Abstract

Identification of functionally connected regions while at rest has been at the forefront of research focusing on understanding interactions between different brain regions. Studies have utilized a variety of approaches including seed based as well as data-driven approaches to identifying such networks. Most such techniques involve differentiating groups based on group mean measures. There has been little work focused on differences in spatial characteristics of resting fMRI data. We present a method to identify between group differences in the variability in the cluster characteristics of network regions within components estimated via independent vector analysis (IVA). IVA is a blind source separation approach shown to perform well in capturing individual subject variability within a group model. We evaluate performance of the approach using simulations and then apply to a relatively large schizophrenia data set (82 schizophrenia patients and 89 healthy controls). We postulate, that group differences in the intra-network distributional characteristics of resting state network voxel intensities might indirectly capture important distinctions between the brain function of healthy and clinical populations. Results demonstrate that specific areas of the brain, superior, and middle temporal gyrus that are involved in language and recognition of emotions, show greater component level variance in amplitude weights for schizophrenia patients than healthy controls. Statistically significant correlation between component level spatial variance and component volume was observed in 19 of the 27 non-artifactual components implying an evident relationship between the two parameters. Additionally, the greater spread in the distance of the cluster peak of a component from the centroid in schizophrenia patients compared to healthy controls was observed for seven components. These results indicate that there is hidden potential in exploring variance and possibly higher-order measures in resting state networks to better understand diseases such as schizophrenia. It furthers comprehension of how spatial characteristics can highlight previously unexplored differences between populations such as schizophrenia patients and healthy controls.

Highlights

  • The human brain in a complex network of regions that are interconnected structurally and functionally

  • We introduce measures of spatial component level variability which through simulations allows us to identify one possible origin of variance in independent vector analysis (IVA) components in resting fMRI data that differentiate schizophrenia patients and healthy controls

  • Studies provide abundant evidence that IVA captures individual subject variability in spatial patterns and others substantiate this observation in simulations and in evaluating dynamic functional network connectivity patterns as well as in large datasets to differentiate schizophrenia patients from healthy controls (Ma et al, 2013, 2014; Michael et al, 2013, 2014; Gopal et al, 2016; Laney et al, 2015)

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Summary

Introduction

The human brain in a complex network of regions that are interconnected structurally and functionally. Interaction between the different regions of the brain and their functioning is known to impact cognition (Casey et al, 2000; Phan et al, 2002; Amodio and Frith, 2006) This has been the primary reason for the focus on examination of the behavior of functionally connected regions of the brain. Years of cyto-architechtonic, genetic, and environmental studies show that interaction between different brain regions is highly driven by inter-individual differences at the structural, cellular as well as functional levels These differences are known to result in cognitive differences manifesting as varied performance in cognitive activities and possibly as varied symptom expression in populations with neuropsychiatric disorders (Zilles and Amunts, 2010, 2013). Such inconsistency in the population characterized by disorders like schizophrenia makes looking at variability potentially meaningful

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