The influence of basal CO2on neurofluid dynamics measured using resting-state BOLD fMRI

Abstract

AbstractAn understanding of neurofluid dynamics has been gaining importance, in part given the link between neurofluid dynamics and glymphatic flow. As carbon dioxide (CO2) strongly modulates cerebral blood volume (CBV) and cerebrospinal fluid (CSF) flow, modulation of basal CO2 through different capnic conditions may offer insight into the mechanisms through which neurofluid dynamics are influenced. In this work, we report observations of neurofluid dynamics at normocapnia as well as during short-term hyper- and hypocapnia. We use the resting-state BOLD fMRI signal in neurofluid regions of interest (i.e. blood vessels, CSF compartments) as a surrogate of neurofluid dynamics. From these BOLD signals, we extract the power and central frequency of signal oscillations. We found that 1) Relative to a normocapnic steady state, both hypocapnic and hypercapnic steady states are associated with increased BOLD signal power and shifts in BOLD signal frequency in vascular ROIs in a band-dependent manner; 2) Relative to hypocapnia, hypercapnia is associated with both increased and decreased BOLD signal power in vascular ROIs, depending on the frequency band; 3) these trends are largely reproduced in the CSF ROIs and in the CSF velocity dynamics; 4) these power and frequency variations across capnic conditions are mostly driven by respiratory and heart-rate differences rather than by steady-state CO2and associated vascular-tone variations; 5) the cardiac and respiratory response functions differ substantially across capnic conditions. This work contributes to the establishment of the BOLD signal as a surrogate for neurofluid flow, and highlight the role of the autonomic nervous system (ANS) in linking vascular and CSF dynamics in the brain. The findings suggest that the ANS is also instrumental in the regulation of neurofluid flow in response to alterations of cerebral hemodynamic homeostasis. Furthermore, our findings suggest that this mechanism of ANS regulation differs across capnic states, or more broadly, across individuals with different basal capnic states.