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Background We provide an umbrella review of the reported polysomnographic changes in patients with neuropsychiatric diseases compared with healthy controls. Methods An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO. Meta-analyses of case–control studies investigating the polysomnographic changes in patients with neuropsychiatric diseases were included. For each meta-analysis, we estimated the summary effect size using random effects models, the 95% confidence interval, and the 95% prediction interval. We also estimated between-study heterogeneity, evidence of excess significance bias, and evidence of small-study effects. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were ranked as follows: not significant, weak, suggestive, highly suggestive, or convincing. Results We identified 27 articles, including 465 case–control studies in 27 neuropsychiatric diseases. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were highly suggestive for increased sleep latency and decreased sleep efficiency (SE) in major depressive disorder (MDD), increased N1 percentage, and decreased N2 percentage, SL and REML in narcolepsy, and decreased rapid eye movement (REM) sleep percentage in Parkinson's disease (PD). The suggestive evidence decreased REM latency in MDD, decreased total sleep time and SE in PD, and decreased SE in posttraumatic stress disorder and in narcolepsy. Conclusions The credibility of evidence for sleep characteristics in 27 neuropsychiatric diseases varied across polysomnographic variables and diseases. When considering the patterns of altered PSG variables, no two diseases had the same pattern of alterations, suggesting that specific sleep profiles might be important dimensions for defining distinct neuropsychiatric disorders.

This study aims to explore the polysomnographically measured sleep and leg movement differences between idiopathic restless legs syndrome (RLS) patients and healthy controls.An electronic literature search was conducted in EMBASE, MEDLINE, all EBM databases, CINAHL, and PsycINFO. Only observational case-control studies were included in the meta-analysis. The differences in 13 sleep parameters and 23 leg movement parameters between RLS patients and healthy controls were explored.Thirty-eight studies were identified for systematic review, 31 of which were used for meta-analysis. Meta-analyses revealed significant reductions in total sleep time, sleep efficiency, stage N2 and rapid eye movement (REM) sleep percentages, and increases in wake time after sleep onset, stage shifts per hour, stage N1 percentage, REM latency, arousal index, and apnea-hypopnea index. Some leg movement parameters, such as periodic limb movement during sleep (PLMS) index, PLMS sequence duration, number of PLMS sequence, and periodicity index, were higher in RLS patients compared with healthy controls. Further, our meta-analysis revealed a higher PLMS index during non-REM sleep compared with that during REM sleep.RLS patients manifest a lightening of sleep, increased sleep fragmentation, and greater sleep-related breathing disruption and limb movements during sleep relative to healthy normal individuals. The distributions of PLMS during a night's sleep may provide more information to clarify the specific characteristics of leg movements in RLS. PLMS in RLS are concentrated in non-REM sleep. The periodicity index may be a more sensitive and specific marker of RLS than the PLMS index.Zhang H, Zhang Y, Ren R, et al. Polysomnographic features of idiopathic restless legs syndrome: a systematic review and meta-analysis of 13 sleep parameters and 23 leg movement parameters.

Cocaine, one of the most abused drugs worldwide, is capable of activating microglia in vitro and in vivo. Several neuroimmune pathways have been suggested to play roles in cocaine-mediated microglial activation. Previous work showed that cocaine activates microglia in a region-specific manner in the brains of self-administered mice. To further characterize the effects of cocaine on microglia and neuroimmune signaling in vivo, we utilized the brains from both sexes of outbred rats with cocaine self-administration to explore the activation status of microglia, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activity, corticotropin-releasing factor (CRF) signaling, and NF-κB levels in the striatum and hippocampus (HP). Age-matched rats of the same sex (drug naïve) served as controls. Our results showed that cocaine increased neuroinflammation in the striatum and HP of both sexes with a relatively higher increases in male brains. In the striatum, cocaine upregulated NLRP3 inflammasome activity and CRF levels in males but not in females. In contrast, cocaine increased NLRP3 inflammasome activity in the HP of females but not in males, and no effects on CRF signaling were observed in this region of either sex. Interestingly, cocaine increased NF-κB levels in the striatum and HP with no sex difference. Taken together, our results provide evidence that cocaine can exert region- and sex-specific differences in neuroimmune signaling in the brain. Targeting neuroimmune signaling has been suggested as possible treatment for cocaine use disorders (CUDs). Our current results indicate that sex should be taken into consideration when determining the efficacy of these new therapeutic approaches.

