Normal Rapid Eye Movement Sleep Research Articles

A REM-active basal ganglia circuit that regulates anxiety

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 4days 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.

Isolated REM Sleep without Atonia Is Not Equivalent to REM Sleep Behavior Disorder in Early-Stage Parkinson's Disease.

In early-stage Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) predicts poor cognitive and motor outcome. However, the baseline significance and disease evolution associated with isolated REM sleep without atonia (iRWA, ie, enhanced muscle tone during 8.7% of REM sleep, but no violent behavior) are not well understood. The objective is to determine whether iRWA was a mild form of RBD and progressed similarly over time. Participants with early PD (<4 years from medical diagnosis) were included from 2014 to 2021 in a longitudinal study. They underwent interviews and examinations in the motor, cognitive, autonomous, psychiatric, sensory, and sleep domains every year for 4 years along with a video polysomnography and magnetic resonance imaging examination of the locus coeruleus/subcoeruleus complex (LC/LsC) at baseline. The clinical characteristics were compared between groups with normal REM sleep, with iRWA and with RBD, at baseline and for 4 years. Among 159 PD participants, 25% had RBD, 25% had iRWA, and 50% had normal REM sleep. At baseline, the non-motor symptoms were less prevalent and the LC/LsC signal intensity was more intense in participants with iRWA than with RBD. Over 4 years, participants with normal REM sleep and with iRWA had a similar cognitive and motor trajectory, whereas participants with RBD had greater cognitive and motor decline. We demonstrated that iRWA is frequent in early PD, but is not a milder form of RBD. Both groups have distinct baseline characteristics and clinical trajectories. They should be distinguished in clinical routine and research protocols. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Automated Analysis of REM Sleep without Atonia in the Lewy Body Disease Spectrum

AbstractBackgroundQuantitative rapid eye movement (REM) sleep without atonia (RSWA) recorded during polysomnography (PSG) represents loss of normal REM sleep atonia. RSWA is the neurophysiologic signature of REM sleep behavior disorder (RBD). Visually scored RSWA is a candidate biomarker for synucleinopathies. However, visual RSWA scoring requires expert scoring, limiting widespread application. We comparatively analyzed RSWA in DLB and iRBD using the automated Ferri REM Atonia Index (RAI).MethodWe quantitatively analyzed the RAI in 12 DLB and 20 iRBD patients, compared to 20 controls using Hypnolab Software for Sleep Analysis (SWS Soft, Inc, Colognola ai Colli, Italy). PSG data were converted to European Data Format (.EDF), and the submentalis surface electromyogram (EMG) signal was notch‐filtered at 60 Hertz and rectified. Automatically calculated RAI scores were comparatively analyzed across groups (DLB, iRBD, controls) using Kruskal Wallis H tests for group comparisons, and regression analyses determined relationships between diagnosis, age, and sex. Logistic regression ROC determined optimal RAI for distinguishing iRBD from DLB. When interpreting RAI, lower values represent greater amounts of RSWA, and higher values represent more normal REM atonia.ResultMean age was older in DLB than in iRBD or controls (72.6 vs. 68.7 vs. 66.5 years). All 12 DLB participants were men, the iRBD group had 18 men and 2 women, and controls were comprised of 16 men and 4 women. Mean RAI was lowest in DLB (0.46), intermediate in iRBD (0.71) and highest in controls (0.96), indicating a gradient in RSWA amounts from DLB patients (highest) to controls (lowest) (Figure). Regression demonstrated diagnosis independently predicted RAI, controlling for age and sex (adjusted R2 = 0.49, p = 0.0001). The RAI that optimally distinguished iRBD from DLB was 0.46 (specificity 85%, sensitivity 58%, AUC = 0.75).ConclusionThe RAI demonstrated a clear gradient throughout the Lewy body spectrum; highest (indicating lowest RSWA amounts) in controls, intermediate in iRBD, and lowest (indicating greatest RSWA) in DLB. The RAI is a promising, time efficient and broadly applicable candidate biomarker for DLB and iRBD. Automated quantitative RSWA could be a valuable tool for deep phenotyping throughout the Lewy body disease spectrum.

