Shared EEG correlates between non-REM parasomnia experiences and dreams.

Sleepwalking and related parasomnias result from incomplete awakenings out of non-rapid eye movement sleep. Behavioral episodes can occur without consciousness or recollection, or in relation to dream-like experiences. To understand what accounts for these differences in consciousness and recall, here we recorded parasomnia episodes with high-density electroencephalography (EEG) and interviewed participants immediately afterward about their experiences. Compared to reports of no experience (19%), reports of conscious experience (56%) were preceded by high-amplitude EEG slow waves in anterior cortical regions and activation of posterior cortical regions, similar to previously described EEG correlates of dreaming. Recall of the content of the experience (56%), compared to no recall (25%), was associated with higher EEG activation in the right medial temporal region before movement onset. Our work suggests that the EEG correlates of parasomnia experiences are similar to those reported for dreams and may thus reflect core physiological processes involved in sleep consciousness.

Nocturnal exposure to a preferred ambient scent does not affect dream emotionality or post-sleep core affect valence in young adults.

Emotions experienced within sleep mentation (dreaming) affect mental functioning in waking life. There have been attempts at enhancing dream emotions using olfactory stimulation. Odors readily acquire affective value, but to profoundly influence emotional processing, they should bear personal significance for the perceiver rather than be generally pleasant. The main objective of the present sleep laboratory study was to examine whether prolonged nocturnal exposure to self-selected, preferred ambient room odor while asleep influences emotional aspects of sleep mentation and valence of post-sleep core affect. We asked twenty healthy participants (12 males, mean age 25 ± 4 years) to pick a commercially available scented room diffuser cartridge that most readily evoked positively valenced mental associations. In weekly intervals, the participants attended three sessions. After the adaptation visit, they were administered the odor exposure and odorless control condition in a balanced order. Participants were awakened five minutes into the first rapid eye movement (REM) stage that took place after 2:30 a.m. and, if they had been dreaming, they were asked to rate their mental sleep experience for pleasantness, emotional charge, and magnitude of positive and negative emotions and also to evaluate their post-sleep core affect valence. With rs < 0.20, no practically or statistically significant differences existed between exposure and control in any outcome measures. We conclude that in young, healthy participants, the practical value of olfactory stimulation with self-selected preferred scents for enhancement of dream emotions and post-sleep core affect valence is very limited.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Spinal bestrophin-1 and anoctamin-1 channels have a pronociceptive role in the tactile allodynia induced by REM sleep deprivation in rats.

Bestrophin-1 and anoctamin-1 are members of the calcium-activated chloride channels (CaCCs) family and are involved in inflammatory and neuropathic pain. However, their role in pain hypersensitivity induced by REM sleep deprivation (REMSD) has not been studied. This study aimed to determine if anoctamin-1 and bestrophin-1 are involved in the pain hypersensitivity induced by REMSD. We used the multiple-platform method to induce REMSD. REM sleep deprivation for 48 h induced tactile allodynia and a transient increase in corticosterone concentration at the beginning of the protocol (12 h) in female and male rats. REMSD enhanced c-Fos and α2δ-1 protein expression but did not change activating transcription factor 3 (ATF3) and KCC2 expression in dorsal root ganglia and dorsal spinal cord. Intrathecal injection of CaCCinh-A01, a non-selective bestrophin-1 blocker, and T16Ainh-A01, a specific anoctamin-1 blocker, reverted REMSD-induced tactile allodynia. However, T16Ainh-A01 had a higher antiallodynic effect in male than female rats. In addition, REMSD increased bestrophin-1 protein expression in DRG but not in DSC in male and female rats. In marked contrast, REMSD decreased anoctamin-1 protein expression in DSC but not in DRG, only in female rats. Bestrophin-1 and anoctamin-1 promote pain and maintain tactile allodynia induced by REM sleep deprivation in both male and female rats, but their expression patterns differ between the sexes.

Cardiac autonomic nervous activity during different sleep stages in individuals with spinal cord injury: The influence of physical training.