Previous studies on the association of insomnia with body mass index (BMI) have been controversial. Physiological hyperarousal, the key pathological mechanism of insomnia, may be an important reason for different findings. We explored whether insomnia with physiological hyperarousal measured by the multiple sleep latency test (MSLT) is associated with body-weight differences. A total of 185 normal sleepers and 440 insomniacs were included in this study. Insomnia was defined by standard diagnostic criteria with symptoms lasting ≥6 months. All subjects underwent one night of laboratory polysomnography followed by a standard MSLT. We used the median MSLT value (i.e., ≥14 min) to define physiological hyperarousal. BMI was based on measured height (cm) and weight (kg) during the subjects’ sleep laboratory visit. BMI > 25 kg/m2 was defined as overweight, while BMI 2 was defined as underweight. After controlling for confounders, the odds of lower weight rather than overweight were significantly increased among insomnia patients with increased MSLT: insomnia with MSLT 14–17 min and MSLT > 17 min increased the odds of lower weight by approximately 89% (OR = 1.89, 95% CI 1.00–4.85) and 273% (OR = 3.73, 95% CI 1.51–9.22) compared with normal sleepers, respectively. In contrast, insomnia in patients with MSLT 11–14 min and 8–11 min was not different from normal sleepers in terms of body weight. Insomnia associated with physiological hyperarousal, the most severe phenotype of chronic insomnia, is associated with higher odds of lower weight and underweight compared with normal sleepers. This is a novel finding consistent with previous physiologic data and has significant clinical implications.

Pharmacological and optogenetic studies have demonstrated that the basolateral amygdala (BLA) plays a pivotal role in regulating fear-conditioned changes in sleep, in particular, rapid eye movement sleep (REM). However, the linkage between BLA and REM regulation has been minimally examined. In this study, we optogenetically activated or inhibited BLA selectively during spontaneous REM, and determined the effects on REM amounts and on hippocampus regulated EEG-theta (θ) activity. Excitatory (CaMKIIα-hChR2 (E123A)-eYFP-WPRE) or inhibitory (CaMKIIα-eNpHR3.0-eYFP-WPRE) optogenetic constructs were stereotaxically delivered targeting glutamatergic cells in BLA (BLAGlu) of mice. Viral constructs without opsin (CaMKIIα-eYFP-WPRE) were used as controls. All mice were implanted with telemetry transmitters for monitoring electroencephalography (EEG), activity, and body temperature, and with optic cannulas for light delivery to the BLA. BLAGlu were optogenetically activated by blue light (473 nm), or inhibited by green light (532 nm), in 10 s epochs during REM, or non-REM (NREM), in undisturbed mice. Sleep amounts and EEG activity were analyzed. Projections from BLAGlu to neurons in hippocampus were immunohistochemically (IHC) examined. Brief optogenetic activation of BLAGlu during REM immediately reduced EEG theta activity (5–8 Hz, REM-θ), without affecting overall amount and propensity of sleep, while optogenetic inhibition increased REM-θ. Stimulation during NREM had no effect on EEG spectra or sleep. IHC results showed that glutamatergic and GABAergic cells in CA3 of the hippocampus received inputs from BLAGlu projection neurons. Activation of BLAGlu reduced, and inhibition increased, REM-θ without otherwise altering sleep. Optogenetic stimulation of BLAGlu may be useful for systematically manipulating sleep-related amygdalo-hippocampal interactions.

This study aims to explore the polysomnographically measured sleep differences between multiple sclerosis (MS) and healthy controls (HCs).An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO inception to Mar 2022. A random effects model was applied to explore the pooled effect sizes of polysomnographic differences between MS patients and controls.Thirteen studies were identified for meta-analysis. Meta-analyses revealed significant reductions in N2 and sleep efficiency, and increases in wake time after sleep onset, periodic limb movement index, and periodic limb movement arousal index in MS patients compared with controls. Meta-regression analyses showed that some of the heterogeneity was explained by age and daytime sleepiness of MS patients.Our study showed that polysomnographic abnormalities are present in MS. Our findings also underscore the need for a comprehensive PSG assessment of sleep changes in patients with MS. Furthermore, the effects of age and daytime sleepiness in MS patients on sleep changes should also be carefully considered and closely monitored in the management of MS.

