Modulation of neurofluid dynamics using carbon dioxide in awake humans

Motivation: The pathways for modulating glymphatic flow are still unknown. Goal(s): This study determines the factors linking basal carbon dioxide to altered blood and cerebrospinal fluid (CSF) flow dynamics using resting-state fMRI. Approach: We compared arterial, venous and all CSF BOLD signal fluctuations across CO2 level, and characterized the cardiac (CRF) and respiratory response function (RRF) for these signals. Results: We found greater neurofluid fluctuations during hyper- and hypocapnia and significant differences in the CRF and RRF. This suggests that neurofluid flow differences may be driven by CRF and RRF, which reflect the involvement of the autonomic nervous system. Impact: We used CO2 modulation to highlight the involvement of slow-wave heart-rate and respiratory variability in modulating neurofluid flow, implicating the autonomic nervous system. This demonstrates that it is possible to modulate neurofluid flow through other means than sleep.