Monthly Sleep Research Trainee Seminar

Titre: Caractérisation spectrale et temporelle des états du cycle veille-sommeil chez l’homme et de leur continuum dans différentes pathologies neurologiques

Type: Clinical research

Mon projet de thèse s’intéresse à la macro- ainsi que la microarchitecture du sommeil et ses caractéristiques spectrales dans différents troubles neurologiques du sommeil ou impactés par le sommeil. En particulier mes travaux s’intéressent à l’hypersomnie idiopathique, afin d’en explorer la régulation circadienne, d’un point de vue organisation du sommeil, aussi bien au laboratoire qu’en conditions écologiques, et homéostatique via l’activité en ondes lentes pendant le sommeil. Je cherche également à mieux comprendre grâce à l’EEG de haute densité les caractéristiques phénotypiques de la pathologie comme l’ivresse du réveil ou la somnolence diurne excessive, utilisant le modèle du sommeil local. Un autre aspect de mes travaux s’intéresse à la narcolepsie de type 1, et en particulier la recherche de biomarqueurs de la cataplexie, d’une part via l’activité EEG, et d’autre part via l’étude du système nerveux autonome. Un second volet de ma thèse s’intéresse aux pathologies neurodégénératives, en particulier la maladie d’Alzheimer, afin de comprendre les facteurs sommeil pouvant prédire le déclin cognitif dans la pathologie, utilisant à la fois des données longitudinales en population générale, mais également en étudiant l’architecture loco-régionale du sommeil en EEG haute densité sur des données transversales.

Title: Promoting Healthy Sleep: Evaluation of an eLearning Professional Development Program for Healthcare Providers

Type: Clinical research

Approximately one third of Canadian children have insomnia or symptoms of insomnia, defined as chronic and frequent difficulties with falling and/or staying asleep. Most healthcare providers in Canada do not receive formal training in screening, assessment, or management of pediatric insomnia. While the first-line treatment for insomnia is behavioural interventions, almost 70% of family physicians and over 75% of pediatricians recommend sedating medication to treat insomnia among children, even though there are no approved medications for pediatric insomnia. The current study will examine the perceived usefulness of an eLearning professional development program for healthcare providers, titled Promoting Healthy Sleep (PHS): An eLearning Program for Healthcare Providers. The goal of this program is to provide accessible, online sleep education to healthcare providers who will be screening, assessing, and treating pediatric insomnia. In the first study, people that have relevant lived experience (i.e., parents/caregivers of children with pediatric insomnia) will review the program and participate in qualitative interviews, where they will provide feedback about the content of the program. For the second study, twenty healthcare providers working in Canada will be recruited from four groups (i.e., physicians, psychologists, nurses, allied health professionals), where they will assess the usability of the program from the end users’ perspective. Healthcare providers will complete the eLearning program, complete questionnaires about their sleep knowledge before and after the program, as well as questionnaires after each of the four sessions and at the end of the program in order to collect feedback about the program’s usability. We predict that participants will find the program useful and ready to be implemented with minimal modifications to the program. If the program is deemed appropriate and useful, then next steps will be to test the effectiveness of the program. The results for both studies will be finalized by January 2024.

Title: Sleep for Health in Hospital and at Home (Shhh)

Type: Clinical and Fundamental research

We conducted a mixed methods study exploring the sleep experiences of pediatric in-patients and their co-resident parents on a Pediatric Medical Unit (PMU) and at home. Purposive sampling was used to include children with a range of personal and medical characteristics. We measured sleep (sleep diaries, questionnaires and actigraphy), activity (time-use diaries), mood, disruptions experienced in hospital, and light and sound recordings. Five parents (2 fathers and 3 mothers) also completed semi-structured interviews. A survey of healthcare providers (HCPs) explored personal experiences of sleep and knowledge of sleep promoting and disrupting factors on PMU.

We found that current hospital routines, timing of staff changes, scheduling of vitals checks and prescribed interventions had not been designed with children’s normal sleep routines in mind. Restrictions associated with the COVID-19 pandemic presented further challenges to achieving healthy sleep. Sound levels regularly exceeded WHO guidelines, and participants were not meeting daytime light recommendations. Parents’ knowledge of good sleep habits and how to optimize sleep in hospital was very variable.

Both staff and parents had many excellent, achievable suggestions, some of which have already been implemented and others need to be carried out more consistently. Completing the measures raised participants’ awareness of positive sleep habits, and some reported subsequently modifying their sleep habits with good effect. A ‘Translating Research Into Care’ project is now underway guided by parents, HCPs, and youth. We will implement positive changes, ensure their consistent adoption and explore solutions for some system-based challenges. We will also develop information resources.