OBJECTIVE: The present study assessed the influence of physical training on cardiac autonomic activity in individuals with spinal cord injury (SCI) during different sleep stages. METHODS: Twenty-six volunteers were allocated into three groups: 9 sedentary individuals without SCI (control, CON); 8 sedentary tetraplegic individuals with chronic SCI (SED-SCI); 9 physically trained tetraplegic individuals with chronic SCI (TR-SCI). All participants underwent nocturnal polysomnography to monitor sleep stages: wakefulness, non-rapid eye movement (NREM) sleep (N1, N2, and N3 stages), and REM sleep. The electrocardiography data obtained during this exam were extracted to analyze the heart rate variability (HRV). RESULTS: Sleep stages influenced HRV in the time [RR interval and root mean square of successive RR interval differences (RMSSD)] and frequency [low-frequency (LF) and high-frequency (HF) powers and LF-to-HF ratio] domains (P < 0.05). SED-SCI individuals showed unchanged HRV compared to CON (P > 0.05). When comparing the TR-SCI and SED-SCI groups, no significant differences in HRV were reported in the time domain (P > 0.05). However, in the frequency domain, more accentuated HF power was observed in TR-SCI than in SED-SCI individuals during the N2 and N3 stages and REM sleep (P < 0.05). Moreover, TR-SCI had higher HF power than CON during the N3 stage (P < 0.05). CONCLUSIONS: TR-SCI individuals have greater HF power, indicative of parasympathetic modulation, than sedentary (injured or not injured) individuals during different sleep stages. Therefore, enhanced parasympathetic activity induced by physical training may improve cardiac autonomic modulation during sleep in individuals with chronic SCI.

Most dynorphin neurons in the zona incerta-perifornical area are active in waking relative to non-rapid-eye movement and rapid-eye movement sleep.

Dynorphin is an endogenous opiate localized in many brain regions and spinal cord, but the activity of dynorphin neurons during sleep is unknown. Dynorphin is an inhibitory neuropeptide that is coreleased with orexin, an excitatory neuropeptide. We used microendoscopy to test the hypothesis that, like orexin, the dynorphin neurons are wake-active. Dynorphin-cre mice (n = 3) were administered rAAV8-Ef1a-Con/Foff 2.0-GCaMP6M into the zona incerta-perifornical area, implanted with a GRIN lens (gradient reflective index), and electrodes to the skull that recorded sleep. One month later, a miniscope imaged calcium fluorescence in dynorphin neurons during multiple bouts of wake, non-rapid-eye movement (NREM), and rapid-eye movement (REM) sleep. Unbiased data analysis identified changes in calcium fluorescence in 64 dynorphin neurons. Most of the dynorphin neurons (72%) had the highest fluorescence during bouts of active and quiet waking compared to NREM or REM sleep; a subset (20%) were REM-max. Our results are consistent with the emerging evidence that the activity of orexin neurons can be classified as wake-max or REM-max. Since the two neuropeptides are coexpressed and coreleased, we suggest that dynorphin-cre-driven calcium sensors could increase understanding of the role of this endogenous opiate in pain and sleep.

A new perspective on positive symptoms: expression of damage or self-defence mechanism of the brain?

Usually, positive neurological symptoms are considered as the consequence of a mere, afinalistic and abnormal increase in function of specific brain areas. However, according to the Theory of Active Inference, which argues that action and perception constitute a loop that updates expectations according to a Bayesian model, the brain is rather an explorer that formulates hypotheses and tests them to assess the correspondence between internal models and reality. Moreover, the cerebral cortex is characterised by a continuous "conflict" between different brain areas, which constantly attempt to expand in order to acquire more of the limited available computational resources, by means of their dopamine-induced neuroplasticity. Thus, it has recently been suggested that dreams, during rapid eye movement sleep (REMS), protect visual brain areas (deprived of their stimuli during rest) from being conquered by other normally stimulated ones. It is therefore conceivable that positive symptoms also have a functional importance for the brain. We evaluate supporting literature data of a 'defensive' role of positive symptoms and the relevance of dopamine-induced neuroplasticity in the context of neurodegenerative and psychiatric diseases. Furthermore, the possible functional significance of idiopathic REMS-related behavioural disorder as well as phantom limb syndrome is examined. We suggest that positive neurological symptoms are not merely a passive expression of a damage, but active efforts, related to dopamine-induced plasticity, to maintain a correct relationship between the external world and its brain representation, thus preventing healthy cortical areas from ousting injured ones.

Impact of endogenous analgesia triggered by acupuncture, stress, or noxious stimulation on REM sleep-deprived rats.

