Working Memory Related Brain Network Connectivity in Individuals with Schizophrenia and Their Siblings

Grega Repovš,Deanna M Barch

doi:10.3389/fnhum.2012.00137

Abstract

A growing number of studies have reported altered functional connectivity in schizophrenia during putatively “task-free” states and during the performance of cognitive tasks. However, there have been few systematic examinations of functional connectivity in schizophrenia across rest and different task states to assess the degree to which altered functional connectivity reflects a stable characteristic or whether connectivity changes vary as a function of task demands. We assessed functional connectivity during rest and during three working memory loads of an N-back task (0-back, 1-back, 2-back) among: (1) individuals with schizophrenia (N = 19); (2) the siblings of individuals with schizophrenia (N = 28); (3) healthy controls (N = 10); and (4) the siblings of healthy controls (N = 17). We examined connectivity within and between four brain networks: (1) frontal–parietal (FP); (2) cingulo-opercular (CO); (3) cerebellar (CER); and (4) default mode (DMN). In terms of within-network connectivity, we found that connectivity within the DMN and FP increased significantly between resting state and 0-back, while connectivity within the CO and CER decreased significantly between resting state and 0-back. Additionally, we found that connectivity within both the DMN and FP was further modulated by memory load. In terms of between network connectivity, we found that the DMN became significantly more “anti-correlated” with the FP, CO, and CER networks during 0-back as compared to rest, and that connectivity between the FP and both CO and CER networks increased with memory load. Individuals with schizophrenia and their siblings showed consistent reductions in connectivity between both the FP and CO networks with the CER network, a finding that was similar in magnitude across rest and all levels of working memory load. These findings are consistent with the hypothesis that altered functional connectivity in schizophrenia reflects a stable characteristic that is present across cognitive states.

Highlights

A growing body of work focused on understanding the neurobiological bases of cognitive impairment in schizophrenia suggests that changes in the function of a single brain region, or even a brain system, cannot explain the functional impairments seen in this illness
We focused on working memory because of the consistent evidence for impairment in this cognitive domain in schizophrenia (Forbes et al, 2009), the fact that the largest number of task-based connectivity studies in schizophrenia have focused on working memory, and due to existing previous work in healthy individuals examining connectivity changes as a function of memory load during working memory
The goal of the current study was to examine the degree to which changes in functional connectivity in schizophrenia were dependent on the cognitive state of the individual as a means to shed light on the potential mechanisms leading to altered functional connectivity in this illness

Summary

Introduction

A growing body of work focused on understanding the neurobiological bases of cognitive impairment in schizophrenia suggests that changes in the function of a single brain region, or even a brain system, cannot explain the functional impairments seen in this illness. Research has increasingly focused on understanding the integrity of neural circuits that work together to support sensory, cognitive, and emotional processes (Calhoun et al, 2009). This approach to understanding schizophrenia is consistent with the hypothesis that this illness reflects a “dysconnection” syndrome (Stephan et al, 2009). Much of this work has focused on examining different aspects of functional brain connectivity, either when the individual is at rest, or when the individual is performing a specific task (e.g., working memory) Both types of studies have provided robust evidence for altered functional connectivity in schizophrenia (Brown and Thompson, 2010). The goal of the current study was to examine functional brain connectivity in known neural networks during rest and during different working memory loads in individuals with schizophrenia, their siblings, and healthy controls

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