Learning stable and predictive network-based patterns of schizophrenia and its clinical symptoms

Schizophrenia is often associated with disrupted brain connectivity. However, identifying specific neuroimaging-based patterns pathognomonic for schizophrenia and related symptom severity remains a challenging open problem requiring large-scale data-driven analyses emphasizing not only statistical significance but also stability across multiple datasets, contexts and cohorts. Accurate prediction on previously unseen subjects, or generalization, is also essential for any useful biomarker of schizophrenia. In order to build a predictive model based on functional network feature patterns, we studied whole-brain fMRI functional networks, both at the voxel level and lower-resolution supervoxel level. Targeting Auditory Oddball task data on the FBIRN fMRI dataset (n = 95), we considered node-degree and link-weight network features and evaluated stability and generalization accuracy of statistically significant feature sets in discriminating patients vs. controls. We also applied sparse multivariate regression (elastic net) to whole-brain functional connectivity features, for the first time, to derive stable predictive features for symptom severity. Whole-brain link-weight features achieved 74% accuracy in identifying patients and were more stable than voxel-wise node-degrees. Link-weight features predicted severity of several negative and positive symptom scales, including inattentiveness and bizarre behavior. The most-significant, stable and discriminative functional connectivity changes involved increased correlations between thalamus and primary motor/primary sensory cortex, and between precuneus (BA7) and thalamus, putamen, and Brodmann areas BA9 and BA44. Precuneus, along with BA6 and primary sensory cortex, was also involved in predicting severity of several symptoms. Overall, the proposed multi-step methodology may help identify more reliable multivariate patterns allowing for accurate prediction of schizophrenia and its symptoms severity.Neuroimaging: Brain connectivity pattern predicts symptom severityBrain network analyses from functional magnetic resonance imaging (fMRI) data may help diagnose schizophrenia and predict symptom severity. Detecting neuroimaging patterns requires large-scale analysis across multiple data sets. Mina Gheiratmand and colleagues from the University of Alberta, along with researchers at the IBM T.J. Watson Research Center analyzed brain imaging data from the Function Biomedical Informatics Research Network, a study designed to test the reproducibility of brain scan results taken on different fMRI machines from people with schizophrenia and schizoaffective disorders, as well as healthy controls. They studied brain networks at different levels of resolution from data gathered while study participants conducted a common auditory test. The researchers showed that they could discriminate between patients with schizophrenia and controls with 74% accuracy across multiple neuroimaging sites using the strength of connection in a functional network. They observed the most robust and discriminative connectivity differences between the thalamus and primary motor and sensory cortices as well as between the precuneus and other brain regions. Moreover, they could determine symptom severity based on the connectivity changes involving these areas. This new approach towards finding objective, reliable neuroimaging biomarkers for schizophrenia and its severity could be used for diagnosis and to assess disease progression and therapeutic efficacy.