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Virtual reality is seeing an upsurge in use by mental health practitioners for treating conditions such as post-traumatic stress disorder, panic disorders and anxiety in a safe and controlled manner. With the advent of affordable VR headsets and technological advances, companies and researchers worldwide are seizing on the opportunity to bring such techniques as VR exposure therapy and cognitive behavioral therapy to telemedicine, specialty clinics and directly to consumers to improve outcomes and better lives.





A growing number of researchers and companies worldwide are exploring the power of virtual reality (VR) and gaming technologies for developing innovative solutions to help clinicians diagnose, treat and manage some of the most challenging behavioral conditions. Researchers believe that the use of VR technologies is rising for health care applications, fueled largely by technological innovations, such as the Oculus Rift headset, which are making VR therapies more affordable. This article takes a closer look at how VR is being used for exposure therapy at the U.S. Department of Veterans Affairs to help soldiers recover from post-traumatic stress disorder (PTSD), for cognitive behavioral therapy at Akili Interactive Labs Inc., which filed for US FDA approval for its Echo: Project to treat attention-deficit hyperactivity disorder (ADHD) and by researchers in the Netherlands to prevent relapse in patients recovering from mental illness. We'll also address limiters and growth opportunities and other projects in the works in this trending space.





One of the most promising and widely used VR technologies today is an interactive VR-based exposure therapy tool to assess and address PTSD in soldiers, which was developed at the University of Southern California Institute for Creative Technologies.



USC Institute for Technological Innovation


Bravemind is designed to recreate the most traumatic experiences that patients encountered during combat situations in the virtual world. It uses a VR head-mounted display, directional 3-D audio vibrations and even smells and exposure therapy, where patients, guided by a therapist, are taken back to the memory of their trauma over and over until their triggers no longer produce anxiety.



Peter Tuerk, associate professor of Psychiatry and Behavioral Sciences, Medical University of South Carolina, and director of the PTSD Clinical Telehealth Team Charleston, VAMC, told Medtech Insight psychiatrists call this process habituation, where through repetition, the bad memory is slowly robbed of its power.



"We need to process emotional information and the ability to create file folders to organize new information," Tuerk explained. "It's not necessarily that the event was so stressful, it's that the event is so emotionally different from anything we've experienced that we don't have a file folder and the associated feelings are so intense that it prevents us from making one … this little bit of unprocessed chaos bouncing around in us destroys or seriously undermines our natural and necessary assumption about how the world works and who we are in it. If avoidance is preventing natural recovery, we need to do prolonged exposure therapy."



"We need to process emotional information and the ability to create file folders to organize new information, said Peter Tuerk, director of the PTSD Clinical Telehealth Team Charleston, VAMC. "If avoidance is preventing natural recovery, we need to do prolonged exposure therapy."



Skip Rizzo, research director at USC, noted that researchers aren't erasing memories. He said, people still remember what they've been through, but they don't have the same intense, emotional power that they had before treatment.



Prolonged exposure therapy started in the 1950s. But it wasn't until 1997 that researchers from Georgia Tech linked exposure therapy with emerging VR in a pioneering clinical study dubbed, "Virtual Vietnam". The study enrolled ten veterans who suffered from PTSD and had not responded to multiple treatments and exposed them to two virtual environments, a virtual Huey helicopter flying over a virtual Vietnam and a clearing surrounded by a jungle. After a month's treatment, all ten men showed significant improvement.



The lead investigator of the Virtual Vietnam study was Barbara Rothbaum, who in 1996 co-founded Decatur, Georgia-based Virtually Better, Inc., which sells Bravemind, Virtual Iraq and Virtual Afghanistan and produces other VR modalities to treat phobias, addiction, fear of flying, fear of storms, of public speaking, among others.



Dawn McDaniel, executive director of research at Virtually Better Inc., told Medtech Insight its clients include more than 50 VA health systems worldwide and military hospitals, as well as hospital systems such as Cedars-Sinai Medical Center and academic institutions such as George Washington University and New York University.



Its top-of-the-line VR exposure system, including Bravemind, encompasses 25 different types of software divided up into suites such as phobia, relaxation and addiction. It is the only system that comes with a 'scent' machine. The price tag is $10,000-$40,000, depending on the desired features, McDaniel said.



"We developed this integrative platform basically so you can get the most that we can out of Bravemind," McDaniel said. "You're feeling the vibration of the Humvee, you're smelling the market (including body odor, cigarettes, market spices) and you're seeing the scenes, you're hearing what's going on in the environment, and you're carrying (what feels like a real) weapon."



