Disrupted Structure-Function Integration in Systemic Lupus Erythematosus and Its Impact on Cognitive Flexibility

Area of Science:

• Neuroscience
• Autoimmune Diseases
• Cognitive Function

Background:

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease often associated with cognitive dysfunction.
• Cognitive flexibility, crucial for daily functioning, relies on integrated brain structure and function.
• The specific brain alterations underlying reduced cognitive flexibility in SLE remain unclear.

Purpose of the Study:

• To investigate alterations in brain structure-function integration in SLE patients.
• To determine the relationship between these alterations and cognitive flexibility.
• To explore the role of the executive control network (ECN) in these changes.

Main Methods:

• Employed diffusion MRI and task-based fMRI during the Montreal Card Sorting Test (MCST) in 22 SLE patients and 60 healthy controls.
• Quantified brain structural-functional alignment and liberality to assess integration.
• Analyzed subnetworks within the ECN (ECN-A, ECN-B, ECN-C) and their association with cognitive performance and clinical variables.

Main Results:

• SLE patients exhibited globally higher liberality and lower alignment compared to controls, primarily within the ECN.
• Specific alterations were noted in ECN-A and ECN-B, but not ECN-C.
• Increased liberality and decreased alignment in the ECN correlated with poorer cognitive flexibility (MCST performance) in SLE patients and across all participants.

Conclusions:

• Aberrant structure-function integration within the fronto-parietal ECN is a key feature of SLE.
• These disruptions significantly impact cognitive flexibility in SLE.
• Findings suggest that impaired ECN structure-function integration contributes to cognitive impairment in SLE and may be influenced by clinical factors.