To modulate or not to modulate: differing results in uniquely shaped Williams syndrome brains

Voxel based morphometry (VBM) studies of Williams syndrome (WS) have demonstrated remarkably consistent findings of reduced posterior parietal gray matter compared to typical controls. Other WS VBM findings have been inconsistent, however. In particular, different findings have been reported for hypothalamus and orbitofrontal gray matter regions. We examined a sample of 8 WS and 9 control adults and show that the hypothalamus and orbitofrontal cortex results depend on whether the images undergo Jacobian modulation. Deformation based morphometry (DBM) analysis demonstrated that major brain shape differences between the groups accounted for the Jacobian modulated gray matter findings. These results indicate that cautious interpretations of modulated gray matter findings are warranted when there are gross shape and size differences between experimental groups. This study demonstrates the importance of methodological choices towards understanding a disorder like WS, but also highlights the consistency of parietal lobe, orbitofrontal, and midbrain findings for this disorder across methodologies, participants, and research groups.