Periodic Reporting for period 1 - GlymphoSleep (Exploring neuro-glymphatic coupling during sleep using wearable technology)
Période du rapport: 2023-03-01 au 2025-02-28
Sleep is a fundamental biological process with wide-ranging effects on cognition, emotional regulation, immune function, and overall brain health. In recent years, growing evidence has revealed a crucial role of sleep in clearing metabolic waste from the brain via the glymphatic system - a brain-wide fluid transport pathway that relies on coordinated neural and vascular activity. This brain-clearance process is closely linked to slow-wave activity during non-rapid eye movement sleep (SWA during NREM; 0.5–2 Hz) observed in electroencephalographic (EEG) recordings. Increased SWA has been associated with increased cerebrospinal fluid (CSF) flow, enabling glymphatic system function. Disruption of the glymphatic clearance process is increasingly associated with ageing and neurodegenerative diseases such as Alzheimer’s.
Despite growing interest in this field, due to the lack of non-invasive easy-to-use technological solutions, studying glymphatic clearance in natural at-home sleep conditions has remained a challenge. The goal of the action “Exploring neuro-glymphatic coupling during sleep using wearable technology” (GlymphoSleep project) is to overcome these limitations by validating the usage of the first wearable solution capable of assessing changes in CSF dynamics. This technology relies on the multi-wavelength functional near-infrared spectroscopy (fNIRS) which is sensitive to changes in hemodynamics (changes in blood oxygenation), and, importantly, CSF flow. The device “G-meter” was developed by a team of engineers at the University of Oulu, Finland, the main collaborators of this project. By using a combination of CSF-sensitive fNIRS and EEG to monitor electrophysiological sleep markers, this portable setup allows assessing neuro-glymphatic coupling during natural sleep in an at-home environment. Additionally, the project employed non-invasive closed-loop auditory stimulation (CLAS) to enhance SWA, to causally test the link between sleep electrophysiology and brain clearance. CLAS is a validated method that reliably enhances slow waves without inducing awakenings or altering the natural sleep structure.
Thus, the main scientific objectives of the GlymphoSleep project were to: (1) characterize the relationship between sleep neurophysiology and glymphatic clearance; (2) test whether enhancing SWA would change CSF flow; and (3) explore how variability in this coupling depends on the individual genetic profile. While the third objective was not pursued due to logistical reasons, the first two have been fully addressed through successful data collection and publications in preparation.
By bridging neuroscience, biomedical engineering, and sleep research, the GlymphoSleep project contributes to the EU’s strategic goals in health innovation, ageing research, and digital transformation. The technological outputs have implications for early detection of neurodegenerative risk and personalised sleep medicine. Ultimately, the project lays a foundation for wearable tools to monitor brain clearance in ageing populations, supporting preventive health strategies across Europe and beyond.
Despite growing interest in this field, due to the lack of non-invasive easy-to-use technological solutions, studying glymphatic clearance in natural at-home sleep conditions has remained a challenge. The goal of the action “Exploring neuro-glymphatic coupling during sleep using wearable technology” (GlymphoSleep project) is to overcome these limitations by validating the usage of the first wearable solution capable of assessing changes in CSF dynamics. This technology relies on the multi-wavelength functional near-infrared spectroscopy (fNIRS) which is sensitive to changes in hemodynamics (changes in blood oxygenation), and, importantly, CSF flow. The device “G-meter” was developed by a team of engineers at the University of Oulu, Finland, the main collaborators of this project. By using a combination of CSF-sensitive fNIRS and EEG to monitor electrophysiological sleep markers, this portable setup allows assessing neuro-glymphatic coupling during natural sleep in an at-home environment. Additionally, the project employed non-invasive closed-loop auditory stimulation (CLAS) to enhance SWA, to causally test the link between sleep electrophysiology and brain clearance. CLAS is a validated method that reliably enhances slow waves without inducing awakenings or altering the natural sleep structure.
Thus, the main scientific objectives of the GlymphoSleep project were to: (1) characterize the relationship between sleep neurophysiology and glymphatic clearance; (2) test whether enhancing SWA would change CSF flow; and (3) explore how variability in this coupling depends on the individual genetic profile. While the third objective was not pursued due to logistical reasons, the first two have been fully addressed through successful data collection and publications in preparation.
By bridging neuroscience, biomedical engineering, and sleep research, the GlymphoSleep project contributes to the EU’s strategic goals in health innovation, ageing research, and digital transformation. The technological outputs have implications for early detection of neurodegenerative risk and personalised sleep medicine. Ultimately, the project lays a foundation for wearable tools to monitor brain clearance in ageing populations, supporting preventive health strategies across Europe and beyond.
During the course of the GlymphoSleep project, a multimodal approach to study the interaction between sleep-related electrical brain activity and glymphatic system function in naturalistic, at-home settings, was successfully implemented.
In Study 1, a technical milestone was achieved through the synchronized acquisition of EEG and CSF-sensitive fNIRS data during single-night overnight sleep in healthy young adults outside of the laboratory environment. During this part of the project, the RadboudUMC team of sleep researchers and engineers from Oulu have worked in close collaboration, pushing further the technical development and validation of the G-meter prototype. In Study 2, multi-night recordings were conducted using closed-loop auditory stimulation (CLAS) to selectively enhance SWA, to further investigate its causal relationship with glymphatic activity. As an outcome, a large dataset comprising over 200 high-quality multimodal full-night sleep recordings was collected.
