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Sleep well, breathe easy
Distinguished Professor Ronald Harper to deliver 21st annual H.W. Magoun Lecture

Ronald Harper has dedicated his research career to what happens in our heads when the lights go out. When we sleep, we are entrusting our well-being to our brains – but these are sometimes negligent guardians, whose actions, or lack of them, can be life threatening. It’s an unnerving thought, even for one of the foremost sleep researchers in the United States. Sleep doesn’t come easy.

“Oh yes – I’m terrified, every night!” says Harper, half jokingly.

The Distinguished Professor in Neurobiology will be sharing the scares during the 21st Annual Magoun Lecture, “Sleep, Breathing, and the Heart.” A soft-spoken scientist, Harper does not intend to frighten anyone, but sleep research necessarily touches on some dark areas. When we sleep, the brain is busily reorganizing itself. But this isn’t a risk-free process, says Harper. There are a great number of things that may go wrong.

“The brain can shut off the upper airway muscles, or even all breathing muscles, and as a result, you stop moving air for periods of time. That cessation of breathing has tremendous cardiovascular consequences, and substantial implications for survival of neurons in the brain.”

Harper explains that it is not just lack of air from sleep apnea that kills neurons, but rather the toxic spike of oxygen when breathing resumes, and those spikes happen many times with each cessation and restarting of breathing. Unfortunately, those damaged neurons tend to be in areas that govern respiration and cardiovascular action, meaning it’s a self-perpetuating problem. However, the disorder can also damage brain areas that regulate memory and emotional behavior as well. Patients with sleep-disordered breathing are prone to anxiety and depression. “These people are literally destroying their brain every time they sleep,” says Harper.

"If CCHS kids sit in front of the TV and they become drowsy, they’ll turn blue, unless their mother is there to yell at them to breathe"

- Dr. Ronald Harper

The sleep research Harper does is built into the DNA of the BRI. Harper explains that Horace Magoun, the founder of the BRI, laid the foundations of sleep research. His insights on how structures in the brain stem regulate motor and muscle activity during different states put UCLA at the forefront of sleep research.

It is fitting that Ron Harper – who arrived at the BRI in 1968, only a few years before Magoun left – would be chosen for the honor of delivering the H.W. Magoun Lecture. BRI Director Chris Evans explains that the award is meant to recognize not only research excellence – but also service to the neuroscience community.

“Ron is a great example of what the Magoun lecture series is meant to honor – he has never hesitated to share his expertise with his colleagues here in the UCLA neuroscience community, and more importantly, he has given so much back to the wider scientific community, especially with his translationally significant studies on SIDs and Congenital Central Hypoventilation syndrome,” says Evans.

SIDS – Sudden Infant Death Syndrome, and Congenital Central Hypoventilation syndrome (CCHS) have been increasingly the focus of Harper’s research over the last few decades. Both will be featured in his talk. Of the two, CCHS is less well known, if equally as frightening to new parents. Children born with the condition have no ability to breathe during sleep. They do not breathe faster with higher levels of CO2 in the air, even when awake. They also do not experience the sensation of smothering, and won’t fight to breathe when their mouth is covered. They dare their non-affected playmates for underwater endurance in swimming pools- a game they always win. “If they sit in front of the TV, if they become drowsy, they’ll turn blue, unless their mother is there to yell at them to breathe,” says Harper.

These children will have to stay on a ventilator during sleep their entire life, but Harper says that studying this condition has already led to insights on how the brain regulates breathing. “What’s very interesting, if they go out and play ball, they need more air because they’re exercising. You’d think they’d flop down face first, but they don’t. It turns out that Nature has built in a secondary system that picks up breathing before you even start moving. We found the brain structures involved in that coupling of limb movement and breathing, which include pontine and cerebellar areas.”

These insights might help shed light on SIDS. For years, the cause of “crib death” – which still claims the lives of 500 babies every year in the United States - was little understood. The finger of blame was pointed at everything from toxic mattresses to homicidal mothers. In fact, rare heart rate and breathing recordings that Harper gathered from infants who succumbed to SIDS showed that those who died had high heart rates before the fatal incident, but continued to breathe while heart rate slowed precipitously, and, when gasping set in, the breathing efforts had no effect on recovering heart rate. This indicated a disconnect between the normal coupling of the circulatory and respiratory systems. Harper says that such a pattern mimics trends found in shock, and appeared in nearly 90 percent of a group of 53 infants who died from SIDS. Shock may be triggered by deep visceral pain, infection, or a number of other processes. Failing to recover from a shock pattern may result from raphé and cerebellar structures; the latter, Harper explains, has a role in smoothing blood pressure, keeping it from going too low or high, in addition to it’s better-known role in fine motor control. Harper says that SIDS infants often show late development of cerebellar Purkinje neurons, sometimes exhibit damage to inferior olivary and vestibular neurons which send projecting fibers to the cerebellum, and show altered levels of the neurotransmitter serotonin; the raphé, source of serotonin fibers, sends some of those fibers to the cerebellum.

Since coming to UCLA in 1968, by way of McMaster University in Canada, Harper has trained dozens of graduate students and post docs. Many of those students have done exceptionally well in their careers (President of the American Physiological Society, Chief Physician, University of Chicago, multiple professorial appointments at major universities). He has received many honors for his research, among them the Annenberg Award for Sudden Infant Death Research and the Sleep Research Society’s Distinguished Research Award.

His resume boasts hundreds of articles, chapters, books, and abstracts, as well as NIH review committee memberships, conference invitations and consultancies – clearly exactly the kinds of scientific good citizenship the Magoun award was designed to honor at UCLA. However, Harper makes no special claims for himself: “Basically, I just showed up here as a post-doc and stuck around until they gave me a job.”

- By Mark Reynolds

The 21st H.W. Magoun Lecture, March 9, 2010, Neuroscience Research Building Auditorium, 4PM. Reception to follow in room 1357 of the Gonda (Goldschmied) Building.

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