Dysfunctional cortico–basal ganglia–thalamic circuit and altered hippocampal–amygdala activity on cognitive set‐shifting in non‐neuropsychiatric systemic lupus erythematosus

OBJECTIVE: To explore sequential brain activities throughout cognitive set-shifting, which is critical to understanding the basic pathophysiology of cognitive dysfunction, in patients with new-onset systemic lupus erythematosus (SLE) without neuropsychiatric symptoms. METHODS: Fourteen patients with new-onset SLE but without neuropsychiatric symptoms and 14 healthy controls matched for age, sex, education level, and intelligence quotient with the patients performed a cognitive set-shifting task derived from the Wisconsin Card Sorting Test while they were undergoing event-related functional magnetic resonance imaging of the brain. Blood oxygen level-dependent signals were compared between different stages of cognitive set-shifting in the lupus patients and in the healthy subjects. RESULTS: Lupus patients and healthy subjects demonstrated comparable cognitive function performance, but the cortico-basal ganglia-thalamic-cortical circuit and amygdala-hippocampus coupling, which were involved in response inhibition and active forgetting-learning dynamics, respectively, were demonstrated to be compromised in patients with SLE. Moreover, an increase in contralateral cerebellar-frontal activity was found to compensate for the compromised cortico-basal ganglia-thalamic-cortical circuit in lupus patients in order to maintain their cognitive test performance as comparable to that of the healthy subjects. CONCLUSION: Our study revealed significant differences in the sequential brain signals during cognitive set-shifting between patients with SLE without neuropsychiatric symptoms and healthy subjects. The results prompt further in-depth investigation for the functional neural basis of cognitive dysfunction involving the aforementioned neural circuits and compensatory pathways in patients with SLE.