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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.

Low-frequency changes in cerebral hemodynamics have recently been shown to drive cerebrospinal fluid (CSF) movement in the human brain during non-rapid eye movement (NREM) sleep and resting state wakefulness. However, whether the coupling strength between these neurofluids varies between wake and sleep states is not known. In addition, the principal origin (i.e., neuronal vs. systemic) of these slow cerebral hemodynamic oscillations in either state also remains unexplored. To investigate this, a wake/sleep study was conducted on eight young, healthy volunteers, concurrently acquiring neurofluid dynamics using functional Magnetic Resonance Imaging, neural activity using Electroencephalography, and non-neuronal systemic physiology with peripheral functional Near-Infrared Spectroscopy. Our results reveal that low-frequency cerebral hemodynamics and CSF movements are strongly coupled regardless of whether participants were awake or in light NREM sleep. Furthermore, it was also found that, while autonomic neural contributions are present only during light NREM sleep, non-neuronal systemic physiology influences neurofluid low-frquency oscillations in a significant way across both wake and sleep states. These results further our understanding regarding the low-frequency hemodynamic drivers of CSF movement in the human brain and could help inform the development of therapies for enhancing CSF circulation.

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Background: Cerebrospinal fluid movement (CSF) 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 both been shown to independently drive CSF in humans. Here, we hypothesize that CSF movement may be driven simultaneously (and in synchrony) by both mechanisms and we study their independent and interactive effects on CSF movement using novel neck fMRI scans.Methods: Caudad CSF movement at the fourth ventricle and hemodynamics of the major neck blood vessels (internal carotid arteries and internal jugular veins) were captured 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) were independently investigated in corresponding frequency ranges. Possible interactions between these mechanisms were also studied using cross-frequency coupling.Results: The results from this study validated that the caudad CSF movement may be driven by both low frequency hemodynamics (0.01 Hz – 0.1 Hz) and respiration (0.2 Hz - 0.4 Hz), through different mechanisms. 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 at the fourth ventricle. We also demonstrate that there exists a cross-frequency interaction between two separable mechanisms.Conclusions: The human CSF system is capable of responding to multiple interacting physiological forces at the same time. This information may help inform the pathological mechanisms behind CSF movement-related disorders and facilitate new approaches to therapeutic interventions.