Digital Therapeutics Extend Their Reach in Neurology

In recent years, a new genre of medical intervention has started to emerge — digital therapeutics. In the wake of promising results in a number of conditions, one high-profile approval by the US Food and Drug Administration (FDA), and several ongoing clinical studies, neurologists (and other doctors) may soon be prescribing video games alongside conventional therapies for several conditions.

“Digital therapeutics refers to a software-based intervention. It’s not just digital information or digital monitoring, it’s an alternative treatment option based on software,” said John Krakauer, MD, professor of neurology, neuroscience, and physical medicine and rehabilitation at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Krakauer explained that the nervous system is especially amenable to gamified therapies because of its unique ability to learn. “It’s an experience-dependent plastic system. You really want to have a high-intensity, high-dose behavioral intervention to try and rewire and train the nervous system.”

“In other words, digital therapeutics complement what happens in physical and occupational therapy sessions with scientifically-informed behavioral interventions based on technology and software,” he said.

The Digital Dolphin Treating Stroke

Krakauer, who is also the chief scientific advisor to the company MindMaze, studies immersive digital therapies to enhance neurorehabilitation following stroke. He works on MindPod Dolphin, a virtual reality game that trains motor control of the upper extremities by having the patient simulate swimming in the ocean like a dolphin.

“Your movement is tracked, there are artificial intelligence algorithms controlling the difficulty, and the whole purpose is to take your nervous system for a ride, outside the context of activities of daily living. Patients are so engaged and immersed that they don’t even realize they’re making high-quality, high-intensity, high-dose movements of their arm.”

In a pilot trial called SMARTS2, his group found that MindPod Dolphin was about twice as effective as regular rehabilitation for upper extremity motor recovery in patients who had had a stroke. A larger trial is currently underway in New Zealand.

Another preliminary study found that MindPod Dolphin had positive effects on the physical and cognitive health of elderly patients in an assisted-living facility. Now, MindPod Dolphin is being studied around the world in patients with multiple sclerosis, Parkinson’s disease, concussion, and traumatic brain injury (TBI). There is even a Department of Defense-funded trial underway for veterans with TBI.

Reaching Young Patients Through Virtual Play

Isabela Granic, PhD, director of the Games for Emotional and Mental Health Lab, and professor and chair of the developmental psychopathology department in the Behavioural Science Institute at Radboud University in the Netherlands, studies gamified therapy for depression and anxiety.

“We take evidence-based techniques in the mental health clinical world or developmental research, such as cognitive-behavioral therapy (CBT) or exposure therapy, and then embed them in games to use a different engine for delivering something we otherwise know works,” she told Medscape in 2020.

Data for a game she developed called MindLight are promising so far. “We have randomized controlled trials showing that we can cut young people’s anxiety in half after they have as little as five 1-hour sessions per week. We’ve shown that we can get the same benefits as CBT for these young people, which is huge.” MindLight also has proven effective for treating anxiety in children with autism.

A First for Therapeutic Video Games

In the summer of 2020, EndeavorRx, made by Akili Interactive, became the first prescription video game to be approved by the FDA. The game, which is designed to improve attention function, is currently authorized for children ages 8 to 12 with attention-deficit/hyperactivity disorder.

Players complete “missions” by steering an aircraft through complex obstacle courses and collecting targets. The prescription directs the child to complete five missions each day for 5 days per week. It is recommended that patients use EndeavorRx for at least 4 weeks. Researchers are hopeful that, moving forward, the game will also prove effective for other cognitive disorders, including dementias and mild cognitive impairment.

Now, EndeavorRx is even being studied for its efficacy in combatting brain fog in COVID long-haulers. A team of researchers led by Faith Gunning, PhD, psychologist and vice chair of research in the department of psychiatry at Weill Cornell Medicine, New York City, is performing a trial of EndeavorRx for post-COVID cognitive dysfunction.

“This therapeutic game gives repeated stimulation of the cognitive processes and networks that support multitasking and attention. And in doing that, my hypothesis is that there will be a restoration of function to that cognitive control network,” said Gunning. Gamified interventions, she added, are more fun and engaging for patients compared with more conventional therapies.

The fully remote trial will randomize approximately 100 participants to digital cognitive intervention and control groups. Over 6 weeks, the experimental group will be asked to play EndeavorRx at least 5 days per week, for about 25 minutes per day. Pre- and postintervention cognitive assessments will be compared between the groups.

“As far as digital interventions for mental health and cognitive disorders, the pandemic has just really accelerated the work…that means that in the future more people can actually access what we’re doing in our labs and clinical research,” said Gunning. “I hope this is going to lead to more scalable approaches that will have a farther reach in the community.”

Krakauer envisions a future where neurologists prescribe medications, devices, and “immersive, plasticity-enhancing digital interventions.”

Hopefully, the synergy of these treatments will be a game changer for our patients.

Leah Croll, MD, is a fellow in the department of neurology at New York University Langone Health in New York City and has disclosed no relevant financial relationships.

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