Orbitofrontal Gray Matter Relates to Early Morning Awakening: A Neural Correlate of Insomnia Complaints?

Diederick Stoffers,Eus J W Van Someren,Dick J Veltman,Nic J A Van Der Wee,Sarah Moens,Marie-José Van Tol,Brenda W J H Penninx,Jeroen Benjamins

doi:10.3389/fneur.2012.00105

Abstract

Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18–56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated.

Highlights

With prevalence estimates of 4–11%, chronic insomnia belongs to the most common disorders
We investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in gray matter (GM) density are associated with differences in difficulties initiating sleep (DIS), difficulties maintaining sleep (DMS), and early morning awakening (EMA)
We aimed to investigate whether individual differences in GM density in a region of interest (ROI) compatible with the border of Brodmann areas 13L and 47/12M of the left orbitofrontal cortex (OFC) are associated with individual differences in the self-reported degree by which they experienced DIS, DMS, and EMA

Summary

Introduction

With prevalence estimates of 4–11%, chronic insomnia belongs to the most common disorders. The most important risk factor for insomnia is age; estimates of the prevalence in elderly people reach up to about 40% (Foley et al, 1995; Morphy et al, 2007). Major sleep complaints can be discriminated, which can be present with variable severity; difficulties initiating sleep (DIS), difficulties maintaining sleep (DMS), and early morning awakening (EMA; American Psychiatric Association, 1994; American Academy of Sleep Medicine, 2005). Of these three, complaints of EMA most clearly increase with age, while DIS may decrease with age; both in clinically diagnosed insomniacs and in the general population of elderly people (Abe and Suzuki, 1985; National Sleep Foundation, 2003a,b). Additional daytime complaints of insomniacs concern non-restorative sleep and problems with daytime functioning

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