Brain Region Ided That Can Be Stimulated To Reduce The Cognitive Deficits Of Sleep Deprivation

NEW YORK –A Columbia University Medical Center research team has uncovered how stimulation of a particular brain region can help stave off the deficits in working memory, associated with an extended sleep deprivation.

Brain Region Affected by Sleep Deprivation Identified Working memory is a specific form of short-term memory that relates to the ability to store task-specific information for a limited timeframe, e.g., where your car is parked in a huge mall lot or remembering a phone number for few seconds before writing it down. It has long been established that cognitive performance, such as working memory, declines with sleep deprivation. “We are excited about the possibilities of using brain stimulation to improve cognitive function,” said Bruce Luber, Ph.D., lead author of the paper and an instructor in clinical psychiatry at Columbia University College of Physicians & Surgeons and the New York State Psychiatric Institute. “We recently published a study 1 in which we were able to improve the working memory performance of young adults for the first time and this new study extends our findings.”

“In this research, we were able to non-invasively manipulate a brain network identified by imaging to partially remediate the effects of sleep deprivation using repetitive transcranial magnetic stimulation (rTMS), which has already shown promise in treating depression and other disorders," said Sarah H. Lisanby, M.D., senior author of the study and co-principal investigator of the DARPA grant funding this research. Dr. Lisanby is associate professor of clinical psychiatry and chief of the Brain Stimulation and Therapeutic Modulation Division, at the Columbia University College of Physicians & Surgeons and the New York State Psychiatric Institute.

“These findings have important implications for better understanding the neural bases of cognitive decline in the elderly. And the rTMS used in this study may potentially be useful in exploring and treating cognitive deficits due to aging and neuropathology in general,” said Yaakov Stern, Ph.D., a professor of clinical neuropsychology in neurology and psychiatry at the Taub Institute for the Research on Alzheimer’s Disease and the Aging Brain and the Gertrude H. Sergievsky Center at Columbia University Medical Center. Dr. Stern was principal investigator of the DARPA grant.

Findings were published online on Jan. 17, 2008 in Cerebral Cortex; the paper will be published in an upcoming print issue of the journal.

Study Designed to Test Sleep Deprivation Network, by Influencing the Expression of Key Brain Areas in the Network

In a previous study 2, the investigators identified a sleep deprivation network of brain areas that was active during the performance of a working memory task. Expression of this network was reduced following sleep deprivation. They also found a relationship between reduced expression of this network following sleep deprivation and poorer performance on the working memory task.

In the study, 15 young, healthy subjects underwent sleep deprivation for 48 hours. Working memory was tested using a letter recognition test, known as the delayed match to sample (DMS) task, in which subjects have to recall as quickly as possible whether a letter was included in a set of letters they had just seen. Participants performed this task during fMRI sessions both before sleep deprivation and at the conclusion of the sleep deprivation period.

The researchers used repetitive transcranial magnetic stimulation (rTMS) to test whether stimulation of three brain regions in the previously identified network following the sleep deprivation period, could improve performance on the working memory task. rTMS administers a rapid sequence of magnetic pulses to a specific brain area.

Results showed that stimulation at a site over left lateral occipital cortex, a prominent part of the brain network identified with fMRI, resulted in a reduction of sleep-induced slower reaction time without a corresponding decrease in accuracy. This improvement in performance was most marked in those individuals who showed the greatest reduction in the expression of the brain network following sleep deprivation.

“In addition to expanding our understanding of cognitive decline in the elderly, these findings may also have implications for new ways to treat sleep deprivation, a pervasive problem for soldiers, truck drivers and night-shift workers, which can result in impairment on the job and accidents,” said Dr. Stern.

“Cognitive Reserve” Varies Among Individuals

Elderly persons show a broad range of individual differences in the degree to which they experience cognitive deficits as they age. One hypothesis to explain these differences was first formulated by Dr. Stern in 2002 and has since been adopted by neuroscientists worldwide, and is known as cognitive reserve. The theory of cognitive reserve suggests that some individuals are better able to cope with age-related or other neuropathology because they can call upon more neural resources.

These present findings are consisted with the concept of cognitive reserve because some participants suffered larger deficits in working memory performance due to sleep deprivation, while others were much less affected. These susceptibility differences were related to differential expression of a brain network.

This suggests that the activity of the sleep deprivation network exhibited properties of neural reserve, where a greater capacity or efficiency in the network allowed some individuals to maintain performance in the face of sleep deprivation. Moreover, these results suggest that rTMS was able to somehow enhance the network activity in those who were not able to maintain performance, artificially facilitating neural reserve.

This research was supported by a grant from the Defense Advanced Research Projects Agency (DARPA), the central research and development organization for the U.S. Department of Defense.

1 Luber B, Kinnunen LH, Rakitin BC, Ellsasser R, Stern Y, Lisanby SH. 2007. Facilitation of performance in a working memory task with rTMS stimulation of the precuneus: Frequency and time-dependent effects. Brain Res 1128: 120-129.

2 Habeck C, Rakitin BC, Moeller J, Scarmeas N, Zarahn E, Brown T, Stern Y. 2004. An event-related fMRI study of the neurobehavioral impact of sleep deprivation on performance of a delayed-match-to-sample task. Cogn Brain Res 18: 306-321.]

- ### -

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first institution in the country to grant the M.D. degree. Among the most selective medical schools in the country, the school is home to the largest medical research enterprise in New York State and one of the largest in the country. For more information, please visit www.cumc.columbia.edu.