Neurofluid coupling during sleep and wake states.

BACKGROUND: In clinical populations, the movement of cerebrospinal fluid (CSF) during sleep is a growing area of research with potential mechanistic connections in both neurodegenerative (e.g., Alzheimer's Disease) and neurodevelopmental disorders. However, we know relatively little about the processes that influence CSF movement. To inform clinical intervention targets this study assesses the coupling between (a) real-time CSF movement, (b) neuronal-driven movement, and (c) non-neuronal systemic physiology driven movement. METHODS: This study included eight young, healthy volunteers, with concurrently acquired neurofluid dynamics using functional Magnetic Resonance Imaging (MRI), neural activity using Electroencephalography (EEG), and non-neuronal systemic physiology with peripheral functional Near-Infrared Spectroscopy (fNIRS). Neuronal and non-neuronal drivers were assessed temporally; wherein, EEG measured slow wave activity that preceded CSF movement was considered neuronally driven. Similarly, slow wave oscillations (assessed via fNIRS) that coupled with CSF movement were considered non-neuronal systemic physiology driven. RESULTS AND CONCLUSIONS: Our results document neural contributions to CSF movement were only present during light NREM sleep but low-frequency non-neuronal oscillations were strongly coupled with CSF movement in all assessed states - awake, NREM-1, NREM-2. The clinical/research implications of these findings are two-fold. First, neuronal-driven oscillations contribute to CSF movement outside of deep sleep (NREM-3); therefore, interventions aimed at increasing CSF movement may yield meaningful increases with the promotion of NREM sleep more generally - a focus on NREM S3 may not be needed. Second, non-neuronal systemic oscillations contribute across wake and sleep stages; therefore, interventions may increase CSF movement by manipulating systemic physiology.

Human CSF movement influenced by vascular low frequency oscillations and respiration.

Cerebrospinal fluid (CSF) movement through the pathways within the central nervous system is of high significance for maintaining normal brain health and function. Low frequency hemodynamics and respiration have been shown to drive CSF in humans independently. Here, we hypothesize that CSF movement may be driven simultaneously (and in synchrony) by both mechanisms and study their independent and coupled effects on CSF movement using novel neck fMRI scans. Caudad CSF movement at the fourth ventricle and hemodynamics of the major neck blood vessels (internal carotid arteries and internal jugular veins) was measured from 11 young, healthy volunteers using novel neck fMRI scans with simultaneous measurement of respiration. Two distinct models of CSF movement (1. Low-frequency hemodynamics and 2. Respiration) and possible coupling between them were investigated. We show that the dynamics of brain fluids can be assessed from the neck by studying the interrelationships between major neck blood vessels and the CSF movement in the fourth ventricle. We also demonstrate that there exists a cross-frequency coupling between these two separable mechanisms. The human CSF system can respond to multiple coupled physiological forces at the same time. This information may help inform the pathological mechanisms behind CSF movement-related disorders.

Monitoring anesthesia using simultaneous functional Near Infrared Spectroscopy and Electroencephalography.

OBJECTIVE: This study aims to understand the neural and hemodynamic responses during general anesthesia in order to develop a comprehensive multimodal anesthesia depth monitor using simultaneous functional Near Infrared Spectroscopy (fNIRS) and Electroencephalogram (EEG). METHODS: 37 adults and 17 children were monitored with simultaneous fNIRS and EEG, during the complete general anesthesia process. The coupling of fNIRS signals with neuronal signals (EEG) was calculated. Measures of complexity (sample entropy) and phase difference were also quantified from fNIRS signals to identify unique fNIRS based biomarkers of general anesthesia. RESULTS: A significant decrease in the complexity and power of fNIRS signals characterize the anesthesia maintenance phase. Furthermore, responses to anesthesia vary between adults and children in terms of neurovascular coupling and frontal EEG alpha power. CONCLUSIONS: This study shows that fNIRS signals could reliably quantify the underlying neuronal activity under general anesthesia and clearly distinguish the different phases throughout the procedure in adults and children (with less accuracy). SIGNIFICANCE: A multimodal approach incorporating the specific differences between age groups, provides a reliable measure of anesthesia depth.