May 2017

A lot of interesting things are afoot in our research area, all on the path to changing the world very much for the better. I’d like to share with you a few new and exciting studies, ongoing trials, and industry updates from the last several months.


Posit Science outranks the competition
Cognitive training programs have received public scrutiny due to unsubstantiated claims made by some companies who have not done the legwork to validate their products. Independent researchers Drs. Tejal Shah, Ralph Martins, and colleagues recently published the first systematic review (Neuropsychological Review, March 2017) of the science behind commercially available brain-training programs. They identified 18 companies and found that 11 companies had no clinical trials or empirical evidence indicating that they helped with healthy aging. The remaining seven companies were classified into three levels of evidence with the highest level requiring at least two well-designed randomized controlled trials, at least one of which met gold standards. BrainHQ outranked Cognifit, Cogmed, BrainAge2, My Brain Trainer, Dakim, and Lumosity by a large margin, with more than twice the number of highest-standards controlled trials than any other commercial competitor.

This work clearly demonstrates that when it comes to brain training, not all programs are alike. A firm commitment to validation before commercialization is exactly what we need to separate the wheat from the chaff. We need this now more than ever, and we need it before the people we are trying to help become disillusioned by those companies masquerading as wheat.

Hushed ringer
The high prevalence of tinnitus is undoubtedly a consequence of modern-day living. Loud sounds and the myriad sources of white noise found in and outside our homes—fans, traffic, and washing machines, to name a few—compounded by a high stress environment is known to induce the pathophysiological changes that cause perceived ringing-in-the-ears.

Brain training may help. In an open-label, intent-to-treat randomized clinical trial, Drs. Jay Piccirillo, Dorina Kallogjeri and colleagues randomized participants with tinnitus to either BrainHQ auditory exercises (n=20) or a no-contact control (n=20) (JAMA Otolaryngology Head & Neck Surgery, Jan 2017). Healthy aged-matched participants (n=20) served as an additional control. MRI neuroimaging as well as a number of neuropsych and self-report measures, such as the Tinnitus Handicap Inventory (THI), were taken before and after 40 hours of training. Resting-state functional connectivity in neural networks largely responsible for attention and cognitive control reliably improved at post-test in the tinnitus BrainHQ group only. There was a numerical reduction (although it was not statistically significant) in THI scores in BrainHQ training over tinnitus controls, with more than twice the number of trained participants showing a clinically meaningful reduction on THI scores (35% vs 15%), and self-reporting an improvement in their tinnitus (50%) or in their ability to learn and remember (70%).

The authors attribute the absence of statistical evidence in the self-report measures to the limitation of existing tinnitus assessments to accurately reflect moment-to-moment symptomology. To improve the characterization of tinnitus, Ecological Momentary Assessment tools (EMAs) are being developed to measure current status multiple times per day to capture natural fluctuations in severity on an ongoing basis. New tools, ones that are sensitive enough to assess health status as it changes in near real-time, are a critical stepping stone to the effective treatment of conditions that threaten our collective well-being.

Brain training in schizophrenia
Schizophrenia is the most widely studied patient population by external researchers of BrainHQ. Dr. Sophia Vinogradov from the University of Minnesota wrote a fantastic piece in Nature Human Behavior (Feb 2017) on the utility of perceptual, cognitive, and social-affective training to transform standard practice of schizophrenia treatment and assessment to one that comprehensively harnesses the advanced set of biomarkers we have at our disposal.

Drs. Greg Light, Veronica Perez, and colleagues are developing just these sorts of individualized, much-needed biomarkers. In a paper in Neuropsychopharmacology (Mar 2017), they found that an event-related potential component (the mismatch negativity, MMN), accurately predicts brain-training gains. Twenty-eight patients played a single hour of Sound Sweeps (an exercise in BrainHQ) in between pre and post measurements of MMN. Larger MMN amplitudes at baseline predicted larger training gains. In addition, amplitudes decreased with training (i.e., processing became more efficient) indicating that Sound Sweeps induced neuroplastic changes that could be measured in as little as one hour.

Using MMN as a predictive biomarker may provide a more nuanced approach to brain training in the future such that an optimal training schedule may be developed, and monitored for effectiveness, on an individual-by-individual basis.

Brain training for acquired brain injury
The damage caused by acquired brain injury often results in cognitive, behavioral, and emotional impairments. In a pilot study, Drs. Therese O’Neil-Pirozzi & Henry Hsu reported the feasibility and benefits of brain training to remediate cognitive function in acquired brain injury (Brain Injury, Sept 2016). In the five-month study, fourteen participants with moderate-to-severe cognitive impairments following brain injury participated in either BrainHQ training or no training. An average of approximately 87% of the total number of required sessions were completed and benefits in memory and verbal fluency (as measured by standard neuropsych testing) were evident. Answers recorded in a semi-structured interview post training indicate that training improved life satisfaction in all but one of the study completers (80%) remarking that their everyday ability to think had improved.

