Functional Neuroimaging of Alcoholism Vulnerability (PIT)

This project compares Family History Positive (FHP) for alcoholism subjects to matched Family
History Negative (FHN) subjects derived from the project Principal Investigator's National
Institute on Alcohol Abuse and Alcoholism-funded longitudinal study of drinking behavior in a
2000 college freshman population (known as the Brain and Alcohol Research in College Students
study (BARCS)). The age of these subjects is a valuable one at which to capture the
transition from harmful use to abuse/dependence. This project explores the effects of
memantine in a double-blind, randomized, counterbalanced manner on alcoholism risk-relevant
tasks. More specifically, this project studies functional MRI tasks related to different
aspects of reward and/or impulsivity-related behavior in different contexts, compares the
underlying neural circuitry across tasks, and uses a pharmacologic probe of the glutamatergic
system to examine NMDA/DA interactions. The combined measures provide the opportunity to
advance our understanding of specific aspects of brain function related to familial
alcoholism vulnerability in an already well-characterized population as some members evolve
into alcohol abuse. In addition to conventional within-task analyses, functional network
connectivity and allied approaches will be used to examine brain networks across tasks.

The investigators will study adult male and female subjects in equal numbers who are either
offspring of an alcoholic parent or are FHN matched controls. The investigators will recruit
and assess a total of 84 (42 FHP and 42 matched FHN) subjects between the ages of 18-21 years
on initial BARCS contact. The investigators will use 4 cognitive tasks during the functional
MRI (fMRI) which include: 1) a Monetary Incentive Delay Task that distinguishes networks
engaged in motivational (anticipation) and consummatory (outcome) components of reward
processing; 2) a Go/No-Go Task that measures the ability to inhibit response to a pre-potent
stimulus; 3) an Alcohol Cue Reactivity Task that examines Nucleus Accumbens response to
alcohol-related versus matched soft drink stimuli; and 4) a Pavlovian-to-Instrumental
Transfer (PIT) Task that dissects a component of the Monetary Incentive Delay (MID) Task, and
provides an imaging assay of a transfer-like process that can be related to real-world
drinking behavior, thus informing upon and extending the key findings from CTNA-2.