Combat-related blast exposure and traumatic brain injury influence brain glucose metabolism during REM sleep in military veterans

Abstract

Traumatic brain injury (TBI), a signature wound of Operations Enduring and Iraqi Freedom, can result from blunt head trauma or exposure to a blast/explosion. While TBI affects sleep, the neurobiological underpinnings between TBI and sleep are largely unknown. To examine the neurobiological underpinnings of this relationship in military veterans, [(18)F]-fluorodeoxyglucose positron emission tomography (FDG PET) was used to compare mTBI-related changes in relative cerebral metabolic rate of glucose (rCMRglc) during wakefulness, Rapid Eye Movement (REM) sleep, and non-REM (NREM) sleep, after adjusting for the effects of posttraumatic stress (PTS). Fourteen veterans with a history of blast exposure and/or mTBI (B/mTBI) (age 27.5±3.9) and eleven veterans with no history (No B/mTBI) (age 28.1±4.3) completed FDG PET studies during wakefulness, REM sleep, and NREM sleep. Whole-brain analyses were conducted using Statistical Parametric Mapping (SPM8). Between group comparisons revealed that B/mTBI was associated with significantly lower rCMRglc during wakefulness and REM sleep in the amygdala, hippocampus, parahippocampal gyrus, thalamus, insula, uncus, culmen, visual association cortices, and midline medial frontal cortices. These results suggest that alterations in neurobiological networks during wakefulness and REM sleep subsequent to B/mTBI exposure may contribute to chronic sleep disturbances and differ in individuals with acute symptoms.

Trial registration: ClinicalTrials.gov NCT00871650 NCT01637584.

Keywords: Blast exposure; Cerebral glucose metabolism; Military veterans; Rapid eye movement sleep; mTBI.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1

Areas of the brains where blast/TBI exposed veterans showed lower rCMRglc relative to veterans who did not report blast ormTBI exposure. (la:above) Render images depicting 2 clusters of significance in medial frontal region, and in paralimbic/limbic and temporal and occipital cortices. (1b: right). Coronal section (4mm thickness) depicting the same contrast. Colors correspond to degree of PET scan activation, as measured by relative regional cerebral metabolic rate of glucose metabolism(rCMRglc), with yellow colors indicating higher activation than red colors.

Figure 2

Areas of the brains where blast/TBI exposed veterans showed lowerrCMRglc relative to veterans who did not report blast or mTBI exposure. (2a:above) Render images depicting one cluster of significance in the brainsteam, basal ganglia, amygdala, hippocampus, insula and uncus, and extending into middle temporal gyrus. (2b: right) Coronal section (4mm thickness) depicting these brains regions for the same contrast. Colors correspond to degree of PET scan activation, as measured by relative regional cerebral metabolic rate of glucose metabolism (rCMRglc), with yellow colors indicating higher activation than red colors.

Figure 3

Detectable in rCMR in regions of interest between veterans with blast and/or mTBI exposure and veterans with no blast and/or mTBI exposure during wakefulness and REM sleep.