Invited Speaker Abstracts

Session: Symposium—Maternal stress during pregnancy may shape the rest of your life.

Presentation: Long-term effects of perinatal stress exposure on adult health in animal models.

Speaker: Viviana Lo Martire, Italy.

Summary

The Developmental Origins of Health and Disease (DOHaD) theory hypothesizes that environmental exposures during early life (particularly the in-utero period) can permanently influence health and vulnerability to diseases later in life. Adult-onset diseases may be linked to early life environmental conditions. The brain regions involved have not yet been identified but, among other areas, the hippocampus is likely to be permanently modulated by early life stress. This structure is involved in the regulation of the activity of the hypothalamic–pituitary–adrenal (HPA) axis, the primary component of stress response. A growing body of evidence suggests that perinatal stress exposure leads to diseases in adult life associated to a hyperactivation of the HPA axis, possibly through an epigenetic programming of the hippocampus, a key structure in the coordination of the hormonal stress response. The persistent hyperactivation of the HPA axis has several consequences also on wake–sleep bahavior, since its mediators acts as wake-promoting molecules. There is a bidirectional relationship between stress and sleep: stress inducing factors may alter sleep–wake architecture and sleep impairment may deeply impact several biological pathways, including stress responses and, eventually, quality of life. However, a new aspect is emerging: the moment of life in which stress is acting should be considered as a relevant factor in mediating the effects of this bidirectional relationship. Here, data from animal studies are collected and presented in order to demonstrate that perinatal stress exposure has long-term effects on sleep phenotype during adulthood. Moreover, the hypothesis that maternal sleep loss during pregnancy can be considered as a prenatal stress factors with the potential to program wake–sleep behaviour, leading to sleep disturbances in adulthood, will be considered. Animal studies produce compelling evidence that: (1) perinatal stress may lead, possibly through epigenetic mechanisms, to health problems in adults, including sleep derangements; (2) sleep loss during pregnancy may be responsible for long-term negative outcomes, including wake–sleep disorders. In conclusion, stress exposure during pregnancy should be considered a big issue not only for mothers but also for children's health in the long-term. Thus, preserving mothers' mental health during pregnancy should be a worldwide priority.

Conflict of Interest: No.

Session: Symposium—What can we learn about sleep from aperiodic neural activity?

Presentation: Fractal cycles of sleep: A new aperiodic activity-based definition of sleep cycles.

Speaker: Yevgenia Rosenblum, Netherlands.

Summary

Nocturnal human sleep consists of 4–6 ninety-minute cycles defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. Sleep cycles are fundamental sleep units, yet there is a lack of research progress in this field mainly due to the absence of a data-driven definition of sleep cycles. Here, we proposed to base such a definition on fractal (aperiodic) neural activity, a well-established EEG marker of sleep and arousal.

Based on the observed pattern of fluctuations in temporal dynamics of fractal activity during sleep, we introduced a new concept of “fractal cycles” defined as a time interval during which fractal activity descends from its local maximum to its local minimum and then leads back to the next local maximum. Next, we assessed correlations between fractal and classical (i.e., non-REM—REM) sleep cycle durations. We also studied cycles with skipped REM sleep where the REM phase is replaced by lightening of sleep.

Regarding the sample, we examined fractal cycles in (1) 205 healthy adults aged 18–75 years; (2) 21 children and adolescents aged 8–17 years, the group characterized by deeper sleep and a higher frequency of cycles with skipped REM sleep; (3) 111 patients with major depressive disorder (MDD), the condition characterized by altered REM sleep (in addition to its clinical symptoms).

We found that fractal and classical cycle durations (89 ± 34 vs. 90 ± 25 min) correlated positively (r = 0.5, p < 0.001). Overnight cycle-to-cycle dynamics showed an inverted U-shape of fractal and classical cycle durations. The fractal cycle duration and adult participant's age correlated negatively (r = −0.2, p = 0.006). Children and adolescents had shorter fractal cycles compared to young adults (76 ± 34 vs. 94 ± 32 min). The fractal cycle algorithm detected cycles with skipped REM sleep in 90/97 (95%) cases while the inter-human rate agreement was 61% only. Medicated MDD patients showed longer fractal cycles compared to their own unmedicated state (107 ± 51 vs. 92 ± 38 min) and controls (104 ± 49 vs. 88 ± 31 min).

In conclusion, fractal cycles are an objective way to display the cycling nature of sleep useful in healthy, paediatric and clinical populations. Fractal cycles should be extensively studied to advance theoretical research on sleep structure.

Conflict of Interest: No.

Session: Closing Session & Hot Topic.

Presentation: Hot Topic presentation—Female features of OSA.

Speaker: Athanasia Pataka, Greece.

Summary

OSA is a heterogeneous condition with different pathophysiological causes, polysomnographic findings, clinical presentations and health consequences. OSA is often considered as primarily male disease. Recent studies have found that globally almost 1 billion adults suffer from OSA with a mean prevalence been around 27% in men and 22% in women. The clinical presentation, symptoms and co-morbidities of OSA differ between genders. However few studies assessed specifically women OSA phenotypes. Menopause, pregnancy and the different phases of the menstrual cycle with different levels of estradiol and progesterone are associated with the heterogenity of sleep architecture and symptoms in women. The differences between genders in the severity of OSA tend to attenuate during the postmenopausal years, as OSA incidence increases after menopause.

Men and women perceive sleepiness differently. Women with OSA report nonspecific symptoms as fatigue, morning headache, insomnia and depression. Additionally they present more frequently with nocturia, frequent awakenings and restless leg syndrome.

Co-morbid insomnia and sleep apnea (COMISA) rates have been found higher for females compared to males. Studies report that females with OSA exhibit lower AHI, less hypoxic burden, shorter apneic episodes and more apneas during rapid eye movement (REM) sleep. Women seem to present with lower NREM AHI that usually reflects the total AHI, thus remain undertreated, increasing the cardiovascular risk in women with predominantly REM AHI.

Co-morbidities as asthma, thyroid disease and depression are more commonly reported in women suffering from OSA. Female patients suffering from severe disease are at increased cardiovascular risk.

The effect of gender on OSA treatment indications has not been well studied. As OSA is under diagnosed in women, its treatment is delayed compared to men.

In the current presentation the different features of OSA in women will be summarized.

Conflict of Interest: No.

Session: Symposium—A physiologial approach to CBT-I effectiveness: Assessing, Predicting and Phenotyping.

Presentation: Physiological phenotypes of short vs. normal sleep duration and their response to CBT-I.

Speaker: Julio Fernandez-Mendoza, United States.

Summary

Insomnia Disorder (ID) is the most prevalent sleep disorder, but it is highly heterogenous in its phenotypic presentation. ID should be diagnosed based on clinical interviewing and patient-reported outcomes used also to test treatment efficacy. Accumulating rigorous research supports that objective sleep measures not only show high heterogeneity (phenotypes) within individuals with ID, but that they can inform its pathophysiology, morbidity, clinical course and treatment response. This presentation will summarize the current evidence for subtyping ID into objective short (ISSD) versus normal sleep duration (INSD) phenotypes, how they respond to CBT-I treatment, and what phenotype-specific therapeutic interventions they may require based on objectively-measured outcomes.

Conflict of Interest: No.

Session: Invited Symposium—European Academy of Dental Sleep Medicine (EADSM)—Dental Medicine on Sleep Medicine: An Integrative Model Cooperation.

Presentation: Bruxism in paediatric OSA: Role of arousal and sleep fragmentation.

