TY - JOUR
T1 - Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus
AU - DiFrancesco, Mark W.
AU - Gitelman, Darren R.
AU - Klein-Gitelman, Marisa S.
AU - Sagcal-Gironella, Anna Carmela P.
AU - Zelko, Frank
AU - Beebe, Dean
AU - Parrish, Todd
AU - Hummel, Jessica
AU - Ying, Jun
AU - Brunner, Hermine I.
N1 - Funding Information:
This study is supported by the NIAMS Clinical Research Center P60-AR047884. This publication was also supported by an Institutional Clinical and Translational Science Award, NIH/NCRR Grant Number 5UL1RR026314-03. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This study would not have been possible without the dedicated clinical research personnel, namely Aimee Baker, Blair Dina, Adlin Cedeno, Jessica Sage, Shannen Nelson, Erin Thomas, and Aisha Ali. We thank Drs Megan Curran, Jennifer Huggins, Esi Morgan-DeWitt, Dan Lovell, Alexei Grom, Tracy Ting, Michael Henrickson, and PNP Janalee Taylor for providing us with access to their patients with cSLE. We would also like to thank Meredith Amaya, April German, Allison Clarke, Kate Dahl, Antoinette Dezzutti, Lev Gottlieb, Jennifer Heil, Jennifer Keller, Andrew Phillips, Michal Rischall, Rebecca Wasserman Lieb, Lisa Welcome, Donna Diedenhofer, Cindy Scharf and Mariah Wells for their assistance with neuropsychological testing. We are indebted to the children and adolescents with cSLE and their parents for participating in this study. The assistance of Azmi Banibaker for scanning the subjects at the Northwester site is greatly appreciated.
PY - 2013/3/7
Y1 - 2013/3/7
N2 - 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.
AB - 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.
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U2 - 10.1186/ar4197
DO - 10.1186/ar4197
M3 - Article
C2 - 23497727
AN - SCOPUS:84874591381
VL - 15
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
SN - 1478-6354
IS - 2
M1 - R40
ER -