The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central-peripheral system interaction

Haiyang Zhang; Yuting Liu; Duojin Xia; Mengda Jiang; Yinwei Li; Jing Sun; Haixia Guan; Ling Zhu; Xuefei Song; Jue Wang; Xianqun Fan; Huifang Zhou

doi:10.1186/s12974-024-03044-4

The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central-peripheral system interaction

J Neuroinflammation. 2024 Feb 17;21(1):51. doi: 10.1186/s12974-024-03044-4.

Authors

Haiyang Zhang^#^{1

2}, Yuting Liu^#^{1

2}, Duojin Xia³, Mengda Jiang⁴, Yinwei Li^{1

2}, Jing Sun^{1

2}, Haixia Guan⁵, Ling Zhu⁴, Xuefei Song^{1

2}, Jue Wang⁶, Xianqun Fan^{7

8}, Huifang Zhou^{9

10}

Affiliations

¹ Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
³ School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
⁴ Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
⁶ Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, China. juefirst@cdsu.edu.cn.
⁷ Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. fanxq@sjtu.edu.cn.
⁸ Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. fanxq@sjtu.edu.cn.
⁹ Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. fangzzfang@sjtu.edu.cn.
¹⁰ Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. fangzzfang@sjtu.edu.cn.

^# Contributed equally.

Abstract

Background: Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status.

Methods: This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters.

Results: When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups.

Conclusions: This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central-peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central-peripheral system interaction mechanisms involved in autoimmune diseases.

Keywords: Functional connectivity; Functional magnetic resonance imaging; Insular cortex; Neuroimmunomodulation; Thyroid eye disease.

MeSH terms

Animals
Brain
Brain Mapping / methods
Graves Ophthalmopathy*
Humans
Insular Cortex*
Magnetic Resonance Imaging / methods
Mice
Neuroimaging

Abstract

MeSH terms

Grants and funding