Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2024

Open Access 01-12-2024 | Magnetic Resonance Imaging | Research

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

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

Published in: Journal of Neuroinflammation | Issue 1/2024

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Burch HB, Perros P, Bednarczuk T, Cooper DS, Dolman PJ, Leung AM, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022;32(12):1439–70.CrossRefPubMedPubMedCentral
2.
Lehmann GM, Garcia-Bates TM, Smith TJ, Feldon SE, Phipps RP. Regulation of lymphocyte function by PPAR γ: relevance to thyroid eye disease-related inflammation. PPAR Res. 2008;2008:1–12.CrossRef
3.
Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Investig Opthalmol Vis Sci. 2014;55(3):1735.CrossRef
4.
5.
Naik VM, Naik MN, Goldberg RA, Smith TJ, Douglas RS. Immunopathogenesis of thyroid eye disease: emerging paradigms. Surv Ophthalmol. 2010;55(3):215–26.CrossRefPubMedPubMedCentral
6.
Wiersinga WM. Quality of life in Graves’ ophthalmopathy. Best Pract Res Clin Endocrinol Metab. 2012;26(3):359–70.CrossRefPubMed
7.
Bartalena L, Piantanida E, Gallo D, Lai A, Tanda ML. Epidemiology, natural history, risk factors, and prevention of graves’ orbitopathy. Front Endocrinol. 2020;11: 615993.CrossRef
8.
9.
Northrup L, Christopher MA, Sullivan BP, Berkland C. Combining antigen and immunomodulators: emerging trends in antigen-specific immunotherapy for autoimmunity. Adv Drug Deliv Rev. 2016;98:86–98.CrossRefPubMed
10.
Schepers M, Paes D, Tiane A, Rombaut B, Piccart E, Van Veggel L, et al. Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin damaging hallmarks of multiple sclerosis. Brain Behav Immun. 2023;109:1–22.CrossRefPubMed
11.
Harms AS, Ferreira SA, Romero-Ramos M. Periphery and brain, innate and adaptive immunity in Parkinson’s disease. Acta Neuropathol (Berl). 2021;141(4):527–45.CrossRefPubMed
12.
Li Y, Zou C, Chen C, Li S, Zhu Z, Fan Q, et al. Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury. Proc Natl Acad Sci. 2023;120(5): e2219091120.CrossRefPubMedPubMedCentral
13.
Ramı́rez-Amaya V, Alvarez-Borda B, Ormsby CE, Martı́nez RD, Pérez-Montfort R, Bermúdez-Rattoni F. Insular cortex lesions impair the acquisition of conditioned immunosuppression. brain Behav Immun. 1996;10(2):103–14.
14.
Ramı́rez-Amaya V, Alvarez-Borda B, Bermudez-Rattoni F. Differential effects of NMDA-induced lesions into the insular cortex and amygdala on the acquisition and evocation of conditioned immunosuppression. Brain Behav Immun. 1998;12(2):149–60.
15.
Koren T, Yifa R, Amer M, Krot M, Boshnak N, Ben-Shaanan TL, et al. Insular cortex neurons encode and retrieve specific immune responses. Cell. 2021;184(24):5902-5915.e17.CrossRefPubMed
16.
Silkiss RZ, Wade AR. Neuroanatomic variations in Graves’ dysthyroid ophthalmopathy as studied with MRI. Trans Am Ophthalmol Soc. 2016;10:T9.
17.
Qi CX, Wen Z, Huang X. Spontaneous brain activity alterations in thyroid-associated ophthalmopathy patients using amplitude of low-frequency fluctuation: a resting-state fMRI study. NeuroReport. 2021;32(18):1416–22.CrossRefPubMed
18.
Biswal B, Zerrin Yetkin F, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar mri. Magn Reson Med. 1995;34(4):537–41.CrossRefPubMed
19.
Friston KJ, Frith CD, Liddle PF, Frackowiak RSJ. Functional connectivity: the principal-component analysis of large (PET) data sets. J Cereb Blood Flow Metab. 1993;13(1):5–14.CrossRefPubMed
20.
Jiang W, Liu J, Zhou J, Wu Q, Pu X, Chen H, et al. Altered dynamic brain activity and functional connectivity in thyroid-associated ophthalmopathy. Hum Brain Mapp. 2023;44:5346.CrossRefPubMedPubMedCentral
21.
Jiang M, Zhang H, Liu Y, Wu S, Qu J, Tang Y, et al. Abnormal regional spontaneous neural activity and functional connectivity in thyroid-associated ophthalmopathy patients with different activity: a resting-state fMRI study. Front Neurol. 2023;14:1199251.CrossRefPubMedPubMedCentral
22.
Chen W, Wu Q, Chen L, Zhou J, Chen H, Xu X, et al. Aberrant brain voxel-wise resting state fMRI in patients with thyroid-associated ophthalmopathy. J Neuroimaging. 2021;31(4):773–83.CrossRefPubMed
23.
Chen W, Hu H, Wu Q, Chen L, Zhou J, Chen HH, et al. Altered static and dynamic interhemispheric resting-state functional connectivity in patients with thyroid-associated ophthalmopathy. Front Neurosci. 2021;15: 799916.CrossRefPubMedPubMedCentral
