Breathing and sleep state are tightly linked. The traditional approach to evaluation of breathing in rapid eye movement sleep has been to focus on apneas and hypopneas, and associated hypoxia or hypercapnia. However, rapid eye movement sleep breathing offers novel insights into sleep physiology and pathology, secondary to complex interactions of rapid eye movement state and cardiorespiratory biology. In this review, morphological analysis of clinical polysomnogram data to assess respiratory patterns and associations across a range of health and disease is presented. There are several relatively unique insights that may be evident by assessment of breathing during rapid eye movement sleep. These include the original discovery of rapid eye movement sleep and scoring of neonatal sleep, control of breathing in rapid eye movement sleep, rapid eye movement sleep homeostasis, sleep apnea endotyping and pharmacotherapy, rapid eye movement sleep stability, non-electroencephalogram sleep staging, influences on cataplexy, mimics of rapid eye movement behaviour disorder, a reflection of autonomic health, and insights into cardiac arrhythmogenesis. In summary, there is rich clinically actionable information beyond sleep apnea encoded in the respiratory patterns of rapid eye movement sleep.

Rapid eye movement (REM) sleep has been hypothesized to promote emotional resilience, but any neuronal circuits mediating this have not been identified. We find that in mice, somatostatin (Som) neurons in the entopeduncular nucleus (EPSom)/internal globus pallidus are predominantly active during REM sleep. This unique REM activity is both necessary and sufficient for maintaining normal REM sleep. Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively. Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula (LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic scheme to periodically inhibit the LHb over 4 days selectively removed a significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep, in part generated by the EP → LHb → VTA circuit identified here, could contribute to stabilizing reactions to habitual aversive stimuli.

Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs in mice. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

Several brainstem, subcortical and cortical areas are involved in the generation of rapid eye movement (REM) sleep. The alteration of these structures as a result of a neurodegenerative process may therefore lead to REM sleep anomalies. REM sleep behaviour disorder is associated with nightmares, dream-enacting behaviours and increased electromyographic activity in REM sleep. Its isolated form is a harbinger of synucleinopathies such as Parkinson\'s disease or dementia with Lewy bodies, and neuroprotective interventions are advocated. This link might also be present in patients taking antidepressants, with post-traumatic stress disorder, or with a history of repeated traumatic head injury. REM sleep likely contributes to normal memory processes. Its alteration has also been proposed to be part of the neuropathological changes occurring in Alzheimer\'s disease.

While research interest in the relationship between sleep and epilepsy is growing, it primarily centres on the effects of non-rapid eye movement (NREM) sleep in favouring seizures. Nonetheless, a noteworthy aspect is the observation that, in the lives of patients with epilepsy, REM sleep represents the moment with the least epileptic activity and the lowest probability of having a seizure. Studies demonstrate a suppressive effect of phasic REM sleep on interictal epileptiform discharges, potentially offering insights into epilepsy localisation and management. Furthermore, epilepsy impacts REM sleep, with successful treatment correlating with improved REM sleep quality. Novel therapeutic strategies aim to harness REM\'s anti-epileptic effects, including pharmacological approaches targeting orexinergic systems and neuromodulation techniques promoting cortical desynchronisation. These findings underscore the intricate relationship between REM sleep and epilepsy, highlighting avenues for further research and therapeutic innovation in epilepsy management.

The world-wide prevalence of insomnia disorder reaches up to 10% of the adult population. Women are more often afflicted than men, and insomnia disorder is a risk factor for somatic and mental illness, especially depression and anxiety disorders. Persistent hyperarousals at the cognitive, emotional, cortical and/or physiological levels are central to most theories regarding the pathophysiology of insomnia. Of the defining features of insomnia disorder, the discrepancy between minor objective polysomnographic alterations of sleep continuity and substantive subjective impairment in insomnia disorder remains enigmatic. Microstructural alterations, especially in rapid eye movement sleep (\"rapid eye movement sleep instability\"), might explain this mismatch between subjective and objective findings. As rapid eye movement sleep represents the most highly aroused brain state during sleep, it might be particularly prone to fragmentation in individuals with persistent hyperarousal. In consequence, mentation during rapid eye movement sleep may be toned more as conscious-like wake experience, reflecting pre-sleep concerns. It is suggested that this instability of rapid eye movement sleep is involved in the mismatch between subjective and objective measures of sleep in insomnia disorder. Furthermore, as rapid eye movement sleep has been linked in previous works to emotional processing, rapid eye movement sleep instability could play a central role in the close association between insomnia and depressive and anxiety disorders.