White matter microstructure in Parkinson's disease with and without elevated rapid eye movement sleep muscle tone.

People with Parkinson’s disease who have elevated muscle activity during rapid eye movement sleep (REM sleep without atonia) typically have a worse motor and cognitive impairment compared with those with normal muscle atonia during rapid eye movement sleep. This study used tract-based spatial statistics to compare diffusion MRI measures of fractional anisotropy, radial, mean and axial diffusivity (measures of axonal microstructure based on the directionality of water diffusion) in white matter tracts between people with Parkinson’s disease with and without rapid eye movement sleep without atonia and controls and their relationship to measures of motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson’s disease and 21 matched control subjects underwent ultra-high field MRI (7 T), quantitative motor assessments of gait and bradykinesia and neuropsychological testing. The Parkinson’s disease cohort was separated post hoc into those with and without elevated chin or leg muscle activity during rapid eye movement sleep based on polysomnography findings. Fractional anisotropy was significantly higher, and diffusivity significantly lower, in regions of the corpus callosum, projection and association white matter pathways in the Parkinson’s group with normal rapid eye movement sleep muscle tone compared with controls, and in a subset of pathways relative to the Parkinson’s disease group with rapid eye movement sleep without atonia. The Parkinson’s disease group with elevated rapid eye movement sleep muscle tone showed significant impairments in the gait and upper arm speed compared with controls and significantly worse scores in specific cognitive domains (executive function, visuospatial memory) compared with the Parkinson’s disease group with normal rapid eye movement sleep muscle tone. Regression analyses showed that gait speed and step length in the Parkinson’s disease cohort were predicted by measures of fractional anisotropy of the anterior corona radiata, whereas elbow flexion velocity was predicted by fractional anisotropy of the superior corona radiata. Visuospatial memory task performance was predicted by the radial diffusivity of the posterior corona radiata. These findings show that people with mild-to-moderate severity of Parkinson’s disease who have normal muscle tone during rapid eye movement sleep demonstrate compensatory-like adaptations in axonal microstructure that are associated with preserved motor and cognitive function, but these adaptations are reduced or absent in those with increased rapid eye movement sleep motor tone.

REM Sleep Without Atonia and Gait Impairment in People with Mild-to-Moderate Parkinson's Disease.

Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson's disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.

A data-driven system to identify REM sleep behavior disorder and to predict its progression from the prodromal stage in Parkinson's disease

ObjectivesTo investigate electroencephalographic (EEG), electrooculographic (EOG) and micro-sleep abnormalities associated with rapid eye movement (REM) sleep behavior disorder (RBD) and REM behavioral events (RBEs) in Parkinson's disease (PD). MethodsWe developed an automated system using only EEG and EOG signals. First, automatic macro- (30-s epochs) and micro-sleep (5-s mini-epochs) staging was performed. Features describing micro-sleep structure, EEG spectral content, EEG coherence, EEG complexity, and EOG energy were derived. All features were input to an ensemble of random forests, giving as outputs the probabilities of having RBD or not (P (RBD) and P (nonRBD), respectively). A patient was classified as having RBD if P (RBD)≥P (nonRBD). The system was applied to 107 de novo PD patients: 54 had normal REM sleep (PDnonRBD), 26 had RBD (PD + RBD), and 27 had at least two RBEs without meeting electromyographic RBD cut-off (PD + RBE). Sleep diagnoses were made with video-polysomnography (v-PSG). ResultsConsidering PDnonRBD and PD + RBD patients only, the system identified RBD with accuracy, sensitivity, and specificity over 80%. Among the features, micro-sleep instability had the highest importance for RBD identification. Considering PD + RBE patients, the ones who developed definite RBD after two years had significantly higher values of P (RBD) at baseline compared to the ones who did not. The former were distinguished from the latter with sensitivity and specificity over 75%. ConclusionsOur method identifies RBD in PD patients using only EEG and EOG signals. Micro-sleep instability could be a biomarker for RBD and for proximity of conversion from RBEs, as prodromal RBD, to definite RBD in PD patients.

Developmental Changes in Ultradian Sleep Cycles across Early Childhood.

