New research has found that people with narcolepsy type 1 exhibit patterns of slow brain pulsations that resemble those seen in healthy sleep. The findings, published in PNAS, suggest that orexin—a neuropeptide involved in maintaining wakefulness—may play a key role in the brain’s fluid-clearing system, known as the glymphatic system. This study offers insights into how altered brain activity in narcolepsy may influence the transport of waste out of the brain, a process believed to be important for protecting against neurodegeneration.
Narcolepsy type 1, also known as NT1, is a rare neurological disorder characterized by the loss of orexin-producing neurons in the hypothalamus. People with this condition often experience sudden sleep episodes, cataplexy, and fragmented nighttime sleep. While the disorder is typically understood in terms of disrupted arousal and sleep-wake regulation, recent work has begun to explore its broader effects on brain physiology.
One area of interest is the glymphatic system, a clearance pathway that removes metabolic waste from the brain. This system is more active during non-rapid eye movement (NREM) sleep, when the brain enters a state of slow, rhythmic pulsation. These pulsations are thought to drive the flow of cerebrospinal fluid (CSF) through brain tissue, aiding in the removal of waste products such as amyloid beta.
Because orexin influences both arousal and noradrenaline release—two systems that affect these pulsations—the researchers wanted to understand whether people with narcolepsy type 1 exhibit brain pulsation patterns similar to those seen in sleep. They proposed that orexin deficiency might reshape the forces driving glymphatic flow, and that these changes could be measured using advanced brain imaging.
“NT1 is a rare and life-long disease and thus new research shedding insights into the pathology is valuable to these patients,” said study author Matti Järvelä of the University of Oulu. “Our lab is interested in brain pulsations that drive intracranial fluid flow and thus facilitate brain clearance. As NREM sleep, a state where orexinergic activation is low, has been shown to increase efflux of fluid and waste from the brain, NT1 presents a natural human model to study how the lack of orexins/hypocretins may affect the drivers of this efflux.”
