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As any medical resident, college student, or new parent can tell you, going without sleep can be painful, aggravating, and depressing. But what if we could stimulate the brain so it could handle periods of sleep deprivation and still function at high levels?

Dr. Yaakov Stern, professor of clinical neuropsychology (in neurology and psychiatry, and in the Gertrude H. Sergievsky Center and Taub Institute), and colleagues at Columbia Health Sciences are testing human endurance in a sleep deprivation and brain imaging study funded by the U.S. Department of Defense's Defense Advanced Research Projects Agency, the agency that funded the development of Stealth technology and the Internet.

The study is unique because it employs brain imaging to understand what allows some people to cope with sleep deprivation better than others, says Dr. Stern, principal investigator. The researchers will compare data from those who perform well under sleep-deprived conditions with others who do not do so well and use the information to help both groups. The ultimate goal of the two-part grant, which was awarded early this year and began in March, is to help soldiers successfully complete a mission without sleep.

In the first part of the study, Dr. Stern and his colleagues are assessing two days of sleep deprivation in 30 civilian volunteers. Participants are monitored physiologically and psychologically, take showers and eat meals, and are observed the entire time to make sure they stay awake.

The researchers use fMRI to take snapshots of the participants' brains while they perform memory tests before and after the 48 hours without sleep. fMRI detects oxygenated hemoglobin as blood flows through the brain. The scans can determine differences in the utilization of different parts of the brain during task performance with and without sleep. The researchers expect to see that sleep-deprived people who perform well on memory tests use certain regions of the brain more than people who perform poorly on the tests.

With the information collected from the fMRI and memory tests, Dr. Stern and his colleagues are beginning to determine where a new method to stimulate the brain, called transcranial magnetic stimulation (TMS), could be directed to help individuals who do not cope well with sleep deprivation and to enhance the performance of those who perform better without sleep.

TMS is a brief but powerful magnetic field that sends electrical pulses into the brain to activate specific areas, says Dr. Sarah H. Lisanby, associate professor of clinical psychiatry, director of the Columbia TMS laboratory, and study co-principal investigator. No one knows whether TMS can improve cognition in a sleep-deprived person, but the technology has shown promise in assisting brain function in studies of depression, schizophrenia, and in normal volunteers performing certain memory tasks, Dr. Lisanby says.

When Dr. Stern and his colleagues find stronger evidence for a linkage between certain regions of the brain and performance under sleep-deprived conditions and show how TMS can help, the next phase of the study will occur. Dr. Lisanby would then apply TMS to 75 sleep-deprived soldiers and test how they perform on both memory tests and simulated military tasks, such as docking a submarine. The investigators will use fMRI to image the effect of TMS on brain function.

So far 15 subjects have completed the first half of the sleep-deprivation study and more are being lined up. Based on preliminary data, Dr. Lisanby has begun exploring the effect of TMS delivered to brain areas that appear to be affected by sleep deprivation.

Besides having relevance for the armed services, whose members often are in combat conditions without sleep, the sleep-deprivation research might shed light on the stressed brain and new therapies for it. "The opportunity to examine people before and after the cognitive challenge of sleep deprivation might give us a better perspective on what happens in early stage dementia, where we would like to figure out why some brains cope better than others," Dr. Stern says. "TMS may help clarify how brain circuits are affected by illnesses like dementia and may lead to new treatments for these disorders," Dr. Lisanby adds.

For more information about the study, which is being funded by the U.S. Department of Defense's Defense Advanced Research Projects Agency, please call either 342-1729 or 543-5615 or email rhe26@columbia.edu.


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