Nocturnal human sleep is composed of cycles between rapid eye movement (REM) sleep and non-REM (NREM) sleep. In adults, the structure of ultradian cycles between NREM and REM sleep is well characterized; however, less is known about the developmental trajectories of ultradian sleep cycles across early childhood. Cross-sectional studies indicate that the rapid ultradian cycling of active-quiet sleep in infancy shifts to a more adult-like pattern of NREM-REM sleep cycling by the school-age years, yet longitudinal studies elucidating the details of this transition are scarce. To address this gap, we examined ultradian cycling during nocturnal sleep following 13 h of prior wakefulness in 8 healthy children at 3 longitudinal points: 2Y (2.5-3.0 years of age), 3Y (3.5-4.0 years of age), and 5Y (5.5-6.0 years of age). We found that the length of ultradian cycles increased with age as a result of increased NREM sleep episode duration. In addition, we observed a significant decrease in the number of NREM sleep episodes as well as a nonsignificant trend for a decrease in the number of cycles with increasing age. Together, these findings suggest a concurrent change in which cycle duration increases and the number of cycles decreases across development. We also found that, consistent with data from adolescents and adults, the duration of NREM sleep episodes decreased with time since lights-off whereas the duration of REM sleep episodes increased over this time period. These results indicate the presence of circadian modulation of nocturnal sleep in preschool children. In addition to characterizing changes in ultradian cycling in healthy children ages 2 to 5 years, this work describes a developmental model that may provide insights into the emergence of normal adult REM sleep regulatory circuitry as well as potential trajectories of dysregulated ultradian cycles such as those associated with affective disorders.

Narcolepsy type 1 and hypersomnia associated with a psychiatric disorder show different slow wave activity dynamics.

The aim of the study was to compare electrophysiological parameters of night sleep in narcolepsy type 1 and hypersomnia associated with a psychiatric disorder. Fortyfour patients: 15 with narcolepsy type 1, 14 with hypersomnia associated with a psychiatric disorder and 15 age- and sex-matched controls participated in the study. The study subjects filled in the Athens Insomnia Scale (AIS) and the Beck Depression Inventory (BDI). The severity of daytime sleepiness was quantified subjectively using the Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS), and objectively using the Multiple Sleep Latency Test (MSLT). All subjects underwent polysomnography (PSG) on the two consecutive nights. The data from the second night was analysed. The slow wave activity (SWA, 1-4 Hz) was calculated for the three consecutive sleep cycles, and topographic delta power maps were plotted. In contrast to narcoleptics, psychiatric hypersomniacs had undisturbed nocturnal sleep, high sleep efficiency, normal non-rapid eye movement (NREM) and rapid eye movement (REM) sleep proportions, normal REM latency and sleep latencies on MSLT and PSG. The subjective and objective sleepiness was significantly higher in narcolepsy group than in psychiatric hypersomnia group. In all the study groups SWA was the most prominent in frontal areas, while the greatest between-group differences were found in the central areas. There were significant differences between the groups in SWA in the second NREM episode. The highest SWA was observed in the hypersomnia group, while the lowest in the narcolepsy group. Psychiatric hypersomniacs and controls did not differ in the SWA exponential decline over consecutive NREM episodes, whereas narcoleptics exhibited a steeper dissipation of sleep pressure from the first to the second NREM episode. In conclusion, narcolepsy type1 and hypersomnia associated with psychiatric disorder differ in the SWA dynamics. Narcoleptics presented with the altered dynamics of sleep homeostasis, whereas psychiatric hypersomniacs showed normal nocturnal sleep and normal sleep homeostasis.

Noradrenaline from Locus Coeruleus Neurons Acts on Pedunculo-Pontine Neurons to Prevent REM Sleep and Induces Its Loss-Associated Effects in Rats.

