Posttraumatic stress disorder increases the odds of REM sleep behavior disorder and other parasomnias in Veterans with and without comorbid traumatic brain injury.

STUDY OBJECTIVES: To describe the crude prevalence of rapid eye movement (REM) sleep behavior disorder (RBD) following traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) in Veterans, given potential relationships between TBI, PTSD, RBD, and neurodegeneration. METHODS: Veterans (n = 394; 94% male; 54.4 ± 15.5 years of age) were prospectively/cross-sectionally recruited from the VA Portland Health Care System and completed in-lab video-polysomnography and questionnaires. TBI and PTSD were assessed via diagnostic screening and medical record review. Subjects were categorized into four groups after assessment of REM sleep without atonia (RSWA) and self-reported dream enactment: (1) "Normal," neither RSWA nor dream enactment, (2) "Other Parasomnia," dream enactment without RSWA, (3) "RSWA," isolated-RSWA without dream enactment, and (4) "RBD," RSWA with dream enactment. Crude prevalence, prevalence odds ratio, and prevalence rate for parasomnias across subjects with TBI and/or PTSD were assessed. RESULTS: Overall prevalence rates were 31%, 7%, and 9% for Other Parasomnia, RSWA, and RBD, respectively. The prevalence rate of RBD increased to 15% in PTSD subjects [age adjusted POR: 2.81 (1.17-4.66)] and to 21% in TBI + PTSD subjects [age adjusted POR: 3.43 (1.20-9.35)]. No subjects met all diagnostic criteria for trauma-associated sleep disorder (TASD), and no overt dream enactment was captured on video. CONCLUSIONS: The prevalence of RBD and related parasomnias is significantly higher in Veterans compared with the general population and is associated with PTSD and TBI + PTSD. Considering the association between idiopathic-RBD and synucleinopathy, it remains unclear whether RBD (and potentially TASD) associated with PTSD or TBI + PTSD similarly increases risk for long-term neurologic sequelae.

Strong correlation of novel sleep electroencephalography coherence markers with diagnosis and severity of posttraumatic stress disorder.

Objective biomarkers of the presence and severity of posttraumatic stress disorder (PTSD) are elusive, yet badly needed. Electroencephalographic (EEG) coherence represents a promising approach to identifying and understanding brain biomarker activity in PTSD. Overnight polysomnography data containing EEG across sleep and wake states was collected in n = 76 Veterans with and without PTSD from a single site under IRB approval. Brain coherence markers (BCM) were calculated from EEG signals using a novel approach to produce one index for PTSD diagnosis (PTSDdx), and another index for PTSD severity (PTSDsev). PTSDdx showed strong sensitivity to the presence of PTSD in the awake state, during non-rapid eye movement (NREM) stage N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. PTSDsev showed a strong correlation with PTSD symptom severity (using the PTSD Checklist 5, or PCL5 survey) in the awake state, during N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. Thus, sleep EEG-based brain coherence markers can be utilized as an objective means for determining the presence and severity of PTSD. This portable, inexpensive, and non-invasive tool holds promise for better understanding the physiological mechanisms underlying PTSD and for tracking objective responses to treatment.

Early-life sleep disruption increases parvalbumin in primary somatosensory cortex and impairs social bonding in prairie voles.

Across mammals, juveniles sleep more than adults, with rapid eye movement (REM) sleep at a lifetime maximum early in life. One function of REM sleep may be to facilitate brain development of complex behaviors. Here, we applied 1 week of early-life sleep disruption (ELSD) in prairie voles (Microtus ochrogaster), a highly social rodent species that forms lifelong pair bonds. Electroencephalographic recordings from juvenile voles during ELSD revealed decreased REM sleep and reduced γ power compared to baseline. ELSD impaired pair bond formation and altered object preference in adulthood. Furthermore, ELSD increased GABAergic parvalbumin immunoreactivity in the primary somatosensory cortex in adulthood, a brain region relevant to both affected behaviors. We propose that, early in life, sleep is crucial for tuning inhibitory neural circuits and the development of species-typical affiliative social behavior.

Categorizing Sleep in Older Adults with Wireless Activity Monitors Using LSTM Neural Networks.

Novel approaches are needed to accurately classify and monitor sleep patterns in older adults, particularly those with cognitive impairment and non-normative sleep. Traditional methods ignore underlying sleep architecture in these patient populations, and other modern approaches tend to focus on healthy, normative patient populations. In this paper, we developed a model using a long-short-term memory neural network (LSTM) and trained it on a sample of older, non-normative patients. The 22 nights of data collected were trained on gold-standard polysomnography (PSG) as ground truth and were compared against the clinical standard threshold-based method for sleep detection. The LSTM more than doubled the traditional method's ability to detect clinically-relevant wakefulness during sleep (37.7% vs. 15%) without significantly sacrificing accuracy (67.7% vs. 75%) or precision (90.7% vs. 94%) of sleep classification.

Effects of traumatic brain injury on sleep and enlarged perivascular spaces.

