Impaired decision-making and functional neuronal network activity in systemic lupus erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) is associated with cognitive deficit but the exact neural mechanisms remain unclear.

Purpose: To explore sequential brain activities using functional magnetic resonance imaging (fMRI) during the performance of a decision-making task, and to determine whether serum or clinical markers can reflect the involvement of the brain in SLE.

Subjects: Sixteen female SLE patients without overt clinical neuropsychiatric symptoms and 16 healthy controls were included.

Field strength/sequence: 1.5T, T₁ -weighted anatomic images, gradient-echo echo-planar imaging sequence, and 3D images.

Assessment: The computer-based Iowa Gambling Task (IGT) for assessing decision-making was performed by SLE patients and 16 matched controls; brain activity was recorded via blood oxygen level-dependent (BOLD) fMRI. The amplitudes of the average BOLD responses were calculated for each individual subject, and activation data from fMRI experiments were compared between the two groups.

Statistical tests: Two-sample t-test; repeated-measures analysis of variance (ANOVA); linear regression analyses.

Results: Imaging revealed activity in a distributed network of brain regions in both groups, including the ventromedial prefrontal cortex (vmPFC), the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC), the posterior cingulate cortex (PCC), and the striatum, as well as the insular, parietal, and occipital cortices. Compared to controls, SLE patients showed lower activation in a convergence zone and the limbic system, namely, the OFC, vmPFC, ACC, and PCC, but greater activation in memory, emotion, and behavior systems involving the dlPFC, the insular cortex and the striatum. Furthermore, brain activation in the vmPFC was positively correlated with IGT scores (r = 0.63, P < 0.001), but inversely related to disease activity (r = -0.57, P < 0.01).

Data conclusion: The dynamics among the aforementioned neural systems (some hyperfunctioning, others hypofunctioning) may shed some light on the pathologic mechanisms underlying SLE without overt clinical neuropsychiatric symptoms. In addition, disease activity may potentially be used as an effective biomarker reflecting cerebral involvement in SLE.

Level of evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;48:1508-1517.

Keywords: Iowa Gambling Task; cognitive deficit; decision-making; functional imaging; systemic lupus erythematosus.

Figure 1

An illustration of the experimental tasks. Each run contained five blocks of the IGT (blue) and five blocks of the control task (gray). Each trial lasted 6 seconds. In the IGT task, an ongoing monetary score showed on the upper right‐hand side of the screen across all the trials.

Figure 2

Performance on the IGT between groups. (a) Performance differences between SLE and controls on the IGT, based on the mean performance scores (net score = number of cards from the advantage decks minus number of cards from the disadvantage decks). (b) IGT performance over time in SLE and controls across five blocks expressed as mean (SE) (*P < 0.01; **P < 0.001).

Figure 3

Whole‐brain analysis of task‐related brain activity during decision‐making (IGT‐control task). T‐statistic maps of healthy control subjects (a) and SLE patients (b). Red/yellow areas indicate activation; green/blue areas indicate deactivation. R: right hemisphere; L: left hemisphere; F1: ventromedial prefrontal cortex; F2: orbitofrontal cortex; F3: dorsolateral prefrontal cortex; AC: anterior cingulate; PC: posterior cingulate; S: striatum; I: insular; PL: parietal lobe; OL: occipital lobe.

Figure 4

Functional correlation. Regions in the vmPFC were positively correlated with IGT scores but inversely related to disease activity (a). Scatterplots of correlations between IGT scores and percentage BOLD signal change in the vmPFC (b). Scatterplots of correlations between disease activity and percentage BOLD signal change in the vmPFC (c) (*P < 0.01; **P < 0.001).