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

项目总结/摘要 酒精中毒（FHP）家族史是酒精使用发展的一个公认的危险因素 疾病（AUD）。这种脆弱性是多方面的，因为它与几个单独的风险因素有关， 认知控制受损，对酒精的反应水平低。认知控制是 执行功能的一个重要方面，使个人能够灵活地应对不断变化的环境 通过整合过去的经验和当前的目标导向行为来满足需求。神经影像学证据显示 有效的认知控制依赖于外侧和内侧前额叶皮质（PFC）的激活， 区域之间的功能连接。虽然有限，但神经生理学和 血流动力学方法表明FHP中神经激活模式和功能连接的改变 个体认知控制障碍通过自我意识的减弱与AUD的发展密切相关， 控制酒精消费。除了认知控制缺陷外，FHP还表现出较低的主观LR 酒精的影响，需要更大的数额，感觉类似的影响，个人没有家族史。 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 导致冲动性饮酒超过预期。然而，很少有研究探讨了 酒精对认知控制的神经回路的影响受FHP的影响。因此，总体目标是 该建议是表征认知控制的神经指标及其对酒精影响的敏感性， 以及潜在网络的功能连接，在FHP个体与匹配组相比， 没有酗酒家族史的人。拟议的项目将使用多模式成像方法 有两个主要目的：（1）使用解剖学约束脑磁图（aMEG）方法检查 酒精中毒对FHP个体θ振荡和长程协同振荡的影响， 认知要求高的任务，如Stroop任务;（2）表征神经功能网络的基础 使用基于MRI的功能连接（fcMRI）的认知控制作为酗酒家族史的函数。 aMEG方法结合了MEG的时间精度和结构MRI制作的空间映射 可以检查酒精对θ振荡和共振荡的影响。事件相关θ 振荡对认知努力敏感，而共振荡整合皮层之间的神经通信， 认知控制期间的区域。作为一种补充方法，fcMRI的空间映射可用于 检查神经功能网络内区域之间连接的固有差异。多式 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以帮助 阐明增加FHP个体发展AUD风险的神经生物学贡献。

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.