The protocol involved in this project is 09-M-0123, NCT00884702. During the 2013 funding period, we addressed the following: In collaboration with our colleagues from the Walter Reed Army Institute of Research (T.Balkin and D. Picchioni, we use the L-1-11Cleucine PET method to measure rCPS in human subjects during sleep. To address the restoration hypothesis of sleep, we measure rCPS in the same subject during normal wakefulness, sleep-deprived wakefulness, and sleep. We hypothesize that rCPS is increased during sleep, but that during sleep-deprived wakefulness, rCPS remain at levels comparable to rested wakefulness. Subjects undergo the initial scan in the awake, sleep-sated state. Subjects are then kept awake over the next 30 h and subsequently undergo a second PET scan in the sleep-deprived but awake state. Subjects are then encouraged to sleep in the scanner while they undergo a third scan during slow wave sleep. Subjects are healthy male and female volunteers between the ages of 18 and 28 y. We exclude subjects with a history of neurological and psychiatric disorders, chronic medical conditions, and sleep disorders. Our preliminary results indicate trends for elevated rCPS in some brain regions during slow wave sleep. To address the role of protein synthesis in memory consolidation, we are determining whether sleep-dependent increases in rCPS are associated with sleep-dependent improvements in memory. We use the Texture Discrimination Task (TDT) to assess learning and memory. Improvement on performance of this task has been demonstrated to depend on sleep. The TDT is retinotopically specific, so training in one hemisphere (due to stimuli in the contralateral visual field) does not improve performance in the opposite hemisphere. This allows us to determine changes in rCPS in the trained hemisphere of the primary visual cortex and use the untrained hemisphere as a control. The task is administered at 8 AM, subjects are randomized to nap (12:30-2 PM) or no-nap groups, and the task is re-administered at 6 PM. The stimulus of the TDT is always in the lower half of the visual field and we randomize the stimulated side (left or right). From 12:30-2 PM (no nap or nap opportunity), subjects undergo simultaneous L-1-11Cleucine PET and electroencephalography (EEG). We hypothesize that an increase in rCPS in the trained hemisphere will be observed in subjects who spent a significant time in slow wave sleep during the nap opportunity. We further hypothesize that this increase will correlate with the improvement in performance between the two administrations of the task. All subjects are sleep-deprived prior to the first administration of the task. Subjects in the nap group are encouraged to sleep during the 90 min PET scan;those in the no nap group are kept awake. Our preliminary results indicate that performance on the TDT tends to deteriorate over time in the no nap subjects, but not in the subjects who napped. We determine rCPS in the lingual and cuneate gyri of the left and right hemispheres. The lingual and cuneate gyri map to the upper and lower parts, respectively, of the contralateral visual field. In our preliminary data, subjects in the nap group spent more than 50% weighted time in slow wave sleep during the scan. We find no trained-to-untrained side differences in either the cuneate or lingual gyri in the no nap group. In contrast, we find in the nap group a statistically significant trained-to-untrained side difference in rCPS in the cuneate gyrus (P<.001), but not in the lingual gyrus. These preliminary results suggest a direct relationship between protein synthesis and sleep-dependent memory consolidation.

Project Start
Project End
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Budget End
Support Year
2
Fiscal Year
2013
Total Cost
$544,940
Indirect Cost
Name
U.S. National Institute of Mental Health
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