An fMRI Study of Ventral Striatal Deficits During Reward and Punishment

酒精依赖的风险存在于家庭中。这种可遗传的酗酒风险的一个组成部分是 与其他上瘾、反社会和冲动行为有共同之处。CTNA将探索这样的假设 这些酒精中毒的“共同”危险因素(ACRF)涉及与会聚相关的突触病理 谷氨酸和多巴胺输入腹侧纹状体以及相关的“动力”回路。从一个 从认知/行为神经科学的角度来看，这种脆弱性的证据表现为 由于延迟的奖惩，导致正常的激励回路能力受损， 使个人偏向于直接的回报(以酒精为例)和冲动的行为。一个 这种传播的脆弱性的一个方面被假设为涉及大脑电路的问题，以获得奖励 和惩罚期望--一种“报酬赤字假说”。我们将使用两个截然不同但互为补充的 行为任务，结合功能磁共振，量化动机回路中的反应，以 涉及对奖惩的期望和接受以及倾向的情况 在其中一项任务上冒险。我们将对80名成年男性和女性受试者进行等量研究 要么是酗酒父母的子女，要么是家族病史阴性的配对对照组。使用两个 功能磁共振成像(FMRI)中的互补认知任务，将解剖大脑中的功能异常。 聚集在腹侧纹状体的环路，可能导致酒精中毒和其他 冒险或冲动的行为。这两个范例是：1)货币激励延迟任务，区别于 参与奖励的激励性(预期)和消耗性(结果)组成部分的网络 处理；2)Domino任务，探索报酬处理的预期和完成阶段 在促进冒险的背景操纵(不确定性、社会互动)下。主观性 对任务的反应将被量化为一项重要的从属衡量标准。在CTNA内部的协同作用中，我们将 探索：(遗传学核心)影响多巴胺和谷氨酸能的基因变异 功能调节动机回路的完整性；(项目3)NMDA受体是否增加 功能导致动力回路的功能异常；(项目5)临床相关性 酒精依赖受试者动机回路的功能完整性。

The risk for alcohol dependence runs in families. A component of this heritable risk for alcoholism is common to other addictions, sociopathy, and impulsive behavior. CTNA will explore the hypothesis that these Alcoholism "Common" Risk Factors (ACRF) involve synaptic pathology related to the convergence of glutamate and dopamine inputs to the ventral striatum and associated "motivation" circuitry. From a cognitive/behavioral neuroscience perspective, evidence for this vulnerability is expressed as general impairments in the normal ability to engage motivational circuitry by delayed rewards and punishments, biasing individuals toward immediate rewards, (exemplified by alcohol), and impulsive behavior. An aspect of this transmitted vulnerability is hypothesized to involve problems in the brain circuitry for reward and punishment expectation- a "Reward Deficit Hypothesis." We will use two distinct but complementary behavioral tasks, in combination with functional MRI, to quantify responses in motivational circuitry to situations involving both expectation of and receipt of rewards and punishments, as well as the propensity to take risks on one of the tasks. We will study 80 adult male and female subjects in equal numbers who are either offspring of an alcoholic parent or are family history negative matched controls. Use of two complementary cognitive tasks during functional MRI (fMRI), will dissect functional abnormalities in the circuits converging on the ventral striatum that may contribute to the vulnerability to alcoholism and other risky or impulsive behaviors. The 2 paradigms are: 1) a Monetary Incentive Delay Task, that distinguishes networks engaged in motivational (anticipation) and consummatory (outcome) components of reward processing; 2) a Domino Task, that explores anticipatory and consummatory phases of reward processing under contextual manipulations (uncertainty, social interaction) that promote risk-taking. Subjective responses to tasks will be quantified as an important dependent measure. In synergy within CTNA, we will explore: (Genetics Core) whether variation in genes that influence dopaminergic and glutamatergic function moderate the integrity of motivation circuitry; (Project 3) whether increases in NMDA receptor function contribute to functional abnormalities in motivation circuitry; (Project 5) the clinical relevance of the functional integrity of motivation circuitry in alcohol dependent subjects.