The Effects of Expectation on Natural and Drug -Induced Rewards

• INCLUSION CRITERIA:

All participants must:

i) Be between the ages of 18-45. Justification: This study aims to further understanding of reward expectancy processes in the adult brain. In addition, it involves intravenous delivery of a stimulant with no potential for direct benefit. It is therefore inappropriate to include children. Many cognitive processes change with age. In addition, the risk of difficult-to-detect medical abnormalities such as silent cerebral infarcts increases with age. Older individuals, defined as those over 45, will, therefore, be excluded. Assessment tool(s): driver's license, birth certificate or other government-issued form of identification.

ii) Be in good health. Justification: Many illnesses can alter fMRI signal, alter cognition, and pose an increased risk of adverse cardiac events following intravenous methylphenidate. Assessment tool(s): Participants will provide a brief health history during phone screening, and undergo a history and physical examination with a qualified IRP clinician.

iii) Be right-handed. Justification: Many of the brain functions to be assessed in this protocol have shown some evidence of being lateralized in the brain. In order to reduce the variance in the data from this possibility, participants must be right-handed. Assessment tool(s): Edinburgh Handedness Inventory.

NIDA.

Cocaine using participants must be regular users of cocaine.

Control participants must not use cocaine nor be dependent on any other drug except perhaps nicotine.

EXCLUSION CRITERIA:

Participants will be excluded if they:

1. Are not suitable to undergo an fMRI experiment due to pregnancy, implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology or claustrophobia. Justification: MR scanning is the primary measurement tool used in the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Pregnancy tests will be performed on all female subjects before each experimental session. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and may be placed in the mock scanner during their screening visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to physically fit into the scanner.
2. Have cardiovascular disease, including but not limited to clinically significant arrhythmia, coronary artery disease and hypertension. Justification: Significant cardiovascular abnormalities may increase the risk of receiving intravenous methylphenidate, which is likely to produce a transient increase in blood pressure and heart rate. Note: Participants for experiment one may have mild cardiovascular disease not allowable for participants in experiment two. Assessment tool(s): History (including family history) and physical examination by a qualified IRP clinician. Potential participants with SBP NIDA visit average over 140 mm Hg or DBP NIDA visit average over 90 mm Hg or resting pulse NIDA visit average over 100 bpm at rest on three successive NIDA visits will be disqualified. Any abnormality on ECG will be reviewed by cardiology prior to further participation. A 3-minute rhythm strip showing more than 3 PVCs will be exclusionary. The MAI will retain discretion to disqualify at lower levels, depending on the clinical presentation.
3. Have coagulopathies, history of or current superficial or deep vein thrombosis, musculoskeletal abnormalities restricting an individual's ability to lie flat for extended periods of time. Justification: MR scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately two hours. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) or dangerous (e.g. familial hypercoagulability syndrome, history of thrombosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort issues.
4. Have HIV or syphilis. Justification: HIV and syphilis can both have CNS sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): HIV blood test, syphilis serology (positive RPR).
5. Have any neurological illnesses to include, but not limited to, seizure disorders, frequent migraine, multiple sclerosis, movement disorders, or CVA, CNS tumor Justification: CNS diseases alter CNS function and, possibly, the neuronal-vascular coupling that forms the basis of the BOLD fMRI signal to be used in this study. Assessment tool(s): History and physical examination by a qualified IRP clinician, urine drug screening for anticonvulsants not disclosed by history.
6. Have an abnormality on screening MRI scans that would place the participant at increased risk from blood pressure elevations related to protocol procedures (methylphenidate injections) or would impair the quality of data gathered on the participant. Assessment tool(s): The following MRI scans will be obtained: sagittal T1, axial T2, axial FLAIR, diffusion weighted image, MR angiography, Circle of Willis. (about 15 minutes).

7. Have other major medical illnesses likely to interfere with study results or safety of an individual during participation. Justification: Many illness not covered here may increase risk or alter important outcome measures. Assessment tool(s): History and physical examination by a qualified IRP clinician and CBC, urinalysis, NIDA chemistry panel (liver function tests, electrolytes, kidney function). The following individual laboratory results will independently disqualify individuals. The MAI will retain discretion to exclude at less extreme values, depending on the clinical presentation.

   • Cholesterol > 250 mg/dl
   • Hemoglobin < 10.5 g/dl
   • WBC < 2400/microl
   • LFTs > 3 times normal
   • HCG positive
   • Serum glucose > 200 mg/dl
   • Urine protein > 1 plus

   Serum glucose over 140 mg/dl will be followed up with a fasting serum glucose. Those with fasting glucose below 100 mg/dl may be considered for the protocol. Others will be rejected and referred for work up. MAI will make the final judgment on any questionable lab results.

8. Have any current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders, or substance-induced psychiatric disorders Justification: Psychiatric disorders involve the CNS and, therefore, can be expected to alter the fMRI measures being used in this study. Assessment tool(s): Computerized SCID-NP and ASRS (adult ADHD self-report scale) confirmed by clinician interview.
9. Regularly use any prescription, over-the-counter or herbal medication that may alter CNS function, cardiovascular function or neuronal-vascular coupling. Justification: Compounds that alter BOLD signal will alter the primary measure used in the study. Assessment tool(s): History and comprehensive urine drug screening to detect antidepressants, benzodiazepines, antipsychotics, anticonvulsants, barbiturates and other common medications and drugs of abuse.
10. Are lactating. Justification: Avoidance of possible exposure of an infant to methylphenidate. Assessment tool(s): Clinical interview.
11. cognitively impaired or learning disabled. Justification: cognitive impairment and learning disabilities are associated with alterations in brain regions used to accomplish tasks, and, therefore, may introduce significant variably into the data. In addition, cognitive impairment may affect ability to give informed consent. Assessment tool(s): History of known learning disability or cognitive impairment. Vocabulary subtest of the WASI will be given. IQ estimate must be over 85 (corresponding to a vocabulary subtest score > 48). In cases of suspected non-verbal learning disability or mild verbal deficit, a full WASI may be given to obtain a more robust estimate of IQ.