Speaker: Susana Falardo Ramos, Portugal.

Summary

Paediatric sleep bruxism represents 3.5%–40.6% prevalence among pre-schooler and scholarly children population between 2 and 10 years old, the incidence in girls is greater, but decrease with age.

Recently research related SB to respiratory events and to cortical microarousals, acting as a protector mechanism of the upper airway collapse, occurring predominantly on sleep stage N2 and N3.. Also, SB can associate with gastroesophageal reflux which is a risk factor for SB and perform a protective function by stimulating saliva flow through SB.

Sleep bruxism is a sleep disturbance of movement, that by itself causes sleep fragmentation and cortical micro arousals, contributing to modifications of the architecture of sleep, decreasing deep sleep and memory consolidation children may experience fatigue the next day, leading to poor school performance and cognitive impairment.

Sleep Bruxism may lead to long term effects as masticatory muscle hypertrophy, tooth surface loss, fracture of restorations or teeth, hypersensitive or painful teeth, gingival recession, loss of periodontal support and chronic orofacial pain.

Dentist can also play a role on the prevention and early diagnose of sleep bruxism identifying intra-oral signs as for example: dental fracture, enamel fracture, abfractions or fissure, TMJ pain or discomfort, malocclusion or misalign teeth, tongue scalloping and ridging on the cheek mucosa “Linea alba”. Also, same parafunctional habits can be associated as a sign: nail biting, objects biting and sucking thumb.

Management of SB should be directed at protecting the oral structures from the effects of SB, with conservative strategies which includes: oral splints (mainly recommended for adults) behavioural therapies with bio feedback, relaxation or meditation, acupuncture, physiotherapy and improvement of sleep hygiene. The use of medication (antidepressants, muscle relaxants, benzodiazepines, etc…) have been use. However, further research is needed to confirm the efficacy and effectiveness of the drugs.

Conflict of Interest: No.

Session: Invited Symposium—European Academy of Dental Sleep Medicine (EADSM)—Dental Medicine on Sleep Medicine: An Integrative Model Cooperation.

Presentation: Dental Medicine on Sleep Medicine: An Integrative Model Cooperation.

Speaker: Susana Falardo Ramos, Portugal.

Summary

Dental Medicine interest in Sleep medicine has been rising. Knowledge and awareness on sleep related disturbance by Dentists, Maxillo-Facial Surgeons and others oral health professionals has increased. The need for screening sleep related breathing disorders, movement disorders and the relation on sleep and orofacial pain, establish the necessity of creating a multidisciplinary collaboration between sleep experts. As part of an integrative model with the goal of a sleep medicine under the same roof, this symposium aims to approach the multidisciplinary cooperation.

Conflict of Interest: No.

Session: Symposium—Breathing related arousals in Paediatric OSA: Impact on Diagnosis and Management.

Presentation: Myofunctional therapy on breathing control on arousals.

Speaker: Susana Falardo Ramos, Portugal.

Summary

Dental Medicine interest in Sleep medicine has been rising. Knowledge and awareness on sleep related disturbance by Dentists, Maxillo-Facial Surgeons and others oral health professionals has increased. The need for screening sleep related breathing disorders, movement disorders and the relation on sleep and orofacial pain, establish the necessity of creating a multidisciplinary collaboration between sleep experts. As part of an integrative model with the goal of a sleep medicine under the same roof, this symposium aims to approach the multidisciplinary cooperation.

Conflict of Interest: No.

Session: Symposium—Dilated insights: Understanding the Eye's Role in Sleep–Wake Control.

Presentation: Sleep deprivation does not change the electroretinogram in mice.

Speaker: Tom De Boer, Netherlands.

Summary

Whether and how sleep homeostatic pressure and circadian rhythms interact and influence each other's functioning is an important question in sleep research, particularly in the context of the Two-process model of sleep regulation. It has been shown in the past that the two interact and that particularly sleep pressure may influence functioning of the circadian clock.

The strongest effect on circadian clock functioning was found in the phase shifting capacity of the circadian clock to light, which is greatly reduced when an animal is sleep deprived. Combining this work with the application of caffeine suggests that the effect is mediated via release of adenosine during sleep deprivation reducing neuronal activity in the phase shift inducing pathway, probably in the suprachiasmatic nucleus (SCN). Additional work with caffeine suggests that also circadian period may be influenced by adenosine.

These findings are discussed in the context of the pathway the light information takes from the retina to the SCN and further downstream to the output of the clock. Effects of treatment with caffeine, counteracting the effects of increased sleep pressure will be included. In this context circadian period of behaviour and phase shifting of this behaviour will be discussed, but also changes in SCN neuronal activity, and putative changes in the electroretinogram, as the eye is the first station in the pathway.

Conflict of Interest: No.

Session: Symposium—Dilated insights: Understanding the Eye's Role in Sleep–Wake Control.

Presentation: Retinal mechanisms underlying caffeine effects on human sleep–wake regulation.

Speaker: Carolin Reichert, Switzerland.

Summary

Sleep pressure modulates the circadian timing system, which is synchronized to the external world by light–dark information extracted in the eye by the so-called intrinsically photosensitive ganglion cells (ipRGCs). In vitro it has been shown that responses of ipRGCs to light are reduced by adenosine, that is a neuromodulator which increases during sleep deprivation and which is antagonized by caffeine. In the evening during light exposure, caffeine can delay circadian timing and supress melatonin secretion in humans. We recently investigated whether these caffeine-induced effects can be traced back to a differential circadian light processing in the eye. In a full crossover within-subject design with two factors (1: “caffeine vs. placebo” and 2: “bright light vs. dim light”) we measured repeatedly ipRGC sensitivity by silent substitution pupillometry, baseline pupil size and salivary melatonin during 6 h in the evening. The analyses reveal strong evidence that the given dose of caffeine (3 mg/kg bodyweight) does not increase light sensitivity of ipRGCs (Bayes Factor BF <0.1). In line with earlier studies in humans, the data do furthermore moderately indicate that caffeine increases baseline pupil size (BF >3) and can therefore increase retinal illumination. Additionally, under pharmacological dilation of the pupil to rather stable levels across the evening, the well-known effects of caffeine on salivary melatonin remained absent (0.33 > BF >3). Together the current evidence suggests that a regular dose of caffeine does not change human circadian light sensitivity in the retina after a normal waking day. The typical circadian effects of caffeine on human melatonin secretion in the evening might rather be due to a caffeine-induced higher retinal illumination and/or central effects of the adenosine antagonist, for example on light-induced activity-changes of the circadian pacemaker.

Conflict of Interest: No.

Session: Symposium—From ions to sleep.

Presentation: Towards human systems biology of sleep/wake cycles: Phosphorylation hypothesis of sleep.

Speaker: Hiroki Ueda, Japan.

Summary

Calcium influx in neurons not only excites cells but also plays a crucial role in neurotransmission. We hypothesized that while calcium maintains wakefulness by exciting neurons, it might also indirectly promote sleep. This idea lead us to hypothesize that sleep homeostasis might not necessarily require “sleep substances,” but rather that mechanisms integrating the history of “arousal substances,” particularly calcium, could be sufficient to explain it.

To explore the hypothesis that calcium, an arousal substance, could also induce sleep pressure, we created animal models with specific gene knockouts related to calcium dynamics. Targeting 25 genes involved in calcium movement, we required new technologies. In 2010, we conceived “next-generation genetics,” enabling the creation of knockout and knockin mice without crossbreeding. With the advent of CRISPR-Cas9 in 2012, we developed the “Triple CRISPR method,” achieving over 95% efficiency in generating knockout mice (Sunagawa, Cell Reports, 2016). This allowed us to discover that calcium promotes sleep (Tatsuki, Neuron, 2016).

