Fig. 1: Effect of glymphatic function on parenchymal resistance analysed via dynamic impedance spectroscopy.

a, Glymphatic function involves the influx of cerebrospinal fluid along perivascular spaces surrounding penetrating arteries (centre). Glymphatic flow is driven by arterial pulsation, vasomotor oscillations and synchronous neural activity (right). Astrocytic endfoot processes create the barrier between the PVS and the brain parenchyma, with gaps allowing CSF to exchange through the brain interstitial space. The arrows represent cerebrospinal fluid flow along the perivascular spaces and into the brain interstitial space. b, Data from physiological studies in rodents suggest that glymphatic function is increased in conditions of reduced heart rate, increased vasomotor pulsations, reduced EEG beta power and increased EEG delta power¹¹. c, The interstitial space is dynamically regulated. Under conditions common to the awake state, it is narrow and tortuous, forming a high-resistance pathway that suppresses glymphatic flow. When alternating current is injected into the brain parenchyma, at low frequencies the current cannot penetrate the cell membranes and its propagation depends primarily on the resistive pathway of the interstitial fluid. At high current frequencies, the current readily penetrates the cell membranes and its propagation depends on the resistance of the total tissue volume. This frequency difference is the β-dielectric dispersion of the underlying tissue. A change in the dielectric dispersion reflects a change in the low-frequency resistance pathway of the interstitial fluid. d, In the sleep state, fluid shifts from the intracellular compartment into the interstitial space, enhancing glymphatic function by ~60% in rodent studies². This widening of interstitial pathways reduces the current resistance at low frequencies, which reduces the measured dielectric dispersion. e, An impedance–frequency graph shows the change in dielectric dispersion between the two sleep/wake states. The change in parenchymal resistance between these two states is inversely proportional to the relative change in the dielectric dispersion. f, Contrast-enhanced MRI following intravenous GBCA injection shows vascular regions that enhance immediately (t = 30 min) upon GBCA injection (red), and CSF and brain parenchymal regions that enhance late (t = 3 h) after leakage of GBCA first into the CSF and then into the brain interstitium (green). A given MRI voxel includes GBCA within the blood, CSF and brain interstitial fluid compartments. Illustrations: Applied Cognition.