"We developed this integrative platform basically so you can get the most that we can out of Bravemind," McDaniel said. "You're feeling the vibration of the Humvee, you're smelling the market (including body odor, cigarettes, market spices) and you're seeing the scenes, you're hearing what's going on in the environment, and you're carrying (what feels like a real) weapon."



Asked about the fastest growing therapeutic area for the VR product, McDaniel said that the company is seeing an increased demand for PTSD.



"Across the literature there is a discussion about a rise in incidence of PTSD and along with that there's more awareness and because of that awareness, I think there is an increased demand for both evidence-based approaches and solutions for PTSD, but also for innovation around the treatment of PTSD," she said.



Rizzo said in published reports that in 2013, about 69,000 new cases of PTSD were diagnosed in veterans from Afghanistan and Iraq as well as 62,000 newly diagnosed Vietnam veterans, which, according to the researcher, is often due to people getting older and becoming more emotionally vulnerable.



Conventional treatment of PTSD has included medication, psychotherapy and exercise and using graduated exposure therapy, which involves the gradual repeated "reliving" of the traumatic event under a clinician's care. For many patients reliving their traumatic experience was too much of a challenge, which led USC researchers to develop Bravemind.



The potential of VR for treating PTSD is supported by previous reports in which patients with the disorder, who were unresponsive to previous imaginal prolonged exposure therapy treatment, went on to respond successfully to VR exposure therapy.



According to USC, Bravemind is especially appealing to the younger generation, which grew up with digital technology and may actually prefer this type of treatment over traditional "talk therapy."



But McDaniel finds that VR therapy appeals to a wider demographic of people who have played video games all of their lives.



"There is a group of people who are coming to our office who may not otherwise come, because they are curious and they're used to seeing game-controlled and technology displays," she said. "It's more comfortable and acceptable to them than talk therapy with a health provider."



VR is effective, because no matter how abstract the world around one is, the mind is tricked into believing that the patient has entered that world, researchers found. Virtually Better has developed solutions that are more affordable, and thus, can be used in the doctor's office, and is now also working on bringing mobile-based apps directly to consumers.


According to McDaniel, most of the clinical solutions today are used by therapists in anxiety specialty clinics known for work in cognitive behavioral therapy. These systems, which offer a vibrating chair and visual and auditory stimulation, run between $699 and $1,395, she said.



The company's mobile systems, which can be used with an iPhone 5 or laptop, currently come with five programs, McDaniel said, adding but new programs are in the works.



"We're very excited about the ability to take everything that we've learned from the other two systems and making it for a price point that's affordable for the private practitioner," she said.



Asked about the competitive landscape, McDaniel said there are numerous companies that are trying to replicate Virtually Better's solutions, but she feels her company has a competitive advantage.



"We have seen an increase in companies that are trying what we've been doing for a long time, but we have not only been selling and developing these systems, we test them, so we can make sure they maintain their quality," she said.



Among their rivals are two Spanish companies -- Psious, which offers solutions for PTSD and phobias, and VirtualRet, which also offers tools to therapists for treating phobias.




Akili Interactive Labs, a subsidiary of UK biopharmaceutical company PureTech Health PLC, is one of the first companies to develop a VR cognitive therapy tool that is up for regulatory approval (Also see "Game On For Akili's Cognitive Control Tech" - Medtech Insight, 13 Apr, 2017.).



Akili has shown in a pilot study that playing its video game not only improved cognitive test scores of children with sensory processing dysfunction (SPD), but also produced neurological changes in the prefrontal cortex of the brain. Akili is currently evaluating its leading product, Project: EVO in a late-stage trial for treating pediatric attention deficit hyperactivity disorder. Results are expected in the first quarter of 2018, upon which Akili plans to file for FDA approval.



Akili licensed the technology from UC San Francisco and developed proprietary adaptive algorithms. In a TED Talk, Adam Gazzaley, founding director of the Neuroscience Imaging Center at UC San Francisco, explained some of the research behind the technology and addressed key aspects of "multi-tasking" and "adaptivity" that have shown to improve cognition in some populations.


Dr. Adam Gazzaley, Closing the Loop between the brain and education


Gazzaley said to appeal to children, the game incorporates aspects of music, art and story-telling as well as the key aspect of "adaptivity," meaning as the participant plays the game in real time, the game becomes more difficult as performance improves. This keeps the person engaged where it's not too hard where they get frustrated, but also not so easy, where the person becomes bored, all of which has shown to maximize neuroplasticity in the brain and improves cognition.



