Multivariate pattern analysis of brain structure predicts functional outcome after auditory-based cognitive training interventions

Cognitive gains following cognitive training interventions are associated with improved functioning in people with schizophrenia (SCZ). However, considerable inter-individual variability is observed. Here, we evaluate the sensitivity of brain structural features to predict functional response to auditory-based cognitive training (ABCT) at a single-subject level. We employed whole-brain multivariate pattern analysis with support vector machine (SVM) modeling to identify gray matter (GM) patterns that predicted higher vs. lower functioning after 40 h of ABCT at the single-subject level in SCZ patients. The generalization capacity of the SVM model was evaluated by applying the original model through an out-of-sample cross-validation analysis to unseen SCZ patients from an independent validation sample who underwent 50 h of ABCT. The whole-brain GM volume-based pattern classification predicted higher vs. lower functioning at follow-up with a balanced accuracy (BAC) of 69.4% (sensitivity 72.2%, specificity 66.7%) as determined by nested cross-validation. The neuroanatomical model was generalizable to an independent cohort with a BAC of 62.1% (sensitivity 90.9%, specificity 33.3%). In particular, greater baseline GM volumes in regions within superior temporal gyrus, thalamus, anterior cingulate, and cerebellum predicted improved functioning at the single-subject level following ABCT in SCZ participants. The present findings provide a structural MRI fingerprint associated with preserved GM volumes at a single baseline timepoint, which predicted improved functioning following an ABCT intervention, and serve as a model for how to facilitate precision clinical therapies for SCZ based on imaging data, operating at the single-subject level.