To further investigate, we utilized whole-cell analysis techniques based on tissue-clearing technology developed since 2010 (Susaki, Cell, 2014, Tainaka, Cell, 2014). Although calcium is typically seen as an “accelerator” of neuronal excitability, our knockout studies suggested it might also act as a “brake.” Using whole-brain clearing techniques, we confirmed that calcium suppresses neuronal excitability (Tatsuki, Neuron, 2016).

Neuronal calcium dynamics are rapid, yet slower processes, like the buildup of sleepiness, require downstream mechanisms. We focused on the calcium-dependent kinase II (CaMKII) family. Knockout studies revealed that CaMKIIα and CaMKIIβ promote sleep (Tatsuki, Neuron, 2016). Phosphorylation at specific sites, including Thr286 in CaMKIIα and Thr287 in CaMKIIβ, was found to induce sleep (Tone, PloS Biology, 2022). Further studies indicated that other kinases, such as PKA, inhibit sleep, while phosphatases like calcineurin and PP1 promote it by acting on postsynaptic sites (Wang, Biorxiv 2023).

Our findings suggest that sleep might strengthen, rather than weaken, synapses, leading us to propose the WISE (Wake Inhibition Sleep Enhancement) mechanism (Kinoshita, Biorxiv, 2024), in contrast to the SHY (Synaptic Homeostasis) hypothesis. The WISE hypothesis predicts that prolonged wakefulness weakens synapses, aligning with phenomena like depression. These ideas will be experimentally tested in near future.

Conflict of Interest: Yes. HRU is a co-founder of CUBICStars Inc. and ACCELStars Inc and filed patents on ACCEL and CUBIC.

Session: Symposium—Light, emotional brain function, and mental health outcomes.

Presentation: Morning light treatment for traumatic stress: The role of amygdala reactivity

Speaker: Helen Burguess, United States.

Summary

Trauma exposure can result in anxiety, depression, and posttraumatic stress disorder. Although psychotherapies and pharmacotherapies exist for traumatic stress, many individuals remain symptomatic. New interventions for traumatic stress that target underlying mechanisms (e.g. amygdala reactivity) and are safe and acceptable are needed. Here we report on a randomized clinical trial in which we tested 3 doses of a 4-week morning light treatment in people with traumatic stress.

Fifty adults (34 females, 19–57 years) with traumatic stress (experienced a DSM-5 Criterion A trauma, DASS score >22, and ≥2 moderate hyperarousal symptoms) enrolled in a 5-week protocol. In the first week each participant slept at home, ad lib, on their usual sleep schedule. Thereafter, they followed a fixed sleep schedule and a 4-week morning light treatment (randomized to 15, 30 or 60 mins of light each morning). Amygdala reactivity (emotional faces task—fMRI), clinician rated symptoms (PSSI, HAM-A, HAM-D) and self-reported symptoms (PCL-5, DASS) were assessed at baseline, and after 4 weeks of morning light treatment.

No group differences were observed in left amygdala reactivity, but right amygdala reactivity significantly reduced only in the 30 and 60 min groups with medium effect sizes (ps ≤ 0.04). Clinical symptoms reduced in all groups with medium to large effect sizes. Self-reported depression and anxiety scores reduced significantly more in the 60 min group than in the 15 min group (p = 0.02). Side effects were minimal, one participant withdrew due to light-induced headaches. Treatment satisfaction (average 7/10) and adherence (average 91%) were similar between groups (ps > 0.05).

The results suggest that 4 weeks of morning light treatment of at least 30 min per day can reduce amygdala reactivity and symptoms of traumatic stress. Morning light treatment should be further explored as a potential treatment for traumatic stress, given it is relatively safe, acceptable, accessible and scalable.

Conflict of Interest: Yes. Dr. Burgess is a consultant for Natrol, a supplements manufacturer. Grant awarded from NIMH R61 MH117157.

Session: Symposium—Development of sleep, thermoregulation and cardiorespiratory control: Clinical implications.

Presentation: Maturation of temperature regulation during sleep in infants.

Speaker: Véronique Bach, Netherlands.

Summary

Studies in adult humans and animals have demonstrated that sleep and body thermoregulation are closely linked. In a cool or warm environment, there is a functional conflict between the need for sleep and the maintenance of body homeothermia in non-human mammals and in human adults. This conflict might be especially harmful in infants.

In contrast to adults, the thermoregulatory responses (increased metabolism in a cool environment, sweating in a warm one) are fully operational during rapid eye movement (REM) sleep in preterm neonates, at least in the range of ambient temperature usually studied. This protects them from long periods of poikilothermy. Because of the lack of data on this aspect in older infants or adolescents, we do not currently know when the switch from neonatal characteristics (greater thermoregulatory efficiency and a greater amount of REM sleep when exposed to a cool environment) to adult characteristics (i.e. poor thermoregulatory efficiency and partial REM sleep deprivation in cool or warm conditions) occurs.

Another aspect of the link between sleep and thermoregulation refers to the distal skin vasodilation observed as a part of “sleep preparedness” in adults, leading to body heat loss and promoting sleep. Similar vasodilation has been described in school-aged children before evening sleep onset. In preterm neonates weighting 1.3 kg in average, we pointed out a progressive distal cutaneous vasodilation occurring during the last 20 min of wakefulness. The larger the vasodilation on the hands and feet, the more rapid the sleep onset. Conversely, we observed a progressive vasoconstriction on hands and feet before spontaneous awakenings.

These vasodilation and vasoconstriction observed despite age-related differences in sleep structure, rhythm and maturation and thermoregulatory functions and centers raise the question of whether thermal or non-thermal manipulation could improve infants' sleep and wakefulness by inducing distal cutaneous vasodilation or vasoconstriction, as proposed in adults with sleep/wake disturbances.

Conflict of Interest: No.

Session: Symposium—Snooze and cleanse: Understanding the role of sleep in brain clearance.

Presentation: Clinical perspectives: How to improve brain clearance in health & disease.

Speaker: Rolf Fronczek, Netherlands.

Summary

Brain clearance, the drainage of waste from the brain, plays a pivotal role in preserving cognitive processes and neurological well-being. Importantly, impaired clearance of waste, resulting in protein accumulations, is proposed to contribute to neurodegeneration as seen in for example Alzheimer's and Parkinson's Disease.

Dr. Rolf Fronczek will review work on brain clearance (during sleep) in neurological disorders such as stroke, Alzheimer's and Parkinson's Disease, and Cerebral Amyloid Angiopathy. He will discuss possibilities to improve waste clearance via sleep, through medicated (i.e. hypocretin antagonists, sodium oxybate) and non-medicated (i.e. light therapy) approaches.

Conflict of Interest: No.

Session: Joint Symposium—European Academy of Neurology (EAN) & ESRS.

Presentation: Case 3—Sleep and headache.

Speaker: Rolf Fronczek, Netherlands.

Summary

Headache and sleep problems are extremely prevalent complaints in the general population, affecting the quality of life and brain health of millions of people worldwide. Often these complaints are the prime reason for referral to a neurologist. Although the interaction between headache & sleep is bidirectional, multifactorial and complex, there are “quick wins” that can efficiently improve people's lives. A case will be presented with headache and sleep features. Important topics that will be covered in a practical manner are (1) migraine and sleep patterns, (2) hypnotic and analgesic overuse & (3) trigeminal autonomic cephalalgias (TACs) attacks during sleep.

