Single-channel EOG sleep staging on a heterogeneous cohort of subjects with sleep disorders.

Objective.Sleep staging based on full polysomnography is the gold standard in the diagnosis of many sleep disorders. It is however costly, complex, and obtrusive due to the use of multiple electrodes. Automatic sleep staging based on single-channel electro-oculography (EOG) is a promising alternative, requiring fewer electrodes which could be self-applied below the hairline. EOG sleep staging algorithms are however yet to be validated in clinical populations with sleep disorders.Approach.We utilized the SOMNIA dataset, comprising 774 recordings from subjects with various sleep disorders, including insomnia, sleep-disordered breathing, hypersomnolence, circadian rhythm disorders, parasomnias, and movement disorders. The recordings were divided into train (574), validation (100), and test (100) groups. We trained a neural network that integrated transformers within a U-Net backbone. This design facilitated learning of arbitrary-distance temporal relationships within and between the EOG and hypnogram.Main results.For 5-class sleep staging, we achieved median accuracies of 85.0% and 85.2% and Cohen's kappas of 0.781 and 0.796 for left and right EOG, respectively. The performance using the right EOG was significantly better than using the left EOG, possibly because in the recommended AASM setup, this electrode is located closer to the scalp. The proposed model is robust to the presence of a variety of sleep disorders, displaying no significant difference in performance for subjects with a certain sleep disorder compared to those without.Significance.The results show that accurate sleep staging using single-channel EOG can be done reliably for subjects with a variety of sleep disorders.

Temporal dynamics of awakenings from slow-wave sleep in non-rapid eye movement parasomnia.

Non-rapid eye movement parasomnia disorders, also called disorders of arousal, are characterized by abnormal nocturnal behaviours, such as confusional arousals or sleep walking. Their pathophysiology is not yet fully understood, and objective diagnostic criteria are lacking. It is known, however, that behavioural episodes occur mostly in the beginning of the night, after an increase in slow-wave activity during slow-wave sleep. A better understanding of the prospect of such episodes may lead to new insights in the underlying mechanisms and eventually facilitate objective diagnosis. We investigated temporal dynamics of transitions from slow-wave sleep of 52 patients and 79 controls. Within the patient group, behavioural and non-behavioural N3 awakenings were distinguished. Patients showed a higher probability to wake up after an N3 bout ended than controls, and this probability increased with N3 bout duration. Bouts longer than 15 min resulted in an awakening in 73% and 34% of the time in patients and controls, respectively. Behavioural episodes reduced over sleep cycles due to a reduction in N3 sleep and a reducing ratio between behavioural and non-behavioural awakenings. In the first two cycles, N3 bouts prior to non-behavioural awakenings were significantly shorter than N3 bouts advancing behavioural awakenings in patients, and N3 awakenings in controls. Our findings provide insights in the timing and prospect of both behavioural and non-behavioural awakenings from N3, which may result in prediction and potentially prevention of behavioural episodes. This work, moreover, leads to a more complete characterization of a prototypical hypnogram of parasomnias, which could facilitate diagnosis.

A computationally efficient algorithm for wearable sleep staging in clinical populations.

This study describes a computationally efficient algorithm for 4-class sleep staging based on cardiac activity and body movements. Using an accelerometer to calculate gross body movements and a reflective photoplethysmographic (PPG) sensor to determine interbeat intervals and a corresponding instantaneous heart rate signal, a neural network was trained to classify between wake, combined N1 and N2, N3 and REM sleep in epochs of 30 s. The classifier was validated on a hold-out set by comparing the output against manually scored sleep stages based on polysomnography (PSG). In addition, the execution time was compared with that of a previously developed heart rate variability (HRV) feature-based sleep staging algorithm. With a median epoch-per-epoch κ of 0.638 and accuracy of 77.8% the algorithm achieved an equivalent performance when compared to the previously developed HRV-based approach, but with a 50-times faster execution time. This shows how a neural network, without leveraging any a priori knowledge of the domain, can automatically "discover" a suitable mapping between cardiac activity and body movements, and sleep stages, even in patients with different sleep pathologies. In addition to the high performance, the reduced complexity of the algorithm makes practical implementation feasible, opening up new avenues in sleep diagnostics.

Prescription Drugs Used in Insomnia.

In insomnia, the subjective aspects of the sleep complaint are paramount in the diagnostic criteria. Epidemiologic studies increasingly point to a link between insomnia and somatic morbidity and mortality, but until now, only in the subgroup of objectively poor sleepers. Although pharmacologic treatment might offer some benefits to this subgroup of insomnia patients, to date, there is no evidence that hypnotics can ameliorate their health risks. Further unraveling of the neurobiology and genetics of sleep regulation and the pathophysiology of insomnia will help the development of drugs that not only improve subjective sleep complaints but also objective health outcomes.

