The influence of sulcal variability on morphometry of the human anterior cingulate and paracingulate cortex

Human anterior cingulate (ACC) and paracingulate (PaC) cortices play an important role in cognitive and affective regulation and have been implicated in numerous psychiatric and neurological conditions. The region they comprise displays marked inter-individual variability in sulcal and gyral architecture, and although recent evidence suggests that this variability has functional significance, it is often ignored in automated and region-of-interest (ROI) morphometric investigations. This has lead to confounded interpretation of results and inconsistent findings across a number of studies and in a variety of clinical populations. In this paper, we present a reliable method for parcellating the dorsal, ventral, and subcallosal ACC and PaC that accounts for individual variation in the local cortical folding pattern. We also investigated the effect of one well characterized morphological variation, the incidence of the paracingulate sulcus (PCS), on regional volumes in 24 (12 male, 12 female) healthy participants. The presence of a PCS was shown to affect both ACC and PaC volumes, such that it was associated with an 88% increase in paracingulate cortex and a concomitant 39% decrease in cingulate cortex. These findings illustrate the potential confounds inherent in morphometric approaches that ignore or attempt to minimize inter-individual variations in sulcal and gyral anatomy and underscore the need to consider this variability when attempting to understand disease processes or characterize brain structure-function relationships.