Normally, rapid eye movement sleep (REMS) does not appear during waking or non-REMS. Isolated, independent studies showed that elevated noradrenaline (NA) levels inhibit REMS and induce REMS loss-associated cytomolecular, cytomorphological, psychosomatic changes and associated symptoms. However, the source of NA and its target in the brain for REMS regulation and function in health and diseases remained to be confirmed in vivo. Using tyrosine hydroxylase (TH)-siRNA and virus-coated TH-shRNA in normal freely moving rats, we downregulated NA synthesis in locus coeruleus (LC) REM-OFF neurons in vivo. These TH-downregulated rats showed increased REMS, which was prevented by infusing NA into the pedunculo-pontine tegmentum (PPT), the site of REM-ON neurons, normal REMS returned after recovery. Moreover, unlike normal or control-siRNA- or shRNA-injected rats, upon REMS deprivation (REMSD) TH-downregulated rat brains did not show elevated Na-K ATPase (molecular changes) expression and activity. To the best of our knowledge, these are the first in vivo findings in an animal model confirming that NA from the LC REM-OFF neurons (1) acts on the PPT REM-ON neurons to prevent appearance of REMS, and (2) are responsible for inducing REMSD-associated molecular changes and symptoms. These observations clearly show neuro-physio-chemical mechanism of why normally REMS does not appear during waking. Also, that LC neurons are the primary source of NA, which in turn causes some, if not many, REMSD-associated symptoms and behavioral changes. The findings are proof-of-principle for the first time and hold potential to be exploited for confirmation toward treating REMS disorder and amelioration of REMS loss-associated symptoms in patients.

Clinical Considerations of Obstructive Sleep Apnea with Little REM Sleep.

Background and PurposeObstructive sleep apnea (OSA) is more severe during rapid eye movement (REM) sleep than during non-REM sleep. We aimed to determine the features of patients with OSA who experience little REM sleep.MethodsPatients with a chief complaint of sleep-disordered breathing were enrolled. All subjects underwent overnight polysomnography (PSG) and completed questionnaires on sleep quality. Patients were divided into the following three groups according to the proportion of REM sleep detected in overnight PSG: little REM sleep [REM sleep <20% of total sleep time (TST)], normal REM sleep (20–25% of TST), and excessive REM sleep (>25% of TST). Multiple logistic regression analyses were applied to the data. The success rate of continuous positive airway pressure (CPAP) titration was estimated in these groups.ResultsThe age and body mass index of the patients were 47.9±15.9 years (mean±SD) and 25.2±4.1 kg/m2, respectively. The 902 patients comprised 684 (76%) men and 218 (24%) women. The apnea-hypopnea index (AHI) in the little-REM-sleep group was 22.1±24.4 events/hour, which was significantly higher than those in the other two groups (p<0.05). Multiple logistic regression showed that a higher AHI (p<0.001; odds ratio, 1.512; 95% confidence interval, 1.020–1.812) was independently predictive of little REM sleep. The titration success rate was lower in the little-REM-sleep group than in the normal-REM-sleep group (p=0.038).ConclusionsThe AHI is higher and the success rate of CPAP titration is lower in OSA patients with little REM sleep than those with normal REM sleep.

English

Data from the sleep disorder institute showed that subjects with similar apnea hypopnea index (AHI) but different body mass index (BMI) had no difference in oxygen saturation in rapid eye movement (REM) or non-rapid eye movement (NREM) sleep. Only 6 pairs of subjects were evaluated in the study and they were not age-matched. The objective of this study was to evaluate, in age-matched subjects, if there are any differences in oxygen saturation and duration of apenic spells in subjects with similar AHI but different BMI. Ninety eight (98) subjects paired for AHI within one event/hour and BMI difference of 5 and above were grouped in 9 groups. Subjects belonged mainly to normal, mild and moderate AHI group. Diagnostic nocturnal polysomnography inclusion criteria were normal REM sleep and total sleep time of 5 h. Oxygen saturation was continuously assessed throughout the nocturnal polysomnography (NPSG), and was calibrated for each NPSG study, and was visually identified by sleeping physician and artifacts were eliminated from the analyses. For all age groups, differences between matched pairs on BMI were regressed on the following factors: baseline oxygen saturation, lowest oxygen saturation, average oxygen saturation difference between pairs, apnea maximum and mean durations. Mean BMI differences between age- and AHI-matched pairs were 10.2 ± 5.7 (range 5.0 to 29.0). Stepwise regression indicated that BMI differences between pairs best predicted minimum oxygen saturation (p = 0.008, 1-tail). One-way analysis of variance (ANOVA) showed that age differences contributed to the robust finding regarding how BMI differences predicted lowest oxygen saturation. Using a very conservative Bonferroni correction for multiple comparisons, lowest saturation differed only between lower age groups [group 1 < group 2 (p = 0.3) < group 3 (p = 0.001) and < group 4 (p = 0.02)]. Difference in BMI (when AHI is matched), especially between ages 25 and 44 years old, predicts differences in minimum oxygen saturation. Caution is warranted as severe apneics were not evaluated in small sample sizes in subject older than 40. Key words: Obstructive sleep apnea (OSA), apnea hypopnea index (AHI), body mass index (BMI), nocturnal polysomnography (NPSG), oxygen saturation, sleep disorder.

