MRI Measurement of Brain Metabolism Across the Sleep-Wake Cycle
Condition: Sleep
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Keywords: Magnetic Resonance Imaging; Functional Imaging; Cerebral Blood Flow; BOLD Effect; Sleep