0369 State-Dependent Coupling: Differential Roles for Microarousals in NREM Glymphatic Dynamics

Abstract Introduction Recent evidence highlights that noradrenergic (NE) fluctuations from the locus coeruleus drive infraslow neurovascular oscillations, which are essential for regulating glymphatic clearance. Microarousals (MAs) correlate with these NE surges and glymphatic activity, suggesting they may have a beneficial physiological role. This study examines the relationship between MAs and fluid dynamics across sleep stages in human sleep, distinguishing between spontaneous and apnea-related events. Methods Polysomnogram and noninvasive functional near-infrared spectroscopy (fNIRS) measured sleep stages and frontal cortex water concentrations. A custom automated pipeline filtered and labeled manually scored microarousals within 10 seconds of apneic events as apneic MAs to separate them from spontaneous MAs. Results Preliminary analysis reveals a biphasic relationship: In N2, increased MAs positively correlate (Pearson r = 0.68, p = 0.011) with water concentration, suggesting a regulatory role of MAs for clearance initiation. In N3, the relationship reverses, with MAs negatively correlating (Pearson r = -0.53, p =0.185) with water concentration, suggesting an overall disruptive effect on deep sleep clearance. Significantly, pooling N2 and N3 data markedly reduces the correlation (Pearson r = 0.21, p = 0.484). This cancellation suggests that MAs serve different roles depending on the sleep stage. The negative N3 correlation is likely skewed by pathogenic, apneic MAs, which inhibit flow and dominate the signal. Conclusion Our findings demonstrate that the coupling between MAs and water flux is sleep stage-dependent, with MAs potentially driving flux in N2 but disrupting in N3. The attenuation of this effect when both stages are combined strongly supports the hypothesis that N2 MAs may be supportive of restorative sleep events, similar to spindles, while N3 MAs serve as disruptors to low-frequency-linked clearance. Future work will isolate spontaneous versus apneic MAs, which will clarify how neurovascular coupling, consistent with the NE mechanism, drives deep sleep. Furthermore, we will analyze the temporal distribution of water flux immediately preceding and following spontaneous MAs to characterize the mechanism of NE-driven slow oscillations and waste clearance. Support (if any) The project was funded by CDMRP. The opinions expressed do not reflect the official policy or position of the Uniformed Services University of the Health Sciences or the Department of Defense.