24.
25.
26.
Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, et al. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185(4):G43-67.CrossRefPubMed
27.
Oculoplastic and Orbital Disease Group of Chinese Ophthalmological Society of Chinese Medical Association, Thyroid Group of Chinese Society of Endocrinology of Chinese Medical Association [Chinese guideline on the diagnosis and treatment of thyroid-associated ophthalmopathy (2022)]. Zhonghua Yan Ke Za Zhi Chin J Ophthalmol. 2022;58(9):646–68.
28.
29.
Yan CG, Wang XD, Zuo XN, Zang YF. DPABI: data processing & analysis for (resting-state) brain imaging. Neuroinformatics. 2016;14(3):339–51.CrossRefPubMed
30.
Liu TT. Reprint of ‘Noise contributions to the fMRI signal: an overview.’ Neuroimage. 2017;154:4–14.CrossRefPubMed
31.
Yan CG, Cheung B, Kelly C, Colcombe S, Craddock RC, Di Martino A, et al. A comprehensive assessment of regional variation in the impact of head micromovements on functional connectomics. Neuroimage. 2013;76:183–201.CrossRefPubMed
32.
Satterthwaite TD, Elliott MA, Gerraty RT, Ruparel K, Loughead J, Calkins ME, et al. An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data. Neuroimage. 2013;64:240–56.CrossRefPubMed
33.
Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage. 2002;17(2):825–41.CrossRefPubMed
34.
35.
Zhu P, Liu Z, Lu Y, Wang Y, Zhang D, Zhao P, et al. Alterations in spontaneous neuronal activity and microvascular density of the optic nerve head in active thyroid-associated ophthalmopathy. Front Endocrinol. 2022;13: 895186.CrossRef
36.
Molinari M, Leggio MG. Cerebellar information processing and visuospatial functions. Cerebellum. 2007;6(3):214–20.CrossRefPubMed
37.
Coulter I, Frewin S, Krassas GE, Perros P. Psychological implications of Graves’ orbitopathy. Eur J Endocrinol. 2007;157(2):127–31.CrossRefPubMed
38.
Qi CX, Wen Z, Huang X. Reduction of interhemispheric homotopic connectivity in cognitive and visual information processing pathways in patients with thyroid-associated ophthalmopathy. Front Hum Neurosci. 2022;16: 882114.CrossRefPubMedPubMedCentral
39.
Wen Z, Wan X, Qi CX, Huang X. Local-to-remote brain functional connectivity in patients with thyroid-associated ophthalmopathy and assessment of its predictive value using machine learning. Int J Gen Med. 2022;15:4273–83.CrossRefPubMedPubMedCentral
40.
Jia Z, Yu S, Tang W, Zhao D. Altered functional connectivity of the insula in a rat model of recurrent headache. Mol Pain. 2020;16:174480692092211.CrossRef
41.
Amrhein V, Greenland S, McShane B. Scientists rise up against statistical significance. Nature. 2019;567(7748):305–7.ADSCrossRefPubMed
42.
Antonelli A, Fallahi P, Elia G, Ragusa F, Paparo SR, Ruffilli I, et al. Graves’ disease: clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy. Best Pract Res Clin Endocrinol Metab. 2020;34(1): 101388.CrossRefPubMed
43.
Hidaka Y, Amino N, Iwatani Y, Kaneda T, Nasu M, Mitsuda N, et al. Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease. Autoimmunity. 1992;11(4):239–46.CrossRefPubMed
44.
Pedersen BK, Feldt-Rasmussen U, Bech K, Perrild H, Klarlund K, Høier-Madsen M. Characterization of the natural killer cell activity in Hashimoto’s and Graves’ diseases. Allergy. 1989;44(7):477–81.CrossRefPubMed
Metadata
Title
The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central–peripheral system interaction
Authors
Haiyang Zhang
Yuting Liu
Duojin Xia
Mengda Jiang
Yinwei Li
Jing Sun
Haixia Guan
Ling Zhu
Xuefei Song
Jue Wang
Xianqun Fan
Huifang Zhou
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-024-03044-4

Other articles of this Issue 1/2024

Journal of Neuroinflammation 1/2024 Go to the issue

Research

Enhanced meningeal lymphatic drainage ameliorates lipopolysaccharide-induced brain injury in aged mice

Research

Neuroinflammation driven by human immunodeficiency virus-1 (HIV-1) directs the expression of long noncoding RNA RP11-677M14.2 resulting in dysregulation of neurogranin in vivo and in vitro

Research

Immunotherapy with an antibody against CD1d modulates neuroinflammation in an α-synuclein transgenic model of Lewy body like disease

Research

Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis

Research

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

Research

Immunoregulatory and neutrophil-like monocyte subsets with distinct single-cell transcriptomic signatures emerge following brain injury