September 2018

Many 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 a few new and exciting studies with you, they provide some new information about ongoing trials and industry updates that have come up over the past several months.

You’re receiving this newsletter because you are a former collaborator or scientific friend—or you have collaborated with me or other scientists at Posit Science—and I thought you might be interested in keeping up with ‘what’s happening’. Please let me know if you’d like to be removed from this list. We can still be friends.





Mechanisms of action behind brain training gains
BrainHQ’s Double Decision exercise, widely known as Useful Field of View (UFOV) training, is designed to drive positive, system-wide neurological changes. The accurate representation of information across space and time is dependent upon high cortical sampling rates and short integration times, which, in an aging brain, normally requires improvements in spatial, spectral, temporal and intensive processing accuracies, and increased adaptation and distractor suppression. With those improvements lower-level processes in the brain feed-forward more strongly correlated (more reliable; more salient) inputs to higher-order system levels, enabling recovery of functional connectivity in major brain networks.

Dr. Lesley Ross and colleagues from Penn State University and The University of Alabama at Birmingham recently published evidence of the recovery of network changes associated with Double Decision training (The Journals of Gerontology: Psychological Sciences, 2018). In their trial, 51 healthy older adults (aged 65+) were randomized into one of three arms: (1) speed of processing training using Double Decision, (2) executive function games that included activities such as math problems, puzzles, and brain teasers, or (3) a no-contact control. Treatment was for 10 hours, delivered over 5 weeks. Assessments of cognitive function (measured by the UFOV assessment), brain activation (measured by performance on a selective attention task performed in an fMRI scanner), and brain connectivity (measured by resting state functional neuroimaging) were used to evaluate the impacts of the Double Decision exercise on brain structure and function, before and immediately after training.

Participants randomized to Double Decision improved on all assessment measures relative to participants in the other two arms. The Double Decision group showed significant improvements on the cognitive function assessment (Cohen’s d = 0.74). When performing an untrained selective attention task in the fMRI, the Double Decision group exhibited evidence of transfer, with significantly reduced brain activity in the majority (six of eight) regions of interest (ROIs) associated with effortful information processing (d ranged between 0.62 to 0.73 across ROIs) relative to the executive function group (reduction in one of eight ROIs) and the no-contact control group (no reduction in any ROI). Finally, fMRI brain connectivity analysis indicated that Double Decision showed a large increase in network connectivity at rest (d = 0.92). The other two groups showed no increase.

Double Decision made the brain more efficient by strengthening network connections in brain regions important for executive function, specifically between the anterior insula and anterior cingulate cortex, anterior insula and visual cortex, anterior insula and supplemental motor area, and the dorsolateral prefrontal cortex and supplemental motor area. This increase in efficiency reduced the amount of neural activity required to accomplish the task. Increased connection strength is the probable primary neurological basis by which Double Decision improves cognition and transfers to improve untrained functional abilities. This study clearly shows that brain training targeting attention, accuracy and speed directly and positively impact organic brain health.

Plastic change is not achieved by the central nervous system in a vacuum. The peripheral nervous system, often overlooked, may contribute meaningfully to the neuroplastic benefits derived from brain training. In a second study investigating potential mechanisms of action, Feng Vankee Linn and colleagues from the University of Rochester discussed the role of the parasympathetic nervous system in training-induced plasticity (Curr Alzheimer Res, 2017). A cohort of 21 amnestic MCI patients trained for 6 weeks on either BrainHQ’s Visual Intensive course, or on active control games that included Crosswords, Solitaire, and Sudoku. Participants were hooked up electrocardiographically, to measure high-frequency heart-rate variability during two of their training sessions. Resting-state neuroimaging of striatum-related neural networks and near- and far- transfer cognitive assessments (Useful Field of View and working memory tasks from NIH EXAMINER, respectively) was recorded before and after treatment. Only the trained group showed a U-shaped pattern of heart rate variability, which was associated with restored (i.e., decreased) connectivity between bilateral striatal and prefrontal brain regions, and significant gains on the near-transfer cognitive assessment. These important findings extend our understanding of the relationship between heart health and brain health, and provocatively indicate that the peripheral nervous system is playing a significant role in mediating or moderating central nervous system plasticity. Happy heart, happy brain.


I’ve rather arbitrarily chosen to introduce you to one of the 250+ trials using computer-delivered brain training programs that are now underway. Let me know about yourprojects so that we can tell other professionals in our research family about your work in future newsletters.

Behavioral Interventions to Prevent or Delay Dementia
We are seeing a surge in trials that implement multimodal approaches to tackle the multifactorial nature of dementia onset and progression. Drs. Glenn Smith, Julie Fields, and colleagues are in the data analysis phase of a multi-site PCORI-funded trial at the Mayo Clinic that uses HABIT, a clinical program representing an intensive behavioral and lifestyle approach to preventing progression in MCI. In this unique 10-day intervention, several hundred couples were randomized to have one of the five interventions withheld while receiving the other four. The five interventions were brain training via BrainHQ, cognitive rehabilitation via memory compensation training, patient and partner support groups, wellness education, and yoga. The BrainHQ training schedule implemented in this trial was not tightly constrained; participants were free to choose the exercises they wanted to play. A follow-up analysis may determine whether certain participants performed better based on the exercises they chose. You may find the published protocol here.


New guidelines proposed by the AAN in the treatment of MCI
The American Academy of Neurology (AAN) convened an expert panel led by Dr. Ronald Petersen at the Mayo Clinic to address four questions regarding the prevalence, prognosis, and treatment of Mild Cognitive Impairment. The primary goals were to understand the prevalence of MCI in the general population, the prognosis for patients diagnosed with MCI for progression to a diagnosis of dementia, and the efficacy of pharmacologic and non-pharmacologic treatments.

The panel concluded that MCI is prevalent among older adults, especially among those with lower levels of education, and that a diagnosis of MCI has a high probability of progressing to dementia. Most notably, a review of evidence suggested that non-pharmacologic interventions show greater efficacy than pharmacologic agents such as cholinesterase inhibitors. Based on these results, the AAN updated its guidelines to now list brain training and physical exercise as clinical recommendations for those with MCI (see also physician and patient tools and materials here). Our field has been wrought with controversy due to a few bad players who have stolen the limelight. I am delighted that the judges of major independent organizations are making recommendations for the public’s health based on the totality of the evidence.

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.