ORIGINAL RESEARCH article
Front. Physiol.
Sec. Medical Physics and Imaging
Modulation of neurofluid fluctuation frequency by baseline carbon dioxide in awake humans: the role of the autonomic nervous system
Provisionally accepted
- 1Department of Medical Biophysics, University of Toronto, Toronto, Canada
- 2Rotman Research Institute, Toronto, Canada
- 3Department of Electrical and Computer Engineering; Department of Computer Science; Department of Biomedical Engineering, Vanderbilt University, Nashville, United States
- 4Department of Medical Biophysics; Department of Biomedical Engineering, University of Toronto, Toronto, Canada
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Cerebrospinal fluid (CSF) pulsations are linked to hemodynamics, with autonomic mechanisms, suggested to modulate slow-wave induced pulsations. To explore autonomic regulation's role in neurofluid flow, independent of sleep and neural activity, we hypothesized that modulating basal CO2 (altering vascular tone, cardiac activity and respiration) would highlight this link. Using resting-state BOLD fMRI in neurofluid regions under different CO2 levels (capnic states), we found: 1) biomechanical modulation does not explain neurofluid dynamic variations across capnias; 2) beyond respiration, heart-rate variability independently drives low-frequency neurofluid flow, indicating autonomic control; 3) altered CO2 primarily affects neurofluid dynamics through the frequency (and not amplitude) of heart-rate and respiratory-volume variability. These results suggest that both hyper-and hypocapnia disrupt how CSF responds to autonomic regulation, seen in deviations from normal cardiac and respiratory responses. Our work reveals neurofluid dynamics' sensitivity to CO2's frequency response, best explained by autonomic modulation. Modulating basal CO2 offers a new way to influence human neurofluid dynamics, independent of sleep or neuronal activity.
Keywords: Autonomic Nervous System, biomechanical modulation, Carbon Dioxide, Cerebrospinal Fluid, frequency modulation, Heart rate variability, respiratory volume pertime, sympatheticactivity
Received: 19 Nov 2025; Accepted: 23 Jan 2026.
Copyright: © 2026 Zhong, Chang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaole Zhong
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