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Sleep-Wake differences in relative regional cerebral metabolic rate for glucose among patients with insomnia compared with good sleepers
Kay DB, Karim HT, Soehner AM, Hasler BP, Wilckens KA, James JA, Aizenstein HJ, Price JC, Rosario BL, Kupfer DJ, Germain A, Hall MH, Franzen PL, Nofzinger EA and Buysse DJ
SLEEP 2016, 39:1779-1794

The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. Working with his mentor, Dr. Daniel Buysse, and other investigators, Dr. Daniel Kay compared relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS).

The research team recruited 44 individuals with primary insomnia PI and compared them to 40 good sleeper controls matched for age, sex, and race. The investigators conducted [18F]fluoro-2-deoxy-dglucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc.

Results of this study showed significant group-by-state interactions in relative rCMRglc in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness.

Findings from this study show that insomnia involves brain dysregulation on a regional or circuit level. This contrasts with the prevailing view of insomnia as a disorder of global sleep-wake states. The regional findings may also help to explain why individuals with insomnia experience conscious awareness even when polysomnographic studies indicate sleep. Finally, this study raises the possibility that treatments directed at regional brain dysfunction, such as rTMS, may provide novel methods to improve insomnia.

Contributors:
Daniel B. Kay, PhD, Adriane M. Soehner, PhD, Brant P. Hasler, PhD, Kristine A. Wilckens, PhD, Howard J. Aizenstein, MD, PhD, David J. Kupfer, MD, Anne Germain, PhD, Martica H. Hall, PhD, Peter L. Franzen, PhD and Daniel J. Buysse, MD (Department of Psychiatry, University of Pittsburgh School of Medicine)

Helmet T. Karim, BS (Department of Bioengineering, University of Pittsburgh)

Jeffrey A. James, BS and Julie C. Price, PhD (Department of Radiology, University of Pittsburgh)

Eric A. Nofzinger, MD (Cerêve Inc.)

Bedda L. Rosario, PhD (Department of Epidemiology, University of Pittsburgh Graduate School of Public Health)

This article appeared in the journal SLEEP.  Click here to view the abstract.