Lupus (2020) 0, 1–9 journals.sagepub.com/home/lup PAPER Altered hippocampal functional connectivity in primary Sjo¨gren syndrome: a resting-state fMRI study X-D Zhang 1 , L-R Zhao 2 , J-M Zhou 1,3 , Y-Y Su 4 , J Ke 4 , Y Cheng 1 , J-L Li 1,3 and W Shen 1 1 Department of Radiology, Tianjin First Central Hospital, Tianjin, China; 2 Department of Rheumatology, Tianjin First Central Hospital, Tianjin, China; 3 Department of Radiology, Tianjin First Central Clinical Hospital, Tianjin Medical University, Tianjin, China; and 4 Department of Radiology, First Affiliated Hospital, Soochow University, Suzhou, China Structural and metabolic abnormalities in the hippocampus have been associated with the pathophysiological mechanism of central nervous system involvement in primary Sjo¨gren syndrome (pSS). Nevertheless, how hippocampal function is altered in pSS remains unknown. The purpose of our study is to investigate the alterations in hippocampal functional connect- ivity (FC) in pSS by using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-eight patients with pSS and 38 age- and education level-matched healthy controls (HCs) underwent magnetic resonance imaging examination. Prior to each MRI examination, neuropsychological tests were performed. Left and right hippocampal FCs were analyzed by using seed-based whole-brain correlation and compared between pSS and HCs. Spearman correlation analysis was performed between the z-value of hippocampal FC in brain regions with significant difference between the two groups and neuropsychological tests/clinical data in pSS. Compared with the controls, the patients with pSS showed decreased hippocampal FC between the left hippocampus and the right inferior occipital gray (IOG)/inferior temporal gray (ITG), as well as between the right hippocampus and right IOG/middle occipital gray (MOG), left MOG, and left middle temporal gray. In addition, increased hippocampal FCs were detected between the left hippocampus and left putamen, as well as between the right hippocampus and right cerebellum posterior lobe. Moreover, the visual reproduction score positively correlated with the FC between right hippocampus and right IOG/MOG. The white matter hyperintensity score negatively correlated with the FC between left hippocampus and right IOG/ITG. In conclusion, patients with pSS suffered decreased hippocampal FC mainly sited in the occipital and temporal cortex with right hippocampal laterality. Altered hippo- campal FC might be a potential biomarker in detecting brain function changes and guiding neuroprotection in pSS. Lupus (2020) 0, 1–9. Key words: Primary Sjo¨gren syndrome; hippocampus; magnetic resonance imaging; resting- state; functional connectivity Introduction Primary Sjo¨ gren syndrome (pSS) is a systemic auto- immune disease characterized by lymphocytic infil- tration of the exocrine glands in the absence of other autoimmune diseases, leading to xerophthal- mia and xerostomia as the main symptoms. 1 Importantly, as a systemic autoimmune disease, pSS can affect the central nervous system (CNS). 2 Recently, greater attention has been paid to explor- ing the involvement of the CNS in pSS. The preva- lence of CNS involvement in pSS remains inconsistent and varies between 2% and 60%. 3,4 Patients with CNS involvement display epileptic seizures, optic neuritis, disseminated encephalop- athy and, in particular, cognitive disorders, with common manifestations such as attention and memory deficits. 3 In addition, pSS can also reduces quality of daily life 3 and produces greater fatigue. 5 To date, the exact pathophysiological mechanism underlying the CNS involvement in pSS remains unclear; it may be related to autoimmune antibo- dies, cytokines and a deficit in the microcircula- tion. 1 However, as the diagnosis of cognitive Correspondence to: Jing-Li Li, Department of Radiology, Tianjin First Central Hospital, No.24 Fukang Road, Tianjin 300192, China. Email: tmulijingli@163.com Wen Shen, Department of Radiology, Tianjin First Central Hospital, No.24 Fukang Road, Tianjin 300192, China. Email: shenwen66happy@163.com Received 17 October 2019; accepted 4 February 2020 ! The Author(s), 2020. Article reuse guidelines: sagepub.com/journals-permissions 10.1177/0961203320908936