Development Of Neuroimaging Methods To Assess The Neurobiology Of Addiction

• Objectives: To improve sensitivity as well as spectral and spatiotemporal resolutions in magnetic resonance (MR) studies assessing structural, neurochemical, hemodynamic and electrophysiological changes that occur in the human brain during the resting state as well as those that occur in response to novel sensory, motor, cognitive or emotional stimulation paradigms.
• Study population: We intend to complete studies in 128 healthy volunteers, (64 males and 64 females, 18 years or older).
• Design: We will conduct pilot studies, each with up to 16 subjects, to optimize MR pulse sequences and/or functional MR imaging (fMRI) task paradigms pertinent to the theme of Addiction . MR pulse sequences and/or fMRI task paradigms will be validated against

appropriated gold-standard methods/tasks. These studies are required to maximize the sensitivity of new imaging techniques and fMRI tasks used for clinical and research applications that take advantage of 3T MRI scanners at NIH. If an exploratory study leads to results of interest, and if a larger population is necessary to reach statistical significance, a separate protocol will be submitted with a priori hypotheses, specific study design and power analysis adapted from the pilot studies performed in the present protocol.

• Outcome parameters: Although multiple measures will be collected, the primary outcome will be amplitude and reliability of regional-specific BOLD fMRI signals.
• MRI: we will analyze measures such as the amplitude and the reliability of the test-retest measures of fMRI signals; functional connectivity metrics; tractography between seed and target regions of interest (diffusion tensor imaging, DTI); brain morphometry (using

automatic segmentation and voxel-brain morphometry, VBM); and brain metabolite levels in regions of interest (using MR spectroscopy, MRS).

• EEG (electroencephalography): we will quantify measures such as event or task-related potentials, and coherence between sensors or sources located close to the brain areas of interest.
• Behavioral measures: during fMRI we will quantify measures such as reaction times and accuracy (using MRI compatible response pads) as well as eye movement (using MRI compatible eye trackers) and self-reports of the study experience (i.e., degree of interest

and motivation and alertness).

-Physiological measures: During fMRI, we will record physiological parameters such as blood pressure, skin conductance, respiratory frequency, or heart rate, to interpret outcome measures.

• INCLUSION CRITERIA:

• Eighteen years or older.
• Ability to provide written informed consent as determined by physical examination and verbal communication. Capacity to consent will be determined by those obtaining the informed consent.
• Willingness to abstain from drug use on scheduled testing days.

Exclusion criteria

• Positive urine pregnancy test in females.
• Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces as determined by the self-report checklist.
• Claustrophobia.
• Body weight >550 lbs, which is the weight limit of the MR scanner.
• Current DSM-5 diagnosis of a psychiatric disorder (other than nicotine/caffeine use disorders) as determined by history and clinical exam including substance use disorder, alcoholism and alcohol dependence. Past history of a mental disorder as defined by DSM-IV or DSM-5 will be excluded only if it was severe enough as to require hospitalization (any length), or chronic medication management (more than 4 weeks), or that could impact brain function at the time of the study. Subjects receiving psychotherapy may be included in the study.
• Those with a binge drinking history every month continuously for the last 10 years will also be excluded. Binge drinkers are those who being female consume 4 or more drinks and males consume 5 or more drinks in one occasion at least once a month.
• Serious neurological disorder such as MS, Parkinson s Disease, ALS, sensory loss or peripheral neuropathy.
• Currently taking any psychoactive drugs such as Celexa (TM), Prozac (TM), Wellbutrin (TM), Zoloft (TM), and/or stimulants other than caffeine such as Adderall (TM), Dexedrine (TM) and Ritalin (TM). Subjects taking PRN medications (e.g., sleep medications) may be included in the study.
• Clinically significant laboratory or examination results.
• Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).
• *Non-English speakers (must also be able to read and comprehend English).

• The intent of the research has no prospect of direct benefit to the subject. Therefore, we are excluding non-English speakers in this research study since our fMRI paradigms (particularly the Delay Discounting task) require that the subject be able to speak, read and comprehend English.

Subjects will not be excluded from enrollment onto this study if their urine test or breath alcohol level (BAL) is positive for drugs/alcohol on initial screening. However, if they test positive on scheduled study procedure days involving MRI, the procedures will be postponed and rescheduled. We will allow for up to 3 rescheduled study days that were the result of positive urine drug or BAL screens. If the drug/BAL tests is/are positive on the third rescheduled visit, the participant will be withdrawn from the study.