Robust hierarchically organized whole-brain patterns of dysconnectivity in schizophrenia spectrum disorders observed after Personalized Intrinsic Network Topography

Background Spatial patterns of brain functional connectivity can vary substantially at the individual level. Applying cortical surface-based approaches with individualized rather than group templates may accelerate the discovery of biological markers related to psychiatric disorders. We investigated cortico-subcortical networks from multi-cohort data in people with schizophrenia spectrum disorders (SSDs) and healthy controls using individualized connectivity profiles. Methods We utilized resting state and anatomical MRI data from n=406 participants (n = 203 SSD, n = 203 healthy controls) from four cohorts. For each participant, functional timeseries were extracted from 80 cortical regions of interest, representing 6 intrinsic networks using 1) a volume-based approach 2) a surface-based group atlas approach, and 3) Personalized Intrinsic Network Topography (PINT), a personalized surface-based approach (Dickie et al., 2018). Timeseries were also extracted from previously defined intrinsic network subregions of the striatum (Choi et al 2011), thalamus (Ji et al 2019), and cerebellum (Buckner et al 2011). Results Compared to a volume-based approach, the correlations between all cortical networks and the expected subregions of the striatum, cerebellum, and thalamus were increased using a surface-based approach (Cohen’s D volume vs surface 0.27-1.00, all p<10^-6) and further increased after PINT (Cohen’s D surface vs PINT 0.18-0.96, all p <10^-4). In SSD vs HC comparisons, controlling for age, sex, scanner and in-scanner motion, we observed robust patterns of dysconnectivity that were strengthened using a surface-based approach and PINT (Number of differing pairwise-correlations: volume: 357, surface: 562, PINT: 630, FDR corrected). These patterns were found from four different cortical networks – frontal-parietal, sensory-motor, visual, and default mode -- to subcortical regions. Conclusion Our results indicate that individualized approaches can more sensitively delineate cortical network dysconnectivity differences in people with SSDs. These robust patterns of dysconnectivity were visibly organized in accordance with the cortical hierarchy, as predicted by computational models (Murray et al 2019). Our results also change our understanding of the specific network-network functional connectivity alterations in people with SSDs, and the extent of those alterations. Future work will examine these new patterns of dysconnectivity with behaviour using dimensional models. Highlights - We evaluated the impact of cortical mapping method (volume-based, surface-based, vs surface personalized: PINT) on resting-state fMRI results in Schizophrenia Spectrum Disorders (SSD). - The use of surface-based approaches and PINT increased the connectivity of cortical networks with the expected subregions of the striatum, thalamus and cerebellum, in comparison to a volume-based approach - whole-brain case-control differences in functional connectivity were more pronounced after surface-based approach and PINT, in comparison to a volume-based approach