Global neuronal activity drives cerebrospinal fluid motion mediated by brain blood volume changes in humans

Directed motion of cerebrospinal fluid (CSF flux) is instrumental for removing waste products from the brain. Fluctuations in global cerebral blood volume (CBV), induced by concerted changes of brain-wide neuronal activity, are suggested to drive CSF-flux. To test this hypothesis, we performed two related experiments in healthy humans, namely electro-encephalography and blood oxygenation level-dependent functional-MRI during burst-suppression anesthesia, and arterial spin labeling and functional-MRI during transient hypercapnia challenges. Changes in total CBV, induced by changes in instantaneous global neuronal activity during burst-suppression or brain blood flow during hyper-normocapnia transitions, cause opposite functional-MRI signal changes in the basal cisternae, marking CSF flux from and into the brain. This direct coupling of global neuronal activity, brain blood volume and CSF flux indicates a mechanism to enhance brain waste clearance. ### Competing Interest Statement The authors have declared no competing interest.