Brave study

Study Results Show How to Help Vets with Signature Injury of Recent Wars Interview with:

Henry Mahncke, PhD Chief Executive Officer Posit Science

Dr. Mahncke

Henry Mahncke, PhD
Chief Executive Officer
Posit Science

Dr. Mahncke earned his PhD at UCSF in the lab where lifelong brain plasticity as discovered. At the request of his academic mentor, he currently leads a global team of more than 400 brain scientists engaged in designing, testing, refining, and validating the computerized brain exercises found in the BrainHQ app from Posit Science, where he serves as CEO.

This week, interviews Dr. Mahncke about a new study, with breakthrough results for service members and Veterans grappling with the signature injury of recent wars. What makes this study newsworthy?

Response: As the last troops come home from Afghanistan, the battle is not over for many who served and continue to grapple with the signature injury of recent conflicts — mild Traumatic Brain Injury (or mTBI). Typically, such injures were caused by blasts or concussions, and they’ve been diagnosed in more than 300,000 service members. Most recover within a couple days or weeks, but for many — some estimate fifteen percent — physical, psychological, emotional, and cognitive problems persist for years. Such injuries often go untreated, because treatments focus on in-person, customized, cognitive rehabilitation, which can be helpful, but is costly, time-consuming, requires travel for treatment, and relies on the craft and expertise of the healthcare provider.

Up until now, there’s been no effective intervention that’s highly-scalable and that can be delivered remotely. This study showed that remotely-administered BrainHQ computerized exercises improved overall cognitive performance in a population with very persistent cognitive issues. On average, patients in this study had cognitive issues for more than seven years. That means we finally have a tool shown effective in a gold-standard study that practitioners can employ in treating this large and underserved population, who sacrificed so much to serve our nation. Who funded and ran the study? How was it designed?

Brave studyResponse: The US Department of Defense funded the BRAVE study with a research grant from the Congressionally Directed Medical Research Program to examine the use of a brain-plasticity-based cognitive training program (BrainHQ) as an intervention for service members and Veterans suffering from cognitive impairment following mTBI. The study was conducted through a nationwide network of five military and Veterans’ medical centers (NICoE/Walter Reed National Military Medical Center in Bethesda; Schofield Barracks/Tripler Army Medical Center in Honolulu; Baylor/Michael E. DeBakey VA Medical Center in Houston; Yale/VA Connecticut Healthcare System in West Haven; and Harvard/VA Boston Healthcare System in Boston); with Posit Science in San Francisco serving as the study coordination center.

In terms of design, this was a multi-year, multi-site, prospective, parallel-armed, double-blinded, randomized controlled trial, with an active control group. It’s a gold-standard design.

BRAVE enrolled 83 participants with a history of mTBI and diagnosed with cognitive impairment, and randomized subjects into a treatment group (BrainHQ) and an active control group (computer games). Both activities were plausibly expected to have some positive impact due to their demands on cognitive realms, such as attention, memory, and reasoning. Each group self-administered training in their own homes, with telephone supervision from trained coaches, and were asked to train for one hour per day, five days per week, for twelve weeks. Comprehensive cognitive assessments were performed before training, after training, and after a twelve-week, no-training, follow-up period. Who was in the study?

Response: Participants had an average age of 33 years and were 81% male. Before training, they showed meaningful cognitive impairment, testing about 2 standard deviations below normal scores on the ANAM (a standardized cognitive test used by the military to screen for cognitive impairment). Typically, they had been deployed to combat areas and, on average, had their most recent mTBI more than seven years earlier. Across a standardized set of emotional and psychological health measures (including depressive symptoms, PTSD symptoms, and cognitive symptoms), participants scored in the mild-moderate impairment range. On the whole, these participants were representative of service members with a history of mTBI who seek treatment for their cognitive issues so they can re-integrate with, and contribute to, society. What did the study show?

Brain Study. BrainHQ PositResponse: The BrainHQ group had a statistically and clinically significant improvement on overall cognitive function compared to the computer games group, and this benefit persisted for at least twelve weeks after training ended. Cognitive function improvements were nearly four times larger in the BrainHQ group than the computer games group, as measured immediately following training, and nearly five times larger when measured again 12 weeks later (with no further training).

Twice the percentage in the BrainHQ group showed reliable improvements compared to the computer games group – with 77% in the intervention group experiencing clinically significant change compared to 38% in the active control; and with 37% in the intervention group experiencing a full standard deviation of change compared to 18% in the active control.

On average, participants in the BrainHQ group improved on the cognitive performance composite measure by 24 percentile ranks – as though they went from the 50th percentile to the 74th percentile.

While results on the primary cognitive measure were significant, analysis of functional and self-report measures did not show significant between group differences. However, on many measures both groups showed improvement, suggesting general benefits of cognitive engagement and study inclusion. What are the implications? 

Response: Treatment of mTBI is complex, and patients typically manifest distinctive sets of physical, mental, emotional and cognitive symptoms that require individualized courses of treatment.

This trial provides significant evidence that this specific form of self-administered brain-plasticity-based cognitive training can be incorporated as part of an evidence-based treatment plan to improve cognitive function in people with cognitive symptoms following mTBI.

This is the first broadly-applicable and highly-scalable approach in mTBI shown effective in a randomized controlled trial.

This is the first such approach applicable even in remote location – meaning that trained clinicians who currently can only see patients in-person once or twice a week can extend their reach and supervise patients over the internet doing daily brain training anywhere in country – or in the world. This means that any service member or Veteran in need of help could have the opportunity to receive evidence-based treatment, remotely supervised by a trained clinician. When will this be widely available as a treatment for service members with mTBI?

face-to-face, BrainHQ, PositResponse: BrainHQ has been used in dozens of military and Veterans’ facilities for cognitive rehabilitation, under the supervision of healthcare professionals; however, that has not made it broadly available to service members and Veterans.

With the publication of these results, Posit Science, the maker of BrainHQ, has indicated it intends to work with clinicians, payors, and regulators to make this widely available, as quickly as possible. What was most surprising about the study?

Response: I suppose for many practitioners and policymakers it will be a surprise that these brain exercises can drive this kind of change — even when administered remotely.

To me — and probably to the relatively modest number of scientists closely following studies of BrainHQ — these results were not surprising. After all, a very convincing case (based on prior studies) had to be made to win the highly competitive CDMRP grant that funded the study. Back then, there were dozens of peer-reviewed studies of BrainHQ; now, there are hundreds.

Even though it is well known among brain scientists that running a study among brain-injured patients can be challenging and time-consuming, I was somewhat surprised how long it took to complete this study.

However, I suppose what is most surprising to me — after spending years and millions of dollars to get to this result, which addresses a large unmet need of our military and Veteran is t — is that an even longer, steeper road lies ahead in getting this evidence-based solution into the hands of those it can help. I very much welcome the support we seem to be getting from policymakers, since the announcement of the results, and am resolute in my resolve to work with like-minded supporters of our troops to make this widely available.


Henry W Mahncke, Joseph DeGutis, Harvey Levin, Mary R Newsome, Morris D Bell, Chad Grills, Louis M French, Katherine W Sullivan, Sarah-Jane Kim, Annika Rose, Catherine Stasio, Michael M Merzenich, A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury, Brain, 2021;, awab202,



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Last Updated on August 12, 2021 by Marie Benz MD FAAD