Hebrew University Studies Home-Based Brain Stimulation Plus Video Game Training for Depression

19 Oct Hebrew University Studies Home-Based Brain Stimulation Plus Video Game Training for Depression

Prof. Mor Nahum

MedicalResearch.com Interview with:

Prof. Mor Nahum PhD

Lab Director, Computerized Neurotherapy Lab

The School of Occupational Therapy, Faculty of Medicine, Hebrew University

MedicalResearch.com: What is the background for this study?

Response: Major depressive disorder is one of the leading contributors to the global burden of disease. While antidepressant medication and psychotherapy are effective for many patients, a substantial proportion do not respond adequately, experience side effects, or face barriers to accessing care. There is therefore a clear need for alternative and more accessible treatment options.

At the brain level, depression has been associated with reduced activity in prefrontal regions, particularly the left dorsolateral prefrontal cortex, and with disrupted function of the frontoparietal network that supports cognitive control. These alterations are thought to contribute both to the mood symptoms of depression and to the difficulties in attention, inhibition and flexible thinking that many patients experience. The rationale behind non-invasive brain stimulation is that restoring activity in these circuits may help alleviate symptoms.

Transcranial direct current stimulation (tDCS) is particularly appealing in this context because it is inexpensive, safe and portable enough to be used at home. However, when applied on its own, its antidepressant effects have been modest and inconsistent. Because the effects of stimulation are known to depend on the brain’s state at the time it is delivered, one promising strategy is to combine tDCS with a task that actively engages the targeted circuits. We therefore paired stimulation with a gamified cognitive control training program. It was designed to engage the same prefrontal and frontoparietal systems, and to do so in a way that is motivating enough to sustain at home over several weeks.

MedicalResearch.com: How was the study performed, and how did the stimulation work?

Response: The DiSCoVeR trial was a multicenter, double-blind, randomized controlled trial conducted at three university hospitals: Hadassah Medical Center in Jerusalem, LMU University Hospital in Munich, and Riga Stradins University in Latvia. A total of 109 adults with major depression were randomly assigned to one of two groups. Participants were asked to complete 30 sessions of 30 minutes each, on weekdays over six weeks. Treatment began with one to five supervised sessions at the clinic, after which participants continued at home under remote supervision by the study team.

For stimulation, participants wore a neoprene cap holding two sponge electrodes, with the anode over the left and the cathode over the right dorsolateral prefrontal cortex. The electrodes were connected to a home stimulation device. In the active condition, a weak current of 2 milliamps was delivered for 30 minutes, typically felt as no more than a mild tingling. To ensure consistent electrode placement across sessions, participants used dedicated software developed within our consortium. The video game was launched automatically together with the stimulation.

The active group received real stimulation while playing Legends of Hoa’Manu, a cognitive training game developed by the consortium. It integrates action video game mechanics with tasks targeting attention, inhibitory control, working memory and planning, and it adapts its difficulty to each player’s performance. The control group received sham stimulation, a brief current at the beginning and end of each session that mimics the sensation of active stimulation without delivering a meaningful dose. They played a game matched in visual style and structure but slower-paced and without the cognitive control demands. Neither the participants nor the clinicians assessing their symptoms knew which group they were in.

MedicalResearch.com: What are the main findings? Were there significant benefits or side effects?

Response: The primary aim of the study was to establish feasibility, and this was clearly achieved. In total, 79% of participants completed at least 20 of the 30 sessions, and almost 2,500 sessions were completed across the three countries. This demonstrates that a relatively complex home-based protocol can be carried out reliably by people with depression after only brief in-person instruction.

With regard to clinical outcomes, both groups showed a substantial reduction in depressive symptoms. On the Montgomery–Åsberg Depression Rating Scale, a standard clinician-rated measure, scores decreased by an average of 7.3 points in the active group and 8.2 points in the control group. The difference between the groups was small and not statistically significant. We therefore found no evidence that the combined treatment was more effective than the control condition, and the results were similar at follow-up four weeks after treatment ended.