He referred to this as "closing the loop," where decisions in the brain guide behaviors, which influences the game; the game reacts adaptively in real time to challenge the player, which changes the environment, and then cycles back to the brain to close the loop and actively changes the brain.



The idea of using video gaming technology to activate specific brain regions that underlie cognitive deficiencies in patients sets Akili's technology apart from other video gaming technologies and made it an attractive investment target, said Edward Kliphuis, investment director in the New Business Fund in digital health and solutions at Merck Ventures BV, Amsterdam. Merck Ventures, part of Germany-based Merck KGAA , together with Shire PLC , Amgen Ventures, and other financial investors poured $42.4m in a Series B funding into Akili (Also see "Akili Has Big Pharma Buy-In For Cognitive Disorder Video Games" - Medtech Insight, 26 Feb, 2016.).



"If the goal is to induce neuroplasticity, we can redefine a whole realm of where you can use all of these different solutions," Kliphuis told Medtech Insight. Akili is also currently testing its technology platform for depression, Alzheimer's disease,traumatic brain injury and a range of other indications.



"If the goal is to induce neuroplasticity, we can redefine a whole realm of where you can use all of these different solutions," Edward Kliphuis said.



Results from a four-week study of 57 children with sensory processing disorder (SPD) – half of which had ADHD symptoms, who received at-home treatment with the gaming technology, then underwent post-treatment cognitive, behavorial and neurological assessments – showed that all children improved. And those with SPD and inattention showed even greater improvement in the Vanderbilt Assessment Scale, considered the gold standard for evaluating ADHD symptoms.



Last December, Akili also announced results of a study with Pfizer using a different screening platform that could detect biomarkers of Alzheimer's disease. The company is also working toward further clinical validation with one potential future path being FDA approval as a non-invasive diagnostic for neurological indications, Kliphuis said.



In older adults, playing the game has shown improvement in their abiity to multi-task and their ability to sustain attention on different tasks, as well as working memory, Dr. Gazzaley explained in the TED Talk.



Kliphuis said a decline in cognitive abilities is a major societal burden.



"We haven't found an agent that works in Alzheimer's," he said. "This is exciting, because it means we can have potentially a non-invasive screening tool to identify if people are prone to Alzheimer's disease or not. The key to the Akili solution is to do initial screening, and thus, reduce the number of PET scans that have to be conducted, which are cumbersome and unpleasant for patients. We hope that doctors will give it to their patients to play the game.



Asked about other investments in health-oriented video gaming technologies, Kliphuis said, this is the only such investment, saying it hits the "ABCs" of gaming.



"'A'; autonomy gives you control over your own situation; 'B'; belonging connects you with other subjects; and 'C'; competence gives you a sense of autonomy, or a sense of satisfaction to master a task, which is very interesting for us, if people will continue using it," he said.



When asked about the potential market size of Akili's technology, Kliphuis couldn't offer a figure, but said instead that "the sky is the limit."



It is worth noting that drug company, Merck, is also exploring using video gaming technologies as therapy. In this case, it developed the "MS Dialogue Ecosystem" to watch for the progression of the disease in multiple sclerosis patients.




Micah Hrehovcsik, lecturer and game designer at the HKU University of the Arts Utrecht, has a long history of working with Dutch companies and therapists and patients at various health systems on developing VR tools for therapeutic use in mental health care settings.



One of his recent projects is the multi-player game, Moodbot, designed to help patients who are recovering from mental illness, such as psychosis, to avoid relapse of violent behavior. He talked about some of the research that went into creating Moodbot and addressed key challenges in trying to find common ground between all stakeholders involved in creating the game.



Moodbot takes place in a fantasy water world where each player owns a room in a large spaceship. Players work together to make the ship move and collect points by performing actions, such as adjusting their own "moodbot," a robot that depicts mood by facial expression. Each player can also enter another player's room and offer encouragement, if the other player's moodbot shows negative feelings. The ultimate community goal is to move the ship forward, which reaps the players a reward.



"We ask them (players) how they feel in the real world," Hrehovcsik told Medtech Insight. The ultimate goal of the game is to allow patients to help each other keep their emotions in check by allowing communication. He said players play daily for five to 10 minutes with health care professionals being able to track and monitor all the action at the backend.