Validation of the Dutch translation of the Paris Arousal Disorders Severity Scale for non-REM parasomnias in a 1-year and 1-month version.

STUDY OBJECTIVES: We created a Dutch version of the Paris Arousal Disorders Severity Scale (PADSS), which assesses non-rapid eye movement (NREM) parasomnia symptoms over the past year (PADSS-year). This questionnaire was previously validated in patients with sleep walking and/or sleep terrors (SW/ST). We validated the questionnaire in SW/ST patients, and in a broader population, including patients with confusional arousals, comorbidities, and medication users ("other NREM parasomnias"). Furthermore, we introduced a version covering the past month (PADSS-month), with the potential purpose of evaluating symptom evolution and treatment response. METHODS: We compared PADSS scores among 54 SW/ST patients, 34 age-matched controls, and 23 patients with other NREM parasomnias. We evaluated discriminative capacity, internal consistency, and construct validity. Furthermore, we assessed the test-retest reliability and treatment response of PADSS-month. RESULTS: Healthy controls scored significantly lower than both patient groups. We found an excellent diagnostic accuracy (area under the curve PADSS-year 0.990, PADSS-month 0.987) and an acceptable internal consistency. Exploratory factor analysis identified 3 components: "behaviors outside the bed," "behaviors in/around the bed," and "violent behaviors," with the former 2 factors reflecting the distinction between SW and ST. PADSS-month showed an acceptable test-retest reliability (0.75). Additionally, PADSS-month significantly decreased after pharmaceutical and/or behavioral treatment. This change was correlated with the clinical impression of the caregiver, implying that PADSS-month is sensitive to treatment effects. CONCLUSIONS: The Dutch PADSS questionnaire can be used as a screening tool in a broad population of patients with NREM parasomnia, not only SW/ST. Furthermore, we validated a PADSS-month version to assess the evolution of symptoms and treatment effect. CITATION: van Mierlo P, Hermans L, Arnulf I, Pijpers A, Overeem S, van Gilst M. Validation of the Dutch translation of the Paris Arousal Disorders Severity Scale for non-REM parasomnias in a 1-year and 1-month version. J Clin Sleep Med. 2022;18(4):1135-1143.

Awakening to sleep disorders in Europe: Survey on education, knowledge and treatment competence of European residents and neurologists.

OBJECTIVES: Sleep-wake disorders are common in the general population and in most neurological disorders but are often poorly recognized. With the hypothesis that neurologists do not get sufficient training during their residency, the Young European Sleep Neurologist Association (YESNA) of the European Academy of Neurology (EAN) performed a survey on postgraduate sleep education. METHODS: A 16-item questionnaire was developed and distributed among neurologists and residents across European countries. Questions assessed demographic, training and learning preferences in sleep disorders, as well as a self-evaluation of knowledge based on five basic multiple-choice questions (MCQs) on sleep-wake disorders. RESULTS: The questionnaire was completed by 568 participants from 20 European countries. The mean age of participants was 31.9 years (SD 7.4 years) and was composed mostly of residents (73%). Three-quarters of the participants reported undergraduate training in sleep medicine, while fewer than 60% did not receive any training on sleep disorders during their residencies. Almost half of the participants (45%) did not feel prepared to treat neurological patients with sleep problems. Only one-third of the participants correctly answered at least three MCQs. Notably, 80% of participants favoured more education on sleep-wake disorders during the neurology residency. CONCLUSIONS: Education and knowledge on disorders in European neurological residents is generally insufficient, despite a strong interest in the topic. The results of our study may be useful for improving the European neurology curriculum and other postgraduate educational programmes.

Prescription Drugs Used in Insomnia.

The scope of this article is to review the effects on sleep of prescription drugs that are commonly prescribed for chronic insomnia in adults. The following groups are discussed: benzodiazepines and its receptor agonists, the dual orexin receptor antagonist suvorexant, melatonin and its receptor agonists, sedating antidepressants, and antipsychotics. Together with the neurobiologic and pharmacologic properties of these drugs, clinical effects are described, including subjective and objective effects on sleep duration, continuity, and architecture. Medical prescription information is given when available. Recently published American and European guidelines for the treatment of insomnia serve as reference frame.

Management of insomnia in sleep disordered breathing.

Both obstructive sleep apnoea (OSA) and chronic insomnia disorder are highly prevalent in the general population. Whilst both disorders may occur together by mere coincidence, it appears that they share clinical features and that they may aggravate each other as a result of reciprocally adverse pathogenetic mechanisms. Comorbidity between chronic insomnia disorder and OSA is a clinically relevant condition that may confront practitioners with serious diagnostic and therapeutic challenges. Current data, while still scarce, advocate an integrated and multidisciplinary approach that seems superior over the isolated treatment of each sleep disorder alone.

