Disrupted Structure–Function Integration in Systemic Lupus Erythematosus and Its Impact on Cognitive Flexibility
Bibliographic record
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, with cognitive dysfunction being one of its most common neuropsychiatric manifestations. Cognitive flexibility relies on the integration of brain structure and function, with white matter networks providing anatomical constraints for functional dynamics. Reduced cognitive flexibility is frequently observed in SLE, but the underlying structure-function integration changes remain poorly understood. This study investigated whether brain structure-function integration is altered in SLE and how it links to cognitive flexibility. We examined 22 SLE patients without clinically overt neuropsychiatric manifestation (age: 34.99 ± 10.67; 18 females) and 60 healthy controls (HCs) (age: 28.43 ± 8.56; 29 females). Using diffusion MRI and task-based fMRI acquired during the Montreal Card Sorting Test (MCST), a cognitive flexibility task, we derived brain structural-functional alignment and liberality, which quantify the extent to which brain functional signals are either coupled with or deviate from the underlying anatomical network. We found SLE patients exhibited globally higher liberality and lower alignment compared to HCs, and this was driven by the disrupted structure-function integration in the executive control network (ECN). The ECN comprises three subnetworks: ECN-A and ECN-B comprise key lateral fronto-parietal executive control areas, while ECN-C is anatomically closer to the default mode network. Further analyses revealed that SLE had higher liberality in ECN-A and ECN-B regions, alongside lower alignment in ECN-A, while ECN-C did not show these alterations. Importantly, increased liberality and decreased alignment in the ECN regions were associated with poorer cognitive flexibility (MCST performance) in SLE participants. This association was also observed across all participants. In SLE individuals specifically, liberality and alignment in the fronto-parietal ECN were further linked to clinical variables, including serum albumin and corticosteroid dosage. Additionally, the liberality and alignment in the ECN and its subnetworks were associated with cognitive performance outside the scanner (measured by Automated Neuropsychological Assessment Metrics) across all participants. Our findings suggest that aberrant structure-function integration, particularly within the fronto-parietal ECN, impacts cognitive flexibility and may contribute to the development of cognitive impairment in SLE.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".