Researchers testing a novel video game-based intervention in depressed patients have found that it can reduce the severity of an important form of cognitive deficit—the ability to remain reengaged and pay attention to a task over a sustained interval.

Cognitive deficits are a little-discussed and often overlooked aspect of depression, with the power to seriously impact patients’ ability to function socially or at school or work, often in ways that they themselves do not or cannot perceive.

Problems with cognition are regarded a core symptom of depressive disorder by the DSM-5 diagnostic manual used by psychiatrists. These deficits include potential difficulties with concentration and decision-making, slowed thinking, and forgetfulness.

After antidepressant therapy, when depressed people experience reductions in mood symptoms or even remission, cognitive impairments often remain unaffected. This suggests underlying causes in the brain that may be distinct from those which cause depressed mood and other affective symptoms of depression, say researchers who tested the new video-game based intervention.

The team was led by Richard S.E. Keefe, Ph.D., of Duke University, and Amit Etkin, M.D., Ph.D., of Stanford University. Dr. Keefe, a member of BBRF’s Scientific Council, is a 2003 BBRF Independent Investigator and 1995 and 1991 Young Investigator. Dr. Etkin is a 2012 BBRF Young Investigator. They reported their results in the American Journal of Psychiatry.

Antidepressants have little effect on cognition, although some have effects on specific cognitive domains (e.g., vortioxetine [Trintellix], which can improve processing speed). Forms of talk therapy, including cognitive behavioral therapy, target distorted or problematic thoughts, but not cognition itself. The intervention tested by Drs. Keefe, Etkin and colleagues, called AKL-T03, was assessed for its potential impact on sustained attention, but also on broader measures of cognitive performance as well as on depression symptoms.

Seventy-four subjects with mild to moderate major depression were randomly assigned to two treatment groups. In one group, 37 subjects received AKL-T03, a video game-based intervention designed by Akili Interactive, a software company. The other group of 37 subjects received the control intervention, a video game that presented a word puzzle. The participants, whose average age was about 42 and of whom over 60% were female, were trained to use these games prior to the beginning of the trial.

Both AKL-T03 and the control intervention required participants to pay attention; they were instructed to complete, at home and on tablet devices, five sessions at least 5 days per week for 6 weeks.  The design called for participants to play for 25 minutes per day, at which point the software became locked so that particularly motivated participants would not skew results. The participants knew they were involved in a trial testing an intervention to improve cognition, but did not know whether they were receiving the “active” or placebo intervention.  Both interventions were designed to calibrate to each participant’s initial ability level and become more difficult over time. This feature of the trial was important. A game that was not tailored to individual skill might discourage some who tried it—important in an illness in which motivation, feelings of reward, and negative self-image are key features.

The AKL-T03 video game was specifically designed to activate the brain’s fronto-parietal networks to improve attention and attentional control processes.  It does this by directing game-players to respond to certain targets on screen while ignoring others.  The control intervention asked players to connect letters displayed in an on-screen grid up, down and diagonally to form as many words as they could consisting of two or more letters during each 25-minute session.  It did not specifically target the brain’s fronto-parietal networks.

Patients in the active AKL-T03 group showed “significantly improved performance” in attention compared with those who used the control intervention. The team also reported “a significant difference [i.e., improvement] on a general composite measure of cognition” for those in the AKL-T03 group compared with those in the control group, although this result might have been driven, the researchers noted, by the large improvement in the single area of sustained attention.

The AKL-T03 intervention did not show any advantage vs. placebo in helping participants with working memory, processing speed, task switching, or in their depressive symptoms.  Interestingly, subjects in the control group believed, after the trial’s conclusion, that they had improved cognitively more than they actually had, as measured by the researchers’ objective instruments.  This may have reflected the fact that the word game was more fun to play than the AKL-T03 video game.  In a separate commentary on the research appearing in the same journal, Philip Harvey, Ph.D., of the University of Miami, said “it might be important for digital training efforts to consider enjoyability” to achieve optimal results.  

Drs. Keefe, Etkin and colleagues acknowledged this possibility, noting in addition the possibility that “any engagement at all” with interventions like those they compared may be of real benefit to patients, and have the great advantage of being administered by patients in their own home environments using readily available technology and software. Future tests of this idea should seek data on how long any positive effects last, as well as the impact of any benefit upon real-world function, the team said.