The combined data of the two studies enables a precise analysis of how specific electrophysiological events (e.g. SWA) relate to cerebral hemodynamics and CSF oscillations associated with glymphatic system function. Preliminary findings suggest measurable modulation of fNIRS signals depending on the level of SWA, supporting the potential leading role of non-rapid eye movement sleep in brain clearance.
The processing of the collected data is still in progress and the intermediate results have been presented at several international conferences, increasing the project's visibility in the sleep and neuroimaging communities. After the data processing is completed, the collected dataset comprising over 200 multimodal sleep recordings will be published in open access for research purposes, facilitating reproducibility and further studies. The final scientific results are currently being prepared for submission to open-access peer-reviewed journals, ensuring wide dissemination and long-term impact within the field.
Additionally, part of the collected data was already made publicly available as part of an open dataset and accompanying preprint. Furthermore, the theoretical insights gained during the project regarding the use of CLAS to modulate glymphatic clearance and other sleep-related functions were summarized as a review article and submitted for publication.
In Study 1, a technical milestone was achieved through the synchronized acquisition of EEG and CSF-sensitive fNIRS data during single-night overnight sleep in healthy young adults outside of the laboratory environment. During this part of the project, the RadboudUMC team of sleep researchers and engineers from Oulu have worked in close collaboration, pushing further the technical development and validation of the G-meter prototype. In Study 2, multi-night recordings were conducted using closed-loop auditory stimulation (CLAS) to selectively enhance SWA, to further investigate its causal relationship with glymphatic activity. As an outcome, a large dataset comprising over 200 high-quality multimodal full-night sleep recordings was collected.
The combined data of the two studies enables a precise analysis of how specific electrophysiological events (e.g. SWA) relate to cerebral hemodynamics and CSF oscillations associated with glymphatic system function. Preliminary findings suggest measurable modulation of fNIRS signals depending on the level of SWA, supporting the potential leading role of non-rapid eye movement sleep in brain clearance.
The processing of the collected data is still in progress and the intermediate results have been presented at several international conferences, increasing the project's visibility in the sleep and neuroimaging communities. After the data processing is completed, the collected dataset comprising over 200 multimodal sleep recordings will be published in open access for research purposes, facilitating reproducibility and further studies. The final scientific results are currently being prepared for submission to open-access peer-reviewed journals, ensuring wide dissemination and long-term impact within the field.
Additionally, part of the collected data was already made publicly available as part of an open dataset and accompanying preprint. Furthermore, the theoretical insights gained during the project regarding the use of CLAS to modulate glymphatic clearance and other sleep-related functions were summarized as a review article and submitted for publication.
The GlymphoSleep project has produced pioneering results by implementing, for the first time, a fully wearable solution for monitoring brain clearance mechanisms during natural sleep. Before this project, research on glymphatic activity in humans had been largely limited to expensive and technically demanding techniques such as functional MRI or PET imaging, impractical methods for sleep studies in longitudinal contexts. In contrast, this project demonstrated the feasibility of combining wearable EEG and CFS-sensitive fNIRS to assess brain electrophysiology, hemodynamics and CSF flow outside the lab over multiple nights.
For the Fellow, the project has offered deepened expertise in cutting-edge sleep neurophysiology, wearable neurotechnologies, research leadership, and collaborative research. Importantly, during the project, strong interdisciplinary collaborations have been established between three European institutions: the University of Oulu (Finland), the Donders Institute (RadboudUMC, Netherlands), and the University of Amsterdam (Netherlands), strengthening the European research network in sleep neuroscience.
To ensure further uptake and long-term success, several key developments are needed: (1) integration of fNIRS and EEG technologies into a single, user-friendly wearable device; (2) validation of the system for long-term monitoring and repeated CLAS application over extended periods; (3) clinical testing in at-risk populations such as individuals with early-stage neurodegenerative diseases; and (4) continued refinement of real-time signal processing and stimulation algorithms. Additionally, the potential for creating a startup company based on this technology offers a path to clinical translation, wider dissemination, and commercial sustainability. These steps will help transform GlymphoSleep’s innovative concept into a practical tool for both research and healthcare.
For the Fellow, the project has offered deepened expertise in cutting-edge sleep neurophysiology, wearable neurotechnologies, research leadership, and collaborative research. Importantly, during the project, strong interdisciplinary collaborations have been established between three European institutions: the University of Oulu (Finland), the Donders Institute (RadboudUMC, Netherlands), and the University of Amsterdam (Netherlands), strengthening the European research network in sleep neuroscience.
To ensure further uptake and long-term success, several key developments are needed: (1) integration of fNIRS and EEG technologies into a single, user-friendly wearable device; (2) validation of the system for long-term monitoring and repeated CLAS application over extended periods; (3) clinical testing in at-risk populations such as individuals with early-stage neurodegenerative diseases; and (4) continued refinement of real-time signal processing and stimulation algorithms. Additionally, the potential for creating a startup company based on this technology offers a path to clinical translation, wider dissemination, and commercial sustainability. These steps will help transform GlymphoSleep’s innovative concept into a practical tool for both research and healthcare.