Poor sleep increases pain, at least in part, by disrupting endogenous pain modulation. However, the efficacy of endogenous analgesia in sleep-deprived subjects has never been tested. To assess this issue, we chose three different ways of triggering endogenous analgesia: (1) acupuncture, (2) acute stress, and (3) noxious stimulation, and compared their ability to decrease the pronociceptive effect induced by REM-SD (Rapid Eye Movement Sleep Deprivation) with that to decrease inflammatory hyperalgesia in the classical carrageenan model. First, we tested the ability of REM-SD to worsen carrageenan-induced hyperalgesia: A low dose of carrageenan (30 µg) in sleep-deprived Wistar rats resulted in a potentiated hyperalgesic effect that was more intense and longer-lasting than that induced by a higher standard dose of carrageenan (100 µg) or by REM-SD alone. Then, we found that (1) acupuncture, performed at ST36, completely reversed the pronociceptive effect induced by REM-SD or by carrageenan; (2) immobilization stress completely reversed the pronociceptive effect of REM-SD, while transiently inhibited carrageenan-induced hyperalgesia; (3) noxious stimulation of the forepaw by capsaicin also reversed the pronociceptive effect of REM-SD and persistently increased the nociceptive threshold above the baseline in carrageenan-treated animals. Therefore, acupuncture, stress, or noxious stimulation reversed the pronociceptive effect of REM-SD, while each intervention affected carrageenan-induced hyperalgesia differently. This study has shown that while sleep loss may disrupt endogenous pain modulation mechanisms, it does not prevent the activation of these mechanisms to induce analgesia in sleep-deprived individuals.

Which structure generates paradoxical (REM) sleep: The brainstem, the hypothalamus, the amygdala or the cortex?

Paradoxical or Rapid eye movement (REM) sleep (PS) is a state characterized by REMs, EEG activation and muscle atonia. In this review, we discuss the contribution of brainstem, hypothalamic, amygdalar and cortical structures in PS genesis. We propose that muscle atonia during PS is due to activation of glutamatergic neurons localized in the pontine sublaterodorsal tegmental nucleus (SLD) projecting to glycinergic/GABAergic pre-motoneurons localized in the ventro-medial medulla (vmM). The SLD PS-on neurons are inactivated during wakefulness and slow-wave sleep by PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray (vPAG) and the adjacent deep mesencephalic reticular nucleus. Melanin concentrating hormone (MCH) and GABAergic PS-on neurons localized in the posterior hypothalamus would inhibit these PS-off neurons to initiate the state. Finally, the activation of a few limbic cortical structures during PS by the claustrum and the supramammillary nucleus as well as that of the basolateral amygdala would also contribute to PS expression. Accumulating evidence indicates that the activation of these limbic structures plays a role in memory consolidation and would communicate to the PS-generating structures the need for PS to process memory. In summary, PS generation is controlled by structures distributed from the cortex to the medullary level of the brain.

Selective REM sleep restriction in mice using a device designed for tunable somatosensory stimulation.

BACKGROUND: Sleep perturbation is widely used to investigate the physiological mechanisms that mediate sleep-wake dynamics, and to isolate the specific roles of sleep in health and disease. However, state-of-the-art methods to accomplish sleep perturbation in preclinical models are limited in their throughput, flexibility, and specificity. NEW METHOD: A system was developed to deliver vibro-tactile somatosensory stimulation aimed at controlled, selective sleep perturbation. The frequency and intensity of stimulation can be tuned to target a variety of experimental applications, from sudden arousal to sub-threshold transitions between light and deep stages of NREM sleep. This device was activated in closed-loop to selectively interrupt REM sleep in mice. RESULTS: Vibro-tactile stimulation effectively and selectively interrupted REM sleep - significantly reducing the average REM bout duration relative to matched, unstimulated baseline recordings. As REM sleep was repeatedly interrupted, homeostatic mechanisms prompted a progressively quicker return to REM sleep. These effects were dependent on the parameters of stimulation applied. COMPARISON WITH EXISTING METHODS: Existing sleep perturbation systems often require moving parts within the cage and/or restrictive housing. The system presented is unique in that it interrupts sleep without invading the animal's space. The ability to vary stimulation parameters is a great advantage over existing methods, as it allows for adaptation in response to habituation and/or circadian/homeostatic changes in arousal threshold. CONCLUSIONS: The proposed method of stimulation demonstrates feasibility in affecting mouse sleep within a standard home cage environment, thus limiting environmental stress. Furthermore, the ability to tune frequency and intensity of stimulation allows for graded control over the extent of sleep perturbation, which potentially expands the utility of this technology beyond applications related to sleep.