Conflict of Interest: No.

Session: Symposium—OSA in women: Not just for men anymore.

Presentation: Clinical presentation of OSA in women: Female-specific phenotypes.

Speaker: Athanasia Pataka, Greece.

Summary

OSA is a heterogeneous condition with different pathophysiological causes, polysomnographic findings, clinical presentations and health consequences. OSA is often considered as primarily male disease with a male-to-female ratio ranging from 3:1 to 5:1 in the general population. More recent studies have found that globally almost 1 billion adults suffer from OSA with a mean prevalence been around 27% in men and 22% in women.

The clinical presentation, polysomnographic variables and co-morbidities have been found to differ between men and women with OSA. Female OSA patients complain more frequently of nonspecific symptoms such as fatigue, depression, morning headaches and insomnia. Compared with men, women with OSA have shorter respiratory events, predominantly hypopneas, with less severe desaturations and more frequent events during REM sleep. Additionally, co morbidities as asthma, psychiatric disease, that is depression, diabetes mellitus and thyroid disease, have been found to be more common in female OSA patients.

During the last years several cluster analyses have been conducted in order to identify the different phenotypes of OSA using single or multicentre data. There are several cluster analysis studies that have evaluated the different phenotypes of OSA patients with several of them making a report on the female population or even describing separate female clusters.. However, few studies assessed specifically women phenotypes. In the current presentation the different clinical presentations, specific symptoms and clusters in women will be analysed with a special focus on female specific phenotypes.

Conflict of Interest: No.

Session: Symposium—Dilated insights: Understanding the Eye's Role in Sleep–Wake Control.

Presentation: Melanopsin retinal ganglion cells and their role in regulating sleep and circadian rhythms in neurodegenerative disorders.

Speaker: Chiara La Morgia, Italy.

Summary

Melanopsin retinal ganglion cells (mRGCs) are a small subgroup of RGCs contributing mainly to non-image forming functions of the eye. The most relevant function of these cells is the photoentrainment of circadian rhythms to the light–dark cycle through the projections to the hypothalamic suprachiasmatic nucleus (SCN). They also regulate sleep projecting to the hypothalamic ventrolateral pre-optic (VLPO) nucleus and contribute to the pupillary light reflex (PLR) reaching the olivary pretectal nucleus (OPN). Many neurodegenerative disorders, and in particular Alzheimer's disease (AD) and Parkinson's disease (PD) as well as their prodromal stages, that is mild cognitive impairment (MCI) and Rem Behaviour Disorder (RBD) are characterized by sleep and circadian dysfunction. In both diseases a loss and dysfunction of these cells has been demostrated using different approaches. In particular, postmortem studies showed mRGC loss and degeneration as well as amyloid deposition affecting mRGCs in AD (La Morgia et al., 2016) and mRGC loss and degeneration in PD (Ortuno-Lizaran et al., 2018). Moreover, in AD the presence of circadian and mRGC-mediated PLR dysfunction has been reported using a multimodal approach including chromatic pupillometry, actigraphic recordings evaluating rest-activity circadian rhythm and functional brain MRI (Romagnoli et al., 2022; La Morgia et al., 2023). The occurrence of mRGC-mediated PLR dysfunction has also been found in PD (Joyce et al., 2018) and RBD (La Morgia et al., 2022) patients. These findings highlight a potential role of mRGC function and dysfunction as an early biomarker for neurodegeneration. Finally, the use of light therapy as a counteracting measure for sleep and circadian problems in neurodegenerative disorders is also discussed.

Conflict of Interest: Yes. This work was supported by the Italian Ministry of Health grant GR-2013-02358026 to CLM.

Session: Symposium—Patient participation in Sleep Medicine: The future is digital.

Presentation: Lifestyle intervention: What is enough dose of exercise?

Speaker: Jose Miguel Saavedra, Iceland.

Summary

Sleep-disordered breathing (SDB) is a growing public health issue that includes breathing difficulties during sleep, with obstructive sleep apnea (OSA) being the most common form, affecting approximately one billion people worldwide (Benjafield et al., 2019). OSA can lead to fragmented and non-restorative sleep, resulting in excessive daytime sleepiness, weight gain, and impaired quality of life (Lal et al., 2021). Positive airway pressure (PAP) therapy is the first-line treatment, though long-term adherence is low, particularly in mild cases (Eysteinsdottir et al., 2017). Some studies suggest exercise as a non-PAP treatment, but the evidence is mixed, and it is not considered a primary option (Randerath et al., 2021). Physically active patients tend to snore less (da Silva et al., 2017), and combining diet and exercise has been shown to reduce snoring and OSA severity (Barnes et al., 2009). Exercise has also been shown to significantly improve cardiorespiratory fitness in OSA patients. Various forms of exercise, including high-intensity interval training, aerobic exercise, and a combination of aerobic and resistance training, have all demonstrated effectiveness in enhancing cardiorespiratory fitness (Lins-Filho et al., 2023). Moreover, while exercise is primarily recognized for its cardiovascular and respiratory benefits, it may also contribute to weight management, which is crucial for OSA patients given the strong link between obesity and OSA severity. Although the impact of exercise on body composition in OSA patients has shown mixed results, it remains a promising area for reducing OSA symptoms and improving overall health. Regular physical activity, therefore, could be a key element in managing OSA, complementing traditional treatments like PAP therapy.

This study was funded by the European Union's Horizon 2020 research and innovation program under grant agreement no.965417.

Barnes et al. (2009). Journal of Clinical Sleep Medicine, 5(5), 409–415.

Benjafield et al. (2019). The Lancet Respiratory Medicine, 7(8), 687–698.

da Silva et al. (2022). Sleep Medicine, 95, 37–46.

Eysteinsdottir et al. (2017). Journal of Sleep Research, 26(2), 159–165.

Lins-Filho et al. (2023). Sleep Medicine, 112, 316–321.

Randerath et al. (2021). European Respiratory Review, 30(162), 210200.

Conflict of Interest: No.

Session: Symposium—Development of sleep, thermoregulation and cardiorespiratory control: Clinical implications.

Presentation: Sleep in children born preterm and growth restricted: Clinical implications.

Speaker: Rosemary Horne, Australia.

Summary

Sleep provides a unique window into autonomic control and has been described as “a new cardiovascular frontier.” The autonomic nervous system controls both heart rate and blood pressure changes from wake to sleep and between sleep states. Globally, an estimated 15 million babies are born preterm (<37 weeks gestation) each year and these babies are at increased risk of sleep problems and impaired cardiovascular control. There have been fewer studies which have examined the effects of preterm birth on sleep and cardiovascular control during childhood. Sleep disordered breathing (SDB) is 3 to 6 times more likely in children born preterm compared to those born at term.

Our studies have shown that prematurity and fetal growth restriction were associated with altered sleep macro- and micro-architecture measures indicative of reduced sleep quantity and quality in childhood (Yiallourou et al., 2017). Furthermore, preterm born children with SDB had altered sleep micro-architecture with increased theta power, which has been found after sleep deprivation and increased slow wave activity indicating that the dissipation of slow wave activity was reduced in these children at the start of the night. Together these differences suggest that children born preterm may have reduced dissipation of sleep debt and increased sleepiness (Chan & Wong et al., 2020). Preterm born children also had increased HF heart rate variability suggesting increased work of breathing compared to matched control children (Thomas et al., 2018). Although the pattern of heart rate changes in response to respiratory events was similar, during NREM sleep, preterm born children had a significantly greater surge in heart rate (5% greater) when respiratory events were terminated with an arousal, compared with the term born children. As arousals occur repeatedly throughout the night this elevated surge in heart rate may play a role in long term adverse cardiovascular outcomes in preterm born children with SDB (Walter et al., 2022).