Clearance of perivascular wastes in the brain may be critical to the pathogenesis of amyloidopathies. Enlarged perivascular spaces (ePVS) on MRI have also been associated with amyloidopathies, suggesting that there may be a mechanistic link between ePVS and impaired clearance. Sleep and traumatic brain injury (TBI) both modulate clearance of amyloid-beta through glymphatic function. Therefore, we sought to evaluate the relationship between sleep, TBI, and ePVS on brain MRI. A retrospective study was performed in individuals with overnight polysomnography and 3T brain MRI consented from a single site (n = 38). Thirteen of these individuals had a medically confirmed history of TBI. ePVS were visually assessed by blinded experimenters and analyzed in conjunction with sleep metrics and TBI status. Overall, individuals with shorter total sleep time had significantly higher ePVS burden. Furthermore, individuals with TBI showed a stronger relationship between sleep and ePVS compared to the non-TBI group. These results support the hypothesis that ePVS may be modulated by sleep and TBI, and may have implications for the role of the glymphatic system in ePVS.

Acoustic prepulse inhibition in male and female prairie voles: Implications for models of neuropsychiatric illness.

Sensory gating, the ability to suppress sensory information of irrelevant stimuli, is affected in several neuropsychiatric diseases, notably schizophrenia and autism. It is currently unclear how these deficits interact with other hallmark symptoms of these disorders, such as social withdrawal and difficulty with interpersonal relationships. The highly affiliative prairie vole (Microtus ochrogaster) may be an ideal model organism to study the neurobiology underlying social behavior. In this study, we assessed unimodal acoustic sensory gating in male and female prairie voles using the prepulse inhibition (PPI) paradigm, whereby a lower amplitude sound (prepulse) decreases the startle response to a high amplitude sound (pulse) compared to the high amplitude sound alone. Prairie voles showed evidence of PPI at all prepulse levels compared to pulse alone, with both males and females showing similar levels of inhibition. However, unlike what has been reported in other rodent species, prairie voles did not show a within-session decrease in startle response to the pulse alone, nor did they show a decrease in startle response to the pulse over multiple days, highlighting their inability to habituate to startling stimuli (short- and long-term). When contrasted with a cohort of male wildtype C57Bl/6J mice that underwent a comparable PPI protocol, individual voles showed significantly higher trial-by-trial variability as well as longer latency to startle than mice. The benefits and caveats to using prairie voles in future sensory gating experiments are discussed.

Increased Sleep Disturbances and Pain in Veterans With Comorbid Traumatic Brain Injury and Posttraumatic Stress Disorder.

STUDY OBJECTIVES: Veterans are at an increased risk for traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD), both of which are associated with sleep disturbances and increased pain. Furthermore, sleep disturbances and pain are reciprocally related such that each can exacerbate the other. Although both TBI and PTSD are independently linked to sleep disturbances and pain, it remains unclear whether Veterans with comorbid TBI+PTSD show worse sleep disturbances and pain compared to those with only TBI or PTSD. We hypothesized that sleep and pain would be worse in Veterans with comorbid TBI+PTSD compared to Veterans with only TBI or PTSD. METHODS: Veterans (n = 639) from the VA Portland Health Care System completed overnight polysomnography and self-report questionnaires. Primary outcome variables were self-reported sleep disturbances and current pain intensity. Participants were categorized into four trauma-exposure groups: (1) neither: without TBI or PTSD (n = 383); (2) TBI: only TBI (n = 67); (3) PTSD: only PTSD (n = 126); and (4) TBI+PTSD: TBI and PTSD (n = 63). RESULTS: The PTSD and TBI+PTSD groups reported worse sleep compared to the TBI and neither groups. The TBI+PTSD group reported the greatest pain intensity compared to the other groups. CONCLUSIONS: These data suggest sleep and pain are worst in Veterans with TBI and PTSD, and that sleep is similarly impaired in Veterans with PTSD despite not having as much pain. Thus, although this is a complex relationship, these data suggest PTSD may be driving sleep disturbances, and the added effect of TBI in the comorbid group may be driving pain in this population.

Sleep Disturbances in Traumatic Brain Injury: Associations With Sensory Sensitivity.

STUDY OBJECTIVES: Sleep disturbances following traumatic brain injury (TBI) in Veterans are very common and often persist as chronic sequelae. In addition, sensory sensitivity, ie, discomfort upon exposure to light and noise, is common after TBI. However, the relationship between sleep disturbances and sensory sensitivity in Veterans following TBI has not yet been examined, yet both are established early markers of neurodegeneration. METHODS: Veterans (n = 95) in the chronic phase of recovery from TBI at the VA Portland Health Care System completed an overnight polysomnography and provided self-report data on sensory (eg, light and noise) sensitivity, and sleep disturbances. Participants were categorized into four sensory sensitivity groups: (1) "neither," neither light nor noise sensitivity (n = 36); (2) "light," only light sensitivity (n = 12); (3) "noise," only noise sensitivity (n = 24); and (4) "both," light and noise sensitivity (n = 23). RESULTS: Veterans with TBI reported sleep disturbances that were significantly correlated with the severity of their sensory sensitivity and associated with posttraumatic stress disorder (PTSD). Multiple linear regression revealed insomnia severity to be the strongest predictor of the relationship between sleep disturbances and sensory sensitivity. Furthermore, sensory sensitivity was associated with a higher mean heart rate during sleep, even after controlling for PTSD status. CONCLUSIONS: These data are the first to report the prevalence and association between sensory sensitivity and sleep disturbances in Veterans with TBI. These data also suggest that the underlying mechanism of the sleep-sensory relationship could be due in part to comorbid PTSD and autonomic nervous system hyperarousal.