Weak brain-mental health associations in population neuroimaging tasks reflect a signal evocation bottleneck

Large-scale neuroimaging studies best powered to investigate mental health biomarkers continue to administer a set of in-scanner tasks that, to date, yield weak brain-mental health associations. Triangulating the source of these weak associations is critical to directing the focus of future work. Using these tasks strong brain-cognition associations as a positive control, we analyzed potential sources of weak brain-mental health associations across five popular fMRI tasks and dozens of task-evoked brain networks. Across tasks and networks, latent mental health factors showed substantially weaker brain associations than cognition despite comparable measurement reliability and greater interindividual variability. Moreover, increasing brain-feature dimensionality improved cognitive but not mental health signal, and task-evoked network profiles were 1.8-2.3 times more homogeneous and 3.5 times lower-dimensional than mental health profiles. Findings implicate a signal evocation bottleneck: common fMRI tasks elicit little interindividual variation in mental health-related brain activity relative to the diversity of mental health itself. Overall, these findings motivate a shift in focus to the development and use of tasks in large-scale studies more explicitly designed to evoke mental health-relevant brain activity. Significance StatementIdentification of robust individual-specific mental health-related brain signals from fMRI remains elusive, limiting the clinical utility of brain imaging. To investigate why, we systematically evaluated brain signals evoked by tasks used by the Human Connectome Project-Young Adult study, which are now commonly included in many large-scale neuroimaging studies. Our findings suggest that, more so than analytical or measurement constraints on detecting these signals, a primary limitation is a failure of these prevalent fMRI tasks to evoke mental health-relevant brain signals in the first place. These findings suggest that progress in psychiatric neuroimaging may require tasks more explicitly designed to evoke mental health-relevant brain activity.