A Novel fNIRS Approach for Assessment of Brain Activity, Cerebral Blood Flow, and Glymphatic Function in Sleeping Traumatic Brain Injury Patients

Topic Area: Sleep Disorders

Innovation: Sleep-Wake Intracerebral Fluid Tracking (SWIFT) using near-infrared light in healthy and traumatic brain injury (TBI) patients.

Background: Sleep disorders affect over 70% of Service members and Veterans with TBI. Acute injury results in a cascade of accumulating proteins and potentially toxic cellular waste that is normally removed from the brain during normal deep sleep. If sleep is disrupted, the inability to remove cellular waste products from the brain results in unsatisfying sleep and perpetuates the damage. The waste clearance process was recently discovered and named the 'glymphatic system,' and it involves the movement of intracerebral fluids that surround the brain to transport waste back into the bloodstream. The glymphatic system was identified in animals, and some invasive studies have shown evidence of it in humans, but currently there are no techniques developed to study it in noninvasively during sleep.

Importantly, there is an increased incidence of neurodegenerative diseases such as Alzheimer's, in TBI victims. Chronic disruption of the glymphatic system in animals has been shown to promote the neurodegenerative process, causing an Alzheimer's-like disease process. Human studies seem to corroborate the idea that sleep disruption can increase the risk of Alzheimer's disease, and it is hypothesized that this is related in part to disruption of the glymphatic system. A technology that makes it possible to study the glymphatic system in TBI patients could revolutionize our understanding of the hypothesized TBI – sleep disorder – dementia connection.

Approach: This research will support the development and testing of a new technology capable of using near-infrared light and optical sensors during sleep to perform non-invasive measurements of the movements of intracerebral fluids that surround the brain. By taking advantage of signals classically discarded as 'noise,' we will utilize novel algorithms and state-of-the-art sensor devices to establish normative values for glymphatic system activity in active duty and Veteran Service members. This will be performed alongside classic techniques of the polysomnogram, or 'sleep study,' to corroborate the measurements alongside standard measures of sleep.

Twenty-five healthy active duty and Veteran Service members will be enrolled in this study to establish preliminary normative values for glymphatic system function. They will be fitted with a comfortable wearable cap that can be worn while sleeping. The near-infrared optical neuroimaging sensors, which are traditionally applied during waking conditions, will be fitted within the cap to enable high fidelity recordings that will not interfere with the standard polysomnogram. Next, a pilot TBI study will be conducted by enrolling 12 active duty, Veteran, or retired Service members with a diagnosis of TBI and have sleep complaints. Enrollment will occur in a sleep clinic, where the measurements will take place during the evening of an already planned sleep study.

Impact: The final product will be a new technology capable of measuring an important novel component of sleep physiology that was previously unmeasurable. With it, a thorough characterization of the changes that occur after TBI can be performed and utilized as a novel biomarker platform. Various measures may be able to predict clinically valuable parameters such as prognosis (e.g., risk for sleep and cognitive disorders) or even for stratifying patients in clinical trials to develop novel therapies.

Furthermore, this work has potential to revolutionize sleep neuroscience by providing a novel biomarker platform that can be used to study how this novel biology is involved in all sleep disorders beyond those experienced by TBI victims. The data produced will serve as a first step into an exciting field that can be readily adopted by other investigators to study a variety of new aspects of sleep and sleep disorders – potentially extending into the realm of performance enhancement via augmentation of the glymphatic system.