CSF
Discovering the Brain’s Nightly “Rinse Cycle”
Posted on by Dr. Francis Collins
Getting plenty of deep, restful sleep is essential for our physical and mental health. Now comes word of yet another way that sleep is good for us: it triggers rhythmic waves of blood and cerebrospinal fluid (CSF) that appear to function much like a washing machine’s rinse cycle, which may help to clear the brain of toxic waste on a regular basis.
The video above uses functional magnetic resonance imaging (fMRI) to take you inside a person’s brain to see this newly discovered rinse cycle in action. First, you see a wave of blood flow (red, yellow) that’s closely tied to an underlying slow-wave of electrical activity (not visible). As the blood recedes, CSF (blue) increases and then drops back again. Then, the cycle—lasting about 20 seconds—starts over again.
The findings, published recently in the journal Science, are the first to suggest that the brain’s well-known ebb and flow of blood and electrical activity during sleep may also trigger cleansing waves of blood and CSF. While the experiments were conducted in healthy adults, further study of this phenomenon may help explain why poor sleep or loss of sleep has previously been associated with the spread of toxic proteins and worsening memory loss in people with Alzheimer’s disease.
In the new study, Laura Lewis, Boston University, MA, and her colleagues at the Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston. recorded the electrical activity and took fMRI images of the brains of 13 young, healthy adults as they slept. The NIH-funded team also built a computer model to learn more about the fluid dynamics of what goes on in the brain during sleep. And, as it turns out, their sophisticated model predicted exactly what they observed in the brains of living humans: slow waves of electrical activity followed by alternating waves of blood and CSF.
Lewis says her team is now working to come up with even better ways to capture CSF flow in the brain during sleep. Currently, people who volunteer for such experiments have to be able to fall asleep while wearing an electroencephalogram (EEG) cap inside of a noisy MRI machine—no easy feat. The researchers are also recruiting older adults to begin exploring how age-related changes in brain activity during sleep may affect the associated fluid dynamics.
Reference:
[1] Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR, Lewis LD. Science. 2019 Nov 1;366(6465):628-631.
Links:
Sleep and Memory (National Institute of Mental Health/NIH)
Sleep Deprivation and Deficiency (National Heart, Lung, and Blood Institute/NIH)
Alzheimer’s Disease and Related Dementias (National Institute on Aging/NIH)
NIH Support: National Institute of Mental Health; National Institute of Biomedical Imaging and Bioengineering; National Institute of Neurological Disorders and Stroke
Scoliosis Traced to Problems in Spinal Fluid Flow
Posted on by Dr. Francis Collins

Caption: Normal zebrafish (top left) and a normal skeleton (bottom left); zebrafish with scoliosis (top right) and an abnormal scoliotic skeleton (bottom right).
Credit: Grimes DT, Boswell CW, Morante NF, Henkelman RM.
Many of us may remember undergoing a simple screening test in school to look for abnormal curvatures of the spine. The condition known as adolescent idiopathic scoliosis (IS) affects 3 percent of children, typically showing up in the tween or early teen years when kids are growing rapidly. While scoliosis can occur due to physical defects in bones or muscles, more often the C- or S-shaped spinal curves develop for unknown reasons. Because the basic biological mechanisms of IS have been poorly understood, treatment to prevent further progression and potentially painful disfigurement has been limited to restrictive braces or corrective surgery.
Now, in work involving zebrafish models of IS, a team of NIH-funded researchers and their colleagues report a surprising discovery that suggests it may be possible to develop more precisely targeted therapeutics to reduce or even prevent scoliosis. The team’s experiments have, for the first time, shown that mutation of a gene associated with spinal curvature in both zebrafish and humans has its effect by altering the function of the tiny hair-like projections, known as cilia, that line the spinal cord. Without the cilia’s normal, beating movements, the fluid that bathes the brain and spinal cord doesn’t flow properly, and zebrafish develop abnormal spinal curves that look much like those seen in kids with scoliosis. However, when the researchers used genetic engineering to correct such mutations and thereby restore normal cilia function and flow of cerebral spinal fluid (CSF), the zebrafish did not develop spinal curvature.