We also asked participants to guess which treatment they were receiving. The control condition proved convincing: after the first week, nearly two-thirds of control participants believed they were receiving the active treatment, and by the end of treatment neither group guessed better than chance. Interestingly, participants who believed they were in the control group improved significantly less, regardless of which treatment they had actually received.

The treatment was generally well tolerated. Adverse events were reported at similar rates in both groups, and the most common were insomnia, headache, and burning or tingling sensations under the electrodes, which occurred in both the active and control groups. Two participants in the active group were hospitalized during the study, one for worsening depression and one for suicidal ideation; both events were judged unlikely to be related to the treatment. Notably, participants in the active group reported feeling more pressure and lower competence during the training, which may suggest that the cognitive demands of the game were relatively high for people experiencing depression.

MedicalResearch.com: What should readers take away from your report?

Response: First, home-based brain stimulation combined with a digital intervention is feasible and safe. Patients with depression can learn to use such a system after a few clinic visits and adhere to it over several weeks. This is an important step toward more accessible, home-based mental health care.

Second, this specific combination did not outperform a carefully matched control condition. It should therefore not be considered for routine clinical use in its current form. This does not mean that brain stimulation is ineffective for depression. It means that this particular protocol, with these parameters, did not provide added benefit.

Third, and to me the most thought-provoking finding, both groups improved considerably. We still have a great deal to learn about what actually drives improvement in depression: the neuromodulation, the cognitive training, expectations, engagement, ongoing clinical care, or simply the structure of returning to a treatment every day. The association between participants’ beliefs and their improvement should be interpreted with caution. It may reflect a genuine influence of expectations on outcomes, but it could equally indicate that participants who were not improving inferred that they had received the placebo. Our data cannot disentangle these explanations. Either way, the findings underscore how essential credible control conditions, and careful assessment of participants’ expectations, are when evaluating digital and device-based treatments.

MedicalResearch.com: What recommendations do you have for future research?

Response: Because we compared a “double-active” treatment with a “double-sham” control, we cannot separate the contributions of the stimulation and the cognitive training. We also cannot rule out that the two may have interfered with each other. A factorial design, testing each component alone and in combination, would address this directly.

In addition, our training combined several different cognitive tasks within each session. Stimulation may facilitate some cognitive processes while interfering with others, which could attenuate the overall effect. Future studies should therefore first pair tDCS with a single, well-defined cognitive process and carefully calibrate task difficulty, before combining multiple domains. Future work could also examine whether different stimulation parameters, treatment timing, patient groups or levels of clinical support lead to different results, and longer follow-up would help assess the durability of any effects. More broadly, the field needs a stronger mechanistic understanding of when and how stimulation and behavioral interventions interact, rather than assuming that combining two promising approaches will necessarily yield a stronger effect.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: This was a genuinely international collaboration, bringing together clinical teams at Hadassah Medical Center, LMU Munich and Riga Stradins University, technology development at the University of Geneva, EPFL and the Hebrew University, and coordination at the Hebrew University. I would like to thank the participants, who committed to six weeks of daily sessions while coping with depression, as well as the clinical and research teams at all sites.

The study was funded by the national partner organizations under the umbrella of the European ERA-NET NEURON program, including, in Israel, the Ministry of Health. In terms of disclosures, I am a co-inventor, together with colleagues at the University of Geneva, on a patent application for the Legends of Hoa’Manu game used in this study. I also hold a scientific advisory role with Effectivate Inc., which is unrelated to this work. Disclosures for the other authors are listed in the paper.

Information on depression and its treatment is available from the NIMH (National Institute of Mental Health).

For a broader overview of depression treatment research, see this MedicalResearch.com overview of mental health.

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Last Updated on October 19, 2026 by Marie Benz MD FAAD