REM sleep (dreaming sleep) will be employed as a natural probe of an important circuit that may be dysfunctional in schizophrenia, using functional MRI (fMRI). REM sleep may be an ideal, natural brain activation study condition for examining the dynamics of the entire eye-movement-control circuit: natural because the brain circuit is activated by visual imagery in dreaming; ideal because (1) almost all the sensory input to the brain from the environment is blocked, (2) differences in the level of cooperation of subjects are not a confounding factor, and (3) muscle tone is greatly reduced during REM sleep. This approach may be very useful in persons with schizophrenia who may not cooperate well with the task and who move more than normal subjects.
The aim of the study is (1) to determine whether the same brain circuit is involved in eye movements in both REM sleep and wakefulness using fMRI and (2) to determine if the eye-movement-control circuit behaves abnormally in schizophrenia. After we run five normal subjects and establish the methodology, schizophrenic subjects will participate in the study. Each subject will have an adaptation night on the scanner bed, a waking eye movement study, and a REM sleep study. Waking eye movement tasks will include saccades to imagined targets (box-car design) or saccades with the same timing as REM sleep eye movements (event-related design). It is feasible to perform fMRI in sleep, despite the difficulties involved. Attention will be paid to details to increase the subject's comfort. Recorded scanner noise will be played back constantly before they fall asleep and throughout the night, so that subjects do not wake up when the fMRI sequence is turned on. fMRI data will be collected and eye movements will be recorded simultaneously using a video camera (and if possible, electrooculogram with a fiberoptic system) as soon as the REM sleep is clearly identified and as long as the subject remains in REM sleep. fMRI data will be gathered every two seconds in 20 slices (slice thickness = 6 mm) using a blipped echo planar imaging (EPI)-based gradient refocused echo sequence. Event-related fMRI as well as correlational analyses will be used to study the pattern of regional brain activation / inhibition in relation to eye movements. These regional patterns in persons with schizophrenia will be compared to those in normal controls using the coordinate system of the Talairach atlas.
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