Abnormalities of Frontal-Parietal Resting-State Functional Connectivity Are Related to Disease Activity in Patients with Systemic Lupus Erythematosus

Abstract

Cerebral involvement is common in patients with systemic Lupus erythematosus (SLE) and is characterized by multiple clinical presentations, including cognitive disorders, headaches, and syncope. Several neuroimaging studies have demonstrated cerebral dysfunction during different tasks among SLE patients; however, there have been few studies designed to characterize network alterations or to identify clinical markers capable of reflecting the cerebral involvement in SLE patients. This study was designed to characterize the profile of the cerebral activation area and the functional connectivity of cognitive function in SLE patients by using a task-based and a resting state functional magnetic resonance imaging (fMRI) technique, and to determine whether or not any clinical biomarkers could serve as an indicator of cerebral involvement in this disease. The well-established cognitive function test (Paced Visual Serial Adding Test [PVSAT]) was used. Thirty SLE patients without neuropsychiatric symptoms and 25 age- and gender-matched healthy controls were examined using PVSAT task-based and resting state fMRI. Outside the scanner, the performance of patients and the healthy controls was similar. In the PVSAT task-based fMRI, patients presented significantly expanded areas of activation, and the activated areas exhibited significantly higher functional connectivity strength in patients in the resting state. A positive correlation existed between individual connectivity strength and disease activity scoring. No correlation with cerebral involvement existed for serum markers, such as C3, C4, and anti-dsDNA. Thus, our findings may shed new light on the pathologic mechanism underlying neuropsychiatric SLE, and suggests that disease activity may be a potential effective biomarker reflecting cerebral involvement in SLE.

Altered functional neuronal activity in neuropsychiatric lupus: A systematic review of the fMRI investigations

“…A summary of the studies (13)(14)(15)(16)(17)(18)(19)(20)(21)(22) is depicted in Table 1. The largest original study contained 31 participants with SLE, whilst the smallest included 9 patients.…”

“…Disease activity and SLE damage index were obtained using SLE disease activity index (SLEDAI) (23), and systemic lupus international collaborating clinic damage index (SDI) (24) respectively. Disease activity was assessed in relation to functional alteration of different regions of the brain in three studies (13,15,20); whereas disease activity was stable in most of the other studies.…”

“…Hou et al (20) utilized functional connectivity analysis during the resting state to further investigate alteration in cerebral connectivity of cognitive function in SLE patients with no NPSLE. The Paced Visual Serial addition Test (PVSAT) task was selected to assess sustained attention, working memory and speed of information processing.…”

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus

“…Hou et al 19 and Mackay et al 14 did not find any significant correlations between BOLD responses and disease activity as measured by serum biomarkers. Potential explanations for these nonsignificant results could be small numbers in the studies or the use of peripheral blood instead of cerebral spinal fluid (CSF) to assess biomarkers.…”

“…15,[17][18][19][20][21] The majority of these reported that, behaviourally, SLE patients performed similarly to healthy controls 18-21 but showed significant differences in BOLD responses. During tasks examining working memory, learning and executive function increased BOLD responses were seen in areas such as the fusiform gyrus, prefrontal cortex, parietal regions, supplementary Only one study to date has directly compared SLE patients with cognitive impairment to those without using fMRI 16 and this study recruited childhoodonset patients only.…”