Cognitive Task Development and Implementation for Functional MRI Studies

Background:

* Drugs of abuse have effects on mood, behavior, thinking, and decision making that may encourage people to continue using them and make it difficult for them to stop. Researchers who study these effects are interested in developing new tests to evaluate how drugs and drug use affect different areas of the brain.
* Magnetic resonance imaging (MRI) scans allow researchers to study brain activity and changes to brain function. When specific psychological tests are performed during functional MRI (fMRI) scans, researchers can examine the effects of drug use on the brain. By developing and testing new procedures for fMRI studies, more information can be obtained on brain function and activity in drug-using and non-drug-using individuals, and this information can help develop new treatments and therapies for substance abuse.

Objectives:

- To evaluate the effects of newly developed psychological procedures to be performed during fMRI scans.

Eligibility:

* Healthy volunteers between 13 and 65 years of age who are willing to undergo MRI scanning.
* Both drug-using and non-drug-using individuals will be selected for this study.

Design:

* Before the start of the study, participants will complete questionnaires about medical and psychological history, and provide information about past or current drug use. Researchers will introduce the tasks to be performed during the scanning session(s), and will allow participants to practice the test either on a separate computer or on the computer used during the MRI scan.
* During the study, participants will be asked to do one or more tasks selected by the researchers. The tasks will be performed on a computer in an MRI machine, and may involve receiving rewards (such as money or sips of juice) for actions, memory and reaction-time tests, or other tests that involve responding to instructions on the screen.
* Participants will receive compensation for their participation in the study, including hourly compensation for individual visits and lump-sum compensation for each MRI scan.

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 18-65, 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.

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, if they yield measurable and interpretable fMRI results.

Eligibility Criteria:
* INCLUSION CRITERIA:

Participants will be considered for one of eight categories: 379-bench-control, 379-bench-smoker, 379-bench-user, 379-bench-other-psych-diagnosis, 379-control, 379-smoker, 379-user, 379-otherpsych -diagnosis.

1. Male or female between the ages of 18-65.
2. All subjects must be able to provide informed consent/assent.
3. Additional criteria for specific populations:

   1. 379-smoker- regular smoker of tobacco cigarettes with a urine cotinine level corresponding to nicotine user status for the specific test being used (typically corresponding to a urine cotinine above about 200 ng/ml) and have been smoking consistently 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).
4. Additional criteria for MRI phase participants:

Right-handed. Assessment tool: Self-report. 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 lefthanded 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 neurologic injury including but not limited to CVA, CNS tumor, or head trauma with persistent sequelae. Assessment tool: phone screen and medical history. Rationale: Neurologic injury is likely to impair performance on the range of tasks to be piloted under

   this protocol.
2. Current use of psychoactive medications likely to affect the performance of the task under consideration, 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, medical history, urine drug screen. Rationale: certain psychoactive medications may alter performance 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 with symptoms severe enough to impair ability to participate (unless task is being evaluated in a specific clinical population). Assessment tool: self report, medical history. Rationale: Current major mood or psychotic disorders with poorly controlled symptoms may impair performance on the range of tasks to be piloted under this protocol and may impair ability to tolerate the procedures.
5. Non-English speaking. Assessment tool(s): self-report. Rationale: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing study procedures. The inability to effectively communicate safety procedures in a language other than English could compromise the safety of non-English speaking participants.

   Additional criteria for MRI:
6. 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.
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.