In summary, abnormalities in sleep and heart rate control may play a role in the long term adverse cardiovascular outcomes in preterm born children and our studies highlight the need for further investigation and perhaps routine clinical follow-up in this population.

Conflict of Interest: No.

Session: Symposium—Sleep and torpor: Neural substrates and effects of hypometabolism on brain activity and behaviour.

Presentation: Synaptic remodelling during torpor and sleep in Siberian hamsters.

Speaker: Xiao Zhou, United Kingdom.

Summary

Torpor is a controlled and reversible state characterized by decreased body temperature, metabolic rate, and physical activity, typically initiated through non-rapid eye movement (NREM) sleep. Siberian hamsters (Phodopus sungorus), also known as Djungarian hamsters, exhibit spontaneous daily torpor as a winter-specific adaptation, during which their metabolic rate decreases to 30% of the basal metabolic rate (Heldmaier et al., 1999). Daily torpor can be induced by natural or artificially created short-day photoperiods, even without cold exposure or food restriction.

Historically, sleep and torpor were considered homologous processes, with torpor acting as an extension of sleep to further enhance energy conservation under harsh environmental conditions (Walker and Berger, 1980). However, subsequent studies have shown that torpor is followed by elevated levels of EEG slow wave activity (SWA), a physiological marker of sleep pressure, which only diminishes after a period of NREM sleep (Deboer and Tobler, 2000). Animals enter sleep immediately following torpor and even need to periodically arouse from torpor for sleep, suggesting that torpor may suppress the restorative function of sleep.

In ground squirrels, neurons in the cortex, hippocampus, and thalamus show reduced synaptic contacts, retraction of cell bodies, dendrites, and dendritic spines, which are restored within 2 h upon arousal (Popov and Bocharova, 1992; Popov et al., 1992; von der Ohe et al., 2006). These findings lead to the hypothesis that the elevated SWA following torpor is associated with the restoration of dendrites and synapses.

To explore the relationship between spontaneous daily torpor, sleep, and neural plasticity, we examined the ultrastructural, molecular, and behavioural alterations during daily torpor and subsequent sleep in Siberian hamsters. Using serial block-face scanning electron microscopy (SBEM), we investigated changes in the synaptic ultrastructure of the primary motor cortex during and after torpor. This study provides crucial evidence for understanding how short-term torpor bouts and the following sleep may impact spine morphology and neuronal ultrastructure.

Conflict of Interest: No.

Session: Symposium—Dilated insights: Understanding the Eye's Role in Sleep–Wake Control.

Presentation: Pupil size dynamics reveal tight brain state correlations during sleep.

Speaker: Ozge Yuzgec, Switzerland.

Summary

Our experiments involving simultaneous pupillometry and EEG suggest that pupil size dynamics are tightly correlated to the cortical activity across sleep stages. Furthermore spontaneous pupil constrictions support the maintenance of NREM sleep.

Conflict of Interest: No.

Session: Invited Symposium—European Academy of Dental Sleep Medicine (EADSM)—Dental Medicine on Sleep Medicine: An Integrative Model Cooperation.

Presentation: Endotyping for a combined modality treatment in OSA.

Speaker: Venkata Koka, France.

Summary

Obstructive sleep apnea (OSA) is an increasingly common form of sleep-disordered breathing. The pathogenesis of OSA is multifactorial, and four physiological traits have been recognized: upper airway collapsibility, poor muscle responsiveness, low arousal threshold, and high loop gain.

Identifying physiological OSA traits by CPAP dialups and dial-downs is invasive and requires specially equipped sleep laboratories. An automated noninvasive estimate of ventilatory drive based on polysomnographic (PSG) ventilation and a chemoreflex control model made it possible to identify the endotypes from signals from standard PSG. A single therapy directed to a single trait was successful in 25%. In contrast, combination therapy with conventional non-CPAP treatments (Surgery/Mandibular splint/hypoglossal nerve stimulation/pharmacotherapy) for multiple traits increases the success rate to 80% in patients not requiring CPAP.

Clinical examination of upper airway structures (ENT, dental) and diagnostic PSG findings can help identify non-anatomic phenotype traits in a clinical setting when selecting a single or a combined approach on an individual basis. The optimum CPAP therapeutic pressures may also differentiate a mild from a severely collapsible airway. A clinical score using PSG indices discriminates pharyngeal collapsibility and low arousal threshold. Breath-holding to estimate loop gain was reported. Analysis of airflow shapes indicates the site and severity of pharyngeal obstruction. Other physiological estimates of hypoxic burden and heart rate variability identify the phenotype and selection of appropriate treatment.

The structural changes alter the biomechanics and airway dynamics and influence the treatment choice; for example, mouth breathing with expiratory pinching in soft palatal prolapse precludes mandibular advancement device (MAD). Expiratory pinching, high event depth, and high loop gain are discussed as predictors of MAD failure. There is an increasing interest in combining CPAP with non-CPAP treatments to improve CPAP adherence. Orofacial myofunctional therapy has been proposed to restore nasal breathing and enhance the coordination of pharyngeal and parapharyngeal muscles.

Understanding biomechanics and airway dynamics and developing new algorithms for endotyping the physiological traits in OSA patients can help choose a targeted treatment in a combined modality approach.

Conflict of Interest: No.

Session: Symposium—Hypermotor insomnia from the crib to adolescence.

Presentation: Restless sleep disorder in children.

Speaker: Gulcin Benbir Senel; Türkiye.

Summary

Restless sleep disorder (RSD) is a newly defined paediatric sleep disorder, which is characterized by frequent large muscle movements during sleep and daytime consequences. Although restless sleep is very common as a sleep-related symptomatology, it stayed unanswered for many years in patients “otherwise” normal sleep studies. These patients have various forms of movements during sleep, which was quantified as a rate of approximately five large body movements or repositionings per hour of sleep in video-polysomnographic examinations. As RSD is also a chronic disorder, symptoms and/or large muscle movements occur at least three times a week and last for at least 3 months. The main differential diagnosis of RSD includes restless legs syndrome (RLS), whereas urge to move the legs, leg kicks or periodic limb movements during sleep are lacking in RSD. while insomnia is commonly associated with RLS, patients with RSD do not typically present with symptoms of insomnia. Another important differential diagnosis of RSD is periodic extremity movement disorder, which is characterized by the periodic limb movements of at least five times per hour; which should be carefully differentiated and excluded in evaluation of the large body movements of RSD. The pathophysiology of RSD is not well-known, though iron deficiency is accepted as the main contributing mechanism. Patients with RSD were reported to have low ferritin levels (about 20 ng/dL), being lower that those with RLS. In addition, iron supplementation has resulted in improvements in night-time sleep and daytime symptom. This may give some clues about altered dopaminergic pathways involved in motor activity at night in RSD. Other important findings reported in the studies are increased cyclic alternating pattern and heart rate variability in these patients with RSD. These may help to elucidate other underlying mechanisms of RSD. Although some comorbid conditions, like parasomnias or epilepsy, were reported in the literature, the comorbidity of other disorders in RSD should further be investigated to reveal its role contributing to sleep disruption and daytime symptomatology.