Prescription Drugs Used in Insomnia.

The scope of this article is to review the effects on sleep of prescription drugs that are commonly prescribed for chronic insomnia in adults. The following groups are discussed: benzodiazepines and its receptor agonists, the dual orexin receptor antagonist suvorexant, melatonin and its receptor agonists, sedating antidepressants, and antipsychotics. Together with the neurobiologic and pharmacologic properties of these drugs, clinical effects are described, including subjective and objective effects on sleep duration, continuity, and architecture. Medical prescription information is given when available. Recently published American and European guidelines for the treatment of insomnia serve as reference frame.

FDG PET, dopamine transporter SPECT, and olfaction: Combining biomarkers in REM sleep behavior disorder.

BACKGROUND: Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD-related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD-related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder. METHODS: In this cross-sectional study, 21 idiopathic REM sleep behavior disorder subjects underwent 18 F-fluorodeoxyglucose PET, dopamine transporter imaging, and olfactory testing. For reference, we included 18 F-fluorodeoxyglucose PET data of 19 controls, 20 PD patients, and 22 patients with dementia with Lewy bodies. PD-related pattern expression z-scores were computed from all PET scans. RESULTS: PD-related pattern expression was higher in idiopathic REM sleep behavior disorder subjects compared with controls (P = 0.048), but lower compared with PD (P = 0.001) and dementia with Lewy bodies (P < 0.0001). PD-related pattern expression was higher in idiopathic REM sleep behavior disorder subjects with hyposmia and in subjects with an abnormal dopamine transporter scan (P < 0.05, uncorrected). CONCLUSION: PD-related pattern expression, dopamine transporter binding, and olfaction may provide complementary information for predicting phenoconversion. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Sleep related breathing disorders and indications for polysomnography in preterm infants.

There is a range of breathing problems which occur and may persist in preterm infants, such as central apneas, obstructive apneas and periodic breathing. Preterm infants may also suffer from respiratory distress syndrome and chronic lung disease necessitating prolonged use of oxygen therapy after discharge from the hospital. Due to these persistent breathing pattern abnormalities in preterm infants, there is a higher risk of altered sleep and apparent life threatening events. Polysomnography can be a helpful tool to identify those infants who have abnormalities in their breathing pattern, to identify those infants who have an increased risk to get a sleep related breathing event at home and to decide about the discontinuation of oxygen therapy.

Multiple cerebellar zones are involved in the control of individual muscles: a retrograde transneuronal tracing study with rabies virus in the rat.

To identify cerebellar regions that are involved in the control of limb muscles, rabies virus was injected into the tibialis anterior (TA), the gastrocnemius (GC) or, for comparison, into the flexor digitorum (FD) muscles of the rat. Progression of retrograde transneuronal infection at supraspinal levels was assessed after variable time spans and was divided into three groups. Initially, infected neurons were observed in the reticular formation, lateral vestibular nucleus, red nucleus and motor cortex (group 1). Group 2 was characterized by labelling within the cerebellar nuclei as well as of two vermal strips of Purkinje cells (PCs). Double-labelling with zebrin enabled identification of these strips as the lateral part of the A1- and B-zone. For TA both zones were ipsilateral, whereas for GC the A1 strip predominated contralaterally. Group 3 infections showed additional labelling of multiple, in part bilateral, identifiable strips of PCs in vermis, paravermis and hemisphere. FD injections resulted in less robust labelling of vermal strips and more pronounced labelling within paravermal and hemispheral zonal regions. Only sporadic labelling in corresponding regions of the inferior olive and no labelling of cortical interneurons or granule cells was observed. Prolonged infection was seen to result in degeneration of PCs and possibly of motoneurons. We conclude that vermal, paravermal as well as hemispheral zones of the cerebellar cortex converge upon motoneurons that innervate a particular muscle. In addition, individual zones may control motorpools of different muscles and thus contribute to muscle synergies.

Selective impairment of the cerebellar C1 module involved in rat hind limb control reduces step-dependent modulation of cutaneous reflexes.

The cerebellum is divided into multiple parasagittally organized modules, which are thought to represent functional entities. How individual modules participate in cerebellar control of complex movements such as locomotion remains largely unknown. To a large extent, this is caused by the inability to study the contribution of individual modules during locomotion. Because of the architecture of modules, based on narrow, elongated cortical strips that may be discontinuous in the rostrocaudal direction, lesion of a complete module, without affecting neighboring modules, has not been possible. Here, we report on a new method for inducing a selective dysfunction of spatially separated parts of a single module using a small cortical injection of a retrogradely transported neurotoxin, cholera toxin b-subunit-saporin. We show that such a local injection into the C1 module results in climbing fiber and partial mossy fiber deafferentation of functionally related areas of this module, thereby resulting in a severe impairment of the whole module without affecting neighboring modules. A subsequent functional analysis indicates that such an impairment of the hindlimb part of the C1 module did not have a significant impact on skilled walking or overall stepping pattern. However, the modulation of cutaneously induced reflexes during stepping was severely diminished. We propose that the C1 module is specifically involved in the adaptive control of reflexes.

