The Efficacy of Combining Cognitive Training and Non-Invasive Brain Stimulation: A Transdiagnostic Systematic Review and Meta-Analysis.

Over the past decade, an increasing number of studies investigated the innovative approach of supplementing cognitive training (CT) with non-invasive brain stimulation (NIBS) to increase the effects on outcomes. In this review, we aim to summarize the evidence for this treatment combination. We identified 72 published and unpublished studies (reporting 773 effect sizes) including 2518 participants from healthy and clinical populations indexed in PubMed, Medline, PsycINFO, ProQuest, Web of Science, and ClinicalTrials.gov (last search: 8/8/2022) that compared the effects of NIBS combined with CT on cognitive, symptoms and everyday functioning to CT alone at post-intervention and/or follow-up. We performed random-effects meta-analyses with robust variance estimation and assessed risk of bias with the Cochrane R.O.B. tool. Only four studies had low risk of bias in all domains, and many studies lacked standard controls such as keeping the outcome assessor and trainer unaware of the treatment condition. Following sensitivity analyses, only learning/memory robustly improved significantly more when CT was combined with NIBS compared to CT only (g = 0.18, 95% CI [0.07, 0.29]) at post-intervention, but not in the long-term. The effect was small and limited by substantial heterogeneity. The other seven cognitive outcome domains, symptoms, and everyday functioning did not benefit from adding NIBS to CT. Given the methodological limitation of prior studies, more high-quality trials that focus on the potential of combining NIBS and CT to enhance benefits in everyday functioning in the short- and long-term are needed to evaluate whether combining NIBS and CT is relevant for clinical practice.