Conflict of Interest: No.

Session: Symposium—The Mechanisms of sleep restriction therapy for insomnia: From computational science to clinical effects.

Presentation: Treatment processes of sleep restriction therapy for insomnia: A network intervention analysis.

Speaker: Jaap Lancee, Netherlands.

Summary

Sleep restriction therapy is considered an essential component of CBT-I (Cognitive Behavioural Therapy for Insomnia), and it can also be offered as a standalone intervention for insomnia. The theoretical basis for how sleep restriction improves insomnia has been extensively described. Sleep restriction therapy is thought to work by reducing arousal, increasing sleep pressure, regulating the sleep–wake rhythm, and restoring the bed-sleep association. To investigate this, we conducted a randomized controlled trial (RCT) in which we compared sleep restriction therapy (n = 76) with a sleep diary control group (n = 71). Using Network Intervention Analysis (NIA), we monitored the weekly development of insomnia symptoms and theoretically proposed processes. The results showed that sleep restriction therapy, compared to the control group, led to a large and clinically relevant pre-post reduction on the Insomnia Severity Index. The networks revealed that this treatment effect mainly occurred through reduced sleep onset latency, bedtime variability, and reduced pre-sleep arousal. Additionally, we observed that sleep restriction had a quick and direct effect on difficulties falling and staying asleep, consistent with the idea of increased sleep pressure. The findings from this RCT confirm that sleep restriction as a standalone treatment is highly effective and largely operates through theoretically proposed processes.

Conflict of Interest: No.

Session: Symposium—Shift Work Tolerance: An intergrative approach.

Presentation: The importance of tailored interventions for sleep- and circadian related outcomes.

Speaker: Katie Stone, United States.

Summary

Shift work disorder occurs when work-related schedules of sleep and light–dark exposure are imposed, and there is resulting misalignment between the individual's sleep–wake schedule and circadian rhythms (1). This can lead to insufficient sleep as well as disruption of circadian rhythms, both of which are linked to a variety of health outcomes including impaired cognition, cardiovascular disease, and even mortality. This talk will address sleep and circadian disruption more generally, but also applicable to shift work disorder given the common elements reflecting sleep insufficiency and circadian misalignment.

Inter-relationships of sleep and circadian disruptions with mental and physical health are not uniform. There are differences across the lifespan, as well as other important differences based on sex/gender and other factors. A brief overview of health outcomes related sleep and circadian disruption will be reviewed, with a particular emphasis on those impacting older adults. Potential sex differences will be reviewed, such as those observed in sleep and circadian rhythms and their relationship to cognitive aging.

Potential intervention approaches for circadian-related disorders including shift work disorder will be briefly reviewed. The need for more targeted or tailored intervention approaches will be discussed. Determining optimal therapies for the individual patient requires trials designed and adequately powered for examination of heterogeneity of treatment effects, including examination of differences based on factors such as age, sex/gender and other characteristics.

(1) Boivin, D.B., Boudreau, P., Kosmadopoulos, A., 2022. Disturbance of the Circadian System in Shift Work and Its Health Impact. Journal of Biological Rhythms 37, 3–28. https://doi.org/10.1177/07487304211064218.

Conflict of Interest: Yes. Grant funding from Eli Lilly.

Session: Symposium—Shift Work Tolerance: An intergrative approach.

Presentation: New perspectives on individual differences in shift work tolerance.

Speaker: Ingvild Saksvik-Lehouillier, Norway.

Summary

Some individuals seem to tolerate working shift better than others (Degenfellner & Schernhammer, 2021; Saksvik, Bjorvatn, Hetland, Sandal, & Pallesen, 2011), experiencing less sleep problems, sleepiness fatigue, digestive troubles, and problems with aggression and sensitivity when working shifts (Andlauer, Reinberg, Fourre, Battle, & Duverneuil, 1979). We need more knowledge on the emotional problems shift workers face, how these should be operationalized and how stable they are between individuals. Especially, we do not know if the increased aggression and sensitivity represent a general increase in negative affect, or if it can be seen as problems with emotion regulation.

We conducted a one-week ecological momentary assessment study, measuring shift work tolerance at baseline, as well as affect and emotion regulation strategies three times per day in one week among night shift workers. A total of 177 shift workers participated in the baseline assessment, and the n for the different daily measures ranged between 96 and 98. The participants were employed in several different occupations. All of them worked at least one night shift during this week. On average they worked 2.1 night shifts and 1.7 day shifts and had 3.1 days off during this period. Symptoms of shift work intolerance (higher insomnia, fatigue, sleepiness, anxiety and depression as well as more digestive troubles) and emotion regulation strategies (cognitive reappraisal, expressive suppression and emotion crafting) were measured with established self-report measures.

Results showed that shift work intolerance as a whole, as well as all the symptoms of shift work intolerance were positively related to expressive suppression and negatively related to emotion crafting as well as cognitive reappraisal at baseline. Shift work intolerance also predicted higher use of expressive suppression throughout the week, but was unrelated to cognitive reappraisal and emotion crafting during the week.

The findings are in line with emotion regulation theory stating that suppression is related to poorer well-being compared to reappraisal, and that there are individual differences in use of these emotion regulation strategies (Gross & John, 2003). More studies are needed to investigate the predictive power of these findings in a larger sample.

Conflict of Interest: No.

Session: Symposium—Shift Work Tolerance: An intergrative approach.

Presentation: Genetic risk score of clock resilience and its utility in predicting individual vulnerability to night work and chronic disease risk.

Speaker: Magdalena Zebrowska, Austria.

Summary

The large number of night workers and night-active individuals, which is likely to increase in Europe and globally, draws attention to the high importance of diseases associated with shift work. Our study aims to provide a profile of an individual, including genotypic variation, associated with the risk of developing chronic diseases if exposed to disruption of circadian rhythms in the form of night shift work. Eveningness, abnormal sleep duration, frequent insomnia symptoms, high caffeine intake, high neuroticism score and low levels of Vitamin D are just some of the factors associated with increased circadian disruption and negative health outcomes. For the most part, these and other sleep-and circadian related traits are correlated, so considering them individually may not provide a complete picture of their impact on complex diseases. Aiming for identification of individuals at risk of circadian disruption, we propose a simple additive score combining these factors and taking into account mutual phenotypic correlations between its components by attaining higher values for individuals with more circadian disruption factors. However, correlations between sleep-and circadian related traits may also exist at the genetic level, therefore we also performed genome wide association (GWA) analysis of the constructed score and furthermore used genomic structural equation modelling (genomic SEM) to define latent common factors accumulating shared genetic architecture across phenotypes.

Among UK Biobank participants higher values on the constructed score scale were significantly associated with increased risk of cardiac-renal-metabolic conditions. Further genome-wide analysis of the score identified significant loci on genes expressed in brain cerebellar hemisphere. Based on genomic SEM modelling we defined latent factor variables incorporating sleep/activity timing, sleep regularity, sleep duration and daytime alertness, which can further be used for a construction of multi trait polygenic risk score (MTPRS).

References

(1) Grotzinger, A. D. et al. Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. Nat Hum Behav 3, 513–525 (2019).

(2) Goodman, M. O. et al. Genome-wide association analysis of composite sleep health scores in 413,904 individuals. Preprint at https://doi.org/10.1101/2024.02.02.24302211 (2024).

Conflict of Interest: No.

Session: Symposium—Breathing related arousals in Paediatric OSA: Impact on Diagnosis and Management.