Thus far, Hrehovcsik said to the best of his knowledge there haven't been any validation studies done. But he hopes that as more data becomes available, it will allow researchers and therapists to better evaluate the treatment modality in this patient population.



"By collecting more data from psychiatric patients on a daily basis, the information can be used to understand trends and what causes the violence," he said.



On the upside, he noted that health care workers expressed positive views about the reaction of the patients who remained committed to playing the game and reporting their feelings. He said given that health workers have only limited time to interact with each patient, by being able to monitor patients in this new gaming environment, it helped reduce their workload and increased job satisfaction. Patients expressed that they felt they had more say in their treatment and liked the idea of being able to interact with one another and help each other achieve a more positive state of mind or mood.



Asked about his biggest challenges in creating this game, the researcher said that terminology was one issue. The psychiatrists had their ideas of how they wanted to gather information, while patients and game developers had other ideas. He said in creating a successful VR game takes the buy-in of all entities, constant communication and on-going testing during game development.



"Patients need to be engaged in the game, otherwise they won't provide the information and they know while they are playing the game, the information is also being used by healthcare workers," he said.



"Patients need to be engaged in the game," said Micah Hrehovcsik, lecturer and game designer at the HKU University of the Arts Utrecht.



Another key issue that came up during the development of Moodbot was that the parties disagreed on "messaging," he said. Hrehovcsik said the psychiatrists encouraged "free-flowing" conversation where patients could leave messages for one another in the different rooms, which he strongly discouraged. He said free-flowing conversations between patients would have required health care workers to constantly monitor what's being said. It also would have left the door wide open for negative talk. Later everyone agreed on using pre-fabricated messages that were all positive and encouraging like "keep it up" for good behavior or "go outside and get some fresh air," if someone expressed sadness.



Jan-Willem Faessen, who did business development for Red Max, which marketed the game, told Medtech Insight that the company created a simple business case for Moodbot where a user pays €70 to play the game. But he said, thus far, it hasn't been successful in finding investors.



He said most game development companies in Holland are waiting for better times.



"As for the development of the tool and the market, we must conclude there is momentarily very little momentum in investing in the development of games in the Dutch mental health care sector," Faessen said. "The sector and government are very busy sorting out structure, business model, ict architecture, trust data-safety, etc."


Market Limiters


Market limiters for VR therapy extend far beyond Dutch borders, according to some sources.



According to Wolters Kluwer Health, research on health care-related VR applications has significant limitations including small numbers of patients and lack of comparison groups. Also, mental health providers need specific training before integrating VR approaches into the clinical practice.



Another limiter is the problematic connotation of videogaming. Many people still perceive videogaming as having a 'negative impact on children' and having hidden dangers. Some people even believe that videogaming induces ADHD.



Growth Opportunities


Others, see tremendous upside in this space.



Global Industry Analysts, Inc. research projects the global market for VR in health care to reach $3.8bn by 2020, driven by technology advancements in healthcare IT, expanding applications into diverse disciplines, and increasing demand for rehabilitation and simulation training.



McDaniel and Tuerk, who has financial ties to Virtually Better, also believe that VR in health care is on the rise.



"We do see with the second wave of VR [technologies] that the idea of VR is more mainstream," McDaniel said. New hardware technology has made the headsets more comfortable and much more affordable; and with smartphone applications consumers can now stream VR content right at their fingertips.



Tuerk is convinced that VR technology can be an effective part of treatments for phobias, such as PTSD, and allows health care professionals to simulate exposures that otherwise would be too costly or impractical to recreate in real life with a therapist controlling the environment.



And researchers around the globe continue to explore opportunities in this trending field.



At Virtually Better researchers are working on app-based VR tools that can be marketed directly to consumers for self-help and other applications. McDaniel said people hear about it in the news and are curious to see what VR therapy is all about and simply walk into their offices to seek help.



"There are a number of people who might not want to come to a clinical setting, and we would like to get VR into their hands, so they can use some of these tools in the comfort of their own home," she said. One of these areas is likely to be anxieties. "We have a long history of developing tools for the treatment of anxieties, so that makes sense."

In addition, Virtually Better is exploring partnerships with pharmaceutical companies.



"We're really interested in integrating videogaming technologies with medication management systems, so we hope to develop partnerships with pharmaceutical companies," she said.



As researchers and companies continue to work on web-based approaches, telemedicine and technology-based intervention for disorders as well as smartphone application, the opportunities for VR applications look promising. The key challenge remaining today is a lack of clinical evidence.

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