Laurie had survived cancer. But enduring chemotherapy left the Millcreek mother with post-traumatic stress disorder and a lag in her thinking that scared her.

“If I were trying to come up with the word ‘basket,’ I could think of container, wicker, wood and other things around it, but I couldn’t come up with ‘basket,’” she said.

She felt depressed and desperate to get her memory back so she could return to work to support her 34-year-old son, who is disabled and lives at home with her.

She was surprised when her doctor suggested a video game.

But a landmark decision this summer by the U.S. Food and Drug Administration — allowing a video game to be marketed as a treatment for the first time — is a milestone expected to drive more patients to digital therapies.

“The [FDA’s] decision is massive. It changes the landscape for things we can build in the future,” said Roger Altizer, director of digital medicine at the Center for Medical Innovation at the University of Utah.

“A lot of times we treat health care like it’s work,” Altizer said. “We firmly believe that people are really healthy when they play. If we figure out how to get people to be playful in the medical space and not just working, then I think we’ll be on to something special.”

The game approved June 15 by the FDA is EndeavorRx from Boston-based Akili Interactive Labs, a game created to help treat children with attention deficit hyperactivity disorder. Players control a character flying on a hoverboard through corridors, similar to the popular 2011 mobile game Temple Run.

The game Laurie tried is Neurogrow, which invites players to care for a virtual garden with changing demands and conditions. It’s in clinical trials at the U.‘s Therapeutic Games and Apps Lab, or The GApp Lab. (The Salt Lake Tribune agreed to identify Laurie only by her first name to safeguard her medical privacy.)

Neurogrow’s creator is Dr. Sarah Shizuko Morimoto, who has dedicated more than a decade to exploring how video games may revitalize damaged circuits in the frontal lobe that can block the effectiveness of antidepressant medication.

‘Absolutely suffering’

People often overcome stressful events and get back on track without experiencing depression, said Morimoto, a psychiatry professor in Population Health Sciences, in the Division of Health Systems Innovation and Research at the U.

But that recovery mechanism erodes as they get older. When they don’t recognize the signs of mental illness, they may put off seeking help until they are seriously ill.

She began her work on the project in 2007 while she was at the Weill Cornell Institute of Geriatric Psychiatry run by Dr. George Alexopoulos, a top researcher in the field of geriatric depression.

Upwards of 60% of geriatric patients who take antidepressants don’t respond, Morimoto said. Alexopoulos made it his mission to figure who would benefit and who wouldn’t.

He found that certain cognitive tests showed whether a patient was being helped by the medication they were taking. In essence, Morimoto explained, the parts of the brain needed to perform well on the tests no longer function at a high enough capacity for the medication to work effectively, making it difficult to overcome depression.

She compared the circuits in the brain to a phone line. If the line is cut, it doesn’t matter how much signal boosting happens at either end of the phone call. The line needs to be repaired. Antidepressants can help to improve a patient’s mood, but without the proper cognitive infrastructure, the medication is ineffective.

Such patients are “basically perpetually vulnerable to relapsing and then not responding to medication again,” Morimoto said. “In the specialty of geriatric psychiatry, we know those patients as untreatable.”

Geriatric depression patients “are absolutely suffering,” she said. “They’re not able to get out of bed or shower or see their friends. The pain is so palpable. And they worry a lot about their cognition.”

Her research centers on Alexopoulos' findings that the ability to break free from preprogrammed responses is key in recovering from depression. Neurogrow requires a player to be flexible to respond to its challenges. Succeeding at the game theoretically rebuilds broken circuits in the frontal lobe.

“The more specific you get about the brain network involved, the more specific you can get to target it with treatment,” Morimoto said.

Her work also relies on the concept of brain plasticity, or its ability to form or reform pathways for cognitive function. Brain plasticity was once thought to exist only in children, but research by professor Mike Merzenich at the University of California, San Francisco showed the older adult brain can make substantive changes.

Morimoto theorized that video games could help rebuild aged and eroded circuits in the frontal lobe. Because she didn’t have much funding, she teamed with an engineering student at Princeton University to build a simple game.