Presentation: Arousals in paediatric OSA: Challenges in diagnosis.

Speaker: Venkata Koka, France.

Summary

Obstructive sleep apnoea affects 2% to 4% of children and is associated with repetitive arousal in sleep, causing behavioural problems and cognitive deficits, mandating early recognition.

Arousals follow a stereotyped sequence of events characterized by peripheral motor or autonomic responses, subcortical/brainstem responses (subcortical arousal), and subsequent EEG changes (cortical arousal) depending on the intensity of the stimulus.

The neural drive is the predominant mechanism for restoring the airway in children, and the effect of hypercapnia is blunted. Hence, most respiratory events are not terminated with cortical arousal, limiting the clinical utility of conventional polysomnography (PSG) in children with sleep-disordered breathing (SDB).

In NREM sleep, specific patterns of fluctuations in cortical activity defined as cyclic alternating patterns (CAP) consisting of phase A (active) and phase B (inactive), with each phase lasting between 2 and 60 s, were observed. Phase A includes delta bursts, vertex transients, polyphasic bursts, and alpha rhythm and is associated with autonomic and motor activation. CAP A1, A2, and A3 are defined according to the progressive contribution of faster frequencies.

CAP A1 was supposed to contribute to slow wave sleep (SWS) consolidation; Excitatory inputs of the medial subregions of the parabrachial nucleus (PBN) are inhibited by GABAergic neurons in the medullary parafacial zone, leading to increased synchronizing SWS and electrocortical signature of SWS in the CAP A1. Robust respiratory efforts and hypercapnia can stimulate lateral regions of PBN, evoking basal forebrain arousal with an electrocortical signature with alpha and beta bursts in CAP A2 and A3. Descending projections of PBN to medullary canters were reported to exert control over ventilatory effort and airway dilator muscle activity and reinstate breathing.

An increased percentage of CAP A1 in mild and A2 and A3 in moderate to severe OSA was reported. Daytime sleepiness correlates to the duration and rate of A2 and the reduction of phase B.

CAP parameters might serve as a critical EEG biomarker of arousal. In the future, new mathematical models and automated algorithms using CAP with other physiological indices will help in the early diagnosis and estimate the severity of OSA.

Conflict of Interest: No.

Session: Symposium—Top down control of sleep/wake by the cerebral cortex.

Presentation: Somatostatin neurons in prefrontal cortex initiate sleep preparatory behaviour and sleep via the preotic and lateral hypothalamus.

Speaker: Kyoko Tossell, United Kingdom.

Summary

Animals undertake specific behaviours before sleep, yet little is known about whether these innate behaviours, such as nest building, are controlled by intrinsic parts of the sleep-inducing circuitry. The prefrontal cortex (PFC) has an executive function and contributes to planning, and is particularly sensitive to sleep deprivation. We found that rare types of fast-spiking somatostatin-expressing, GABAergic (PFC-Sst-GABA) neurons in mouse PFC become activated during sleep deprivation. These cells project to the lateral preoptic (LPO) and lateral hypothalamus (LH). Stimulating PFC-Sst-GABA terminals in the LPO hypothalamus caused sleep-preparatory behaviour, while stimulating PFC-Sst-GABA terminals in the LH mimicked recovery sleep in the absence of excessive fatigue. Furthermore, these PFC-Sst-GABA terminals had enhanced activity during nesting and sleep, inducing inhibitory postsynaptic currents on diverse GABAergic cells in the respective sublocation of hypothalamus. Our findings provide a circuit link for how the PFC directly instructs the hypothalamus to ensure that optimal sleep takes place in a suitable place.

Conflict of Interest: No.

Session: Symposium—Hypermotor insomnia from the crib to adolescence.

Presentation: Paediatric RLS.

Speaker: Rosalia Silvestri, Italy.

Summary

Paediatric Restless Legs Syndrome (RLS) is a rare sensory-motor often familial sleep disorder with a strong genetic component. It needs to be recognized early in life with a keen differential diagnosis versus other sleep-related motor disorders including Restless Sleep Disorder (RSD), periodic limb movement disorder (PLMD), nocturnal muscle cramps, and sleep-related rhythmic movement disorder. Also, several mimics need to be considered, including positional discomfort, growing pains, anxiety-induced restlessness, and often comorbid diagnoses such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), iron deficient anaemia, and chronic kidney disease. Recent estimates suggest a prevalence of 1.9% in school age and 2% in adolescents, with no sex differences until puberty. Even though RLS is an exquisitely clinical diagnosis, specific diagnostic supportive tests may be important to confirm clinical suspicion in young children with suboptimal verbal fluency. They include the suggested immobilization test (SIT) and standard or ambulatory polysomnography (PSG) to demonstrate PLMs >5/hour and a child-adapted severity scale.

Paediatric RLS impacts four specific domains: sleep, daily activities, mood, and energy/vitality. Inadequate school performance and behaviours are among the major consequences of paediatric RLS. Central iron deficiency is a key factor in most restless hypermotor disorders and impinges on striatal dopaminergic levels and receptors.

Although current guidelines from the American Academy of Sleep Medicine (AASM) do not include specific therapeutic paediatric recommendations, early implemented therapy with oral or intravenous iron supplementation for ferritin <50 mg/L is considered the preferential way to address this disorder. Other off-label drugs with specific age limitations include alfa-delta drugs, alfa-2-adrenergic compounds, and benzodiazepines. Despite a recognized dopaminergic dysfunction, no dopaminergic agents are generally recommended or used, at least in European countries, due to the risk of several side effects, the most dangerous being obsessive-compulsive disorder and early augmentation.

Conflict of Interest: No.

Session: Symposium—Implementation of insomnia interventions in primary care and psychiatric settings—barriers and opportunities.

Presentation: Better Sleep in Psychiatric care—A project to implement evidence-based management of sleep problems in the Stockholm Region.

Speaker: Susanna Jernelöv, Sweden.

Summary

Good sleep is important for everyone, including psychiatric patients. Unfortunately, psychiatric patients often have disturbed sleep which may exacerbate their primary psychiatric disorder and may not necessarily resolve even if the psychiatric issue improves. Identifying and managing sleep problems is therefore crucial in psychiatric care. However, this is rarely done systematically. This ongoing healthcare development project has mapped current practices for managing sleep problems in psychiatric patients as a basis to effectively implement evidence-based and structured management of sleep problems in psychiatric care.

Based on the mapping, as one of several implementation strategies, we are developing materials to support evidence-based and structured management of sleep problems in psychiatric care. These materials, while structured, will remain flexible enough to accommodate the varying needs of different units and their patients. Key components of the structured management include identifying disturbed sleep in psychiatric patients, diagnosing sleep problems, managing disturbed sleep, and following up and evaluating interventions.

We are also developing educational packages which will both include broader subjects such as the neurobiology of sleep, and specifically target key components, and which can be tailored to meet the specific needs of various units.

Moving forward, we aim to pilot and evaluate the implementation at a small number of units before gradually expanding to all psychiatric clinics in the Stockholm Region.

Conflict of Interest: No.

Session: Symposium—Sleep and torpor: Neural substrates and effects of hypometabolism on brain activity and behaviour.

Presentation: The role of circadian clock in Qrfp-expressing neurons induced hibernation.

Speaker: Arisa Hirano, Japan.

