Human Brain Mapping of the Apparent Diffusion Coefficient (ADC) During Sleep and Wakefulness

OBJECTIVES:

The primary objectives are to assess if there is an increase in the apparent diffusion
coefficient (ADC) in the human brain during sleep when compared to the awake state and to
determine if they vary across brain regions. Secondary outcomes are to assess inter subject
variability in the differences in ADC between awake and sleep. We will also run exploratory
analysis to determine if ADC changes with sleep are associated with subjective perception of
rested sleep and to assess if there are differences in T1 in CSF between the scan taken prior
to falling asleep and those taken shortly after waking up.

STUDY POPULATION:

Healthy adults. Males and females will be included.

DESIGN:

Observational study with a technical phase and two research phases.

- The technical phase (discontinued) will recruit controls in order to define best MR
parameters and pulse sequence to be used for optimal ADC signal detection for which we
request permission to recruit up to 20 healthy volunteers. Technical Developmental
Phase: Each participant will have a set of MRI scans at the following two times of day:
the 1st between 11:00 AM and 1:00 PM (noon) and the second between 6:00 PM and 8:00 PM
(evening).

- Research Phase I (complete testing in 10 healthy controls to assess effects on
wake/sleep states on whole brain ADC) and research Phase II (complete testing in a total
of 30 subjects to assess if there are regional differences) and to address the main and
secondary outcomes proposed above. Only if we show that ADC significantly changes during
sleep compared to awake state will we proceed to phase II. For phases I and II, the
participants will spend 3 night in the clinical center and will undergo two MRI scan
sessions following two fo the night stays to quantify brain ADC; once while awake
(following a night of sleep) and the other while asleep (following a night of sleep
deprivation). Scans for both days will be performed in the morning (between 9-12 PM).
Electrocardiogram (ECG) will be recorded during all MRI scanning procedures to monitor
sleep. For the first of the three nights we will simultaneously record the
electroencephalogram (EEG) and ECG on the participants while they sleep which will allow
us to correlate the ECG to their EEG signal, which is the gold standard for measuring
sleep.

OUTCOME PARAMETERS:

ADCs and ECG will be measured at each time point for each study participant (pertinent to
research phase only).

- INCLUSION CRITERIA:

All Participants

1. Between 18 and 60 years of age as determined by self-report.

2. Ability to provide written informed consent as determined by physical examination and
verbal communication.

EXCLUSION CRITERIA:

All Participants

1. Subjects with self-report of insomnia as determined by self-report and/or medical
history;

2. Subjects with any of the following: narcolepsy, obstructive sleep apnea (OSA) and/or
abnormal sleeping patterns (including but not limited to those who use a C-PAP
machine, sleeping during the day, using medication to fall asleep, sleeps less than 6
hours per night, night shift workers), subjects reporting snoring as determined by
self-report using STOP-BANG questionnaire for undiagnosed OSA (3 or more yes answers
will exclude) and/or medical history;

3. Subjects with a history of restless leg syndrome as determined by self-report and/or
medical history;

4. Use, in the past two weeks, of psychoactive medications (four weeks for fluoxetine) or
medications that may affect brain function (including but not limited to opioid
analgesics, tricyclic antidepressants, selective serotonin reuptake inhibitors
[SSRIs], or serotonin norepinephrine reuptake inhibitors [SNRIs], benzodiazepines and
barbiturates) as determined by self-report and/or medical history;

5. 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. 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.

6. Major medical problems that can impact brain function at the time of the scan (e.g.,
problems of the CNS including seizures and psychosis; cardiovascular disease including
hypertension and arrhythmias; metabolic, autoimmune, endocrine disorders) as
determined by self-report, medical history and/or clinical exam.

7. Head trauma with loss of consciousness for more than 30 minutes as determined by
self-report and/or medical history;

8. Positive test for controlled substances (cocaine, methamphetamine, amphetamines,
opioids, cannabinoids, benzodiazepines and barbiturates) on any day of study including
upon check-in to NIH CC as determined by urine toxicology;

9. Pregnant: Females must have negative urine pregnancy test

10. 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.

11. Fear of enclosed spaces (claustrophobia) as determined by self-report and medical
history.

12. Cannot lie comfortably flat on the back for up to 3 hours in the MRI scanner as
determined by self-report.

13. Body weight greater than 250 kg. This is the upper limit that the bed of the MR
scanner can accommodate (clinical exam).

14. Alcohol consumption on the day of the MRI as determined by breath alcohol test

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