Abstract
<jats:p>Resting-state functional MRI (rs-fMRI) studies in schizophrenia commonly rely on normalization to volumetric templates and fixed atlas parcellations derived from neurotypical populations. While these approaches enable group-level comparisons, they may obscure individual variation in cortical organization and intrinsic brain dynamics. In this study, we compared four preprocessing and parcellation strategies across two independent schizophrenia cohorts (MRI site 1, n=159; MRI site 2, n=255) to evaluate how analytic choices affect static functional connectivity and dynamic quasi-periodic pattern (QPP) measures, including default mode-dorsal attention network opposition, QPP component rank, explained variance, event rate, and associations with PANSS symptom severity. Across datasets, individualized surface-based parcellation (IndiPar) consistently detected more pronounced QPP dynamics, stronger default mode / dorsal attention network opposition, and greater explained variance of QPPs relative to atlas-based pipelines. IndiPar also produced larger and more reproducible patient-control differences in functional connectivity and QPP event-rate measures, suggesting improved sensitivity through preservation of subject-specific organization. IndiPar additionally detected a significantly increased QPP event rate and more symptom associations in patients in the larger dataset. However, associations between fMRI measures and symptom severity showed limited stability across cohorts. These findings extend previous reports of altered resting-state activity in schizophrenia, and demonstrate that preprocessing and parcellation choices substantially influence both static and dynamic rs-fMRI results. Individualized surface-based parcellation appears to better preserve subject-specific variability and improves detection of intrinsic brain dynamics. At the same time, the limited cross-dataset replication of symptom associations highlights the challenges of deriving stable brain-symptom relationships from heterogeneous psychiatric cohorts.</jats:p>