Measuring Distress Tolerance With Functional MRI

Objective: The primary objective of the current study is to implement a distress tolerance
assessment for use in fMRI to determine the neurobiological differences between individuals
with low and high distress tolerance. Additionally, other biological and physiological
indicators will be assessed, including genetic polymorphisms, salivary cortisol, galvanic
skin response, and blood pressure. The overall hypothesis is that individuals with low
distress tolerance will exhibit hyperactivation in the extended amygdala and hypoactivation
of the prefrontal cortex and anterior cingulate cortex when experiencing affective distress
and failure during a stressful task, as compared to individuals with high distress tolerance.

Study Population: The study population will consist of healthy male and female adult
volunteers (18-55 years old), as well as an otherwise healthy sample of male and female
treatment seeking substance users with cocaine users (18-55 years old) (see exclusion
criteria).

Experimental Design and Methods: After being medically cleared and giving written informed
consent, each participant will undergo a structural MRI scan of the brain, and undergo an
fMRI scanning session, which will include administration of the distress tolerance and
relevant control tasks. Physiological response to the tasks, including heart rate, blood
pressure, galvanic skin conductance, and salivary cortisol concentrations will be monitored
throughout the fMRI scan. Follow-up assessments on control and cocaine dependent participants
will occur at 1, 3, 6, and 12 months after the baseline assessment. Genetic data collected
under the aegis of protocol 10-DA-N457 will be compared with data collected under this study.

Outcome Measures: Outcome measures include distress tolerance measured as latency in seconds
to task termination on each of the distress tolerance tasks, neural indices of distress
tolerance (for all participants), and substance use treatment outcomes (for cocaine users)
including relapse to drug use, latency to first cocaine use, and number of substance use days
per week at follow-ups.

- INCLUSION CRITERIA:

1. Be between the ages of 18 and 55.

2. Be in good health.

3. Be right-handed.

4. Cocaine dependent participants: Endorse regular cocaine use (i.e., greater than
or equal to 2 times per week) in the past year.

5. Non-drug using controls: will be matched to the cocaine using participants with
respect to age, gender, IQ, socioeconomic factors, and years of education.

EXCLUSION CRITERIA:

1. Pregnant. Urine pregnancy tests will be performed on all female volunteers of
child-bearing age before each experimental session.

2. Have implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial
joints, metal pins, surgical clips or other implanted metal parts) or claustrophobia
rendering them unable to undergo fMRI scanning.

3. Have major medical illnesses to include, but not limited to, hypertension,
cardiovascular disease, asthma, diabetes, peripheral vascular diseases,
coagulopathies, syncope, history of superficial or deep vein thrombosis, HIV, or other
clinically significant infectious diseases.

4. Have current major psychiatric disorders to include, but not limited to, mood,
anxiety, borderline personality disorder, psychotic disorders, or substance-induced
psychiatric disorders,

5. Have neurological illnesses including, but not limited to, seizure disorders,
migraine, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS
tumor.

6. Control participants: Meet DSM-IV criteria for any past or current substance abuse or
dependence; use of illicit substances in the last 30 days or nicotine if use is
greater than 10 cigarettes per day and/or Fagerstrom score is greater than 3.

7. Cocaine using participants:

1. Non-treatment subjects: Meet DSM-IV criteria for substance dependence on any
substance other than nicotine or cocaine in the month prior to study enrollment.
Only (except nicotine or cocaine dependence will be allowed in the month prior to
enrollment. Current abuse on any substance will be acceptable.). While it might
be preferable to exclude individuals whose use of other substances reaches the
threshold of abuse, inclusion of such individuals will not necessarily
contaminate the data.

2. Inpatient cocaine subjects: Those who meet DSM-IV TR criteria for the course
specifier In a Controlled Environment may have a history of dependence on
substances other than cocaine before their admission to the inpatient treatment
program.

8. Regular use of any prescription, over-the-counter, or herbal medication that may alter
CNS function, cardiovascular function or neuronal-vascular coupling. Medications that
could interfere with the BOLD signal include compounds that have been shown to be
vasoactive, including alpha agonists, beta blockers, and calcium channel blockers.

9. Have cognitive impairment as assessed by screening WASI vocabulary subtest below 48,
corresponding to full IQ of 85 (in that case on screening, a full WASI will be done to
verify IQ of 85 or above).

10. Acute drug intoxication or positive urine drug screen at the beginning of the study