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.