Heart rate variability: a tool to explore the sleeping brain?

Sleep is divided into two main sleep stages: (1) non-rapid eye movement sleep (non-REMS), characterized among others by reduced global brain activity; and (2) rapid eye movement sleep (REMS), characterized by global brain activity similar to that of wakefulness. Results of heart rate variability (HRV) analysis, which is widely used to explore autonomic modulation, have revealed higher parasympathetic tone during normal non-REMS and a shift toward sympathetic predominance during normal REMS. Moreover, HRV analysis combined with brain imaging has identified close connectivity between autonomic cardiac modulation and activity in brain areas such as the amygdala and insular cortex during REMS, but no connectivity between brain and cardiac activity during non-REMS. There is also some evidence for an association between HRV and dream intensity and emotionality. Following some technical considerations, this review addresses how brain activity during sleep contributes to changes in autonomic cardiac activity, organized into three parts: (1) the knowledge on autonomic cardiac control, (2) differences in brain and autonomic activity between non-REMS and REMS, and (3) the potential of HRV analysis to explore the sleeping brain, and the implications for psychiatric disorders.

Rapid Eye Movement Sleep Behavior Disorder as an Outlier Detection Problem

Idiopathic rapid eye movement (REM) sleep behavior disorder is a strong early marker of Parkinson's disease and is characterized by REM sleep without atonia and/or dream enactment. Because these measures are subject to individual interpretation, there is consequently need for quantitative methods to establish objective criteria. This study proposes a semiautomatic algorithm for the early detection of Parkinson's disease. This is achieved by distinguishing between normal REM sleep and REM sleep without atonia by considering muscle activity as an outlier detection problem. Sixteen healthy control subjects, 16 subjects with idiopathic REM sleep behavior disorder, and 16 subjects with periodic limb movement disorder were enrolled. Different combinations of five surface electromyographic channels, including the EOG, were tested. A muscle activity score was automatically computed from manual scored REM sleep. This was accomplished by the use of subject-specific features combined with an outlier detector (one-class support vector machine classifier). It was possible to correctly separate idiopathic REM sleep behavior disorder subjects from healthy control subjects and periodic limb movement subjects with an average validation area under the receiver operating characteristic curve of 0.993 when combining the anterior tibialis with submentalis. Additionally, it was possible to separate all subjects correctly when the final algorithm was tested on 12 unseen subjects. Detection of idiopathic REM sleep behavior disorder can be regarded as an outlier problem. Additionally, the EOG channels can be used to detect REM sleep without atonia and is discriminative better than the traditional submentalis. Furthermore, based on data and methodology, arousals and periodic limb movements did only have a minor influence on the quantification of the muscle activity. Analysis of muscle activity during nonrapid eye movement sleep may improve the separation even further.

