Neural Connectivity and the Transition to Alcohol Dependence

描述（由申请人提供）：功能性磁共振成像（fMRI）的出现深刻地促进了对人类大脑的理解。功能磁共振成像最令人兴奋的前沿应用之一是连接分析，它不仅揭示了参与给定神经过程的独立大脑区域，而且还揭示了这些区域相互作用的方式。这种互动的功能障碍可以说是人类精神病理学的关键。连接性分析可能会特别促进对酒精依赖（酒精中毒）神经生物学的理解，酒精依赖是一种每年影响800万美国人的进行性慢性复发性疾病。这种疾病通常始于奖励驱动的大量饮酒，最终发展成习惯性的强迫性使用。成瘾的动物模型表明，这种转变的一个关键因素是大脑行为控制系统连接的普遍变化。最初，饮酒可能会选择一个大脑网络，该网络是目标导向（奖励动机）行为的基础。在依赖开始后，饮酒可能会转移到一个介导习惯学习或强迫性的网络中。人类功能磁共振成像研究表明，当个体暴露在酒精暗示下时，这些网络是活跃的，当他们休息时也是如此。此外，它们的完整性可能与执行功能中的神经认知缺陷有关。然而，这些网络尚未在人类酗酒者中进行系统研究。这项提案将使用fMRI连接分析来测试非依赖性重度饮酒者和酒精依赖者之间目标导向和习惯学习网络的连接。有三个具体目标：1）确定这些组在酒精提示反应期间的连接差异; 2）确定休息时组间的这种差异; 3）确定连接差异是否与神经认知障碍的个体差异有关。了解大脑网络中的优势地位的变化，使奖励和习惯，最终将有助于开发更有效的治疗酒精依赖的方法。

DESCRIPTION (provided by applicant): The advent of functional magnetic resonance imaging (fMRI) has profoundly advanced understanding of the human brain. One of the most exciting cutting-edge applications of fMRI is connectivity analysis, which reveals not only the separate brain regions involved in a given neural process, but also the manner in which these regions interact with each other. Dysfunction in such interactions is arguably the crux of human psychopathology. Connectivity analysis may particularly advance understanding of the neurobiology of alcohol dependence (alcoholism), a progressive, chronically relapsing disease that affects eight million Americans annually. The disease often begins with reward-driven heavy drinking and ultimately develops into a pattern of habitual, compulsive use. Animal models of addiction suggest that one key factor in this transition is a pervasive shift in the connectivity of the brain's behavioral control system. Initially, drinking may co-opt a brain network that underlies goal-directed (reward-motivated) behavior. After dependence onsets, drinking may shift to a network that mediates habit learning, or compulsivity. Human fMRI studies suggest that these networks are active when individuals are exposed to alcohol cues and also when they are at rest. Further, their integrity may be related to neurocognitive deficits in executive functioning. However, these networks have not been studied systematically in human alcoholics. This proposal will use fMRI connectivity analysis to test connectivity of the goal-directed and habit learning networks among non-dependent heavy drinkers and alcohol-dependent individuals. There are three specific aims: 1) to identify the connectivity differences between these groups during alcohol cue reactivity; 2) to identify such differences between groups while at rest; and 3) to determine whether connectivity differences are related to individual differences in neurocognitive impairment. Understanding shifts in the dominance of brain networks subserving reward and habit will ultimately contribute to the development of more efficacious treatments for alcohol dependence.