Sage Journals: Discover world-class research

Abstract

Structural and metabolic abnormalities in the hippocampus have been associated with the pathophysiological mechanism of central nervous system involvement in primary Sjögren 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 connectivity (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 hippocampal FC might be a potential biomarker in detecting brain function changes and guiding neuroprotection in pSS.

Keywords

Primary Sjögren syndrome hippocampus magnetic resonance imaging resting-state functional connectivity

Get full access to this article

View all access options for this article.

References

Nocturne

Mariette

. Advances in understanding the pathogenesis of primary Sjogren’s syndrome. Nat Rev Rheumatol 2013; 9: 544–556.

Soliotis

Mavragani

Moutsopoulos

. Central nervous system involvement in Sjogren’s syndrome. Ann Rheum Dis 2004; 63: 616–620.

Perzynska-Mazan

Maslinska

Gasik

. Neurological manifestations of primary Sjogren’s syndrome. Reumatologia 2018; 56: 99–105.

Bhattacharyya

Helfgott

. Neurologic complications of systemic lupus erythematosus, Sjogren syndrome, and rheumatoid arthritis. Semin Neurol 2014; 34: 425–436.

Segal

Thomas

Rogers

, et al. Prevalence, severity, and predictors of fatigue in subjects with primary Sjogren’s syndrome. Arthritis Rheum 2008; 59: 1780–1787.

Le Guern

Belin

Henegar

, et al. Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in patients with primary Sjogren syndrome: A case-control study. Ann Rheum Dis 2010; 69: 132–137.

Yoshikawa

Hatate

Toratani

, et al. Prevalence of Sjogren’s syndrome with dementia in a memory clinic. J Neurol Sci 2012; 322: 217–221.

Kim

Lee

, et al. Cerebellar degeneration associated with Sjogren’s syndrome. J Clin Neurol 2012; 8: 155–159.

Morreale

Francia

Marchione

, et al. Intracranial hemodynamic changes in primary Sjogren syndrome: A transcranial Doppler case-control study. Neurol Sci 2015; 36: 1589–1595.

10.

Tzarouchi

Tsifetaki

Konitsiotis

, et al. CNS involvement in primary Sjogren Syndrome: Assessment of gray and white matter changes with MRI and voxel-based morphometry. AJR Am J Roentgenol 2011; 197: 1207–1212.

11.

Segal

Mueller

Zhu

, et al. Disruption of brain white matter microstructure in primary Sjogren’s syndrome: Evidence from diffusion tensor imaging. Rheumatology (Oxford) 2010; 49: 1530–1539.

12.

Barkhof

Haller

Rombouts

. Resting-state functional MR imaging: A new window to the brain. Radiology 2014; 272: 29–49.

13.

Sormani

Evangelou

. New imaging language skills required in MS. Neurology 2015; 85: 1096–1097.

14.

Xing

Shi

Leng

, et al. Resting-state fMRI in primary Sjogren syndrome. Acta Radiol 2018; 59: 1091–1096.

15.

Zhang

Liu

Zhang

, et al. Disrupted functional connectivity of the hippocampus in patients with hyperthyroidism: Evidence from resting-state fMRI. Eur J Radiol 2014; 83: 1907–1913.

16.

Smith

Vidaurre

Beckmann

, et al. Functional connectomics from resting-state fMRI. Trends Cogn Sci 2013; 17: 666–682.

17.

Lauvsnes

Beyer

Kvaloy

, et al. Association of hippocampal atrophy with cerebrospinal fluid antibodies against the NR2 subtype of the N-methyl-D-aspartate receptor in patients with systemic lupus erythematosus and patients with primary Sjogren’s syndrome. Arthritis Rheumatol 2014; 66: 3387–3394.

18.

Planaguma

Leypoldt

Mannara

, et al. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice. Brain 2015; 138: 94–109.

19.

Kayser

Dalmau

. The emerging link between autoimmune disorders and neuropsychiatric disease. J Neuropsychiatry Clin Neurosci 2011; 23: 90–97.

20.

Buckner

Andrews-Hanna

Schacter

. The brain's default network: Anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124: 1–38.

21.

Robinson

Salibi

Deshpande

. Functional connectivity of the left and right hippocampi: Evidence for functional lateralization along the long-axis using meta-analytic approaches and ultra-high field functional neuroimaging. Neuroimage 2016; 135: 64–78.

22.

Harrison

Burggren

Small

, et al. Altered memory-related functional connectivity of the anterior and posterior hippocampus in older adults at increased genetic risk for Alzheimer’s disease. Human Brain Mapp 2016; 37: 366–380.

23.

Geng

Kong

, et al. Disrupted structural and functional connectivity in prefrontal-hippocampus circuitry in first-episode medication-naive adolescent depression. Plos One 2016; 11.

