Neural Connectivity and the Transition to Alcohol Dependence

描述(申请人提供)：功能性磁共振成像(FMRI)的出现极大地促进了人们对人脑的理解。功能磁共振成像最令人兴奋的前沿应用之一是连通性分析，它不仅揭示了特定神经过程中涉及的独立大脑区域，而且揭示了这些区域相互作用的方式。可以说，这种相互作用的功能障碍是人类精神病理学的症结所在。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，酒精依赖是一种渐进性、慢性复发的疾病，每年影响800万美国人。这种疾病通常始于受奖励驱动的酗酒，最终发展成一种习惯性、强迫性的使用模式。上瘾的动物模型表明，这种转变的一个关键因素是大脑行为控制系统的连通性普遍发生变化。最初，饮酒可能会选择一个大脑网络，作为目标导向(奖励动机)行为的基础。在依赖后，饮酒可能会转向一个调节习惯学习或强迫症的网络。人类功能磁共振研究表明，当个体接触到酒精暗示时，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的神经认知缺陷有关。然而，在人类酗酒者身上，这些网络还没有得到系统的研究。这项提议将使用功能磁共振连通性分析来测试目标导向和习惯学习网络在非依赖的重度饮酒者和酒精依赖个人之间的连通性。有三个具体的目标：1)确定酒精线索反应时这些组之间的连接性差异；2)确定休息时组之间的这种差异；3)确定连接性差异是否与神经认知障碍的个体差异有关。了解支配奖赏和习惯的大脑网络的变化，最终将有助于开发更有效的酒精依赖治疗方法。

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.