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

Stocker, Ryan; Cieply, Marissa A.; Paul, Ben; Khan, Hassen; Henry, Luke C.; Kontos, Anthony P.; Germain, Anne

doi:10.1016/j.neuroimage.2014.05.067

Cited by 46 publications

(35 citation statements)

References 74 publications

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“…Both approaches have further refined our understanding of the localized and neural underpinnings of healthy and disrupted sleep, as well as of circadian variations in brain functions [68][69][70]. The use of neuroimaging methods such as positron emission tomography and structural and functional magnetic resonance imaging during sleep and wakefulness in concussed, recovered, and never concussed individuals remain scarce, but has a high potential to provide unique and novel insights into the underpinnings of sleep and circadian disturbances in mTBI, and therefore may guide the development of innovative and targeted diagnostic and therapeutic strategies [70][71][72][73][74][75].…”

Section: Advanced Sleep Measurement Methodsmentioning

confidence: 99%

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group

et al. 2016

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Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders.

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Section: Advanced Sleep Measurement Methodsmentioning

confidence: 99%

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group

et al. 2016

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“…Neuroimaging studies of military service members and veterans have documented chronic abnormalities on 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging, which assesses glucose metabolic activity in the brain (4,22,23). Abnormalities of brain white matter tract structural integrity and myelin density in these veteran populations have also been characterized using magnetic resonance diffusion tensor imaging (DTI) and macromolecular proton fraction mapping (5,(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction

et al. 2016

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Blast exposure can cause mild traumatic brain injury (TBI) in mice and other mammals. However, there are important gaps in our understanding of the neuropathology underlying repetitive blast exposure in animal models compared to the neuroimaging abnormalities observed in blast-exposed veterans. Moreover, how an increase in the number of blast exposures affects neuroimaging endpoints in blast-exposed humans is not well understood. We asked whether there is a dose-response relationship between the number of blast-related mild TBIs and uptake of 18 F-fluorodeoxyglucose (FDG), a commonly used indicator of neuronal activity, in the brains of blast-exposed veterans with mild TBI. We found that the number of blast exposures correlated with FDG uptake in the cerebellum of veterans. In mice, blast exposure produced microlesions in the blood-brain barrier (BBB) predominantly in the ventral cerebellum. Purkinje cells associated with these BBB microlesions displayed plasma membrane disruptions and aberrant expression of phosphorylated tau protein.Purkinje cell loss was most pronounced in the ventral cerebellar lobules, suggesting that early-stage breakdown of BBB integrity may be an important factor driving long-term brain changes. Blast exposure caused reactive gliosis in mouse cerebellum, particularly in the deep cerebellar nuclei. Diffusion tensor imaging tractography of the cerebellum of blastexposed veterans revealed that mean diffusivity correlated negatively with the number of blast-related mild TBIs. Together, these results argue that the cerebellum is vulnerable to repetitive mild TBI in both mice and humans.

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“…In a recent study, we have found that blast exposure (beyond the effects of PTSD) was associated with reduced cerebral metabolic activity in brainstem, limbic and paralimbic regions, the basal ganglia, and thalamus during REM sleep in veterans with a blast and mTBI exposure compared to those without blast and mTBI exposure. 20 Together, these preliminary observations suggest that attenuation of REM sleep may be an especially sensitive index of central changes resulting from psychological or physical insults. Given the overlap in symptoms of PTSD and TBI, further investigation of REM sleep mechanisms are needed to elucidate the reasons as to why the presence of both blast exposure and PTSD significantly decreased the amount of REM fragmentation when compared to the group in which only blast exposure or PTSD was present.…”

