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.
Bibliographical noteFunding Information:
This research is supported by the Brain and Behavior Research Foundation Young Investigator Award grants (NARSAD: 17680 and 28188), and NIMH K01 grant (K01MH105615) and R01 grants (R01MH122897) to K.S., as well as an NIMH R01 grant (R01MH82818) to S.V. We are also thankful to Brain and Behavior Research Foundation for supporting work of L.K.-I. through Young Investigator Award No. 28474.
© 2021, The Author(s).