Exploring the influence of functional architecture on cortical thickness networks in early psychosis-A longitudinal study

Cortical thickness reductions differ between individuals with psychotic disorders and comparison subjects even in early stages of illness. Whether these reductions covary as expected by functional network membership or simply by spatial proximity has not been fully elucidated. Through orthonormal projective non-negative matrix factorization, cortical thickness measurements in functionally-annotated regions from MRI scans of early-stage psychosis and matched healthy controls were reduced in dimensionality into features capturing positive covari-ance. Rather than matching the functional networks, the covarying regions in each feature displayed a more localized spatial organization. With Bayesian belief networks, the covarying regions per feature were arranged into a network topology to visualize the dependency structure and identify key driving regions. The features demonstrated diagnosis-specific differences in cortical thickness distributions per feature, identifying reduction-vulnerable spatial regions. Differences in key cortical thickness features between psychosis and control groups were delineated, as well as those between affective and non-affective psychosis. Clustering of the participants, stratified by diagnosis and clinical variables, characterized the clinical traits that define the cortical thickness pat-terns. Longitudinal follow-up revealed that in select clusters with low baseline cortical thickness, clinical traits improved over time. Our study represents a novel effort to characterize brain structure in relation to functional networks in healthy and clinical populations and to map patterns of cortical thickness alterations among ESP patients onto clinical variables for a better understanding of brain pathophysiology.