Targeted memory reactivation (TMR), or the presentation of learning-related cues during sleep, has been shown to benefit memory consolidation for specific memory traces when applied during non-rapid eye movement (NREM) sleep. Prior studies suggest that TMR during REM sleep may play a role in memory generalization processes, but evidence remains scarce. We tested the hypothesis that TMR exerts a differential effect on distinct mnemonic processes as a function of the sleep state (REM vs. NREM) in which TMR is delivered. Mnemonic discrimination and generalization of semantic categories were investigated using an adapted version of the Mnemonic Similarity Task, before and after sleep. Forty-eight participants encoded pictures from eight semantic categories, each associated with a sound. In the pre-sleep immediate test, they had to discriminate \"old\" (targets) from \"similar\" (lures) or \"new\" (foils) pictures. During sleep, half of the sounds were replayed in slow wave sleep (SWS) or REM sleep. Recognition, discrimination, and generalization memory indices were tested in the morning. These indices did not differ between SWS and REM TMR groups or reactivated and non-reactivated item categories. Additional results suggest a positive effect of TMR on performance for highly similar items mostly relying on mnemonic discrimination processes. During sleep, EEG activity after cue presentation increased in the delta-theta and sigma band in the SWS group, and in the beta band in the REM TMR group. These results do not support the hypothesis of a differential processing of novel memory traces when TMR is administered in distinctive physiological sleep states.

Rapid eye movement sleep is associated with distinct changes in various biomedical signals that can be easily captured during sleep, lending themselves to automated sleep staging using machine learning systems. Here, we provide a perspective on the critical characteristics of biomedical signals associated with rapid eye movement sleep and how they can be exploited for automated sleep assessment. We summarise key historical developments in automated sleep staging systems, having now achieved classification accuracy on par with human expert scorers and their role in the clinical setting. We also discuss rapid eye movement sleep assessment with consumer sleep trackers and its potential for unprecedented sleep assessment on a global scale. We conclude by providing a future outlook of computerised rapid eye movement sleep assessment and the role AI systems may play.

UNASSIGNED: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which are prevalent conditions among post-9/11 veterans, increase risks of rapid eye movement (REM) sleep behavior disorder (RBD) and degenerative synucleinopathy. Rates and predictors of RBD symptoms were investigated by screening post-9/11 veterans for RBD with a validated questionnaire.
UNASSIGNED: In this cross-sectional analysis, consecutive patients in the Houston Translational Research Center for TBI and Stress Disorders (TRACTS) were screened with the English translation of the RBD Questionnaire-Hong Kong (RBDQ-HK). In addition to data from the standard TRACTS battery, systematic chart review was used to identify known sleep disorders mimicking or manifesting RBD.
UNASSIGNED: Of the 119 patients with available RBDQ-HK scores, 71 (60%) and 65 (55%) screened positive for RBD, when a total score ≥21 and a factor 2 score ≥8 were used as cutoff scores, respectively. Univariable analyses with both cutoffs showed consistent associations between a positive RBDQ-HK screen and global sleep quality, number of TBI exposures, and PTSD severity. Multivariable logistic regression with total score ≥21 as a cutoff indicated that PTSD severity (odds ratio=1.06, 95% CI=1.02-1.10) and number of TBIs (odds ratio=1.63, 95% CI=1.16-2.41) were independent predictors of a positive screen, whereas global sleep quality was no longer significant. Multivariable logistic regression with factor 2 score ≥8 as a cutoff showed similar results.
UNASSIGNED: Interdisciplinary parasomnia assessment, further validation of RBD screens, and standardized reporting of REM sleep without atonia could provide necessary information on the pathophysiological relationships linking PTSD, TBI, RBD symptoms, and ultimately synucleinopathy risk among post-9/11 veterans.

Prior investigations have established that the manipulation of neural activity has the potential to influence both rapid eye movement and non-rapid eye movement sleep. Low-intensity retinal ultrasound stimulation has shown effectiveness in the modulation of neural activity. Nevertheless, the specific effects of retinal ultrasound stimulation on rapid eye movement and non-rapid eye movement sleep, as well as its potential to enhance overall sleep quality, remain to be elucidated. Here, we found that: In healthy mice, retinal ultrasound stimulation: (i) reduced total sleep time and non-rapid eye movement sleep ratio; (ii) changed relative power and sample entropy of the delta (0.5-4 Hz) in non-rapid eye movement sleep; and (iii) enhanced relative power of the theta (4-8 Hz) and reduced theta-gamma coupling strength in rapid eye movement sleep. In Alzheimer\'s disease mice with sleep disturbances, retinal ultrasound stimulation: (i) reduced the total sleep time; (ii) altered the relative power of the gamma band during rapid eye movement sleep; and (iii) enhanced the coupling strength of delta-gamma in non-rapid eye movement sleep and weakened the coupling strength of theta-fast gamma. The results indicate that retinal ultrasound stimulation can modulate rapid eye movement and non-rapid eye movement-related neural activity; however, it is not beneficial to the sleep quality of healthy and Alzheimer\'s disease mice.