An attempt to identify reproducible high-density EEG markers of PTSD during sleep

Abstract

Study Objectives We examined electroencephalogram (EEG) spectral power to study abnormalities in regional brain activity in post-traumatic stress disorder (PTSD) during sleep. We aimed to identify sleep EEG markers of PTSD that were reproducible across nights and subsamples of our study population. 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 performed spectral-topographical EEG analyses on data from 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. Results In the discovery analysis, compared with non-PTSD participants, PTSD participants exhibited (1) reduced delta power (1–4 Hz) in the centro-parietal regions during nonrapid eye movement (NREM) sleep and (2) elevated high-frequency power, most prominent in the gamma band (30–40 Hz), in the antero-frontal regions during both NREM and rapid eye movement (REM) sleep. These findings were consistent across the two study nights, with reproducible trends in the replication analysis. We found no significant group differences in theta power (4–8 Hz) during REM sleep and sigma power (12–15 Hz) during N2 sleep. Conclusions The reduced centro-parietal NREM delta power, indicating reduced sleep depth, and the elevated antero-frontal NREM and REM gamma powers, indicating heightened central arousal, are potential objective sleep markers of PTSD. If independently validated, these putative EEG markers may offer new targets for the development of sleep-specific PTSD diagnostics and interventions.

Hyper-Activation of mPFC Underlies Specific Traumatic Stress-Induced Sleep–Wake EEG Disturbances

“…Both reduced and increased delta power activity during NREMS have been reported in PTSD patients (Woodward et al, 2000;Germain et al, 2006;Insana et al, 2012;de Boer et al, 2020;Wang et al, 2020). Thus, the SPS mouse model may recapitulate the symptoms of the subset of PTSD patients showing reduced NREMS delta power (Woodward et al, 2000;de Boer et al, 2020;Wang et al, 2020). In our study, we found that chemogenetic inhibition of the mFPC activity could specifically reverse the SPSinduced acute suppression of delta power during NREMS and most of the long-term sleep/wake EEG abnormalities.…”

“…However, future studies are needed to investigate the precise roles of different types of mPFC neurons in the SPS-induced sleep-wake EEG disturbances as the chemogenetic inhibition approach in our study result in the inhibition of all neuronal populations. Both reduced and increased delta power activity during NREMS have been reported in PTSD patients (Woodward et al, 2000;Germain et al, 2006;Insana et al, 2012;de Boer et al, 2020;Wang et al, 2020). Thus, the SPS mouse model may recapitulate the symptoms of the subset of PTSD patients showing reduced NREMS delta power (Woodward et al, 2000;de Boer et al, 2020;Wang et al, 2020).…”

“…For example, there have been reports of increased (Woodward et al, 2000;Insana et al, 2012), decreased (Cohen et al, 2013), or no difference (Mellman et al, 2007) in the beta power of EEG during rapid-eye-movement sleep (REMS) in adult PTSD patients. Both reduced and increased delta power activity during non-rapid-eye-movement sleep (NREMS) and REMS have also been reported in PTSD patients (Woodward et al, 2000;Germain et al, 2006;Insana et al, 2012;de Boer et al, 2020;Wang et al, 2020). These conflicting findings may be attributed to the effects of many confounding variables in the experimental settings, the inter-individual differences and disease heterogeneity, such as differences in initial traumatic stimuli, analysis stages of the illness, comorbidities with other psychiatric conditions, and diversity of underlying neural mechanisms (Kobayashi et al, 2007;Yetkin et al, 2010;Germain, 2013;Baglioni et al, 2016;Khazaie et al, 2016;Deslauriers et al, 2018).…”

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).…”

“…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 ).…”