The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson’s disease

In Parkinson’s disease, rapid eye movement sleep behaviour disorder is an early non-dopaminergic syndrome with nocturnal violence and increased muscle tone during rapid eye movement sleep that can precede Parkinsonism by several years. The neuronal origin of rapid eye movement sleep behaviour disorder in Parkinson’s disease is not precisely known; however, the locus subcoeruleus in the brainstem has been implicated as this structure blocks muscle tone during normal rapid eye movement sleep in animal models and can be damaged in Parkinson’s disease. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex in patients with Parkinson’s disease using combined neuromelanin-sensitive, structural and diffusion magnetic resonance imaging approaches. We compared 24 patients with Parkinson’s disease and rapid eye movement sleep behaviour disorder, 12 patients without rapid eye movement sleep behaviour disorder and 19 age- and gender-matched healthy volunteers. All subjects underwent clinical examination and characterization of rapid eye movement sleep using video-polysomnography and multimodal imaging at 3 T. Using neuromelanin-sensitive imaging, reduced signal intensity was evident in the locus coeruleus/subcoeruleus area in patients with Parkinson’s disease that was more marked in patients with than those without rapid eye movement sleep behaviour disorder. Reduced signal intensity correlated with the percentage of abnormally increased muscle tone during rapid eye movement sleep. The results confirmed that this complex is affected in Parkinson’s disease and showed a gradual relationship between damage to this structure, presumably the locus subcoeruleus, and abnormal muscle tone during rapid eye movement sleep, which is the cardinal marker of rapid eye movement sleep behaviour disorder. In longitudinal studies, the technique may also provide early markers of non-dopaminergic Parkinson’s disease pathology to predict the occurrence of Parkinson’s disease.

Clinical significance of REM sleep behavior disorder in Parkinson’s disease

Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for dementia development in patients with Parkinson's disease (PD); however, the role of subclinical RBD remains unknown. Patients with PD and clinical RBD, subclinical RBD, or with normal REM sleep were examined in a cross sectional study and a longitudinal follow-up. Interviews regarding RBD symptoms and polysomnographies were performed on 82 PD patients divided into RBD subcategories based on the presence/absence of REM sleep without atonia (RWA) and/or RBD symptoms. Descriptive variables were compared and patients were followed-up longitudinally for 21.4±10.8months. The existence of RBD, but not subclinical RBD, was associated with orthostatic hypotension and levodopa dose equivalents (LDEs) in patients with PD. Kaplan-Myer curves indicated that the occurrence of dementia in the PD group with clinical RBD was significantly faster than in the PD group with normal REM sleep (p=0.013). A Cox hazard regression analysis revealed that development to PD with dementia was only significantly associated with the presence of clinical RBD (hazard ratio: 14.1, p=0.017). Clinical RBD symptoms, but not subclinical RBD, were associated with the development of dementia in PD.

Subthalamic nucleus deep brain stimulation restores normal rapid eye movement sleep in Parkinson's disease

In Parkinson's disease, sleep disturbance is a common occurrence. We evaluated sleep in 10 patients with Parkinson's disease (age, 57.5 ± 9.8 years; disease duration, 12.3 ± 2.7 years) before and after subthalamic nucleus deep brain stimulation using the Parkinson's disease sleep scale and polysomnography. Their total sleep scale scores and daytime sleepiness subscale scores significantly improved after subthalamic nucleus-deep brain stimulation. The novel findings from this study significantly increased normal rapid eye movement sleep, and decreased abnormal rapid eye movement sleep without atonia after deep brain stimulation in patients with Parkinson's disease. The improved total sleep scale score correlated with decreased wakefulness after sleep onset. Moreover, improved daytime sleepiness correlated with increased normal rapid eye movement sleep time. Sleep improvement did not significantly correlate with resolution of motor complication or reduced dopaminergic dosages. Subthalamic nucleus-deep brain stimulation may have beneficial effects on sleep disturbance in advanced Parkinson's disease by restoring sleep architecture and normal rapid eye movement sleep.

Narcoleptic orexin receptor knockout mice express enhanced cholinergic properties in laterodorsal tegmental neurons

