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