Abstract

Voxel-based morphometry (VBM) studies have revealed gray matter alterations in smokers, but this type of analysis has poor predictive value for individual cases, which limits its applicability in clinical diagnoses and treatment. A predictive model would essentially embody a complex biomarker that could be used to evaluate treatment efficacy. In this study, we applied VBM along with a multivariate classification method consisting of a support vector machine with recursive feature elimination to discriminate smokers from nonsmokers using their structural MRI data. Mean gray matter volumes in 1,024 cerebral cortical regions of interest created using a subparcellated version of the Automated Anatomical Labeling template were calculated from 60 smokers and 60 nonsmokers, and served as input features to the classification procedure. The classifier achieved the highest accuracy of 69.6% when taking the 139 highest ranked features via 10-fold cross-validation. Critically, these features were later validated on an independent testing set that consisted of 28 smokers and 28 nonsmokers, yielding a 64.04% accuracy level (binomial P = 0.01). Following classification, exploratory post hoc regression analyses were performed, which revealed that gray matter volumes in the putamen, hippocampus, prefrontal cortex, cingulate cortex, caudate, thalamus, pre-/postcentral gyrus, precuneus, and the parahippocampal gyrus, were inversely related to smoking behavioral characteristics. These results not only indicate that smoking related gray matter alterations can provide predictive power for group membership, but also suggest that machine learning techniques can reveal underlying smoking-related neurobiology.

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