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Wake Forest, Kentucky Researchers Study Sleep Deprivation with $1.6 Million Award

WINSTON-SALEM, N.C. – A team of Wake Forest University Baptist Medical Center researchers, joined by investigators at the University of Kentucky, is exploring the effects of sleep deprivation on memory and performance tasks. The project will use monkeys who are already trained to play video games that test decisions, coordination and memory.

The U.S. Department of Defense Advanced Research Projects Agency (DARPA) is paying for the project with an award worth $1.6 million for the first 18 months and potentially up to $4.5 million as part of a much larger effort to mitigate or eliminate the effect of sleep deprivation on military personnel.

"Pilots and soldiers are frequently subject to sleep deprivation," said Sam Deadwyler, Ph.D., professor and vice chair of physiology and pharmacology. The goal is to determine how soldiers can function in a more efficient manner during long missions. Sleep interrupts missions of all types.

"They could perform much more efficiently if they didn''t have to spend a relatively large amount of time sleeping," said Robert Hampson, Ph. D., associate professor of physiology and a co-investigator on the project.

The monkey studies will extend results of prior research testing monkey motor coordination, short term memory and ability to think through variations in the video game. The Wake Forest researchers will add sleep deprivation and see how that affects performance.

They already have a strong hint from one sleepless night the monkeys spent during the earlier study. When they started playing their video games the next day, "they were very disrupted," said Deadwyler, much the same as people who try to work after a sleepless night. But the researchers --including Linda Porrino, Ph.D., professor of physiology and pharmacology, James B. Daunais, Ph.D., an assistant professor -- will couple those experiments with explorations using the noninvasive positron emission tomography (PET) imaging to see which areas of brain are most affected during sleep deprivation.

"The idea is to look at monkeys that are performing a well-learned motor task under normal conditions when they are alert and when they are sleep deprived to determine which areas of the brain might be affected under these conditions," said Porrino.

"Then we want to look again at the same animals while they are performing a complex cognitive (memory) task that undoubtedly engages very different parts of the brain under conditions of alert normal state and under sleep deprivation."

They also will be looking for changes in neurotransmitters in the brain. "That''s important when you are interested in developing new drugs or agents for combating sleep deprivation," said Porrino.

Deadwyler said another co-investigator, Phillip W. Landfield, Ph.D., professor and chair of the Department of Molecular and Biomedical Pharmacology at the University of Kentucky, is working to find genes that are associated with sleep deprivation. "When we find out what those genes are, we might be able to build drugs that are targeted to those pathways."

Deadwyler said the DARPA project "is made to order in terms of what we have already done. We have been training primates to do cognitive tasks and recording their brain activity."

In one video game, an image of computer-generated clip art is flashed on the screen and then the screen goes blank for a few seconds. That''s followed by three to six images, one of which is the same as the prior image. The monkey uses a device like a computer mouse to move a cursor to the one he thinks is correct.

Sometimes, the researchers insert as much as a 60-second delay before giving the monkey the follow-up choice.

"The longer the delay in seconds, the less likely he is to get it correct," said Deadwyler, and the more images to choose from, the less likely the monkey is to choose the right one.

"It is a fun game for the monkeys and they get juice reinforcement," he said.

Deadwyler said Stephanie Hodge, Charles West, Ashley Morgan and Santos Ramirez are in charge of daily testing of the monkeys.

The method has been used to explore what is remembered by adding different colors and changing the clip art images. If the initial image has a red scarf, for instance, some monkeys may pick a different image if it has the same red color, while others will pick out the same image even though the scarf is now a different color.

"Now we will investigate what happens if the monkeys are deprived of sleep the night before," Deadwyler said.

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