Reliability of the Human Brain Connectome

Objectives: The overarching goal of this study is to quantify the reproducibility of multiple
measures of brain functional connectivity (FC) during resting conditions and during task
performance. Secondary objectives are to assess the dynamic properties and energy
requirements of the human brain connectome as well as the effects of physiologic noise,
gender and aging on measures of brain functional connectivity at rest and during task
performance.

Study population: 60 healthy males and 60 healthy females 18 years or older will be included.

Design: Participants will undergo two MRI/MRS sessions to evaluate test-retest reliability of
FC at rest as well as during task performance, and one 18F-Fluorodeoxyglucose (FDG)-PET
session to assess the association between FC and glucose metabolism in the human brain.

Outcome parameters: The variability of the gender and aging effects on FC measures (lFCD, L,
C, and S) collected in RS and TS conditions , which will be quantified using volxelwise ICC.
The variability of brain metabolite concentrations in precuneus.

- INCLUSION CRITERIA:

All Participants:

1. Older than 18 years of age.

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

EXCLUSION CRITERIA:

1. Pregnant or breast feeding. Females of childbearing potential must have negative urine
pregnancy test and not be currently breastfeeding. Post-menopausal or surgically
sterile (tubal ligation or hysterectomy) females satisfy these criteria.

2. Use, in the past two weeks, of psychoactive medications (four weeks for fluoxetine) or
medication that can affect brain function (including but not limited to meperidine,
tricyclic antidpressants, selective serotonin reuptake inhibitors (SSRIs), or
serotonin norepinephrine reuptake inhibitors (SNRIs) as determined by history and
clinical exam.

3. Current or past DSM-IV or DSM-5 diagnosis of a psychiatric disorder as determined by
history and clinical exam including substance use disorder (except for
nicotine/caffeine), alcoholism and alcohol dependence. Those with a binge drinking
history in the last 10 years will also be excluded. Past history of a mental disorder
as defined by DSM-IV or DSM-5 will be excluded only if it required hospitalization
(any length), or chronic medication management (more than 4 weeks), and that could
impact brain function at the time of the study. 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.

4. Major medical problems that can impact brain function at the time of the scan
(including but not limited to HIV; central nervous system including seizures and
psychosis; cardiovascular including hypertension and arrhythmias; metabolic,
autoimmune, endocrine) as determined by history and clinical exam.

5. Any clinically significant laboratory finding as determined during the screening
procedures.

6. Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that,
with the exposure from this study, would exceed NIH annual research limits.

7. Head trauma with loss of consciousness for more than 30 minutes.

8. Presence of ferromagnetic objects in the body that are contraindicated for MRI/MRS of
the head (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), fear of enclosed spaces, or other
standard contraindication to MRI/MRS (self-report checklist).

9. Cannot lie comfortably flat on back for up to 2 hours in the PET and MRI/MRS scanners.

10. Body weight > 250 kg. This is the upper limit that the bed of the MR scanner can
accommodate.

11. NIH employees who are study investigators, 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 study imaging (MRI/MRS and PET) and Neuropsychological
testing, 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.