Title: EEG functional connectivity during sleep and cognitive function in patients with Parkinson’s disease

Type: Mix of Clinical and Fundamental research

Sleep is known to be important for cognitive function, though very little is known about how functional connectivity during sleep relates to cognition. It is well documented that sleep is changed in Parkinson’s disease, from changes in overall sleep architecture as well as in specific oscillations. These changes have been associated with sleep-dependent cognition (i.e., memory consolidation) as well as cognitive decline. In the current work, we are investigating how connectivity during non-REM sleep changes with Parkinson’s disease– comparing patients to healthy controls. We are also investigating how connectivity during non-REM sleep is associated with cognitive function in both patients and healthy adults.

Title: Investigating EEG fractal complexity across vigilance states in diverse mice models of neurological pathologies

Type: Fundamental research

Neurons can fire in a periodic/rhythmic manner (i.e. at a given frequency) and/or an aperiodic/arrhythmic manner (i.e. with no given frequency component). Both types of neuronal activity can be observed and detected in the electroencephalogram (EEG): the first appears as bumps of power at given frequencies in the log-log power spectrum, while the second underlies the 1/f power decay. Although the literature on the physiological relevance of cerebral oscillatory activity and the underlying mechanisms is quite extensive, the same cannot be said regarding aperiodic/arrhythmic neuronal activity. Indeed, this second type of activity was long thought to represent background (random) noise. Some recent studies have, however, shown that such aperiodic/arrhythmic activity changes with behaviour and can be indicative of pathological states. Using a multifractal wavelet-leaders formalism to analyze the mouse EEG, our work investigates this aperiodic/arrhythmic activity in various neurological pathologies across vigilance states. During this talk, I will be showing data regarding models going from neurodevelopmental disorders (Autism spectrum disorders/Schizophrenia/Epilepsy) to neurodegenerative pathologies (Alzheimer’s disease).

Title: Actigraphic and Self-Reported Sleep Outcomes and Relationships to Anxiety and Depression Symptoms in Adolescents and Young Adults With Cystic Fibrosis: A Mixed Methods Study

Type: Clinical research

Cystic Fibrosis (CF) is the most common life-limiting genetic disease in young Canadians. Some research suggests that young people with CF may have more trouble with sleep than people of the same age without chronic illness. Poor sleep can affect a person’s ability to concentrate at school/work and feel well emotionally. This study will measure the sleep and mental health of adolescents and young adults (AYA) with CF and compare this to AYA without chronic illness. This study will: investigate whether those with CF have more sleep difficulties and more mental health concerns; determine if there is a relationship between poor sleep and worse mental health, and will explore sleep experiences from the perspective of those with CF. Participants will complete questionnaires to measure sleep, symptoms of anxiety and depression and pain. They will also keep a sleep diary and use an actigraph to record their sleep for 7-days and 7-nights. Some individuals with CF will also participate in a virtual interview to discuss their sleep experiences. Clinical details will be collected from the Canadian CF Registry on consenting CF participants. This study will be the first to provide information on the relationship between poor sleep, measured by both self-report and actigraphy, and both anxiety and depression symptoms in AYA with CF and will be the first study to integrate the sleep experiences and voices of the participants themselves. More completely understanding the relationship between mental health and sleep could have a significant impact on well-being and quality of life.

Title: Défis et opportunités en matière de devis éthiques pour la recherche sur les rêves et les cauchemars

Type: Clinical research

Les personnes qui participent à des projets de recherche sur les rêves et les cauchemars peuvent dormir en laboratoire sous surveillance vidéo, se prêter à des expériences ou encore procéder à des neuroimageries avant et pendant le coucher. À ces occasions, leur corps, leur image et d’autres marqueurs de leur identité sont sollicités tandis que leurs données biométriques sont examinées. Ces participant·e·s auront alors donné leur consentement à cet effet avant de se trouver dans les états vulnérables incités par le sommeil, mais leur compréhension des enjeux aura-t-elle été suffisante ? Quels sont les droits et devoirs des personnes éveillées face à leur « moi endormi » ? Quelles sont les sources de leur dignité continue ?

Les participant·e·s peuvent tout autant livrer des récits de rêves à teneur confidentielle, par exemple en tenant des journaux auxquels l’équipe de recherche aura accès. Pour conserver une ligne éthique au service des meilleurs standards scientifiques, les récits peuvent être dépersonnalisés, anonymisés, voire détruits, mais comment réguler l’interaction des participant·e·s avec l’équipe de recherche, qui se distingue d’une équipe soignante ?

