Cognitive Task Development and Implementation for Functional MRI Studies

Objective: Drugs of abuse have cognitive and affective effects that may contribute to the
inception and maintenance of their use. In order to measure these effects, psychological
tests suitable for use both in and outside the fMRI scanner need to be developed and
validated. Thus, the objective of this protocol is to allow for the development, assessment
and refinement of cognitive and affective tasks and determination of their practical
feasibility and efficacy for both MRI and non-MRI application.

The design and piloting of psychological tests and fMRI tasks specifically designed for an
adolescent population allows the investigators to determine if the tests/tasks measure
theorized cognitive constructs and result in measurable and interpretable fMRI data in
adolescents. At this time, the protocol is not enrolling adolescents.

Study Population: This minimal-risk protocol will employ volunteer participants aged 18-55,
who must be generally healthy and male or non-pregnant female. In order to ensure
applicability to relevant groups, both drug and non-drug using volunteers as well as those
recruited from clinical populations will be used to validate task design and parameters.
Specially designated tasks may be piloted in prisoner populations.

Design: Participants may pilot tasks outside and/or inside the MRI scanner, depending on the
aspects of task development requiring verification. Tasks developed de novo will undergo both
steps. Modifications to previously published MRI tasks may require only one of the steps.
Upon their successful verification, specific experimental manipulations will be performed
under separate, hypothesis driven protocols.

Outcome measures: Our goal is to determine if the tasks developed reliably and appropriately
measure specific cognitive constructs and behaviors thought to be associated with specific
brain systems and, also if they yield measurable and interpretable fMRI results.

- INCLUSION CRITERIA:

1. Male or female between the ages of 18-55.

2. All subjects must be able to provide informed consent/assent. Additional criteria
for specific populations:

1. 379-smoker- daily smoker of tobacco cigarettes for at least one year
(excluding quit attempts)

2. 379-user- DSM-V substance use disorder on a substance other than nicotine.

3. 379-other-psych-diagnosis- DSM-V disorder, stable and in treatment (i.e., no
medication changes in the previous four weeks and a clearly identified
treating psychiatrist).

3. Additional criteria for MRI phase participants:

Right-handed. Assessment tool: Edinburgh Handedness Inventory. Rationale: Left-handed
individuals may have lateralization of many brain functions that differ from right-handed
individuals who are the majority of the population. Therefore, inclusion of left-handed
individuals may add unwanted noise to imaging data.

C) Exclusion Criteria

Bench Only Phase (Does not require MRI. Task requires gathering of accurate behavioral
data).

1. History of neurological illnesses including but not limited to CVA, CNS tumor, head
trauma, MS or other demyelinating diseases, epilepsy, movement disorders, or migraine
in treatment. Assessment tool: phone screen and history and physical (H&P). Rationale:
Neurological illnesses are likely to impair performance on the range of tasks to be
piloted under this protocol and may impair ability to tolerate the procedures.

2. Current use of psychoactive medications unless required for the psychiatric disorder
for which participants in the 379-user and 379-other-psych-diagnosis subcategories are
being treated. Assessment tool: phone screen, H&P, Triage, comprehensive urine
toxicology. Rationale: psychoactive medications are likely to alter performace on the
range of tasks to be piloted under this protocol.

3. Cognitive impairment. Assessment tool: self report of extended placement in special
education classes for learning problems, history of specific learning disability or
mental retardation. Rationale: Cognitive impairment is likely to impair performance on
the range of tasks to be piloted under this protocol and may impair ability to
tolerate the procedures.

4. Current major mood, anxiety or psychotic disorder (unless task is being evaluated in a
specific clinical population). Assessment tool: self report, H&P. Rationale: Current
major mood or psychotic disorders are likely to impair performance on the range of
tasks to be piloted under this protocol and may impair ability to tolerate the
procedures.

Additional criteria for MRI Phase:

5. Pregnancy. Assessment tool: Urine pregnancy test. Rationale: Since the hormonal
changes of pregnancy have been shown to have an impact on cognitive functioning and
the tasks we are developing may yield only subtle differences between control and drug
abusing subjects, we need to minimize any extraneous variation in the pilot data.
Additionally, fMRI is not accepted as a safe procedure purely for research purposes
during pregnancy.

6. Deep vein thrombosis: Assessment tool: self report during H&P of thrombosis, or a
medical condition that may lead to a hypercoagulable state Rationale: Lying still for
>2 hours may be a risk for the development of DVT in persons with certain medical
conditions. As such, persons with will be excluded.

7. HIV positive individuals. Assessment tool: oral HIV test with serum confirmation of
positive results. Rationale: potential for cognitive and/or other CNS disease that
makes performing cognitive tasks non-reliable and /or non generalizeable to the
general population. Also, potential liver/metabolic/vascular disease can interfere
with the physiological transduction mechanisms for fMRI (i.e. making the measurement
unreliable).

8. Unable to undergo MRI scanning due to possible pregnancy, metallic devices in the
body, claustrophobia or body morphometry.

9. Currently using respiratory, cardiovascular or anticonvulsant medications that may
interfere with the BOLD MRI signal.