Ventral Striatal Functional Deficits and Familial Alcoholism Risk
This study will determine whether FHP healthy subjects and FHP alcohol dependent patients show deficits in ventral striatal activation associated with the anticipation of reward. Both data from Hommer’s NIAAA lab and CTNA-1 fMRI data reviewed above predict that these deficits may contribute to the common risk for alcoholism, impulsivity, and sociopathy. The study will explore whether (1) deficits in ventral striatal activation in the FHP healthy subjects related to increased NMDA receptor function or spinophilin genotype; (2) spinophilin genotype is related to ventral striatal activation deficits in alcohol dependent patients;
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.
Results
During reward anticipation, fMRI data confirmed blunted nucleus accumbens activation in family history positive (FHP) subjects who themselves have had no current or prior histories of alcohol abuse or dependence.
In addition, we found abnormal activation in nucleus accumbens and additional reward-associated brain regions during additional task phases, most notably excessive task-related activation in the FHP group during the A1 (prospect of reward), phase of the MID task.
We further found significant correlations between abnormal nucleus accumbens activation during reward anticipation and prospect and specific impulsivity constructs. Interestingly, diminished activation during the A2 (reward anticipation) phase was significantly correlated with the same impulsivity factor associated with diminished activation during this same task phase in a population of cocaine abusers we are examining in a separate study. Similarly, we observed correlations between nucleus accumbens activation and additional impulsivity factors during the outcome of reward phase in the FHP. Overall, results demonstrate that sensitivity of the reward circuit in general, including NAcc, is functionally compromised in FHP individuals.