Functional magnetic resonance imaging assessment of cognitive function in childhood‐onset systemic lupus erythematosus: A pilot study

Abstract

Objective. To investigate changes in brain activation patterns detected by functional magnetic resonance imaging (FMRI), and the relationship between FMRI activation patterns and results of formal neuropsychological testing, in patients with childhood-onset systemic lupus erythematosus (SLE).Methods. Ten patients with childhood-onset SLE underwent formal neuropsychological testing and FMRI using 3 paradigms: a continuous performance task (CPT) to evaluate attention, an N-Back task to assess working memory, and verb generation to evaluate language processing. Composite Z maps were generated to summarize the brain activation patterns for each FMRI paradigm in patients with childhood-onset SLE and to compare these patterns with those observed in healthy controls. Between-group comparison Z maps showing differences in activation between childhood-onset SLE patients and controls were generated, using a significance level of P < 0.05 in a general linear model.Results. Compared with the control group, the childhood-onset SLE group showed statistically significant increased activation of brain areas involved in the CPT, N-Back, and verb generation tasks. In contrast, in the absence of active stimulus, e.g., during times of the paradigm control tasks, childhood-onset SLE patients consistently undersuppressed activity in the expected brain areas. Activation in selected cortical areas was found to correlate negatively with results of a subset of individual neuropsychological test scores.Conclusion. FMRI abnormalities are present in childhood-onset SLE, manifesting as an imbalance between active and inhibitory responses to an array of stimuli. Differences in brain activation patterns compared with those observed in controls suggest that childhood-onset SLE may be associated with abnormalities in white matter connectivity resulting in neuronal network dysfunction, rather than injury of specific gray matter areas.Childhood-onset systemic lupus erythematosus (SLE) is among the most severe pediatric rheumatic diseases ("pediatric" defined as onset prior to age 16). Often diagnosed in US females of minority populations, SLE is associated with significant morbidity and at least 10 times higher mortality than that of the age-matched general population (1). The reported prevalence of neuropsychiatric involvement in SLE (NPSLE) varies between 15% and 95% (2,3), and children with SLE tend to exhibit a more severe phenotype than adults (4).

Differences in Regional Brain Activation Patterns Assessed by Functional Magnetic Resonance Imaging in Patients with Systemic Lupus Erythematosus Stratified by Disease Duration

“…language processing tasks (24). Similarly, ST patients in this study demonstrated significantly increased neural activation in cortical areas associated with working memory (cingulate gyrus, prefrontal cortex, somatomotor cortex and BA40) compared with the LT group.…”

“…Therefore, fMRI provides an objective measure of functional neural networks solicited by specific probes. Three previous fMRI studies in SLE patients compared with healthy controls have all demonstrated abnormally increased regional brain activation patterns in areas targeted by specific tasks (24)(25)(26). We asked whether these abnormalities also correlate with disease duration.…”

Localization of cerebral functional deficits in patients with non‐neuropsychiatric systemic lupus erythematosus

“…However, the structural MRI has been found to be of limited value in patients with diffuse neuropsychiatric disturbances such as headache, cognitive dysfunction, affective disorders, and confusional states [Rozell et al, 1998;Sabet et al, 1998]. Multiple functional neuroimaging modalities have therefore been used in SLE, including 1 H-magnetic resonance spectroscopy (MRS) [Castellino et al, 2005], SPECT [Appenzeller et al, 2007a], and fMRI [DiFrancesco et al, 2007;Fitzgibbon et al, 2008;Rocca et al, 2006]. These studies have suggested that functional alterations could precede structural changes in NP-SLE [Castellino et al, 2005], and, moreover, they allowed differentiation between patients with or without active CNS involvement [Appenzeller et al, 2007a].…”

“…This method uses deoxyhemoglobin as an endogenous contrast agent to identify areas of altered perfusion. Earlier fMRI studies reported that brain functions including working memory [Fitzgibbon et al, 2008], motor control [Rocca et al, 2006] and cognitive function [DiFrancesco et al, 2007] are altered in SLE patients with central nervous system (CNS) involvement. However, because these studies were generally performed with NP-SLE patients, it is unclear whether the observed changes represent alterations that progressively give rise to neuropsychiatric complications or are a consequence of disease progression following the emergence of neuropsychiatric symptoms.…”

Pathogenesis of neurocognitive and neuropsychiatric manifestations in childhood-onset lupus: an overview

“…In a key study by DiFrancesco et al, 54 fMRI was combined with a (non-CARRA or PED-ANAM) battery of standardized neuropsychological tests, to demonstrate significant agedependent activation differences in 10 patients with childhood-onset SLE compared to healthy age-matched controls, in the attention [using continuous performance task (CPT)], working memory (using N-back task) and language paradigms (using verbal generation task). A deficit in word fluency in childhoodonset SLE seemed to correlate with reduced activation in the Wernicke area and altered activation in the Broca areas involved in wordfinding and language processing.…”