Hypothesis
Associations between individual differences in brain structure or function and cognitive or mental-health phenotypes can be reliably detected at the sample sizes typical of neuroimaging studies (median about 25).
What failed
Across three large datasets totalling roughly 50,000 individuals, brain-wide association effects were smaller than previously thought, leaving typical studies underpowered, with inflated effect sizes and replication failures. Replication rates improved and inflation fell only as samples reached the thousands.
Broken assumption
Sample sizes adequate for classical brain mapping are also adequate for brain–behaviour association studies.
Why
The authors attribute the failures to genuinely small brain–phenotype associations plus variability across population subsamples, and find more robust effects for functional than structural MRI, cognitive tests than mental-health questionnaires, and multivariate than univariate methods.
From the published paper: Marek et al. Nature, 2022. ↗CC BY