This study shows that synchronizing N3 slow oscillations with transcranial electrical stimulation (tES) lowers intracranial electrical impedance across sleep stages in healthy adults, consistent with enhanced CSF inflow and potential glymphatic clearance during deep sleep.

Sleep-driven enhancement of glymphatic-like clearance via a noninvasive, translatable intervention (tES) and a putative impedance biomarker could be leveraged to promote removal of alpha-synuclein in Parkinson's disease, though direct evidence in PD patients and correlation with pathogenic protein…

The age-related impairment of glial-lymph (glymphatic) mechanisms for brain waste clearance has been suspected as a causal factor in the accumulation of toxic metabolites, including amyloid beta and tau proteins in Alzheimer's Disease and alpha synuclein in Parkinson's Disease and Lewy Body Dementia. Because electrical current at low frequencies flows preferentially through extracellular space (ECS), measures of brain electrical impedance may track changes over time in ECS as a function of CSF dynamics that are important to brain waste clearance in sleep. We applied a single-frequency measure of electrical impedance in a study of transcranial electrical stimulation (tES) to enhance deep N3 sleep in healthy adults, using a novel method for estimating the intracranial impedance compartment through separately estimating and subtracting the electrode-skin impedance. The results suggest that, regardless of tES, brain impedance slowly decreases over the course of the night's sleep versus waking, with a marked decrease in REM. Furthermore, the therapeutic tES protocol (applied to synchronize and enhance slow oscillations of N3) resulted in significant brain impedance decreases in the transition from N2 to N3 (as well as in REM), consistent with the fast MRI evidence of respiration-linked CSF inflow at these intervals.