Differences in regional brain activation patterns assessed by functional magnetic resonance imaging in patients with systemic lupus erythematosus stratified by disease duration

Abstract

The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.

Figure 1

Composite activation areas. (A) A composite of activation areas with a minimum size of 10 voxels from all subjects during the two shapes retention phase of the working memory paradigm. Areas with increased activation include BA40 (supramarginal gyrus, parietal lobe), somatomotor cortex, cingulated gyrus, BA9 (granular/prefrontal area), BA22 (superior temporal; auditory) and BA17 (occipital; visual). (B) A composite of activation areas from all subjects during unmasked (conscious) stimulus with fearful and neutral faces.

Figure 2

Group differences during the working memory task. Significant group differences in regional brain activation outside the hippocampus during two figure retention in the working memory paradigm shows increased activation in ST subjects compared to LT subjects in the somatomotor cortex, BA40, cingulated gyrus and prefrontal cortex (P < 0.001). The coordinates and voxel sizes of these clusters are listed in Table 2.

Figure 3

Group differences during the fearful faces paradigm. Significant group differences (P < 0.05) during conscious stimulation with fearful and neutral faces during the fearful faces paradigm shows increased activation in ST subjects compared to LT subjects in the amygdala and BA7 (superior parietal lobe). The coordinates and voxel sizes of these clusters are listed in Table 3.