Monitoring differences in the function of the autonomic nervous system in patients with chronic insomnia using a wearable device.

STUDY OBJECTIVES: to characterize possible differences in the function of the ANS in patients with chronic insomnia compared to a control group, using a wearable device, in order to determine whether those findings allow diagnosing this medical entity. METHODS: Thirty-two patients with chronic insomnia and nineteen patients without any sleep disorder, as a control group, were recruited prospectively. Both groups of patients underwent an in-patient night with simultaneous polysomnography and wearable device recording Empatica E4 a diverse array of physiological signals, including electrodermal activity, temperature, accelerometry, and photoplethysmography, providing a comprehensive resource for in-depth sleep analysis. RESULTS: In polysomnography, patients suffering from insomnia showed a significant decrease in sleep efficiency and total sleep time, prolonged sleep latency, and increased wakefulness after sleep onset. Accelerometry results were statistically significant differences in the three axis (x, y, z) just in stage N3, no differences were observed between both groups in REM sleep. The lowest temperature was reached in REM sleep in both groups. Peripheral temperature did not decrease during the different sleep phases compared to wakefulness in insomnia, unlike in the control group. Heart rate was higher in patients with insomnia than in controls during wakefulness and sleep stage. Heart rate variability was lower in stage N3 and higher in REM sleep compared to wakefulness in both groups. Sweating was significantly higher in patients with insomnia compared to the control group, as indicated by Skin Conductance Variability values and Sudomotor Nerve. CONCLUSIONS: Our study suggests that patients with insomnia have increased sympathetic activity during sleep, showing a higher heart rate. Temperature and sweating significantly influence the different sleep phases.

Sleep physiology in patients with epilepsy: Influence of seizures on rapid eye movement (REM) latency and REM duration.

OBJECTIVE: A well-established bidirectional relationship exists between sleep and epilepsy. Patients with epilepsy tend to have less efficient sleep and shorter rapid eye movement (REM) sleep. Seizures are far more likely to arise from sleep transitions and non-REM sleep compared to REM sleep. Delay in REM onset or reduction in REM duration may have reciprocal interactions with seizure occurrence. Greater insight into the relationship between REM sleep and seizure occurrence is essential to our understanding of circadian patterns and predictability of seizure activity. We assessed a cohort of adults undergoing evaluation of drug-resistant epilepsy to examine whether REM sleep prior to or following seizures is delayed in latency or reduced in quantity. METHODS: We used a spectrogram-guided approach to review the video-electroencephalograms of patients' epilepsy monitoring unit admissions for sleep scoring to determine sleep variables. RESULTS: In our cohort of patients, we found group- and individual-level delay of REM latency and reduced REM duration when patients experienced a seizure before the primary sleep period (PSP) of interest or during the PSP of interest. A significant increase in REM latency and decrease in REM quantity were observed on nights where a seizure occurred within 4 h of sleep onset. No change in REM variables was found when investigating seizures that occurred the day after the PSP of interest. Our study is the first to provide insight about a perisleep period, which we defined as 4-h periods before and after the PSP. SIGNIFICANCE: Our results demonstrate a significant relationship between seizures occurring prior to the PSP, during the PSP, and in the 4-h perisleep period and a delay in REM latency. These findings have implications for developing a biomarker of seizure detection as well as longer term seizure risk monitoring.

Auditory stimulation during REM sleep modulates REM electrophysiology and cognitive performance.

REM sleep is critical for memory, emotion, and cognition. Manipulating brain activity during REM could improve our understanding of its function and benefits. Earlier studies have suggested that auditory stimulation in REM might modulate REM time and reduce rapid eye movement density. Building on this, we studied the cognitive effects and electroencephalographic responses related to such stimulation. We used acoustic stimulation locked to eye movements during REM and compared two overnight conditions (stimulation and no-stimulation). We evaluated the impact of this stimulation on REM sleep duration and electrophysiology, as well as two REM-sensitive memory tasks: visual discrimination and mirror tracing. Our results show that this auditory stimulation in REM decreases the rapid eye movements that characterize REM sleep and improves performance on the visual task but is detrimental to the mirror tracing task. We also observed increased beta-band activity and decreased theta-band activity following stimulation. Interestingly, these spectral changes were associated with changes in behavioural performance. These results show that acoustic stimulation can modulate REM sleep and suggest that different memory processes underpin its divergent impacts on cognitive performance.

