# Modulation of neurofluid fluctuation frequency by baseline carbon dioxide in awake humans: the role of the autonomic nervous system

## TL;DR

This study shows that changes in carbon dioxide levels affect cerebrospinal fluid movement in awake humans through autonomic nervous system control, not just biomechanics.

## Contribution

The study reveals that CO2 modulates neurofluid dynamics via autonomic frequency responses, independent of sleep or neural activity.

## Key findings

- Biomechanical modulation does not explain neurofluid dynamic variations across capnias.
- Heart-rate variability independently drives low-frequency neurofluid flow, indicating autonomic control.
- Altered CO2 affects neurofluid dynamics through frequency, not amplitude, of heart-rate and respiratory-volume variability.

## Abstract

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.