Tracking Sleep-linked Brain Fluid Dynamics Using Modified fNIRS: A Novel Noninvasive Window into Glymphatic Function
Sujasha Gupta1, Srija Seenivasan1, John Kent Werner1
1Uniformed Services University of Health Sciences
Objective:

To use non-invasive, naturalistic fNIRS-EEG methods to investigate the coupling of glymphatic clearance with neural rhythms and slow-wave oscillations. 


Background:

The brain’s glymphatic system, an interstitial waste and signal transport pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange, has pronounced activity during non-rapid eye movement (NREM) sleep and is implicated in neurodegenerative and mood disorders. However, direct measurement in humans is limited because current imaging methods rely on invasive MRI methods, posing a major barrier to advancing glymphatic research in clinical settings.


Design/Methods:
We developed a non-invasive, functional near-infrared spectroscopy (fNIRS) array in a wearable headband using non-standard wavelengths of 860 and 980 nm for increased water sensitivity. We monitored cortical blood and water dynamics during overnight sleep, quantifying oscillations of oxyhemoglobin (HbO) and water across sleep stages. A component of the extracted water metrics is hypothesized to serve as a proxy for glymphatic transport, and EEG data was collected and processed for spectral analysis.
Results:

Water concentrations were highest in slow-wave-sleep (SWS) (d = 1.93, p=0.0002), while HbO concentrations also showed a modest elevation (d = 1.06, ns). After regressing out the HbO contributions, the oscillatory water component correlated with delta power (r=0.63, p=.02). Additionally, low-frequency oscillations (LFOs) of both water and HbO signals exhibited distinct dynamics of suprathreshold envelope peak (SEP) frequencies during NREM as compared to REM and Wake, with effect size (d= 1.31, p = 0.003) for water. These findings indicate that water-sensitive oscillatory processes are selectively amplified during EEG-defined deep sleep, consistent with a role for glymphatic-related fluid transport in human sleep. 


Conclusions:

We report novel cortical water shift parameters that are robustly sensitive to sleep stage transitions via a wearable, non-invasive, scalable headband, consistent with predicted glymphatic activity. Future work will focus on MRI cross-validation.


10.1212/WNL.0000000000217750
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