Near Infrared Spectroscopy-measured Glymphatic Activity is Disrupted Several Years after Concussion
J. Kent Werner1, Sujasha Gupta3, Franck Amyot4, Angeliki Pollatou3, Will Coon5, Elizabeth Metzger3, Clara Scholl5, Angelica Lee2
1Uniformed Services University, 2Neurology, Uniformed Services University, 3The Geneva Foundation, 4National Intrepid Center of Excellence, Walter Reed National Military Medical Center, 5JHU Applied Physics Laboratory
Objective:
To measure water flux during sleep in TBI and Healthy Controls using Near Infrared Spectroscopy.
Background:
The glymphatic system has been shown in animal studies to be impaired in traumatic brain injury (mTBI) and may contribute to neurodegeneration, but human studies are lacking. This study examines sleep-related fluctuations in oxyhemoglobin (HbO) and water, using functional near-infrared spectroscopy (fNIRS) and Electroencephalography (EEG) to characterize glymphatic activity in mTBI and healthy control participants.
Design/Methods:
We used near-infrared spectroscopy (fNIRS) to track HbO and water concentration changes during sleep in mTBI (N=9) and healthy (N=18) controls, alongside electroencephalography (EEG) recordings. After removing movement artifacts, we applied the Modified Beer-Lambert Law (MBLL) to compute HbO and water fluctuations. We then analyzed their spectra in respiratory and cardiac frequency ranges, isolating the periodic component by removing aperiodic power.
Results:
.In healthy controls, water and oxyhemoglobin signals dynamically adjusted amplitude across sleep stages, particularly between NREM and Wake (H₂O: d = 1.7, ***p < 0.001; OxyHb: d = 1.05, ***p < 0.001), reflecting normal physiological fluid and vascular adaptations during sleep. For the mTBI group, these adaptive shifts were absent (H₂O: d = 0.04, ns; OxyHb: d = 0.18, ns). Additionally, healthy participants demonstrated dynamic shifts in the peak frequency of low-frequency oscillations (LFOs) of water and HbO across sleep stages, particularly between NREM and Wake (*d = 1.67, p < 0.001). In mTBI participants, these shifts were blunted or entirely absent (Water LFOs: ns; OxyHb LFOs: ns).
Conclusions:
This suggests mTBI disrupts water flux, which we hypothesize includes glymphatic function, particularly in deep sleep. Additionally, in REM sleep, TBI subjects show reduced cardiac frequency range bandpower, indicating impaired autonomic regulation. These findings warrant further investigation in hemodynamics and water flux / glymphatic exchange in the mTBI population, raising the possibility for potential therapeutic targeting in future work.
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