Xiaole Z. Zhong; Catie Chang; J. Jean Chen (2026).Ìý.ÌýFrontiers in Physiology, 17, 1750101.Ìý
This study investigates howÌýcerebrospinal fluid (CSF)—the fluid that surrounds and cushions the brain and spinal cord—moves within the brain, and how this movement is influenced by the body’s automatic (autonomic) functions, such as heart rate and breathing. CSF flow is important because it helps remove waste and maintain brain health. While previous research has linked CSF movement to sleep and brain activity, the researchers wanted to isolate the role of theÌýautonomic nervous systemÌý(the system that controls involuntary processes like heartbeat and respiration).
To do this, they used fMRI scans to observe fluid-related signals in the brain while changing levels of carbon dioxide (COâ‚‚) in participants’ blood—a method that affects blood vessel tone, breathing, and heart function without directly altering brain activity. They found that changes in CSF movement could not be explained simply by physical or mechanical factors. Instead, variations inÌýheart-rate variabilityÌý(natural fluctuations in the time between heartbeats) played a key role in driving slow CSF flow, independent of breathing. Additionally, changes in COâ‚‚ levels mainly affected how frequently heart rate and breathing patterns fluctuated, rather than how strong those fluctuations were.
Overall, the findings suggest that CSF movement is strongly influenced by autonomic regulation, and that both higher and lower-than-normal CO₂ levels can disrupt this process. This highlights a new way to study and potentially control brain fluid dynamics—by adjusting CO₂ levels—without relying on sleep or direct neural activity, offering potential insights into brain health and disease.
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Fig 1: The predictions of CSF flow dynamics across capnias is based on three different physiological pathways: vascular tone, sympathetic tone, and neuronal activity. According to the vascular-tone theory, CSF fluctuations should be maximal at normocapnia. According to the neuronal-activity theory, CSF fluctuations should be maximized at hypocapnia. Lastly, according to the sympathetic-tone theory, CSF fluctuations should be maximized at hypercapnia. These theories will be tested using empirical data involving different capnias, at which all three variables will be altered.