Morphological bias of the MNI152 brain

The MNI152 template is widely treated as a representative average brain in neuroimaging, computational modeling, and neuromodulation research, yet its fidelity to true population morphology has not been systematically evaluated. In this study, we compared the MNI152 template to 430 individual MRI scans from a publicly available dataset spanning Asian, Black, and White participants. We additionally compared the MNI152 template with the independently developed US200 template, which was generated using a modern diffeomorphic template-building framework, to assess whether a contemporary template better represents human brain morphology. We conducted affine registrations and deformation-based morphometry to detect and quantify gross morphological differences as well as local voxel-level deformations. The MNI152 template consistently required consistent global contraction, and its Jacobian fields revealed spatially heterogeneous deformations, indicating systematic mismatches in both size and shape. In contrast, the US200 template showed mean scaling and deformation values near 1.0, reflecting closer correspondence to real human anatomy. These findings suggest that the MNI152 template is less representative of the morphology of this study population than the US200 template and that linear registration alone cannot eliminate these systematic differences. Reliance on MNI152 may therefore introduce anatomical bias in applications requiring high morphological fidelity. These results further support continued development of modern, unbiased, and potentially demographic-specific templates.