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

DiFrancesco MW, Gitelman DR, Klein-Gitelman MS, Sagcal-Gironella AC, Zelko F, Beebe D, Parrish T, Hummel J, Ying J, Brunner HI - Arthritis Res. Ther. (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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Voxel-wise differences in functional neural network activations during functional magnetic resonance imaging. Differences in neuronal network activation between participants with neurocognitive dysfunction (NCD) (NCD-group; n = 7) and participants without NCD (noNCD-group; n = 14) are depicted. The clusters shown reflect differences between groups of participants at an uncorrected P-value < 0.005 and cluster size threshold of 40 voxels. Neurological convention of image orientation is used. (A) Clusters in which the noNCD-group activated more strongly than the NCD-group for the N-Back working memory paradigm. (B) Continuous performance task-identical pairs (CPT-IP) (attention) displays clusters with the NCD-group activating more strongly than the no-NCD-group. Visuoconstructional ability (VCA) task differential activations with the noNCD-group showing more activation than the NCD-group for (C) the square completion (SC) vs. motor and (D) the matching vs. motor contrasts.
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Figure 2: Voxel-wise differences in functional neural network activations during functional magnetic resonance imaging. Differences in neuronal network activation between participants with neurocognitive dysfunction (NCD) (NCD-group; n = 7) and participants without NCD (noNCD-group; n = 14) are depicted. The clusters shown reflect differences between groups of participants at an uncorrected P-value < 0.005 and cluster size threshold of 40 voxels. Neurological convention of image orientation is used. (A) Clusters in which the noNCD-group activated more strongly than the NCD-group for the N-Back working memory paradigm. (B) Continuous performance task-identical pairs (CPT-IP) (attention) displays clusters with the NCD-group activating more strongly than the no-NCD-group. Visuoconstructional ability (VCA) task differential activations with the noNCD-group showing more activation than the NCD-group for (C) the square completion (SC) vs. motor and (D) the matching vs. motor contrasts.

Mentions: T-maps of differences in activation between the NCD-group and the noNCD-group for the three paradigms are displayed in Figure 2 at nominal thresholds of P < 0.005, uncorrected for multiple comparisons, and a voxel cluster size > 40. The working-memory task produced differences in a cluster of voxels located in the precuneus, extending into the inferior parietal regions, for which the noNCD-group had significantly more brain activation than the NCD-group (P < 0.05 for the entire cluster, after correction for multiple comparisons between groups). The VCA paradigm also produced stronger activation in the noNCD-group compared to the NCD-group, with significant clusters (corrected cluster P-value < 0.05) in the precuneus and right occipital regions for the matching vs. motor contrast of the VCA paradigm. There were also trends in differential brain activation in the basal ganglia between groups for the square completion vs. motor contrast. The square completion vs. matching contrast failed to show activation at the uncorrected P < 0.005 threshold for individual voxels. While the NCD-group exhibited lower brain activation during the working memory and VCA fMRI tasks than the noNCD-group in relevant brain regions, there was a trend toward greater brain activity in the frontal lobe regions in the NCD-group than in the noNCD-group during the CPT-IP attention task.


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

DiFrancesco MW, Gitelman DR, Klein-Gitelman MS, Sagcal-Gironella AC, Zelko F, Beebe D, Parrish T, Hummel J, Ying J, Brunner HI - Arthritis Res. Ther. (2013)

Voxel-wise differences in functional neural network activations during functional magnetic resonance imaging. Differences in neuronal network activation between participants with neurocognitive dysfunction (NCD) (NCD-group; n = 7) and participants without NCD (noNCD-group; n = 14) are depicted. The clusters shown reflect differences between groups of participants at an uncorrected P-value < 0.005 and cluster size threshold of 40 voxels. Neurological convention of image orientation is used. (A) Clusters in which the noNCD-group activated more strongly than the NCD-group for the N-Back working memory paradigm. (B) Continuous performance task-identical pairs (CPT-IP) (attention) displays clusters with the NCD-group activating more strongly than the no-NCD-group. Visuoconstructional ability (VCA) task differential activations with the noNCD-group showing more activation than the NCD-group for (C) the square completion (SC) vs. motor and (D) the matching vs. motor contrasts.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672728&req=5

Figure 2: Voxel-wise differences in functional neural network activations during functional magnetic resonance imaging. Differences in neuronal network activation between participants with neurocognitive dysfunction (NCD) (NCD-group; n = 7) and participants without NCD (noNCD-group; n = 14) are depicted. The clusters shown reflect differences between groups of participants at an uncorrected P-value < 0.005 and cluster size threshold of 40 voxels. Neurological convention of image orientation is used. (A) Clusters in which the noNCD-group activated more strongly than the NCD-group for the N-Back working memory paradigm. (B) Continuous performance task-identical pairs (CPT-IP) (attention) displays clusters with the NCD-group activating more strongly than the no-NCD-group. Visuoconstructional ability (VCA) task differential activations with the noNCD-group showing more activation than the NCD-group for (C) the square completion (SC) vs. motor and (D) the matching vs. motor contrasts.
Mentions: T-maps of differences in activation between the NCD-group and the noNCD-group for the three paradigms are displayed in Figure 2 at nominal thresholds of P < 0.005, uncorrected for multiple comparisons, and a voxel cluster size > 40. The working-memory task produced differences in a cluster of voxels located in the precuneus, extending into the inferior parietal regions, for which the noNCD-group had significantly more brain activation than the NCD-group (P < 0.05 for the entire cluster, after correction for multiple comparisons between groups). The VCA paradigm also produced stronger activation in the noNCD-group compared to the NCD-group, with significant clusters (corrected cluster P-value < 0.05) in the precuneus and right occipital regions for the matching vs. motor contrast of the VCA paradigm. There were also trends in differential brain activation in the basal ganglia between groups for the square completion vs. motor contrast. The square completion vs. matching contrast failed to show activation at the uncorrected P < 0.005 threshold for individual voxels. While the NCD-group exhibited lower brain activation during the working memory and VCA fMRI tasks than the noNCD-group in relevant brain regions, there was a trend toward greater brain activity in the frontal lobe regions in the NCD-group than in the noNCD-group during the CPT-IP attention task.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

Show MeSH
Related in: MedlinePlus