Recurrent Isolated Sleep Paralysis.

Recurrent isolated sleep paralysis has a 7.6% lifetime prevalence of at least one episode in the general population. Episodes resolve spontaneously and are benign. Sleep paralysis represents a dissociate state, with persistence of the rapid eye movement (REM)-sleep muscle atonia in the waking state. The intrusion of alpha electroencephalogram into REM sleep is followed by an arousal response and then by persistence of REM atonia into wakefulness. Predisposing factors include irregular sleep-wake schedules, sleep deprivation, and jetlag. No drug treatment is required. Patients should be informed about sleep hygiene. Cognitive behavioral therapy may be useful in cases accompanied by anxiety and frightening hallucinations.

Rapid Eye Movement Sleep Behavior Disorder: Clinical Presentation and Diagnostic Criteria.

Rapid eye movement (REM) sleep behavior disorder (RBD) classically presents with repetitive complex motor behavior during sleep with associated dream mentation. The diagnosis requires a history of repetitive complex motor behaviors and polysomnographic demonstration of REM sleep without atonia (RSWA) or capturing dream enactment behaviors. RSWA is best evaluated in the chin or flexor digitorum superficialis muscles. The anterior tibialis muscle is insufficiently accurate to be relied upon solely for RBD diagnosis. RBD may present with parkinsonism or cognitive impairment or may present in isolation. Patients should be monitored for parkinsonism, autonomic failure, or cognitive impairment.

Somnotate: A probabilistic sleep stage classifier for studying vigilance state transitions.

Electrophysiological recordings from freely behaving animals are a widespread and powerful mode of investigation in sleep research. These recordings generate large amounts of data that require sleep stage annotation (polysomnography), in which the data is parcellated according to three vigilance states: awake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. Manual and current computational annotation methods ignore intermediate states because the classification features become ambiguous, even though intermediate states contain important information regarding vigilance state dynamics. To address this problem, we have developed "Somnotate"-a probabilistic classifier based on a combination of linear discriminant analysis (LDA) with a hidden Markov model (HMM). First we demonstrate that Somnotate sets new standards in polysomnography, exhibiting annotation accuracies that exceed human experts on mouse electrophysiological data, remarkable robustness to errors in the training data, compatibility with different recording configurations, and an ability to maintain high accuracy during experimental interventions. However, the key feature of Somnotate is that it quantifies and reports the certainty of its annotations. We leverage this feature to reveal that many intermediate vigilance states cluster around state transitions, whereas others correspond to failed attempts to transition. This enables us to show for the first time that the success rates of different types of transition are differentially affected by experimental manipulations and can explain previously observed sleep patterns. Somnotate is open-source and has the potential to both facilitate the study of sleep stage transitions and offer new insights into the mechanisms underlying sleep-wake dynamics.

Altered parasympathetic activity during sleep and emotionally arousing wakefulness in frequent nightmare recallers.

Nightmare disorder is characterized by dysfunctional emotion regulation and poor subjective sleep quality reflected in pathophysiological features such as abnormal arousal processes and sympathetic influences. Dysfunctional parasympathetic regulation, especially before and during rapid eye movement (REM) phases, is assumed to alter heart rate (HR) and its variability (HRV) of frequent nightmare recallers (NM). We hypothesized that cardiac variability is attenuated in NMs as opposed to healthy controls (CTL) during sleep, pre-sleep wakefulness and under an emotion-evoking picture-rating task. Based on the polysomnographic recordings of 24 NM and 30 CTL participants, we examined HRV during pre-REM, REM, post-REM and slow wave sleep, separately. Additionally, electrocardiographic recordings of resting state before sleep onset and under an emotionally challenging picture-rating task were also analyzed. Applying repeated measures analysis of variance (rmANOVA), a significant difference was found in the HR of NMs and CTLs during nocturnal segments but not during resting wakefulness, suggesting autonomic dysregulation, specifically during sleep in NMs. As opposed to the HR, the HRV values were not significantly different in the rmANOVA in the two groups, implying that the extent of parasympathetic dysregulation on a trait level might depend on the severeness of dysphoric dreaming. Nonetheless, in the group comparisons, the NM group showed increased HR and reduced HRV during the emotion-evoking picture-rating task, which aimed to model the nightmare experience in the daytime, indicating disrupted emotion regulation in NMs under acute distress. In conclusion, trait-like autonomic changes during sleep and state-like autonomic responses to emotion-evoking pictures indicate parasympathetic dysregulation in NMs.

