The effect of using group-averaged or individualized brain parcellations when investigating connectome dysfunction: A case study in psychosis

Functional magnetic resonance imaging (fMRI) is widely used to investigate functional coupling (FC) disturbances in a range of clinical disorders. Most analyses performed to date have used group-based parcellations for defining regions of interest (ROIs), in which a single parcellation is applied to each brain. This approach neglects individual differences in brain functional organization and may inaccurately delineate the true borders of functional regions. These inaccuracies could inflate or under-estimate group differences in case-control analyses. We investigated how individual differences in brain organization influence group comparisons of FC using psychosis as a case-study, drawing on fMRI data in 121 early psychosis patients and 57 controls. We defined FC networks using either a group-based parcellation or an individually-tailored variant of the same parcellation. Individualized parcellations yielded more functionally homogeneous ROIs than group-based parcellations. At individual connections level, case-control FC differences were widespread, but the group-based parcellation identified approximately 9% more connections as dysfunctional than the individualized parcellation. When considering differences at the level of functional networks, the results from both parcellations converged. Our results suggest that a substantial fraction of dysconnectivity previously observed in psychosis can be attributed to erroneous ROI delineation, rather than a pathophysiological process related to psychosis.