个：(1)使用解剖受限的脑磁图(AMEG)方法检查 酒精中毒对慢性酒精中毒患者Theta振荡和长程协同振荡的影响 认知要求高的任务，如Stroop任务和(2)表征潜在的神经功能网络 使用基于磁共振成像的功能连接(FcMRI)将认知控制作为酒精中毒家族史的一项功能。 AMEG方法结合了脑磁图的时间精度和结构磁共振成像的空间映射 可以研究酒精对theta振荡和协振荡的影响。与事件相关的题元 振荡对认知努力很敏感，而共振荡整合了大脑皮层之间的神经通讯 认知控制过程中的区域。作为一种补充方法，fcMRI的空间映射可用于 检查神经功能网络中各区域之间连通性的内在差异。多式联运 同时使用aMEG和fcMRI的方法将提供对认知控制的神经指标及其 有酗酒家族史的个体对酒精中毒的敏感性。这些发现可能会有所帮助 阐明增加FHP个体发生AUD风险的神经生物学因素。

PROJECT SUMMARY/ABSTRACT A positive family history of alcoholism (FHP) is a well-established risk factor for the development of alcohol use disorders (AUD). This vulnerability is multifaceted as it is associated with several individual risk factors such as impaired cognitive control and a low level of response (LR) to the effects of alcohol. Cognitive control is an essential aspect of executive function that allows individuals to flexibly respond to changing environmental demands by integrating past experiences with current goal-directed behavior. Neuroimaging evidence indicates that effective cognitive control relies on activation of the lateral and medial prefrontal cortices (PFC) and functional connectivity between regions. Though limited, evidence from both neurophysiological and hemodynamic methods indicates alterations in neural activation patterns and functional connectivity in FHP individuals. Impaired cognitive control is heavily implicated in the development of AUD through diminished self- regulation of alcohol consumption. In addition to cognitive control deficits, FHP exhibit a low LR to the subjective effects of alcohol, requiring greater amounts to feels similar effects as individuals without a family history. Importantly, acute alcohol intoxication selectively attenuates activation of the lateral and medial PFC, which may contribute to impulsively drinking more than intended. Few studies, however, have examined how the effects of alcohol on the neural circuitry subserving cognitive control are influenced by FHP. Therefore, the overall aim of this proposal is to characterize the neural indices of cognitive control and their sensitivity to the effects of alcohol, as well as the functional connectivity of the underlying network, in FHP individuals compared to a matched group of individuals with no family history of alcoholism. The proposed project will use a multimodal imaging approach with two main aims: (1) use an anatomically-constrained magnetoencephalography (aMEG) method to examine the effects of alcohol intoxication on theta oscillations and long-range co-oscillations in FHP individuals during a cognitively demanding task such as the Stroop task and (2) characterize the neurofunctional network underlying cognitive control as a function of a family history of alcoholism using MRI-based functional connectivity (fcMRI). The aMEG method combines the temporal precision of MEG and the spatial mapping of structural MRI making it possible to examine the effects of alcohol on theta oscillations and co-oscillations. Event-related theta oscillations are sensitive to cognitive effort while co-oscillations integrate neural communication between cortical regions during cognitive control. As a complementary method, the spatial mapping of fcMRI can be used to examine inherent differences in connectivity between regions within a neurofunctional network. The multimodal approach using both aMEG and fcMRI will provide insight into the neural indices of cognitive control and their sensitivity to alcohol intoxication in individuals with a family history of alcoholism. These findings could help elucidate the neurobiological contributions that increase the risk for FHP individuals to develop AUD.