Cerebrospinal fluid flow and clearance driven by lateral ventricle volume oscillations

In the human brain, substance clearance is intimately connected to the cerebrospinal fluid (CSF) and its flow. CSF extends from the lateral ventricles (LVs) to the parenchyma’s perivascular spaces. Macroscopic undulating CSF flow is present during both wakefulness and sleep and can be experimentally induced. However, the mechanisms generating this flow and its contribution to brain clearance remain unclear. Using fMRI and PET across various conditions, we demonstrate that LV-volume oscillations drive undulating CSF flow in the ventricles and subarachnoid basal cisternae. LV oscillations are driven by cortical blood-volume changes induced by neuronal activity, heartbeat and respiration. LV oscillations’ amplitudes determine PET-tracer clearance from the LVs. Conclusively, induced by extra- and intracranial physiological drivers and mediated by cortical blood-volume changes, LV-volume oscillations drive macroscopic CSF flow and clearance.