HUMAN CEREBROSPINAL FLUID MOVEMENT ACROSS WAKE AND SLEEP STATES – A MULTIMODAL IMAGING STUDY

The movement of Cerebrospinal Fluid (CSF) within the brain's ventricles and the subarachnoid spaces of both the cranium and spine is crucial for the health and functioning of the central nervous system. Recent research has emphasized CSF movement's importance in metabolic waste clearance and its effect on the pathophysiology of neurodegenerative and neurodevelopmental disorders. Additionally, CSF movement is significantly enhanced during Non-rapid eye movement (NREM) sleep. Despite the critical role of CSF in maintaining brain health, a comprehensive understanding of the mechanisms driving its movement across different states of wakefulness and sleep is lacking. In this work, multimodal imaging was utilized to simultaneously monitor CSF movement and brain hemodynamics via functional Magnetic Resonance Imaging (MRI), neural activity through Electroencephalography (EEG), and non-neuronal systemic physiology via peripheral functional Near-Infrared Spectroscopy (fNIRS). Our findings reveal that CSF movement is influenced by multiple physiological forces concurrently. During wakefulness, both low-frequency vasomotion and respiration interact to regulate CSF movement. Furthermore, systemic physiological changes significantly impact CSF movement during light NREM sleep, even in the presence of autonomic neural activity. Notably, during deep NREM3 sleep, CSF movement magnitude increases independent of the magnitude of brain hemodynamics, suggesting a decrease in impedance to CSF movement and an enhanced exchange between CSF and interstitial fluid (ISF) in the brain. Building on these observations, significant enhancement of CSF movement was also achieved via simple respiratory interventions, thereby demonstrating their potential to be used as clinical protocols across pathologies characterized by reduced CSF movement.