On peut supposer que plusieurs comités d’éthique de la recherche se sont historiquement posé ces questions. Malheureusement, aucune trace de leurs délibérations ne subsiste dans les études, d’autant plus que les défis posés par la recherche sur les rêves et les cauchemars se complexifieront sans doute au rythme où va la sophistication des équipements médicaux et des applications web, qui puisent déjà à même nos insécurités et nos impératifs de productivité pour contrôler et « optimiser » notre sommeil…

Les deux points de vue gagneraient à être représentés : tant celui des équipes que celui des comités d’éthique de la recherche. C’est une opportunité à saisir, le but étant non seulement de créer un précédent pour se préparer aux questions émergentes qui nous guettent et qui, si laissées sans réponse, pourraient céder le pas à des abus, mais également de sensibiliser les équipes aux enjeux éthiques les plus fréquemment soulevés dans leur domaine, les aider à comprendre les motivations des comités, puis, en retour, d’éclairer les comités quant à l’impact de leurs réserves et objections sur la « réalité-terrain».

Title: The impact of equity, diversity, and inclusivity factors on the acceptance, usability, and effectiveness of eHealth treatment for sleep difficulties in Canadian children

Type: Clinical research

Sleep disorders impact physical and mental health and are one of the most common health conditions across the lifespan. Less than 20% of individuals receive evidence-based interventions to treat their insomnia which demonstrates the inequitable access to sleep health care. It is known that individuals facing various EDI (equity, diversity, inclusivity) factors and/or health disparities (e.g., gender, socioeconomic status, geography, sexual orientation) are more likely to have insomnia and are less likely to receive treatment. One potential solution to reduce access to treatment barriers is by delivering insomnia treatment via the internet. Our research team has developed and tested the effectiveness of a digital sleep intervention, Better Nights Better Days, for children aged 1-10 experiencing sleep difficulties. The first study of my research aims to understand the literature that has been done in Canada with children that examines the relationship between sleep health and individuals facing health disparities. The second study explores the demographics (e.g., SES, gender, location) of our past participants who completed our Better Nights, Better Days eHealth sleep interventions. In a third study, using this information, parents of children facing various EDI factors and/or health disparities will complete an interview to better understand the barriers and facilitators they face when completing our online sleep programs. These findings will allow us to learn more from diverse populations to better understand the barriers and facilitators they face when completing our eHealth sleep programs and how to modify these programs to make them more inclusive and culturally informed.

Title: Astrocytic glucocorticoid receptors drive sexually dimorphic effects of stress on orexin neurons and running wheel behaviour

Type: Fundamental research

Astrocytes are the most abundant non-neuronal brain cell and are implicated in regulating a number of complex behaviours including sleep-wake cycles and circadian rhythms. These cells have also previously been shown to be very sensitive to stress induced fluctuations in blood glucocorticoids, a hormone tightly regulated across the light-dark cycle. Astrocytes in the Lateral hypothalamus participate in fueling firing activity of orexin neurons, a population of wake promoting neurons. Given the important link between stress and sleep-wake perturbation, we investigated whether or not astrocytes mediate the effects of early life stress to induce behavioural dysfunction in rodents.

Title: REM sleep behaviour disorder in mouse models of Parkinson’s disease and multiple system atrophy

Type: Fundamental research

RBD is a parasomnia in which patients exhibit abnormal muscle activity during REM sleep. Following RBD onset, 80-90% of patients develop a synucleinopathic disorder such as Parkinson’s disease (PD) or multiple system atrophy (MSA). RBD is thus considered a prodromal disease state and the best predictor of synucleinopathic diseases. Interestingly, RBD is comorbid in only 25-58% of PD patients but is present in almost 100% of MSA patients. Further, the distribution of pathology, disease severity, and targeted cell types (i.e. neurons vs oligodendrocytes) markedly differ between diseases. It is theorized that while one protein may seed all synucleinopathies, small, structural differences may drive different strains of disease, lending to varying clinical outcomes. Whether strains underly differences in RBD development, however, remains to be examined. The current study addresses this gap by examining pathological and behavioural differences between RBD-MSA and RBD-PD mouse models. So far, our findings have demonstrated that these models have distinct disease progressions, with diverging disease severity and symptomology. We have also found that the REM sleep atonia circuit does in fact develop pathology in both disease models, confirming that although disease manifestation differs, the REM sleep atonia circuit is consistently vulnerable to synucleinopathic disease. Lastly, we found that both RBD-MSA and RBD-PD mouse models develop RBD-like symptoms over time. Our collective findings demonstrate disease dependent differences in RBD presentation in MSA and PD models, suggesting that REM sleep atonia generating neurons may exhibit differential vulnerability depending on the specific strain of disease.