Both microgravity and radiation exposure in the spaceflight environment have been identified as hazards to astronaut health and performance. Substantial study has been focused on understanding the biology and risks associated with prolonged exposure to microgravity, and the hazards presented by radiation from galactic cosmic rays (GCR) and solar particle events (SPEs) outside of low earth orbit (LEO). To date, the majority of the ground-based analogues (e.g., rodent or cell culture studies) that investigate the biology of and risks associated with spaceflight hazards will focus on an individual hazard in isolation. However, astronauts will face these challenges simultaneously Combined hazard studies are necessary for understanding the risks astronauts face as they travel outside of LEO, and are also critical for countermeasure development. The focus of this review is to describe biologic and functional outcomes from ground-based analogue models for microgravity and radiation, specifically highlighting the combined effects of radiation and reduced weight-bearing from rodent ground-based tail suspension via hind limb unloading (HLU) and partial weight-bearing (PWB) models, although in vitro and spaceflight results are discussed as appropriate. The review focuses on the skeletal, ocular, central nervous system (CNS), cardiovascular, and stem cells responses.

A meta-analysis was conducted to review the prevalence and associated moderators of depression or depressive symptoms in patients with narcolepsy. An extensive search of the literature yielded 1104 articles and abstracts, of which 31 studies were included in the meta-analysis. Meta-analysis revealed that the overall pooled prevalence of depression or depressive symptoms in patients with narcolepsy was 32% (95% Confidence Interval, 28–36%) with high between-study heterogeneity (Q = 249.77, df = 30, p

This study aims to explore the comparative efficacy and acceptability of psychotherapies, pharmacotherapies, and their combinations for insomnia. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, and ClinicalTrials.gov were searched for randomized clinical trials (RCTs) examining the comparative efficacy in which a psychotherapy and a pharmacotherapy for insomnia were directly compared with each other, or in which a combination of psychotherapy and pharmacotherapy was compared with either alone. The analysis included data from 23 RCTs. In 18 of 23 studies, cognitive behavior therapy for insomnia (CBT-I) was the psychotherapy. At post-treatment, CBT-I showed higher subjective sleep efficiency (SE), and lower subjective wake time after sleep onset (WASO) and insomnia severity index (ISI) score. Compared with CBT-I plus pharmacotherapy, pharmacotherapy showed lower subjective SE, and higher subjective sleep latency (SL), PSG measured SL, subjective WASO, and ISI score. Overall, the findings derived from post-treatment data suggested that CBT-I is more beneficial in treating insomnia compared with pharmacotherapy. CBT-I combined with pharmacotherapy is beneficial in improving some sleep parameters (i.e., subjective SE, SL, WASO, and PSG measured SL) compared with pharmacotherapy alone. Daily clinical decisions should consider these findings on the relative efficacy of the principal approaches to insomnia treatment.

This network meta-analysis compares the efficacy and acceptability of all published psychotherapeutic and pharmacological interventions for trauma-related nightmares (TRN) in adults. The analysis included data from 29 randomized clinical trials involving 14 psychotherapeutic and pharmacological interventions and involved 2214 trauma survivors. Prazosin and image rehearsal therapy (IRT) were found to be the two effective interventions for TRN. Other interventions such as risperidone, paroxetine, cognitive behavioral therapy for insomnia (CBT-I), CBT-I+IRT, prolonged exposure (PE), and IRT+PE, did not show significantly greater efficacy compared with control conditions. The rates of all-cause discontinuations were comparable among majority of the interventions and did not show significant differences compared with control conditions. Prazosin and IRT should be considered as the initial choice of pharmacological and psychotherapeutic interventions for TRN. The efficacy of other pharmacological and psychotherapeutic interventions remains to be demonstrated. Future guidelines and daily clinical decision making on the choice of interventions for TRN should consider these findings.

BackgroundTranscriptome-wide analysis of peripheral blood in post-traumatic stress disorder (PTSD) indicates widespread changes in immune-related pathways and function. Ferroptosis, an iron-dependent regulated cell death, is closely related to oxidative stress. However, little is known as to whether ferroptosis plays a role in PTSD.MethodsWe conducted a comprehensive analysis of combined data from six independent peripheral blood transcriptional studies in the Gene Expression Omnibus (GEO) database, covering PTSD and control individuals. Differentially expressed genes (DEGs) were extracted by comparing PTSD patients with control individuals, from which 29 ferroptosis-related genes (FRGs) were cross-matched and obtained. The weighted gene co-expression network analysis (WGCNA), the Extreme Gradient Boosting (XGBoost) model with Bayesian Optimization, and the least absolute shrinkage and selection operator (LASSO) Cox regression were utilized to construct a PTSD prediction model. Single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT revealed the disturbed immunologic state in PTSD high-risk patients.ResultsThree crucial FRGs (ACSL4, ACO1, and GSS) were identified and used to establish a predictive model of PTSD. The receiver operating characteristic (ROC) curve verifies its risk prediction ability. Remarkably, ssGSEA and CIBERSORT demonstrated changes in cellular immunity and antigen presentation depending on the FRGs model.ConclusionThese findings collectively provide evidence that ferroptosis may change immune status in PTSD and be related to the occurrence of PTSD, which may help delineate mechanisms and discover treatment biomarkers for PTSD.

