title: Differences in regional brain activation patterns assessed by functional magnetic resonance imaging in patients with systemic lupus erythematosus stratified by disease duration.
abstract: The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.
authors.affiliation: Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America. mmackay@nshs.edu
authors.forename: Meggan
authors.initials: M
authors.lastname: Mackay
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Bussa
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aranow
authors.forename: Aziz M
authors.initials: AM
authors.lastname: Uluğ
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Volpe
authors.forename: Patricio T
authors.initials: PT
authors.lastname: Huerta
authors.forename: Miklos
authors.initials: M
authors.lastname: Argyelan
authors.forename: Arthur
authors.initials: A
authors.lastname: Mandel
authors.forename: Joy
authors.initials: J
authors.lastname: Hirsch
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D005145:Face; D005239:Fear; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000473:pathology* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D009928:Organ Specificity; D013647:Task Performance and Analysis; D013997:Time Factors; D055815:Young Adult