As a physical therapist in Shanghai, Zheng Wang worked with people recovering from strokes after their brains had been damaged by oxygen deprivation. They usually followed a predictable recovery pattern, making lots of progress over the first few visits, then hitting a wall. Patients asked when they’d finally feel normal, and Wang told them that they’d get better with time. “But actually,” he remembers, “I knew from the bottom of my heart that they wouldn’t improve much, no matter how hard we tried.”
Meanwhile, halfway across the world, Marc Dalecki, then an associate professor in the School of Kinesiology at Louisiana State University (LSU), couldn’t stop thinking about oxygen. Dalecki spent much of his early career studying scuba diving and remembers divers using nasal cannulas of O2 to help with everything from hypoxia to headaches. He always wondered whether this simple treatment could help neurological patients in rehab. “I promised myself that I would study it when I got my own research lab,” he says.
For its relatively small size, the brain consumes a ridiculous amount of power: 20 to 30 percent of the body’s energy at rest. To fuel all of its neurons, the brain depends on oxygen. When someone has a stroke or a head injury, the flow of oxygenated blood to the brain gets disrupted. Starved of oxygen, the brain tissue is damaged, leading to a host of problems with memory, speech, strength, and motor control.
Rehabilitation from brain trauma usually involves working with a physical therapist to relearn motor skills, building up the strength and coordination required for daily activities, like making coffee, writing, and brushing your teeth. Many physical therapists already use high-tech devices to help patients recover faster, from robots that move impaired limbs to virtual reality games that simulate aspects of day-to-day life that can’t be easily replicated in a hospital setting. But Wang and Dalecki both wondered whether oxygen could be the simple, cheap, accessible addition to neurological rehabilitation they’d been looking for. If they could give patients a little extra oxygen during early motor rehab sessions, they thought, it might help them relearn old skills faster.
The two of them joined forces in Dalecki’s lab at LSU, where Wang, frustrated as a clinician, decided to get a PhD in kinesiology. In a study published last week in Frontiers in Neuroscience, their team showed that sniffing pure oxygen while learning a challenging motor task helped healthy young people learn faster and perform better. They think this relatively low-cost, low-risk idea could be used to speed up stroke recovery.
For their study, they recruited 40 healthy young adults to each sit at a desk while wearing a nasal cannula. Their instructions were simple: Hold a stylus at the center of a tablet screen, then drag it to a target that pops up somewhere else, as quickly and efficiently as possible. But after a few trials, the relationship between the stylus and the screen shifted, creating a 60-degree difference between the line a participant thought they drew and the line that actually appeared on the screen. While the volunteers adjusted their line drawing to these new, more challenging circumstances, air started flowing through the cannula. Half of the participants got pure oxygen, while the other half got medical air (essentially an ultra-clean version of regular air). It was a quick blast, only during these few minutes of initial learning. Then the air flow shut off and the screen went back to normal.
The air tanks were hidden from view, so no one knew whether they received pure oxygen or not. But the participants sniffing pure O2 performed faster and drew more efficient paths—a nearly 30 percent increase in both speed and accuracy—than those who didn’t get an oxygen boost. The biggest improvements happened during early learning.
In a follow-up study that will be published later this year in Behavioral Brain Research, Wang’s team also found that breathing pure oxygen helped healthy young people respond 20 percent faster than those without the oxygen boost in a more cognitively taxing motor task, where they had to learn to quickly press buttons in a specific order (like learning to play the piano). And in a third study, currently under review, they used a noninvasive brain imaging technique called near-infrared spectroscopy to confirm that higher levels of oxygen in the frontal lobe were positively correlated with bigger improvements in response time during the button-pressing task.
It is still unknown exactly how oxygen helps the brain. One theory is that in cases where a brain injury worsens circulation in neural tissues, bringing in more oxygen can help increase plasticity and boost learning and memory, says T. G. Hornby, who is a professor of physical medicine and rehabilitation at Indiana University and was not involved in this study. Wang likens the difference in brain oxygen to the difference between going to the regular grocery store and going to Costco: When you fully stock your pantry, you can sustain yourself for weeks without stress. With better brain oxygenation, he suspects, neurons can draw from a stockpile of extra fuel to help them build new connections.
Even though these studies were conducted in healthy people, Wang and Dalecki think oxygen will be useful for stroke survivors, whose brains need the extra fuel to power motor learning sessions during physical therapy. They envision oxygen someday being used in early stages of rehab—people could use a cannula to breathe air from an oxygen backpack, which would be worn while practicing day-to-day tasks or relearning how to walk. “An oxygen tank could be a very easy add-on to daily training,” says Wang. “It’s just naturally there, not causing lots of distractions. I think it’s very viable.”
Critically, Dalecki says, the boost provided by oxygen during the second test seemed to last overnight—a good sign for rehab, when people need to relearn a wide range of daily tasks and be able to apply the progress they make during physical therapy to their daily lives.
But much more work needs to be done before pure oxygen is incorporated into neurological motor rehab. “We need trials in the right patient population, in more realistic settings. But this is how science starts,” says Hornby. “There are so many other layers to this.”
First of all, stroke risk increases with age, and the brains of young and old people are very different: Will an oxygen treatment that helps twentysomethings also help people over three times their age? With age, learning capacity decreases, blood vessels get stiffer, and metabolism slows down. With older patients, Wang says, “even if you provide them with extra oxygen, it might not help them as much as it helps young people.” But when it comes to relearning lost motor skills, he says, older people generally start at a lower baseline, giving them more room to grow.
Breathing in too much extra oxygen can cause oxygen poisoning, which can present as chest pain, coughing, nausea, and convulsions—and in severe cases, seizures, coma, and death. It’s a risk for scuba divers and people on ventilators, but Dalecki says this is very unlikely to happen in a rehab setting, where people are breathing oxygen at normal atmospheric pressure for less than an hour at a time. The motor task in the first study took about 30 to 45 minutes, about the same amount of time someone in stroke recovery would do physical therapy before getting too tired to continue.
Given the promising early results, low risk, and potential benefit to patients, Wang (who is now a postdoc at the Mayo Clinic) and Dalecki (now at the German University of Health and Sports in Berlin) aim to start testing oxygen in older people, and eventually in older people recovering from a stroke. There are still many details of this treatment to nail down: Should oxygen-assisted learning only happen in the first rehab session or two or does it need to be ongoing? How long will the effects last?
The skills stroke patients want to practice, like walking, speaking, and doing household chores, are much more complex than the simple tasks participants learned in the lab. Dalecki hopes that more scientists will dive into these questions now that the initial work has been done. “It sounds so simple,” he says, “and it’s now out in the world. I’m very excited to see what comes along with that.”
“There is so much to do,” Dalecki adds. “I’ll do it until I’m retired.”