Pharmacological studies of narcoleptic canines indicate that exaggerated pontine cholinergic transmission promotes cataplexy. As disruption of orexin (hypocretin) signaling is a primary defect in narcolepsy with cataplexy, we investigated whether markers of cholinergic synaptic transmission might be altered in mice constitutively lacking orexin receptors (double receptor knockout; DKO). mRNA for Choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and the high-affinity choline transporter (CHT1) but not acetylcholinesterase (AChE) was significantly higher in samples from DKO than wild-type (WT) mice. This was region-specific; levels were elevated in samples from the laterodorsal tegmental nucleus (LDT) and the fifth motor nucleus (Mo5) but not in whole brainstem samples. Consistent with region-specific changes, we were unable to detect significant differences in Western blots for ChAT and CHT1 in isolates from brainstem, thalamus and cortex or in ChAT enzymatic activity in the pons. However, using ChAT immunocytochemistry, we found that while the number of cholinergic neurons in the LDT and Mo5 were not different, the intensity of somatic ChAT immunostaining was significantly greater in the LDT, but not Mo5, from DKO than from WT mice. We also found that ChAT activity was significantly reduced in cortical samples from DKO compared with WT mice. Collectively, these findings suggest that the orexins can regulate neurotransmitter expression and that the constitutive absence of orexin signaling results in an up-regulation of the machinery necessary for cholinergic neurotransmission in a mesopontine population of neurons that have been associated with both normal rapid eye movement sleep and cataplexy.

Do the eyes scan dream images during rapid eye movement sleep? Evidence from the rapid eye movement sleep behaviour disorder model

Rapid eye movements and complex visual dreams are salient features of human rapid eye movement sleep. However, it remains to be elucidated whether the eyes scan dream images, despite studies that have retrospectively compared the direction of rapid eye movements to the dream recall recorded after having awakened the sleeper. We used the model of rapid eye movement sleep behaviour disorder (when patients enact their dreams by persistence of muscle tone) to determine directly whether the eyes move in the same directions as the head and limbs. In 56 patients with rapid eye movement sleep behaviour disorder and 17 healthy matched controls, the eye movements were monitored by electrooculography in four (right, left, up and down) directions, calibrated with a target and synchronized with video and sleep monitoring. The rapid eye movement sleep behaviour disorder-associated behaviours occurred 2.1 times more frequently during rapid eye movement sleep with than without rapid eye movements, and more often during or after rapid eye movements than before. Rapid eye movement density, index and complexity were similar in patients with rapid eye movement sleep behaviour disorder and controls. When rapid eye movements accompanied goal-oriented motor behaviour during rapid eye movement sleep behaviour disorder (e.g. grabbing a fictive object, hand greetings, climbing a ladder), which happened in 19 sequences, 82% were directed towards the action of the patient (same plane and direction). When restricted to the determinant rapid eye movements, the concordance increased to 90%. Rapid eye movements were absent in 38-42% of behaviours. This directional coherence between limbs, head and eye movements during rapid eye movement sleep behaviour disorder suggests that, when present, rapid eye movements imitate the scanning of the dream scene. Since the rapid eye movements are similar in subjects with and without rapid eye movement sleep behaviour disorder, this concordance can be extended to normal rapid eye movement sleep.

Circadian Rhythms: A Tale of Two Nuclei

Uncoupling the oscillators in the dorsal and ventral subdivisions of the rat suprachiasmatic nucleus reveals which one of them regulates the circadian rhythm of rapid eye movement sleep.

Functional Imaging of Cataplexy During Status Cataplecticus

To identify the neural structures and pathways underlying cataplexy during status cataplecticus in a narcoleptic patient, using brain perfusion single photon emission computed tomography (SPECT). A 68-year-old woman with hypocretin-deficient narcolepsy-cataplexy suffered status cataplecticus after having stopped clomipramine. She underwent a 99mTc-ethylcysteinate dimer brain SPECT during an episode of cataplexy; this image was compared with her brain SPECT during an intervening asymptomatic period. Subtraction SPECT coregistered to magnetic resonance imaging (MRI)(SISCOM)-determined anatomic areas differentially perfused during cataplexy and basal wakefulness state. The areas hyperactivated during cataplexy corresponded on brain MRI with the cingular area, the left and right orbitofrontal cortex, the right temporal cortex, and the right putamen. No significant hypoperfused region was observed during the cataplectic episode. Cataplexy during status cataplecticus partially resembles normal rapid eye movement sleep (with high cingular, orbitofrontal, and putamen activity) but without the other imaging characteristics of this state (no hyperactivation of the pons, amygdale, or occipital cortex).