MRI Measurement of Brain Metabolism Across the Sleep-Wake Cycle
MRI Measurement of Brain Metabolism Across the Sleep-Wake Cycle
This study will investigate the spatio-temporal characteristics of brain activity during
 sleep. Functional magnetic resonance imaging (fMRI) studies have shown that in the absence of
 external stimuli, the brain continues to show spatial patterns of activity that resemble
 those during sensory and cognitive tasks. This phenomenon greatly affects the interpretation
 of neuroimaging studies based on positive emission tomography (PET) and fMRI, which rely on
 the contrast between brain activity during a task and activity during rest. In addition,
 resting state activity in itself may reveal information on the large-scale organization of
 neuronal networks and on functional abnormalities related to disease.

 Participants should represent a broad cross section of the healthy adult population. Any
 neurologically and psychiatrically healthy male or nonpregnant female between 18 and 65 years
 old may be eligible.

 Studies will be conducted in the In Vivo NMR Research Center. Concurrent electroencephalogram
 (EEG) and MRI studies will last between 1 and 2 hours. A typical study involves 15 minutes of
 anatomical MRI scanning followed by a 60-minute functional scan during which the subject
 relaxes with eyes closed and is encouraged to sleep while the fMRI/EEG are performed.
 Participants may be scanned 1 to 20 times. No more than 1 scan will be performed per day and
 no more than 20 scans will be performed within a year. During the last 5 to 10 minutes of the
 scan, the participant will open his or her eyes and actively participate in a visual
 stimulation or attention task. The participant's alertness will be measured by a behavioral
 (button-press) response. The visual stimuli (contrast reversing checkerboard displays,
 alternated with uniform grey fields) will be presented using the standard projection system
 available with the MRI scanner. The attention task will involve repeated visual presentation
 of groups of letters and digits; the participant will be asked about the correspondence
 between these groups.

 Magnetoencephalogram (MEG) scans will be performed on some participants. The precise and
 undistorted signals available with MEG will be used to enhance the interpretation of
 alertness and sleep-related characteristics of the EEG signals, which can vary quite
 dramatically across subjects. In addition, the MEG signals will provide preliminary spatial
 localization of the sleep-dependent changes more precisely than is possible with EEG. MRI
 scanner noise will be simulated using tape recordings to allow comparison with the MRI/EEG
 data. MEG scans will last 45 minutes to 2 hours. At all times during any of the brain scans
 the participant will be able to communicate the MRI scientist or MEG/EEG technician and can
 ask to be removed from the device at any time.

 The study will not have a direct benefit for participants. It may be help us learn more about
 brain function, which may lead to better treatments.
Objective. The objective of the proposed study is to investigate the spatio-temporal
 characteristics of brain activity during sleep. A number of recent fMRI (Ogawa, Lee et al.
 1990) studies have shown that in absence of external stimuli, the brain continues to show
 spatial patterns of activity that resemble the networks that activate during sensory and
 cognitive tasks. This phenomenon greatly affects the interpretation of neuroimaging studies
 based on PET and fMRI, since these rely on differential imaging in which activity during a
 task is contrasted against activity during rest. In addition, resting state activity in
 itself potentially contains unique information on the large scale organization of neuronal
 networks and reveals information about functional abnormalities related to disease processes.

 Study Population. To avoid confounding factors related to disease processes, subjects for
 this study will be recruited from the normal adult population. In addition, subjects will be
 screened for sleep behavior, and subjects with abnormal sleep behavior will be excluded.

 Design. The study is designed to facilitate MRI detection of cerebral metabolic differences
 between the sleep and awake states. Wakefulness and sleep, and the various stages will be
 classified in accordance with the EEG criteria, consistent with the guidelines of
 Rechtschaffen and Kales (Rechtschaffen, 1968). For this purpose, we will optimize the
 methodology for the concurrent acquisition of EEG and fMRI signals. Using concurrent EEG and
 state-of-the-art MRI, we plan to establish the precise spatial distribution of changes in
 brain activity that are associated with changes in the sleep/wake state and the various
 stages of sleep, specifically early sleep (stage 1 and 2). Secondly, we plan to investigate
 whether changes in regional brain metabolism as measured by MRI correlates with transitory
 EEG phenomena during sleep, including fluctuations in band-specific power, sleep spindles,
 and K-complexes.

 Outcome Measure. As an outcome of this study, an atlas of activity clusters in normal
 subjects will be established, both during waking conditions, as well as during several sleep
 stages. Further outcomes will be spatial patterns of covariance with EEG band-specific power,
 spindles, and K-complexes. These data will serve as a baseline for comparison with activity
 patterns in patients.
-  INCLUSION CRITERIA:

 Any neurologically and psychiatrically normal, male or female, healthy volunteer between 18
 and 65 years old is in principle eligible for the study. Subjects must be capable of
 understanding the procedures and requirements of this study. Subjects must be willing to
 sign an informed consent document.

 EXCLUSION CRITERIA:

 A subject will be excluded if he/she has a contraindication to MR scanning such as the
 following: pregnancy, aneurysm clip; implanted neural stimulator; implanted cardiac
 pacemaker or auto-defibrillator; cochlear implant; known absent acoustic reflex; ocular
 foreign body (e.g. metal shavings or insulin pump) and any pre-existing eye conditions.
 Subjects who underwent brain surgery, who have a neurological lesion, a psychiatric history
 or recurrent migraines that require medication will also be excluded from this study.

 To minimize potential confounds, subjects with abnormal sleep/wake patterns will be
 excluded. They should report no sleep problems or shift work, or medications that could
 impair sleep, no illegal drugs or tobacco. Subjects will be in good health as assessed by
 medical history, interview and physical exam.

 Subjects will be asked to:

 Refrain from alcohol and caffeinated products for 1 day prior to the study;

 Maintain their habitual bed times and wake-up times for 1 week prior to the study. A
 wrist-worn activity monitor (Actigraph[R], Precision Control Design, Inc., Fort Walton
 Beach, FL) may be used to confirm compliance with the latter instruction.

 Exclusion criteria include:

 Sleep disorder (reported or detected);

 Psychopathology, personal or first-degree relative. (They are likely to place the subject
 at risk for an adverse consequence related to the extended wakefulness portion of the
 study);

 Seizures or head injury with loss of consciousness greater than 5 minutes;

 Substance dependence (diagnosable);

 Smoking tobacco or psychotropic medications (currently);

 Caffeine consumption of 300 mg or 2 ounces of alcohol on a regular daily consumption;

 Cardiac, respiratory, or other medical condition that may affect cerebral metabolism.