Specific brain regions, including those involved in awareness of self and tendency to ruminate, show altered activity in patients with insomnia when compared to good sleepers, according to a new study by researchers at the University of Pittsburgh School of Medicine published in the journal SLEEP.

In what is the largest study of its kind on insomnia, a research group led by Daniel Buysse M.D., professor of psychiatry and clinical and translational science, and the UPMC Professor of Sleep Medicine, University of Pittsburgh School of Medicine, identified differences in brain activity between states of sleep and wakefulness in 44 patients diagnosed with insomnia and 40 good sleepers.

"While patients with insomnia often have their symptoms trivialized by friends, families and even physicians, the findings in this study add strong evidence to the emerging view that insomnia is a condition with neurobiological as well as psychological causes," said Dr. Buysse, who is the senior author on the study. The study also shows that brain activity during sleep is more nuanced than previously thought, with different brain regions experiencing varying 'depths' of sleep.

The findings may help improve current treatments for insomnia such as transcranial magnetic stimulation, and increase understanding of why treatments such as mindfulness meditation are effective in some patients.

Researchers used positron emission tomography (PET) scans during which participants were injected with a solution of glucose molecules tagged with a 'tracer.' Brain regions with higher activity took up a proportionally higher amount of the radioactively tagged glucose and were more metabolically active on the PET scans.

Data from the scans revealed relative activity differences in specific brain regions between states of sleep and wakefulness in patients with insomnia and good sleepers. The differences can be attributed to either decreased activity during wakefulness or heightened activity during sleep, the researchers report.

Dysfunction in the brain regions identified in the study may correlate to specific symptoms in patients with insomnia, including impairments in self-awareness and mood, memory deficits and rumination, according to the authors.

Though the study design did not allow authors to discern whether brain activity changes were the cause or consequence of insomnia, the results do indicate that sleep is not uniform across different parts of the brain, contradicting the prevailing view that the entire brain is 'on' while awake and 'off' while asleep. The study also refines results from an earlier, similar study by researchers at the University of Pittsburgh Sleep Medicine Institute that had fewer participants.

Other study authors include Daniel B. Kay, Ph.D., Helmet T. Karim, B.S., Adriane M. Soehner, Ph.D., Brant P. Hasler, Ph.D., Kristine A. Wilckens, Ph.D., Jeffrey A. James, B.S., Howard J. Aizenstein, M.D., Ph.D., Julie C. Price, Ph.D., Bedda L. Rosario, Ph.D., David J. Kupfer, M.D., Anne Germain, Ph.D., Martica H. Hall, Ph.D., Peter L. Franzen, Ph.D., and Eric A. Nofzinger, M.D., all of the University of Pittsburgh.

The research was funded by grants through the National Institutes of Health (NIH), including MH024652, MH24652, T32HL082610, T32MH018269, T32MH019986, K01AG049879 and K01DA032557, along with partial support from Sepracor, Inc.

Dr. Nofzinger is on the Board of Directors and is Chief Medical Officer for Cerêve, Inc., and Dr. Buysse is a paid consultant to Cerêve, Inc., Emmi Solutions, and Merck. Dr. Aizenstein has received research support from Novartis Pharmaceuticals.

Source: Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers, Daniel J. Buysse, MD. et al., SLEEP, doi: 10.5665/sleep.6154, published 1 October 2016.