Neural Substrates of Approach-Avoidance Conflict

Objective: Continued drug seeking despite knowledge of adverse consequences is a hallmark of
addiction. To model this behavior, we will refine the parameters of a modified Monetary
Incentive Delay (MID) task that will allow us to investigate neural substrates of
approach-avoidance conflict resolution. We will then use this task to investigate functional
magnetic resonance imaging (fMRI) brain activation during pursuit of reward in heavy and
light drinkers.

Study Population: Healthy non-treatment-seeking heavy drinkers and healthy light drinkers
aged 21 to 60.

Design: The study will require 1 to 2 visits. Subjects will play a modified MID task called
Reward Incentive Delay with Shock (RIDS) to measure motivation to earn cue reward points in
conditions that are signaled to be safe or associated with a threat. After playing the RIDS
task subjects will be able to self-administer alcohol and/or food based on the reward points
earned during the task.

Outcome measures: The outcome measures are differences in behavioral task performance and in
blood oxygenation dependent level (BOLD) signal measured using standard fMRI techniques and
analyzed using AFNI software.

- Inclusion criteria (Light Drinkers):

1. In good health as determined by medical history, physical exam, ECG, and lab
tests;

2. Between 21 and 60 years of age;

3. Currently consuming on average 1-10 drinks per week for females and on average
1-14 drinks per week for males, (averaging over the 90 days recorded in the
Alcohol Timeline Followback);

4. Right handed.

Exclusion criteria (Light Drinkers):

1. Have liver function tests (AST, ALT, GGT, ALP) 3-times the upper limit of normal
(ULN); or have Total Bilirubin above 1.5 ULN and Albumin below 3.5 g/dl;

2. Have fulfilled DSM-IV-TR or DSM-5 criteria for alcohol dependence or alcohol use
disorder (past or current) at any time, or other current substance dependence or
substance use disorder (excluding nicotine);

3. Report having received any medication to treat a psychiatric disorder within the past
year, have a past or present diagnosis of a psychotic or bipolar disorder, or have
ever had a head injury requiring hospitalization;

4. Weigh over 330 pounds;

5. Are pregnant, as determined by a positive pregnancy test, or breast feeding; Report to
have a facial, body, and limb flushing response to the consumption of alcohol, as
determined by the Alcohol Flushing Questionnaire;

6. Report to have a "facial flushing" response to the consumption of alcohol

7. Have ferromagnetic objects in their bodies which might be adversely affected by MRI
including implanted pacemakers, medication pumps, aneurysm clips; metallic prostheses
(including metal pins and rods, heart valves or cochlear implants, shrapnel fragments,
permanent eye liner or small metal fragments in the eye that welders and other metal
works may have - any doubt about presence of these objects will result in exclusion
from this study), or if candidates are uncomfortable in small closed spaces (have
claustrophobia), or cannot lie comfortably on their back for up to one hour;

8. Medical illnesses (such as diabetes or stage 2 hypertension systolic blood pressure
greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal
to 100 mm Hg) or neurological illnesses (carpal tunnel syndrome; migraine headaches;
seizure disorders) likely to interfere with the study;

9. Endorse more than 3 symptoms on the Yale Food Addiction Scale;

10. Have colorblindness.

Inclusion criteria (Heavy Drinkers):

1. In good health as determined by medical history, physical exam, ECG, and lab tests;

2. Between 21 and 60 years of age;

3. Currently consuming on average 15+ drinks per week for females and on average 20+
drinks per week for males, as determined by the 90-day Alcohol Timeline Followback, or
fulfilled DSM-IV-TR criteria for current alcohol dependence or DSM-5 criteria for
current alcohol use disorder;

4. Right-handed;

5. Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-AR) score less than 8;

6. Not seeking treatment for their alcohol consumption.

Exclusion criteria (Heavy Drinkers):

All exclusion criteria for Light Drinkers except for Light Drinker exclusion criterion
number two. For Heavy Drinkers this exclusion criterion will read:

Have fulfilled DSM-IV-TR or DSM-5 criteria for any current substance dependence or current
substance use disorder (excluding alcohol or nicotine).