Background Cognitive dysfunction (CD) has been reported to affect up to 80% of systemic lupus erythematosus (SLE) patients. The cause of CD in SLE is unclear and studies examining structural brain abnormalities have been inconclusive. Functional magnetic resonance imaging (fMRI) is well used in other diseases and is now starting to be used in SLE. Preliminary studies have suggested that patients employ compensatory brain mechanisms to maintain adequate cognitive function but many questions remain unanswered.
Objectives Our study aims to examine the effects of disease activity in SLE on CD using fMRI, also considering potential confounding factors such as depression and medication.
Methods 32 SLE participants (11 with active disease, SLE-F, and 21 stable, SLE-S) and 30 healthy controls (HC) undertook a working memory task (n-back) and a facial emotional recognition task (FERT) during fMRI. The n-back task had three levels (0-, 1- and 2-back) with the 2-back level being the most difficult. The FERT displayed faces expressing different emotions: happiness, sadness, fear and neutral. fMRI responses to both tasks were analysed using SPM12, the n-back using a cluster significance threshold of p<0.05 familywise error corrected and the FERT using a region of interest approach focusing on the amygdala. Demographic, mood and disease variables were analysed using SPSS 22.
Results The three groups were matched on age, sex and handedness but varied on IQ and mood scores. The two SLE groups were well-matched on disease characteristics except, as expected, on the measure of current disease activity (SLEDAI) (p<0.001). During the n-back task, the SLE patients had an increased BOLD signal in lateral frontal areas compared to the HC group for the 2-back condition (p<0.05). This was more pronounced in the SLE-F group. Also, in the ventral anterior cingulate cortex (vACC), the SLE-S and HC groups had attenuated BOLD signals compared to the SLE-F group (p<0.05). For the FERT, there was a strong trend towards the SLE groups having a greater BOLD signal in the left amygdala compared to the HC group (p=0.07) (fig. 1).
Conclusions Our results in lateral frontal areas supported findings from previous studies that suggested SLE patients employ compensatory prefrontal mechanisms to maintain adequate cognitive function on effortful tasks. The vACC is part of a “default mode network”, putatively involved in reflective self-focused processing and typically suppressed during cognitive tasks. The inability of the SLE-F to suppress signal in this region may negatively impact their cognitive function by allowing self-reflective processes to interfere with performance. The trend towards an increased BOLD signal in the left amygdala for the SLE groups is similar to that seen in depressed patients, which suggests that low mood in SLE has detectable neuronal effects. Overall, these results indicate that regardless of current disease activity, SLE affects cognitive and emotional function at a neuronal level. Some effects are more pronounced in SLE-F patients, in particular inability to suppress self-reflective “default mode” processing while undertaking cognitive tasks.
Acknowledgement This study is funded by the NIHR Manchester BRU and an unrestricted research grant from Genzyme Sanofi.
Disclosure of Interest None declared