Section: Discussionmentioning

confidence: 80%

“…[55][56][57][58][59][60] Similarly, we have recently reported that blast exposure and/or prior mild TBI was associated with detectable reductions in cerebral glucose metabolism during both wakefulness and REM sleep, despite similar findings on objective measures of sleep continuity and NREM sleep. 20 Probing the functional neuroanatomical correlates of TBI and PTSD separately or when comorbid using sleep neuroimaging methods may reveal group differences during NREM sleep in cerebral perfusion or glucose metabolism relative that are not captured by PSG.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported that blast exposure and/or prior mTBI is associated with hypometabolic cerebral profiles during wakefulness and REM sleep, but not during NREM sleep in a small sample of OEF/OIF service members and veterans. 20 Alterations in regional cerebral metabolism are viewed as a hallmark of mTBI and seen across a number of populations at various post-injury time points with vastly diverse outcomes. [21][22][23][24][25][26][27] Altered cerebral metabolic profiles documented in blast exposure and/or prior mTBI may affect sleep-related processes during REM sleep and NREM sleep that can be captured with polysomnography (PSG).…”

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confidence: 99%

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Effects of Blast Exposure on Subjective and Objective Sleep Measures in Combat Veterans with and without PTSD

Stocker

Paul

Mammen

et al. 2016

Journal of Clinical Sleep Medicine

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Study Objectives: This study examined the extent to which self-reported exposure to blast during deployment to Iraq and Afghanistan affects subjective and objective sleep measures in service members and veterans with and without posttraumatic stress disorder (PTSD). Methods: Seventy-one medication-free service members and veterans (mean age = 29.47 ± 5.76 years old; 85% men) completed self-report sleep measures and overnight polysomnographic studies. Four multivariate analyses of variance (MANOVAs) were conducted to examine the impact of blast exposure and PTSD on subjective sleep measures, measures of sleep continuity, non-rapid eye movement (NREM) sleep parameters, and rapid eye movement (REM) sleep parameters. Results: There was no significant Blast × PTSD interaction on subjective sleep measures. Rather, PTSD had a main effect on insomnia severity, sleep quality, and disruptive nocturnal behaviors. There was no significant Blast × PTSD interaction, nor were there main effects of PTSD or Blast on measures of sleep continuity and NREM sleep. A significant PTSD × Blast interaction effect was found for REM fragmentation. Conclusions:The results suggest that, although persistent concussive symptoms following blast exposure are associated with sleep disturbances, selfreported blast exposure without concurrent symptoms does not appear to contribute to poor sleep quality, insomnia, and disruptive nocturnal disturbances beyond the effects of PTSD. Reduced REM sleep fragmentation may be a sensitive index of the synergetic effects of both psychological and physical insults. I NTRO DUCTI O NMild traumatic brain injury (mTBI) is one of the signature injuries of the Global War on Terror, and is among the leading factors contributing to disability and death among military service members of Operations Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF).1-4 mTBI is defined as a loss of consciousness lasting up to 30 minutes, alteration of consciousness/mental state from a moment up to 24 hours, and posttraumatic amnesia lasting 1 day or less, in the absence of detectable abnormal structural imaging findings.5 Between 30% and 40% of combat infantry and other military personnel who have served in OEF/OIF have been exposed to blast forces resulting from explosives, particularly improvised explosive devices (IEDs).6,7 While mTBI sustained from blast injuries are not the only means of sustaining mTBI (i.e., blunt trauma), blast injuries represent the most common type of mTBI reported in returning military personnel.3,8 Of those exposed to blasts, the reported prevalence rates of subsequent mTBI in warfighters vary between 4.9% to 22%. 6,7,9,10 The projected 2-year costs associated with chronic mTBI, which refers to symptoms and impairments that last more than three months post-injury, could average as much as $591 billion. 10Sleep disturbances are prevalent among both warfighters and civilians with subacute (i.e., < 3 months in duration) and chronic mild traumatic brain injury (cmTBI), and can impede recovery.11,12 As many...

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

Cited by 46 publications

References 74 publications

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group

Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction

Effects of Blast Exposure on Subjective and Objective Sleep Measures in Combat Veterans with and without PTSD

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