Bi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota–gut–brain axis. Male C57BL/6NCrl mice (4 to 5 per cage, fed standard lab chow) experienced SF via mechanical stimulation at 2 min intervals during the light (SF) and dark (DD, dark disturbances) periods. Home cage (HC) controls were undisturbed. After 10 days, fecal samples were collected at light onset, midday, light offset, and midnight. Samples were also collected after 10 days without SF. Subsequently, the mice were randomized across groups and allowed 20 additional days of recovery followed by 10 days of SF or DD. To assess effects on the microbiota, 16S rRNA sequencing was used, and mesenteric lymph nodes (MLNs) and cortex and medial prefrontal cortex were analyzed using cytokine arrays. SF and DD produced significant alterations in the microbiota compared to HC, and DD had greater impact than SF on some organisms. SF produced marked suppression in MLNs of chemokines that regulate inflammation (CCL3, CCL4 and their receptor CCR5) and maintain the immune mucosal barrier (Cxcl13) at the same time that cortical cytokines (IL-33) indicated neuroinflammation. DD effects on immune responses were similar to HC. These data suggest that SF alters the microbiome and suppresses mucosal immunity at the same time that mediators of brain inflammation are upregulated. The translational implications for potential application to clinical care are compelling.

The central nucleus of the amygdala (CNA) projects to brainstem regions that generate and regulate rapid eye movement sleep (REM). We used optogenetics to assess the influence of CNA inputs into reticularis pontis oralis (RPO), pedunculopontine tegmentum (PPT) and nucleus subcoeruleus (SubC) on dark period sleep. We compared these results to effects of microinjections into CNA of the GABA(A) agonist, muscimol (inhibition of cell bodies) and tetrodotoxin (TTX, inhibition of cell bodies and fibers of passage). For optogenetics, male Wistar rats received excitatory (AAV5-EF1a-DIO -hChR2(H134R)-EYFP) or inhibitory (AAV-EF1a-DIO-eNpHR3.0-EYFP; DIO-eNpHR3.0) opsins into CNA and AAV5-EF1a-mCherry-IRES-WGA-Cre into RPO, PPT, or SubC. This enabled only CNA neurons synaptically connected to each region to express opsin. Optic cannulae for light delivery into CNA and electrodes for determining sleep were implanted. Sleep was recorded with and without blue or amber light stimulation of CNA. Separate rats received MUS or TTX into CNA prior to recording sleep. Optogenetic activation of CNA neurons projecting to RPO enhanced REM and did not alter non-REM (NREM) whereas activation of CNA neurons projecting to PPT or SubC did not significantly affect sleep. Inhibition of CNA neurons projecting to any region did not significantly alter sleep. TTX inactivation of CNA decreased REM and increased NREM whereas muscimol inactivation did not significantly alter sleep. Thus, the amygdala can regulate decreases and increases in REM, and RPO is important for CNA promotion of REM. Fibers passing through CNA, likely from the basolateral nucleus of the amygdala, also play a role in regulating sleep.

In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity to sleep disruption. For autophagy, we monitored the levels of various autophagic induction markers including beclin1, LC3II, and p62 as well as the levels of lysosomal associated membrane protein 1 and 2 (LAMP1/2) and the transcription factor EB (TFEB) which are critical for lysosome function and autophagy maturation stage. For the status of microglia and astrocytes, we determined the levels of Iba1 and GFAP in these brain regions. We also measured the levels of CRF and its cognate receptors 1 and 2 (CRFR1/2). Our results showed that 5 days of SF dysregulated autophagy in the striatum and hippocampus but not in the frontal cortex. Additionally, 5 days of SF activated microglia in the striatum but not in the hippocampus or frontal cortex. In the striatum, CRFR2 but not CRFR1 was significantly increased in SF-experienced mice. CRF did not alter its mRNA levels in any of the three brain regions assessed. Our findings revealed that autophagy processes are sensitive to short-term SF in a region-specific manner and suggest that autophagy dysregulation may be a primary initiator for brain changes and functional impairments in the context of sleep disturbances and disorders.