24.

Walther

Stegmayer

Wiest

, et al. Resting state functional connectivity from hippocampus and nucleus accumbens correlates with symptom dimensions in schizophrenia. Biol Psychiatry 2018; 83: S444–S444.

25.

Mousavi

Arcaro

Leung

, et al. Functional connectivity of the hippocampus to the thalamocortical circuitry in an animal model of absence seizures. Epilepsy Res 2017; 137: 19–24.

26.

Shiboski

Seror

, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 2017; 76: 9–16.

27.

Yan

Cheung

Kelly

, et al. A comprehensive assessment of regional variation in the impact of head micromovements on functional connectomics. Neuroimage 2013; 76: 183–201.

28.

Harboe

Tjensvoll

Maroni

, et al. Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjogren syndrome: A comparative population-based study. Ann Rheum Dis 2009; 68: 1541–1546.

29.

Yan

C-G

Wang

X-D

Zuo

X-N

, et al. DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging. Neuroinformatics 2016; 14: 339–351.

30.

Zhang

Zhong

, et al. Grey and white matter abnormalities in minimal hepatic encephalopathy: A study combining voxel-based morphometry and tract-based spatial statistics. Eur Radiol 2013; 23: 3370–3378.

31.

Wahlund

Barkhof

Fazekas

, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001; 32: 1318–1322.

32.

Cox

Chen

Glen

, et al. FMRI clustering in AFNI: False-positive rates redux. Brain connectivity 2017; 7: 152–171.

33.

Kocer

Tezcan

Batur

, et al. Cognition, depression, fatigue, and quality of life in primary Sjogren’s syndrome: Correlations. Brain Behav 2016; 6: e00586–e00586.

34.

Harboe

Tjensvoll

Vefring

, et al.

Fatigue in primary Sjogren’s syndrome – a link to sickness behaviour in animals?

Brain Behav Immun 2009; 23: 1104–1108.

35.

Zheng

Wang

, et al. Different hippocampus functional connectivity patterns in healthy young adults with mutations of APP/Presenilin-1/2 and APOE epsilon 4. Mol Neurobiol 2018; 55: 3439–3450.

36.

Wandell

Dumoulin

Brewer

. Visual field maps in human cortex. Neuron 2007; 56: 366–383.

37.

Misu

Fujihara

Kakita

, et al. Loss of aquaporin 4 in lesions of neuromyelitis optica: Distinction from multiple sclerosis. Brain 2007; 130: 1224–1234.

38.

Estiasari

Matsushita

Masaki

, et al. Comparison of clinical, immunological and neuroimaging features between anti-aquaporin-4 antibody-positive and antibody-negative Sjogren’s syndrome patients with central nervous system manifestations. Mult Scler 2012; 18: 807–816.

39.

Tzarouchi

Zikou

Tsifetaki

, et al. White matter water diffusion changes in primary Sjogren syndrome. AJNR Am J Neuroradiol 2014; 35: 680–685.

40.

Lauvsnes

Maroni

Appenzeller

, et al. Memory dysfunction in primary Sjogren’s syndrome is associated with anti-NR2 antibodies. Arthritis Rheum 2013; 65: 3209–3217.

41.

Huang

Chiu

Kao

, et al. Detecting abnormal regional cerebral blood flow in patients with primary Sjogren’s syndrome by technetium-99m ethyl cysteinate dimer single photon emission computed tomography of the brain – a preliminary report. Rheumatol Int 2003; 23: 174–177.

42.

Akasbi

Berenguer

Saiz

, et al. White matter abnormalities in primary Sjogren syndrome. QJM 2012; 105: 433–443.

43.

Ell S, Sebastien H, Hutchinson S. Contributions of the Putamen to Cognitive Function. Hauppauge, New York: Nova Science Publishers, 2004, pp. 29–52.

44.

Miller

Maletic

Raison

. Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009; 65: 732–741.

45.

Sadeh

Shohamy

Levy

, et al. Cooperation between the hippocampus and the striatum during episodic encoding. J Cogn Neurosci 2011; 23: 1597–1608.

46.

Tang

Zou

Reeb

, et al. An epigenetic induction of a right-shift in hippocampal asymmetry: Selectivity for short- and long-term potentiation but not post-tetanic potentiation. Hippocampus 2008; 18: 5–10.

47.

Robinson

Barron

Kirby

, et al. Neurofunctional topography of the human hippocampus. Hum Brain Mapp 2015; 36: 5018–5037.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.45 MB

Altered hippocampal functional connectivity in primary Sjögren syndrome: a resting-state fMRI study

Abstract

Keywords

Get full access to this article

References

Supplementary Material