In her first clinical trial, the game was tested against antidepressants with patients who hadn’t previously responded to medication. Between 60% and 70% of patients reported that the game provided at least some relief, Morimoto said.

She ran another clinical trial, this time testing the game against a generally stimulating computer program, and found that 60 to 70% of patients reported a 50% reduction in their depression symptoms.

The results were “kind of shocking,” Morimoto said. The game, a noninvasive, nonpharmaceutical treatment, had the potential to address the cognitive breaks.

A move to Utah

Deciding her next step was complicated, she said. Game development is expensive and government grants were unlikely to cover it. Startups offered Morimoto between $500,000 and $1 million to work on the game outside a clinical setting, she said, but she didn’t find the right relationship.

In 2017, she met with Altizer, who was interested in the game, and Morimoto was impressed by The GApp Lab’s student development model.

The U.‘s Entertainment Arts and Engineering (EAE) program is one of the nation’s top game development programs. The GApp Lab works as a bridge between EAE, in the U.‘s College of Engineering, and the Center for Medical Innovation.

Clinicians at the university work with graduate students from EAE to develop medically focused games and digital projects.

“I felt like in order to advance my work, I had to be with people who had done it before and that had a working model to advance that science,” Morimoto said. She moved from New York to Salt Lake City.

Coming to Utah was a “culture shock,” she said, because of the lack of access to geriatric psychiatry. There are three board-certified geriatric psychiatrists in Utah, she said. The only one at the U. has an eight-month waiting list for appointments.

Treating these patients often falls to their primary care physicians — who don’t have a psychiatrist’s specialized knowledge or enough time to see patients once a week, Morimoto said.

She knows some physicians have taken online classes to learn how to more effectively prescribe antidepressants, she said, but she has also encountered patients left on the wrong dose of medication for 10 to 15 years.

“In older adults, there’s a lot of barriers to receiving treatment,” Morimoto said. “People have physical mobility issues. They’re disabled so they can’t drive. They don’t have access to get somewhere. A lot of them don’t have the money because Medicare does not pay for psychiatry.”

Morimoto runs a clinic for treatment resistant depression patients, but she has found that about 50% of the patients referred there aren’t treatment resistant, she said. They just haven’t been given proper care.

In the meantime, Morimoto and the The GApp Lab have continued to develop Neurogrow and other games to treat depression.

‘My brain was exhausted’

Laurie played the games under an helmet that monitored her brain during her first visit to the lab in April last year. She returned twice a week over the next 12 weeks. She would play the games for an hour with intense focus — which she enjoyed — and then return home.

“My brain was exhausted,” Laurie said. After the sessions, she “felt like when you exercise and you’re physically exhausted and need to rest.”

To conserve energy, Morimoto explained, the brain naturally responds the same way over and over when it takes in stimuli. The games work to inhibit that response by constantly changing the activity the player is doing.

“It’s a game, but calling it a game makes it sound fun, and it’s definitely not fun,” Morimoto said. “It’s very difficult.”

The games have adaptive difficulty, meaning that they get harder or easier according to how the player performs.

After weeks of playing the games, Laurie said, she “started noticing that my memory was better. I was starting to come up with the actual words, like ‘basket,’ instead of having to skirt around the words. I also noticed that my depression and anxiety wasn’t as intense as it had been.”

Playing “made a positive influence on my self-confidence,” Laurie said. “I felt better and thought maybe I really could go back into the workforce.”

But in March, when the COVID-19 shutdowns first started, she noticed her memory slipping again. She asked her doctor if she could join another trial.

“I knew that it helped me immensely before,” she said. “I was more depressed about not being my normal self that I was used to. I felt the anxiety of not being able to function like I wanted to function.”

She’s been approved to return for a second trial once coronavirus restrictions lift and the lab can reopen.

‘People get better’

Games used for treatment can evolve to become more effective, just like any other medical prescription, Altizer said.