A meta-analysis exploring polysomnography (PSG) differences between narcolepsy type 1 (NT1)/type 2 (NT2) and idiopathic hypersomnia (IH), particularly one that stratifies the analysis by IH with and without long sleep time (LST), could provide information useful for appropriately re-classifying the central disorders of hypersomnolence. An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO inception to May 2021. Meta-analysis of 26 studies revealed that the effect sizes of differences in some PSG parameters between NT1 and IH were different from those between NT2 and IH. Specifically, there were significant increases in wake time after sleep onset (WASO), arousal index (AI), and N1 percentage, and significant decreases in sleep efficiency, sleep latency, and N2 percentage in NT1 compared with IH, but no differences for these sleep parameters between NT2 and IH. With the exception of rapid eye movement (REM) sleep percentage and REM latency, there were no significant differences in other PSG variables between NT2 and IH without LST. The findings suggest that, NT1, rather than NT2, showed shallower and more fragmented sleep compared with IH. Sleep macrostructure features are very similar between NT2 and IH without LST.

The present study explored whether continuous positive airway pressure (CPAP) treatment impacts nightmare and overall posttraumatic stress disorder (PTSD) symptoms in patients with PTSD and obstructive sleep apnea (OSA). The meta-analysis for six eligibile studies indicates that CPAP can significantly improve nightmare (standardized mean differences (SMD) = -0.778; 95% confidence interval (CI) = -1.228 to -0.327) and overall PTSD symptoms (SMD = -1.298; 95% CI = -2.128 to -0.468) in these patients. A subgroup analysis revealed that the effects of CPAP on improvements of nightmare and overall PTSD symptoms varied across CPAP treatment duration (3 and 6 months), but did not reach a statistically significant level. Furthermore, improvements in overall PTSD symptoms were associated with CPAP adherence. This review emphasizes the importance of the need for a multidisciplinary approach in treating patients with PTSD and OSA, and proposes a hypothetical model of how CPAP improves posttraumatic stress symptoms in patients with PTSD and OSA.

Recent investigations have established that patients with obstructive sleep apnea (OSA) and insomnia have greater daytime impairments and reduced quality of life compared to those with either disorder alone. The present study reviewed current data on the co-occurrence prevalence of insomnia and insomnia symptoms with OSA and assessed its worldwide and regional prevalence based on World Health Organization (WHO) regions. A total of 37 studies were included in the analysis. The overall prevalence rates of insomnia, any insomnia complaints, difficulty falling asleep (DFA), difficulty maintaining sleep (DMS) and early morning awakening (EMA) found in OSA patients were 38%, 36%, 18%, 42%, and 21%, respectively. According to the regional classification of the WHO, the rates of DFA, DMS and EMA in OSA patients in the Western Pacific Region were lower than those in the European Region and the Region of the Americas. We also analyzed the pooled prevalence rates of OSA based on different apnea-hypopnea index (AHI) criteria in insomnia patients. The rates were 35% (AHI≥5) and 29% (AHI≥15), respectively. Regional differences of DFA, DMS and EMA in OSA patients may be related to sex, age and body mass index.

Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator of the effects of stress and fear memories on sleep. However, the molecular mechanisms in BLA regulating the effects of fear conditioning, shock training (ST) and context re-exposure (CTX) on REM sleep are not well known. MicroRNAs (miRNAs) are small, non-coding RNAs and posttranscriptional gene regulators of diverse biological processes. The aim of this study is to investigate ST- and CTX-altered miRNAs in the BLA of resilience and vulnerable animals and on REM sleep regulation. MiRNAs expression profiles in BLA were generated following ST and CTX using the Taqman Low Density rodent microRNA array. The altered BLA miRNAs expression and REM sleep reduction observed in ST and CTX vulnerable animals. AntagomiR-221 microinjection into BLA for one of the upregulated miRNAs, miR-221 in BLA, attenuated the REM sleep reduction. This study suggests that miRNAs in the BLA may play a significant role in mediating the effects of stress and fear memories on REM sleep.

