Joint analysis of area and thickness as a replacement for the analysis of cortical volume

A detailed investigation of the surface-based methods for assessment of cortical volume and area from magnetic resonance images shows that volume mostly mirrors variability in surface area, while having little sensitivity to cortical thickness, and this remains the case even when volume is assessed using an improved analytic method. Using data from young adults born with very low birth weight and coetaneous controls, it is demonstrated that the permutation-based non-parametric combination (NPC) of thickness and area is more sensitive than volume for studying joint effects on these two quantities, giving equal weight to variation in both. NPC can replace current analyses of cortical volume altogether, allowing a better characterisation of processes that can concomitantly influence brain anatomy, even when their effects are in opposite directions. The method is remarkably general and can be extended to other indices of brain structure and function.