Development Of Neuroimaging Methods To Assess The Neurobiology Of Addiction

- Objectives: There are two main goals in this protocol, 1) 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; and 2) to conduct
pilot sub-studies, which are exploratory in nature, in order to gather enough
information for hypothesis generation. The criterion for transition to a new full
protocol will be a sufficient amount of information to generate a power analysis.

- Study population: We intend to complete studies in a healthy volunteers of 120 males and
120 females, 18 years or older.

- Design: We will design small projects as ideas pertinent to the theme of Addiction and
conduct pilot sub-studies, each with up to 16 subjects, to optimize MR pulse sequences
and/or functional MR imaging (fMRI) task paradigms. MR pulse sequences and/or fMRI task
paradigms will be validated against appropriated gold-standard methods/tasks. These
studies are required in order to maximize the sensitivity of new imaging techniques and
fMRI tasks used for clinical and research applications that take advantage of 3T and 7T
MRI scanners in the MR center. If an exploratory sub-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 or exploratory sub-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);
morphometry of brain regions (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. We are also quantifying blink rates from the
electrooculogram (EOG).

- Behavioral measures during fMRI tasks: 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).

- We may measure autonomic data during the course of the fMRI experiment (such as
blood pressure, skin conductance, respiratory frequency and heart rate), which
would correlate to the outcome measures.

- INCLUSION CRITERIA:

1. Eighteen years or older.

2. 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.

3. Willingness to abstain from drug use on scheduled testing days.

EXCLUSION CRITERIA

1. Positive urine pregnancy test in females.

2. 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.

3. Claustrophobia.

4. Body weight >550 lbs, which is the weight limit of the MR scanner.

5. Current or past DSM-IV or 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. Those with a binge drinking
history in the last 10 years will also be excluded. Binge drinkers are those who being
female consume 4 or more drinks and males 5 or more drinks in one occasion at least
once a month. 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.

6. Serious neurological disorder such as MS, Parkinson s Disease, ALS, sensory loss or
peripheral neuropathy.

7. 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.

8. Clinically significant laboratory or examination results.

9. Study investigators and staff, as well as their superiors, subordinates and immediate
family members (adult children, spouses, parents, siblings).

Subjects will not be excluded from enrollment onto this study if their urine test is
positive for drugs. 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 screens. If the drug
test is positive on the third rescheduled visit, the participant will be withdrawn from the
study.