Open Access Research article

Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus

Mark W DiFrancesco1*, Darren R Gitelman23, Marisa S Klein-Gitelman4, Anna Carmela P Sagcal-Gironella5, Frank Zelko6, Dean Beebe7, Todd Parrish3, Jessica Hummel5, Jun Ying8 and Hermine I Brunner5

Author affiliations

1 Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center (CCHMC), 3333 Burnet Ave., Cincinnati, OH 45229, USA

2 Department of Neurology, Feinberg School of Medicine, Northwestern University, 420 East Superior St., Chicago, IL 60611, USA

3 Department of Radiology, Feinberg School of Medicine, Northwestern University, 420 East Superior St., Chicago, IL 60611, USA

4 Division of Rheumatology, Ann & Robert Lurie Children's Hospital, Feinberg School of Medicine, Northwestern University, 420 East Superior St., Chicago, IL 60611, USA

5 Division of Rheumatology, Cincinnati Children's Hospital Medical Center (CCHMC), 3333 Burnet Ave., Cincinnati, OH 45229, USA

6 Department of Child and Adolescent Psychiatry, Ann & Robert Lurie Children's Hospital, Feinberg School of Medicine, Northwestern University, 420 East Superior St., Chicago, IL 60611, USA

7 Division of Behavioral Medicine and Child Psychology, Cincinnati Children's Hospital Medical Center (CCHMC), 3333 Burnet Ave., Cincinnati, OH 45229, USA

8 Department of Public Health, University of Cincinnati, 2600 Clifton Ave., Cincinnati, OH 45221, USA

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Citation and License

Arthritis Research & Therapy 2013, 15:R40  doi:10.1186/ar4197

Published: 7 March 2013

Abstract

Introduction

Neuropsychiatric manifestations are common in childhood-onset systemic lupus erythematosus (cSLE) and often include neurocognitive dysfunction (NCD). Functional magnetic resonance imaging (fMRI) can measure brain activation during tasks that invoke domains of cognitive function impaired by cSLE. This study investigates specific changes in brain function attributable to NCD in cSLE that have potential to serve as imaging biomarkers.

Methods

Formal neuropsychological testing was done to measure cognitive ability and to identify NCD. Participants performed fMRI tasks probing three cognitive domains impacted by cSLE: visuoconstructional ability (VCA), working memory, and attention. Imaging data, collected on 3-Tesla scanners, included a high-resolution T1-weighted anatomic reference image followed by a T2*-weighted whole-brain echo planar image series for each fMRI task. Brain activation using blood oxygenation level-dependent contrast was compared between cSLE patients with NCD (NCD-group, n = 7) vs. without NCD (noNCD-group, n = 14) using voxel-wise and region of interest-based analyses. The relationship of brain activation during fMRI tasks and performance in formal neuropsychological testing was assessed.

Results

Greater brain activation was observed in the noNCD-group vs. NCD-group during VCA and working memory fMRI tasks. Conversely, compared to the noNCD-group, the NCD-group showed more brain activation during the attention fMRI task. In region of interest analysis, brain activity during VCA and working memory fMRI tasks was positively associated with the participants' neuropsychological test performance. In contrast, brain activation during the attention fMRI task was negatively correlated with neuropsychological test performance. While the NCD group performed worse than the noNCD group during VCA and working memory tasks, the attention task was performed equally well by both groups.

Conclusions

NCD in patients with cSLE is characterized by differential activation of functional neuronal networks during fMRI tasks probing working memory, VCA, and attention. Results suggest a compensatory mechanism allows maintenance of attentional performance under NCD. This mechanism appears to break down for the VCA and working memory challenges presented in this study. The observation that neuronal network activation is related to the formal neuropsychological testing performance makes fMRI a candidate imaging biomarker for cSLE-associated NCD.