Maximizing dissimilarity in resting state detects heterogeneous subtypes in healthy population associated with high substance use and problems in antisocial personality

Abstract

Patterns in resting-state fMRI (rs-fMRI) are widely used to characterize the trait effects of brain function. In this aspect, multiple rs-fMRI scans from single subjects can provide interesting clues about the rs-fMRI patterns, though scan-to-scan variability pose challenges. Therefore, rs-fMRI's are either concatenated or the functional connectivity is averaged. This leads to loss of information. Here, we use an alternative way to extract the rs-fMRI features that are common across all the scans by applying common-and-orthogonal-basis-extraction (COBE) technique. To address this, we employed rs-fMRI of 788 subjects from the human connectome project and estimated the common-COBE-component of each subject from the four rs-fMRI runs. Since the common-COBE-component is specific to a subject, the pattern was used to classify the subjects based on the similarity/dissimilarity of the features. The subset of subjects (n = 107) with maximal-COBE-dissimilarity (MCD) was extracted and the remaining subjects (n = 681) formed the COBE-similarity (CS) group. The distribution of weights of the common-COBE-component for the two groups across rs-fMRI networks and subcortical regions was evaluated. We found the weights in the default mode network to be lower in the MCD compared to the CS. We compared the scores of 69 behavioral measures and found six behaviors related to the use of marijuana, illicit drugs, alcohol, and tobacco; and including a measure of antisocial personality to differentiate the two groups. Gender differences were also significant. Altogether the findings suggested that subtypes exist even in healthy control population, and comparison studies (case vs. control) need to be mindful of it.