Title : The absence of Neuroligin-2 differentially modulates wake/sleep architecture and spectral activity in male and female mice

Type: Fundamental research

Neuroligin-2 (NLGN2) is a synaptic adhesion molecule that is associated mainly to GABAergic neurotransmission and regulates behavioural states. Mutations in Nlgn2 have been linked to neurodevelopmental disorders (e.g. autism spectrum disorder) and dysfunction in synaptic plasticity. The loss of NLGN2 in male mice was shown to increase the time spent in wakefulness, decrease the time spent in slow wave sleep, and to alter electrocorticographic spectral activity. However, whether the lack of NLGN2 impacts wake/sleep states in female mice remains to be established. Here, we aimed to compare sexes for the impact of the absence of NLGN2 on the wake/sleep architecture, spectral activity, and responses to sleep deprivation.

Title : Bien dormir, bien grandir: Solutions modernes pour parents en quête de sommeil

Type: Clinical research

Tout humain ayant la chance et le privilège de devenir parent sait que le sommeil, ou plutôt l’absence de sommeil, pendant les premières années de vie d’un enfant, peut amener d’importantes répercussions sur le fonctionnement familial dans son ensemble. Soucieux d’offrir le meilleur accompagnement possible, les parents d’aujourd’hui sont curieux et se renseignent davantage sur ce sujet de prédilection de la parentalité qu’est le sommeil.
Avec les nombreuses recherches en sommeil qui ont été réalisées au cours des dernières années, nous ne pouvons nier les effets collatéraux du manque de sommeil. Particulièrement chez les nouveaux parents qui en sont, pour la plupart, fortement affectés de façon continue ou sporadique. Et si nous avions la capacité de pouvoir les accompagner différemment afin de mieux les préparer aux enjeux du manque de sommeil sans tomber dans le fatalisme ? Sachant que le manque de sommeil est un facteur précipitant important de la dépression post-partum et de l’épuisement parental, comment pourrions-nous en diminuer les impacts ? Quelles sont les solutions sommeil pour venir en aide aux parents épuisés ?
Marie-Pier Villeneuve, autrice de deux livres sur le sujet, vient humblement nous exposer les constats de sa pratique des dernières années auprès de centaines de familles qui ont pu retrouver, grâce à son soutien, un sommeil paisible, une nuit à la fois…

Title: Modulation of hippocampal rhythms by median raphe glutamatergic neurons during sleep

Type: Fundamental research

Two distinct hippocampal rhythms are highly involved in memory consolidation: sharp-wave ripples (~50 ms, 150-250 Hz) during non-rapid eye movement (NREM) sleep and theta oscillations (5 to 12 Hz) during rapid eye movement (REM) sleep. The median raphe is known as a powerful modulator of hippocampal rhythms. Nevertheless, the exact contribution of the median raphe neurons expressing the vesicular glutamate transporter type 3 (VGLUT3) and projecting to the hippocampus is still unclear. In this study, we investigated median raphe VGLUT3+ neuronal population activity in relation to sleep-wake cycles, with focus on hippocampal sharp-wave ripples and theta oscillations. To target median raphe VGLUT3+ neurons, we injected Cre-dependent viral vectors in VGLUT3-Cre mice allowing for specific expression of calcium sensors and optogenetics tools in our population of interest. First, we assessed median raphe VGLUT3+ population activity in relation to hippocampal activity across sleep-wake cycles. To do so, we used simultaneous electrophysiological recordings in the hippocampus with fiber photometry recordings in the median raphe. We observed that VGLUT3+ neurons were highly active during wake and REM sleep while they were active in short bouts during NREM sleep. Second, we optogenetically activated glutamatergic neurons to assess their potential to modulate hippocampal rhythms. Activation of VGLUT3+ neurons during NREM sleep suppressed sharp-wave ripples and modulated theta rhythm frequency and power during REM sleep. Taken together, our results highlight diverse activity patterns of VGLUT3+ median raphe neurons in relation to sleep states and reveal their powerful inhibitory control of hippocampal sharp-wave ripples and theta rhythm.