EndeavorRx, the game approved by the FDA, for example, also was originally targeted for older adults under the name “Neuroracer.” But when the company started to run clinical studies, it found the game was more effective with children, and helped them reach a mental state known in game development as “flow,” Altizer said.

Flow is when “the difficulty of the game and the player’s skill align perfectly,” Altizer said. The player becomes immersed in the gameplay and loses track of time because of the intensity of their focus.

Like Neurogrow, EndeavorRx also is designed to improve cognitive functioning, the company’s website explains, by challenging the brain with stimuli and motor challenges. But critics have questioned whether the focus shown by children playing the game would also affect their schoolwork or behavior, The Washington Post has reported. Akili Interactive Labs did not comment to The Salt Lake Tribune.

Morimoto does not see games as a replacement for psychiatry, but believes they can become an option for those who cannot access treatment or have found their care isn’t working.

“It’s amazing to watch people get better. It’s absolutely the best feeling in the world,” she said. “… Before, we’d have to say, ‘Well, sorry, unfortunately, we don’t have anything else for you.’ Now we can say, with some confidence, [these games] may very well help you.”

And games can be considered a part of the rise of telemedicine, to address both safety concerns in the era of COVID-19 and the costs of in-person care, she said. “What we have right now is a sort of unsustainable model,” she said. “Psychiatrists and psychologists are very expensive. It’s very expensive to train them.”

For now, she’s working with Altizer to arrange an independent trial of Neurogrow — run by professionals with no connection to the GApp Lab — in a hospital or clinic. Ideally, she said, she would like to see health plans provide the game for free or at a low cost to patients.

Altizer and Morimoto have rejected the idea of immediately developing Neurogrow in a commercial setting, despite offers. Morimoto has seen colleagues leave academia and start their own biotech companies, drawn by the chance to raise capital through investors and produce more products more quickly.

The field benefits from competition, she said, but she also worries that games released without the support of empirical research could damage public perception of games as therapeutic devices.

“It’s been a very conscious decision on my part to not go that route,” she continued. “To me, it’s important that the focus remains on the science and on the patients. I would rather hold on to this forever than make a whole bunch of money off of sick older adults.”

Altizer and Morimoto say they have both seen a major shift in how the potential of video games is perceived

“When I first started working on this game 12 years ago, people thought it was a joke,” Morimoto said. “Like, ‘You’re going to make older adults sit there and play a boring, difficult game? They’re going to throw stuff at you.’ But it’s become this really hot area.”

Altizer has had a similar experience. “A decade ago, a lot of my work was convincing people that video games are OK,” he said. “These days I have partners, companies and parents calling on a regular basis asking how they can get involved in video games.”

And as the field of digital therapeutics develops, Altizer said, he expects “massive increases not only in the amount of games being made, but also in the quality of people’s lives because of these games. That’s what really matters most.”

HOW TO JOIN TRIALS
Utahns interested in participating in studies of potential depression treatments through Dr. Sarah Shizuko Morimoto’s clinic can call 801-581-3353.
WHAT ELSE IS IN THE LAB?
Other projects in development in the University of Utah’s GApp Lab:


Virtual reality dental training: Future dentists can use a virtual reality game to develop familiarity with devices and to practice, in a program Dr. Mark Durham is developing.


“Just like a pilot uses a flight training simulator, it would be health care professionals using VR as training tools,” said Director of Digital Medicine Roger Altizer. He hopes to implement similar programs for nursing and surgery.


Recreation and Rehabilitation: The lab is developing a VR simulation that helps people who are paralyzed learn to ski and sail in a chair controlled by the learner’s mouth. With enough practice, people may be able to ski and sail outdoors.


Color Me Healthy: It can be difficult for young cancer patients to describe their symptoms, said Lauri Linder, associate professor and vice chair for the U.’s Division of Acute and Chronic Care.


The Color Me Healthy app helps them convey they’re feeling without saying anything at all. Patients can color in pictures of the human body to communicate, along with other features. Doctors can use a history page to see trends.

Correction: 9 a.m. Aug. 9, 2020: This story has been corrected to update Dr. Sarah Shizuko Morimoto's current title at the University of Utah.