A digital intervention targeting cognitive control network dysfunction in middle age and older adults with major depression.

Nonpharmacological interventions targeting putative network mechanisms of major depressive disorder (MDD) may represent novel treatments. This mechanistic study investigates how a video game-like intervention, designed to improve cognitive control network (CCN) functioning by targeting multitasking, influences the CCN of middle-aged and older adults with MDD. The sample consisted of 34 adults aged 45-75 with SCID-defined diagnosis of MDD, Hamilton depression rating scale scores ≥20, and a deficit in cognitive control. Participants were instructed to play at home for 20-25 min per day, at least 5 times per week, for 4 weeks. Evidence of target engagement was defined a priori as >2/3 of participants showing CCN improvement. CCN engagement was defined as a change in a Z score of ≥0.5 on functional magnetic resonance imaging (fMRI) in activation and functional connectivity of the CCN during task-based and resting-state fMRI, respectively. 74% of participants showed a change in activation of the CCN, and 72% showed an increase in resting-state functional connectivity. Sixty-eight percent demonstrated improved cognitive control function, measured as either improvement on sustained attention or working memory performance or reduced self-reported symptoms of apathy on the frontal systems behavioral scale (FrsBe). Participants also reported a significant reduction in mood symptoms measured by PHQ-9. A remotely deployed neuroscience-informed video game-like intervention improves both CCN functions and mood in middle-aged and older adults with MDD. This easily-disseminated intervention may rescue CCN dysfunction present in a substantial subset of middle-aged and older adults with MDD.