Precise spatial relationships between mossy fibers and climbing fibers in rat cerebellar cortical zones.

Classically, mossy fiber and climbing fiber terminals are regarded as having very different spatial distributions in the cerebellar cortex. However, previous anatomical studies have not studied these two major cerebellar inputs with sufficient resolution to confirm this assumption. Here, we examine the detailed pattern of collateralization of both types of cerebellar afferent using small injections of the bidirectional tracer cholera toxin b subunit into the posterior cerebellum. The cortical and zonal location of these injections was characterized by mapping climbing fiber field potentials, the distribution of retrogradely labeled olivary neurons, and the intrinsic zebrin pattern of Purkinje cells. Labeled climbing fiber collaterals were distributed as longitudinal strips and were always accompanied by clusters of labeled mossy fiber rosettes in the subjacent granular layer. Two- and three-dimensional reconstructions and quantitative analysis showed that mossy fibers also collateralized to other stripe-like regions usually below Purkinje cells with the same zebrin-positive or zebrin-negative characteristics as that of the injection site and associated climbing fiber collaterals. The distribution of retrogradely labeled neurons in two major sources of mossy fibers, the lateral reticular and basilar pontine nuclei, revealed interlobular and some interzonal differences. These data indicate that nonadjacent cerebellar zones, sharing the same climbing fiber input and zebrin identity, also share a common mossy fiber input. Other cerebellar cortical regions that receive collaterals from the same mossy fibers usually also have the same zebrin signature. Together with the distribution of neurons in precerebellar centers, the findings suggest a revision of the modular hypothesis for information processing in the cerebellar cortex.

Organization of pontocerebellar projections to identified climbing fiber zones in the rat.

The organization of pontocerebellar projections to the paravermis and hemisphere of the posterior cerebellum of the rat was studied in relation to the organization of climbing fibers. Small injections of cholera toxin subunit B were placed in the cerebellar cortex at locations predetermined by evoked climbing fiber potentials from selected body parts or based on coordinates. The injection site was characterized with respect to the zebrin pattern and by the distribution of retrogradely labeled neurons in the inferior olive. The following zones were studied: hindlimb-related zones C1 and C2 of lobule VIII; forelimb-related zones C1, C2, and D0/D1 of the paramedian lobule; and face-related zones A2 of the paramedian lobule and C2 and D0 of crus 2B. The results show that the distribution of pontine neurons is closely related to the climbing fiber somatotopy. Injections centered on face-related zones result in distribution of pontine neurons within the pontine core region. Forelimb regions surround this core, whereas hindlimb regions are mostly supplied by caudal pontine regions and by a single patch of more rostrally located neurons. This distribution fits well with published data on the somatotopy of the corticopontine projection from the rat primary somatosensory cortex. However, apart from differences in the participation of ipsilaterally projecting cells, the distribution of pontine neurons does not change significantly when the injection covers different zones of the same lobule such as C1 and C2 of lobule VIII; C1, C2, and D0/D1 of the paramedian lobule; A2 of the paramedian lobule; and C2 and D0 of crus 2B.

Topography of olivo-cortico-nuclear modules in the intermediate cerebellum of the rat.

This study provides a detailed anatomical description of the relation between olivo-cortico-nuclear modules of the intermediate cerebellum of the rat and the intrinsic zebrin pattern of the Purkinje cells. Strips of climbing fibers were labeled using small injections of biotinylated dextran amine into either the medial or dorsal accessory olives, while, in some cases, simultaneous retrograde labeling of Purkinje cells was obtained using gold-lectin injections into selected parts of the interposed nuclei. Our data are represented in a new, highly detailed, cortical surface reconstruction of the zebrin pattern and in relation to the collateral labeling of the climbing fibers to the cerebellar nuclei. We show that the somatotopic regions of the dorsal accessory olive behave differently in their projections to essentially zebrin-negative regions that represent the C1 and C3 zones of the anterior and posterior parts of the cortex. The rostral part of the medial accessory olive projects to zebrin-positive areas, in particular to the P4+ band of the anterior lobe and lobule VI and to the P5+ band of the posterior lobe, indicating that C2 has two noncontiguous representations in the SL and crus 1. By relating the areas of overlap that resulted from the injections in the accessory olives, i.e., labeling of climbing fiber strips and patches of climbing fiber nuclear collaterals, with the results from the injections in the interposed nuclei, i.e., retrograde labeling of Purkinje cells and of inferior olivary neurons, direct verification of the concept of modular cerebellar connections was obtained.