Increased oscillatory frequency of sleep spindles in combat-exposed veteran men with post-traumatic stress disorder

Abstract

Study Objectives Sleep disturbances are core symptoms of post-traumatic stress disorder (PTSD), but reliable sleep markers of PTSD have yet to be identified. Sleep spindles are important brain waves associated with sleep protection and sleep-dependent memory consolidation. The present study tested whether sleep spindles are altered in individuals with PTSD and whether the findings are reproducible across nights and subsamples of the study. Methods Seventy-eight combat-exposed veteran men with (n = 31) and without (n = 47) PTSD completed two consecutive nights of high-density EEG recordings in a laboratory. We identified slow (10–13 Hz) and fast (13–16 Hz) sleep spindles during N2 and N3 sleep stages and performed topographical analyses of spindle parameters (amplitude, duration, oscillatory frequency, and density) on both nights. To assess reproducibility, we used the first 47 consecutive participants (18 with PTSD) for initial discovery and the remaining 31 participants (13 with PTSD) for replication assessment. Results In the discovery analysis, compared to non-PTSD participants, PTSD participants exhibited (1) higher slow-spindle oscillatory frequency over the antero-frontal regions on both nights and (2) higher fast-spindle oscillatory frequency over the centro-parietal regions on the second night. The first finding was preserved in the replication analysis. We found no significant group differences in the amplitude, duration, or density of slow or fast spindles. Conclusions The elevated spindle oscillatory frequency in PTSD may indicate a deficient sensory-gating mechanism responsible for preserving sleep continuity. Our findings, if independently validated, may assist in the development of sleep-focused PTSD diagnostics and interventions.

Inter-channel phase differences during sleep spindles are altered in Veterans with PTSD

“…The sample used in the present study was the same as that used in our previous work, in which we reported the clinical characteristics and sleep architecture parameters of the participants ( Laxminarayan et al, 2020 , Wang et al, 2020a , Wang et al, 2020b ). Briefly, PTSD and non-PTSD participants did not differ significantly with respect to age or the Apnea-Hypopnea Index (AHI) in both the discovery and replication sets ( p > 0.05).…”

“…We visually scored sleep stages in 30-s epochs for each night according to the American Academy of Sleep Medicine standards. The EEG preprocessing and spindle detection methods were as previously described ( Wang et al, 2020b ). Briefly, we segmented the data into 5-s epochs and used previously validated algorithms ( Brunner et al, 1996 , Doman et al, 1995 , Liu et al, 2018 ) to remove all epochs contaminated by muscle and ocular artifacts.…”

“…The lack of reliable sleep markers of PTSD presents an obstacle to understanding the pathophysiology of its associated sleep symptoms and to developing sleep-specific diagnostics and interventions for the disorder. To bridge this gap, we have made several attempts to identify brain activity changes in PTSD during sleep that are reproducible, by examining features of electroencephalogram (EEG) spectral power ( Wang et al, 2020a ), EEG synchrony ( Laxminarayan et al, 2020 ), and sleep spindles ( Wang et al, 2020b ). In particular, sleep spindles are signature neural events during non-rapid eye movement (NREM) sleep that are thought to play key roles in sleep-dependent memory consolidation ( Fogel and Smith, 2011 ) and sleep protection ( Astori et al, 2013 , Luthi, 2014 ).…”

“…In particular, sleep spindles are signature neural events during non-rapid eye movement (NREM) sleep that are thought to play key roles in sleep-dependent memory consolidation ( Fogel and Smith, 2011 ) and sleep protection ( Astori et al, 2013 , Luthi, 2014 ). In a recent study, we made an initial effort to investigate whether sleep spindle characteristics (i.e., amplitude, duration, oscillatory frequency, and density) are altered in subjects with PTSD compared to those without PTSD ( Wang et al, 2020b ). Although spindle amplitude, duration, and density did not differ between the two groups, the oscillatory frequencies of sleep spindles were higher in PTSD subjects than in non-PTSD subjects, with consistent trends across nights and subsamples of the study population.…”

Sleep and PTSD in the Military Forces: A Reciprocal Relationship and a Psychiatric Approach

“…In addition, sleep is more fragmented with more nocturnal awakenings and increased arousal [1,2,66]. With regard to the sleep architecture in PTSD, the results are not consistent, with some studies finding an increase in the proportion of REM sleep and others finding a decrease [3,4,67]. Examples of these findings are shown in Figure 1.…”