The effectiveness of brain training to improve memory in specific types of acquired brain injury, namely stroke, has also been shown by Drs. Jing Wang, Chang-Xiang Chen, and colleagues (Chinese Journal of Physical Medicine and Rehabilitation, 2016). In this abstract, 60 stroke survivors were randomized to 10 hours of BrainHQ or treatment-as-usual. A number of behavioral improvements were noted on the Rivermead Behavioral Memory Test. Our discussion of the details for this project are understandably sparse because we have been unable to locate the full text. If someone else in our community has access to an English version of this paper, please do let me know.


I’ve rather arbitrarily chosen to introduce you to a few of the hundred or two studies using computer-delivered brain-training programs that are now underway. Let me know about your projects so that we can tell other professionals in our research family about your work in future newsletters.

Potential synergy of brain training and tDCS
Brain training and transcranial direct current stimulation may have a synergistic relationship. In an NIA-funded R01, Drs. Adam Woods, Michael Marsiske, and colleagues are gearing up for the largest phase 3 clinical trial in tDCS in history in which they will study whether tDCS boosts the benefits of brain training in older adults. In a multisite, adaptive clinical trial design across three universities with McKnight Brain Institute, 360 participants will be randomized to BrainHQ or an educational control, both with and without tDCS. Participants will train 40 minutes a day, five days a week, for three months and come to the lab weekly for targeted stimulation to the frontal lobes. Structural, functional, neurophysiological, and neuropsychological measures will be taken at baseline, post-test, and at a one-year benchmark to have maximal mechanistic data to understand the neural networks and signatures of plastic change, and importantly, to see if those changes are sustainable over time. The estimated completion date for this project is August 2021. Multimodal approaches such as these are exactly the sort of studies our field needs to advance the science of brain training in humans.

In a smaller dose-response study conducted in parallel with the larger trial described above, Dr. Woods will test whether training intensively over a two-week period offers the same benefits as training over the full three months. Here, 80 participants will train for an hour per day in a two-week intensive intervention and will perform the same measures listed in the larger trial to assess whether tDCS can facilitate neuroplasticity in shorter periods of time.

Ok, but how does brain training work?
One of the questions I receive most often is to provide an explanation of the mechanisms of action through which brain training works. My answer is informed by plasticity research in animal models as well as small-scale studies in humans. But as you all know, high quality clinical trials that target mechanism in humans are sparse. Dr. Feng Vankee Lin and colleagues from University of Rochester are tackling the neurological changes that underlie improved cognition in a large-scale R01-funded clinical trial through NINR. Eighty-six participants with Mild Cognitive Impairment will be randomized to either six months of BrainHQ or an active control. Functional and structural connectivity will be assessed via fMRI and MRI to measure changes in the default mode network and changes in grey- and white-matter tracts. The trial’s estimated completion date is August 2019. If you go to the Alzheimer’s Association International Conference in London this year, make sure to attend Dr. Lin’s talk on cognitive training in MCI.



Brain training is for everyone
Optimal performers need BrainHQ too. As an example, the BrainHQ training strategies focusing on speed of processing are being widely applied in professional sports training. In an interview with Maria Shriver, Tom Brady announced that his TB12 Sports Training Centers specifically use BrainHQ. The goal of this training in competitive sports environments is to improve accurate responding in a complex, fast-changing visual and auditory environment at speed and with cognitive control while also ignoring distraction (e.g., audience noise).

BrainHQ featured on the Today Show
The prevalence of cognitive impairment among aging older adults is far too high. Several weeks ago, the Today Show aired a story on BrainHQ featuring Dr. Mike Roizen, who is the Chief Wellness Officer of the Wellness Institute at Cleveland Clinic and the author of several award-winning books on how to optimize health and longevity. In this clip, Dr. Roizen discusses how to maintain brain health through best practices such as getting adequate sleep and physical activity. BrainHQ’s speed-of-processing exercise Double Decision was included in his list of recommendations. This speed-of-processing training was shown in the ACTIVE trial to reduce the risk of dementia by 48% over a 10-year period in those who trained with booster sessions. Additional studies in this cohort showed that training lowered at-fault automobile accidents and the risk of depression. If that isn’t strong real-world evidence of brain training fundamentally improving the cognitive and functional status of the trained individual then I don’t know what is!

A shared publication database

The scientific literature in our field is scattered across many journals. We try to keep up with it, and am committed to making our efforts public. We ask you to help us keep up with this fast-moving feast!  You can see our shared database of published randomized controlled trials in brain training online. It’s worth taking a look, as you might find something you weren’t aware of before that can be helpful for you.  As always, please email us any papers that you know about that you find to be missing from this compendium.