Effects of clamping end-tidal CO₂ on neurofluidic low-frequency oscillations

In recent years, low-frequency oscillations (LFOs) (0.01-0.1 Hz) have been a subject of interest in resting-state functional magnetic resonance imaging research. They are believed to have many possible driving mechanisms, from both regional and global sources. Internal fluctuations in the partial pressure of CO₂ (PCO₂) has long been thought of as one of these major driving forces, but its exact contributions compared with other mechanisms have yet to be fully understood. This study examined the effects of end-tidal PCO₂ (P_etCO₂) oscillations on LF cerebral hemodynamics and cerebrospinal fluid (CSF) dynamics under "clamped P_etCO₂" and "free-breathing" conditions. Under clamped P_etCO₂, a participant's P_etCO₂ levels were fixed to their baseline average, whereas P_etCO₂ was not controlled in free breathing. Under clamped P_etCO₂, the fractional amplitude of hemodynamic LFOs in the occipital and sensorimotor cortex and temporal lobes were found to be significantly reduced. Additionally, the fractional amplitude of CSF LFOs, measured at the fourth ventricle, was found to be reduced by almost one-half. However, the spatiotemporal distributions of blood and CSF delay times, as measured by cross-correlation in the LF domain, were not significantly altered between conditions. This study demonstrates that, while PCO₂ oscillations significantly mediate LFOs, especially those observed in the CSF, other mechanisms are able to maintain LFOs, with high correlation, even in their absence.