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

Abstract

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 eventrelated 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.Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disorder characterized by protean clinical manifestations. Neuropsychiatric SLE (NPSLE) is one of the most common manifestations of lupus, and it has hindered improvements in the survival of these patients over the last 5 decades (1). Of the various symptoms of NPSLE, cognitive impairment, which primarily affects attention, planning, reasoning, working memory, and executive function, has been frequently described (2). It is evident that the cognitive functioning of patients with NPSLE is inferior to that of lupus patients without neuropsychiatric symptoms and that of healthy individuals (3,4), as they demonstrate poorer performance in a number of domains of cognitive function testing, in particular, attention, information processing, learning, memory, and executive function (3-5).Real-time functional magnetic resonance imaging (fMRI) of the brain while subjects were performing cognitive function tasks revealed that brain activities, which were manifested by blood oxygen leveldependent (BOLD) signals, were significantly altered in patients with NPSLE as compared with healthy subjects (6,7). However, since these fMRI studies involved lupus

Alterations of white matter structural networks in patients with non-neuropsychiatric systemic lupus erythematosus identified by probabilistic tractography and connectivity-based analyses

“…In addition, the DMN regions were demonstrated to possess the highest structure–function connectivity agreement within the entire brain (Horn et al, 2014). Thus, the structural disruption of the regional topological features in DMN was assumed to be the underlying cause of the decrease in the cognitive function of non-NPSLE and NPSLE patients (Mackay et al, 2011, Ren et al, 2012). …”

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

“…The mean age of 37.6 years was reported for adults, and for children was 15.7 years. Two studies had provided intelligence quotient (IQ) scores for the SLE participants in their study (19,21).…”

“…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.…”

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

“…It has been suggested that blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) is a promising approach to study human cognitive function, which utilizes deoxyhemoglobin as an endogenous contrast agent to identify areas of increased perfusion. Using fMRI, several studies have reported working memory [10], motor control [11], attention and language processing [12], and executive function [13] alterations in SLE patients; however, most of the results obtained in the above fMRI studies were performed with neuropsychiatric SLE (NPSLE) patients, while few studies were designed to characterize brain cognitive function alterations in lupus patients without obvious neuropsychiatric symptoms. Given the high prevalence and poor prognosis for NPSLE, it is meaningful to address whether or not brain dysfunction precedes the evolution of NPSLE in lupus patients without clinically obvious neuropsychiatric symptoms.…”