A mammal and bird's-eye-view of the pupil during sleep and wakefulness.

Besides regulating the amount of light that reaches the retina, fluctuations in pupil size also occur in isoluminant conditions during accommodation, during movement and in relation to cognitive workload, attention and emotion. Recent studies in mammals and birds revealed that the pupils are also highly dynamic in the dark during sleep. However, despite exhibiting similar sleep states (rapid eye movement [REM] and non-REM [NREM] sleep), wake and sleep state-dependent changes in pupil size are opposite between mammals and birds, due in part to differences in the type (striated vs. smooth) and control of the iris muscles. Given the link between pupil dynamics and cognitive processes occurring during wakefulness, sleep-related changes in pupil size might indicate when related processes are occurring during sleep. Moreover, the divergent pupillary behaviour observed between mammals and birds raises the possibility that changes in pupil size in birds are a readout of processes not reflected in the mammalian pupil.

REM parameters in drug-free major depressive disorder: A systematic review and meta-analysis.

Previous studies revealed that rapid eye movement (REM) parameters, such as REM latency (RL) and REM density (RD) could be used as electrophysiological markers of depression. Yet these finding should be re-tested in a comorbid-free and drug-free sample. The present systematic review and meta-analysis was conducted to investigate whether drug-free and comorbid-free patients with unipolar depression differentiate from controls with respect to the RL and RD. The PubMed and Web of Science databases were screened from inception to 23 January 2023 for case-control studies comparing RL and RD of patients with unipolar depression and controls. The primary outcome was the standard mean difference. The data were fitted with a random-effects model. Meta-regressions were conducted to investigate patient characteristics and effect size. Publication bias assessment was checked by Egger's Regression and funnel plot asymmetry. Among 43 articles accepted as eligible, 46 RL and 22 RD measurements were included in the meta-analysis. The results indicated shortened RL and increased RD in the patient group than controls. Neither Egger's regression nor funnel plot asymmetry were significant for publication bias. In conclusion, our results tested within drug-free and comorbid-free samples are in line with the literature.

Linking brain structure, cognition, and sleep: insights from clinical data.

STUDY OBJECTIVES: To use relatively noisy routinely collected clinical data (brain magnetic resonance imaging (MRI) data, clinical polysomnography (PSG) recordings, and neuropsychological testing), to investigate hypothesis-driven and data-driven relationships between brain physiology, structure, and cognition. METHODS: We analyzed data from patients with clinical PSG, brain MRI, and neuropsychological evaluations. SynthSeg, a neural network-based tool, provided high-quality segmentations despite noise. A priori hypotheses explored associations between brain function (measured by PSG) and brain structure (measured by MRI). Associations with cognitive scores and dementia status were studied. An exploratory data-driven approach investigated age-structure-physiology-cognition links. RESULTS: Six hundred and twenty-three patients with sleep PSG and brain MRI data were included in this study; 160 with cognitive evaluations. Three hundred and forty-two participants (55%) were female, and age interquartile range was 52 to 69 years. Thirty-six individuals were diagnosed with dementia, 71 with mild cognitive impairment, and 326 with major depression. One hundred and fifteen individuals were evaluated for insomnia and 138 participants had an apnea-hypopnea index equal to or greater than 15. Total PSG delta power correlated positively with frontal lobe/thalamic volumes, and sleep spindle density with thalamic volume. rapid eye movement (REM) duration and amygdala volume were positively associated with cognition. Patients with dementia showed significant differences in five brain structure volumes. REM duration, spindle, and slow-oscillation features had strong associations with cognition and brain structure volumes. PSG and MRI features in combination predicted chronological age (R2 = 0.67) and cognition (R2 = 0.40). CONCLUSIONS: Routine clinical data holds extended value in understanding and even clinically using brain-sleep-cognition relationships.