Measuring and analyzing local field potential (LFP) signals from basolateral amygdala (BLA), hippocampus (HPC) and medial prefrontal cortex (mPFC) may help understand how they communicate with each other during fear memory formation and extinction. In our research, we have formulated a computationally simple and noise immune instantaneous amplitude cross correlation technique which can deduce lead and lag of LFPs generated in BLA, HPC, and mPFC and the directionality of brain signals exchanged between regions. LFP signals are recorded using depth electrodes in the rat brain and cross correlation analysis is applied to theta wave signals after filtering. We found that rats resilient to traumatic conditions (based on post-stress rapid eye movement sleep (REM)) showed a decrease in LFP signal correlation in REM and non-REM (NREM) sleep cycles between BLA-HPC regions after shock training and one day post shock training compared to vulnerable rats that show stress-induced reductions in REM. It is presumed this difference in neural network behavior may be related to REM sleep differences between resilient and vulnerable rats and may provide clues to help understand how traumatic conditions are processed by the brain.

Open-world processes generate information that cannot be captured in a single data set. In fields such as medicine and defense, where precise information can be life-saving, a modeling paradigm is needed in which multiple media and contexts can be logically and visually integrated, in order to inform the engineering of large systems. One barrier is the underlying ontological heterogeneity that multiple contexts can exhibit, along with the need for those facts to be compatible with or translated between domains and situations. Another barrier is the dynamism and influence of context, which has traditionally been difficult to represent. This chapter describes a method for modeling the changes of interpretation that occur when facts cross-over context boundaries, whether those contexts are differentiated by discipline, time or perspective (or all three). We that processing Here, a new modeling environment is developed in which those transitions can be visualized. Our prototype modeling platform, Wunderkammer, can connect video, text, image and data while representing the context from which these artifacts were derived. It can also demonstrate transfers of information among situations, enabling the depiction of influence. Our example focuses on post-traumatic stress disorder (PTSD), combining psychological, neurological and physiological information, with a view to informing the aggregation of information in intelligent systems. These different forms of information are connected in a single modeling space using a narrative-based visual grammar. The goal is to develop a method and tool that supports the integration of information from different fields in order to model changing phenomena in an open world, with a focus on detecting emerging disorders. In turn, this will ultimately support more powerful knowledge systems for fields such as neurobiology, autonomous systems and artificial intelligence (AI).

Ground-based rodent models have established that space radiation doses (approximately those that astronauts will be exposed to on a mission to Mars) significantly impair performance in a wide range of cognitive tasks. Over the last 40 years there has been a progressive increase in both the complexity and the translatability (to humans) of the cognitive tasks investigated. This review outlines technical and conceptual advances in space radiation rodent testing approaches, along with the advances in analytical approaches, that will make data from ground based studies more amenable to probabilistic risk analysis. While great progress has been made in determining the impact of space radiation on many advanced cognitive processes, challenges remain that need to be addressed prior to commencing deep space missions. A summary of on-going attempts to address existing knowledge gaps and the critical role that rodent studies will have in establishing the impact of space radiation on even more complex (human) cognitive tasks are presented and discussed.

Group II metabotropic glutamate receptors (mGluR2/3s) have been implicated in stress and trauma related disorders including post-traumatic stress disorder (PTSD). PTSD is characterized by flashbacks, anxiety, and sleep disturbances. While many people are exposed to trauma in their lifetime, only a small percentage go on to develop PTSD, indicating individual differences in stress and emotional processing. Wistar strain rats display directionally different rapid-eye movement sleep (REM) responses to footshock stress, with resilient rats having no change or an increase in REM and vulnerable rats having a significant reduction in REM compared to baseline. The basolateral nucleus of the amygdala (BLA) is key in regulating individual differences in stress-induced alterations in sleep. Group II metabotropic glutamate receptors (mGluR2/3s) negatively modulate glutamate and are implicated in fear, fear memory, and sleep. The current study evaluated the effect of mGluR2/3 agonist LY379268 (LY37) in BLA on stress and fear memory induced changes in sleep, EEG spectra, behavioral fear expression and physiological stress. These data indicate that vulnerable rats treated with LY37 have an attenuation of the REM reductions generally seen in vulnerable rats. Furthermore, LY37 altered EEG spectra in the delta (0.5-4.5 Hz) and theta (5-9.5 Hz) frequency. LY37 did not impact behavioral fear expression or physiological stress. Therefore, mGluR2/3s within BLA are implicated in regulating individual differences in sleep responses to fear- and stress-related memories.