Summary

The circadian clock regulates the 24 h physiological rhythms in various organisms. In mammals, the suprachiasmatic nucleus (SCN) in the hypothalamus is known as the master/central clock responsible for the synchronization of circadian rhythms in peripheral tissues. The circadian clocks are driven by a transcription-translation based negative feedback loop and multiple steps of mRNA/protein modifications. Although the clock oscillation is mechanistically composed of biochemical reactions, the circadian period is not so much affected by fluctuation of environmental and/or internal temperature, which is known as temperature compensation.

Recently, long-term hibernation-like hypothermia and hypometabolic state was reported in mice and rats, which are not natural hibernators (Takahashi et al., Nature, 2020). Pyroglutamylated RFamide peptide (QRFP)-positive neurons in the anteroventral periventricular nucleus (AVPe) hypothalamus region (called Q neurons) are responsible for this phenomenon. Pharmacological excitation of these neurons triggered the reduction in body temperature and metabolism (oxygen consumption) and it lasted for several days. To examine the brain function in the hypothermic and hypometabolic state in mice, we analysed the circadian oscillator at behavioural, cellular and molecular levels in the SCN and peripheral tissues. We first observed no significant phase shift in the behavioural rhythm after the long hypothermia (~25°C), suggesting the central clock is still oscillating. In vivo imaging of PER2::LUC, which is a fused protein of Luciferase and a core clock protein PER2, revealed that the molecular circadian oscillator also persisted in the hypothermic state, while the cellular metabolic rate is supposed to be largely decreased. On the other hand, the PER2::LUC rhythm in tissue culture at low temperature (25°C) was significantly damped the molecular rhythms, suggesting the specific mechanism keeping the clock function in vivo in low temperature environment. Our findings also demonstrated that the temperature compensation of the circadian clock is observed in mammals in vivo.

Conflict of Interest: No.

Session: Symposium—Beyond slow wave activity—What we can learn from a thorough characterization of the sleep EEG for development.

Presentation: Maturation-dependent changes in cortical and thalamic activity during sleep slow waves.

Speaker: Damiana Bergamo, Italy.

Summary

Slow waves (0.5–4 Hz), a hallmark of NREM sleep, undergo substantial changes throughout development, reflecting the brain's structural and cognitive maturation. Our study used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes.

We analysed data from 14 children with self-limited focal epilepsy who fell asleep during an afternoon EEG-fMRI recording session. By employing voxel-wise regression, we identified brain regions presenting significant BOLD-signal changes related to slow-wave occurrence. Our analysis accounted for potential signal changes caused by interictal epileptic discharges and sleep spindles. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults.

Our findings revealed that slow waves were associated with negative hemodynamic-signal changes in bilateral somatomotor areas. These changes tended to extend to more posterior brain areas in children relative to adults. Furthermore, we observed a positive correlation between age and thalamic hemodynamic changes during slow waves.

Interestingly, previous studies suggested that at least two slow-wave subtypes involving partially distinct synchronization mechanisms may exist. According to this view, smaller and shallower (type II) slow waves may originate from predominantly cortico-cortical synchronization mechanisms, while larger and more widespread (type I) slow waves may be synchronized by subcortical structures including the thalamus. Recent evidence revealed that these slow-wave subtypes follow distinct maturation trajectories and that type I waves may be absent or show immature features in school-age children. Such an observation could be explained by developmental variations in the role of the thalamus in slow-wave regulation and synchronization from childhood to adulthood.

Conflict of Interest: No.

Session: Symposium—OSA in women: Not just for men anymore.

Presentation: Diagnostic approach to female patients with OSA.

Speaker: Özen K Basoglu, Turkey.

Summary

Obstructive sleep apnoea (OSA) is considered as a male disorder, and women are less frequently diagnosed and treated for OSA than men. Although OSA is predominant in men, it is also common in women, especially after menopause. Men more often present with classic symptoms such as witnessed apnoea, loud snoring, and daytime sleepiness. Women are less likely to report snoring or apnoea but are more likely to complain of fatigue, lack of energy, insomnia, morning headaches, and mood disturbance. The clinical picture and diagnosis of the disorder are still based on the typical symptoms and findings in male patients. Therefore, women are often misdiagnosed and treated with depression or insomnia before being diagnosed with OSA.

OSA screening tools consist of questions about typical symptoms that are more common in male patients. The most frequently used questionnaires, such as STOP-BANG and Berlin Questionnaire, have not been validated in the female population. Studies indicate that female-specific cut-off points for commonly used surveys, and new sex-specific screening tools are needed. Otherwise, it may be challenging for both primary care and sleep physicians to diagnose OSA in women.

Diagnostic sleep testing is mandatory in patients with suspected OSA, and unattended polygraphy is specific and sensitive for those with a high pre-test probability. The patients with excessive daytime sleepiness and two of the following: habitual loud snoring; witnessed apnoea or gasping or choking; diagnosed arterial hypertension are considerd high pre-test probability, but high-risk criteria may not be appropriate for women with atypical symptoms. Therefore, women will be more likely to undergo polysomnography, which may result in a longer wait for OSA diagnosis. Sleep testing results are also different in female patients. Women have less severe OSA with a lower apnoea-hypopnea index, shorter apnoea episodes, clustering of apnoea during rapid eye movement sleep, less severe desaturations, and lower rate of positional OSA.

Underdiagnosis of OSA in women is a major public health problem, placing many women at risk for cardiovascular and neurocognitive outcomes and reduced quality of life. Further research is needed on sex-specific diagnostic algorithms to prevent women from being underdiagnosed and undertreated.

Conflict of Interest: No.

Session: Symposium—Breathing related arousals in Paediatric OSA: Impact on Diagnosis and Management.

Presentation: Upper Airway Resistance Syndrome: Challenges in Evaluation and Management.

Speaker: Umakanth Katwa, United States.

Summary

Upper Airway Resistance Syndrome (UARS) is a sleep-related breathing disorder characterized by increased resistance in the upper airway during sleep, leading to sleep fragmentation and daytime symptoms without significant oxygen desaturation. In children, UARS is often underdiagnosed because its symptoms can be subtle and overlap with other conditions like behavioural issues.

Children with UARS may exhibit snoring, restless sleep, frequent arousals, mouth breathing, and difficulty breathing during sleep. Unlike OSA, UARS is characterized by increased airway resistance, leading to increased respiratory effort and effort-related frequent micro-arousals that prevent deep and restorative sleep. Daytime symptoms in children may include hyperactivity, inattention, irritability, difficulty concentrating, and excessive daytime sleepiness, often mimicking attention-deficit hyperactivity disorder (ADHD).

The pathophysiology of UARS involves nasal obstruction, enlarged adenoids, and tonsils narrow upper airways, and increased upper airway collapsibility. Diagnosis is challenging and typically requires a detailed sleep history and physical examination. This condition is challenging to diagnose on polysomnography, as the obstruction is subtle and difficult to quantify.

Treatment for UARS in children focuses on addressing the underlying causes of airway resistance. First-line treatments often involve adeno-tonsillectomy, especially if the child has enlarged tonsils or adenoids. For children with nasal obstruction, treatments may include nasal corticosteroids, antihistamines, or surgery to correct structural issues. Positive airway pressure (PAP) therapy, such as CPAP, may be used in more severe cases. Additionally, orthodontic interventions, such as rapid maxillary expansion, can help in cases where a narrow palate contributes to airway resistance. Sleep hygiene is also an essential component of treatment, helping to improve overall sleep quality and reduce daytime symptoms. Clinical suspicion with early diagnosis and treatment are critical in preventing long-term complications related to UARS in children.

Conflict of Interest: No.