Detecting abnormal connectivity in schizophrenia via a joint directed acyclic graph estimation model.

Functional connectivity (FC) between brain region has been widely studied and linked with cognition and behavior of an individual. FC is usually defined as the correlation or partial correlation of fMRI blood oxygen level-dependent (BOLD) signals between two brain regions. Although FC has been effective to understand brain organization, it cannot reveal the direction of interactions. Many directed acyclic graph (DAG) based methods have been applied to study the directed interactions but their performance was limited by the small sample size while high dimensionality of the available data. By enforcing group regularization and utilizing samples from both case and control groups, we propose a joint DAG model to estimate the directed FC. We first demonstrate that the proposed model is efficient and accurate through a series of simulation studies. We then apply it to the case-control study of schizophrenia (SZ) with data collected from the MIND Clinical Imaging Consortium (MCIC). We have successfully identified decreased functional integration, disrupted hub structures and characteristic edges (CtEs) in SZ patients. Those findings have been confirmed by previous studies with some identified to be potential markers for SZ patients. A comparison of the results between the directed FC and undirected FC showed substantial differences in the selected features. In addition, we used the identified features based on directed FC for the classification of SZ patients and achieved better accuracy than using undirected FC or raw features, demonstrating the advantage of using directed FC for brain network analysis.