Increased Oscillatory Frequency of Sleep Spindles in Combat-Exposed Veteran Men with Post-Traumatic Stress Disorder.
- 作者列表："Wang C","Laxminarayan S","Ramakrishnan S","Dovzhenok A","Cashmere JD","Germain A","Reifman J
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.
研究目的: 睡眠障碍是创伤后应激障碍 (PTSD) 的核心症状，但 PTSD 的可靠睡眠标志物尚未确定。睡眠纺锤波是与睡眠保护和睡眠依赖性记忆巩固相关的重要脑电波。本研究测试了 PTSD 个体的睡眠纺锤波是否发生了改变，以及这些发现在研究的夜晚和子样本中是否具有可重复性。 方法: 78 例有 (n = 31) 和无 (n = 47) PTSD 的战斗暴露的退伍军人在实验室完成了连续两晚的高密度脑电图记录。我们在 N2 和 N3 睡眠阶段确定了慢 (10-13Hz) 和快 (13-16Hz) 睡眠纺锤体，并对纺锤体参数 (振幅、持续时间、振荡频率) 进行了地形学分析,和密度) 在两个晚上。为了评估可重复性，我们使用前 47 例连续参与者 (18 例 PTSD) 进行初始发现，其余 31 例参与者 (13 例 PTSD) 进行复制评估。 结果: 在 discovery 分析中，与非 PTSD 参与者相比，PTSD 参与者表现出 1) 在两个夜晚和 2 上的前额区具有更高的慢纺锤体振荡频率) 第二晚中央顶叶区域上较高的快纺锤体振荡频率。第一个发现保留在复制分析中。我们发现慢或快纺锤体的振幅、持续时间或密度无显著组间差异。 结论: PTSD 中纺锤体振荡频率升高可能表明负责保持睡眠连续性的感觉门控机制存在缺陷。我们的研究结果，如果独立验证，可能有助于开发以睡眠为重点的 PTSD 诊断和干预措施。
METHODS::Multiple sclerosis (MS) is a chronic neurodegenerative disorder with clinical symptoms of neuroinflammation and demyelination in the central nervous system. Recently, herbal medicines are clinically effective against MS as the current disease-modifying drugs have limited effectiveness. Hence, the present study evaluated the therapeutic potential of Ocimum basilicum essential oil (OB) in ethidium bromide (EB)-induced cognitive deficits in the male rats. Further, the effect of OB (50, 100 and 200 μL/kg) was evaluated on EB-induced neuroinflammation, astrogliosis and mitochondrial dysfunction in the pre-frontal cortex (PFC) of the animals. The EB was injected through bilateral intracerebroventricular route into hippocampus to induce MS-like manifestations in the rats. OB (100 and 200 μL/kg) and Ursolic acid (UA) significantly reduced the EB-induced cognitive deficits in Morris water maze and Y-maze test paradigms. OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced neuroinflammation in terms of increase in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the rat PFC. Further, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced astrogliosis in terms of increase in the levels of GFAP (Glial fibrillary acidic protein) and Iba-1 (Ionized calcium binding adaptor molecule-1) in the rat PFC. In addition, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced decrease in the mitochondrial function, integrity, respiratory control rate and ADP/O in the PFC of the rodents. Moreover, OB (100 and 200 μL/kg) and UA significantly reduced the EB-induced mitochondria-dependent apoptosis in the PFC of the rat. Hence, it can be presumed that OB could be a potential alternative drug candidate in the pharmacotherapy of MS.
METHODS::Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.
METHODS:BACKGROUND:Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of in vivo biomarkers. We propose a method for investigating the in vivo stimulation effects using blood-oxygen-level dependent (BOLD) MRI and present the brain activation pattern associated with ANT DBS. METHODS:Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30 second blocks. The scanner was triggered utilizing surface electrophysiological recording to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. RESULTS:Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. CONCLUSIONS:Utilizing block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown suggesting that these nodes may modulate the effect of seizure control with ANT DBS.