Reduction of Interhemispheric Homotopic Connectivity in Cognitive and Visual Information Processing Pathways in Patients With Thyroid-Associated Ophthalmopathy

Abstract

Purpose: Thyroid-associated ophthalmopathy (TAO) is a vision threatening autoimmune and inflammatory orbital disease, and has been reported to be associated with a wide range of structural and functional abnormalities of bilateral hemispheres. However, whether the interhemisphere functional connectivity (FC) of TAO patients is altered still remain unclear. A new technique called voxel-mirrored homotopic connectivity (VMHC) combined with support vector machine (SVM) method was used in the present study to explore interhemispheric homotopic functional connectivity alterations in patients with TAO.

Methods: A total of 21 TAO patients (14 males and 7 females) and 21 wellmatched healthy controls (HCs, 14 males and 7 females), respectively, underwent functional magnetic resonance imaging (fMRI) scanning in the resting state. We evaluated alterations in the resting state functional connectivity between hemispheres by applying VMHC method and then selected these abnormal brain regions as seed areas for subsequent study using FC method. Furthermore, the observed changes of regions in the VMHC analysis were chosen as classification features to differentiate patients with TAO from HCs through support vector machine (SVM) method.

Results: The results showed that compared with HCs, TAO patients showed significantly lower VMHC values in the bilateral postcentral gyrus, lingual gyrus, calcarine, middle temporal gyrus, middle occipital gyrus and angular. Moreover, significantly decreased FC values were found between the right postcentral gyrus/lingual gyrus/calcarine and left lingual gyrus/cuneus/superior occipital gyrus, left postcentral gyrus/lingual gyrus/calcarine and right lingual gyrus/ middle temporal gyrus, right middle temporal gyrus and left cerebellum-8/lingual gyrus/middle occipital gyrus/supplementary motor area, left middle temporal gyrus and right middle occipital gyrus, right middle occipital gyrus/angular and left middle temporal pole (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The SVM classification model achieved good performance in differentiating TAO patients from HCs (total accuracy: 73.81%; area under the curve: 0.79).

Conclusion: The present study revealed that the altered interhemisphere interaction and integration of information involved in cognitive and visual information processing pathways including the postcentral gyrus, cuneus, cerebellum, angular, widespread visual cortex and temporal cortex in patients with TAO relative to HC group. VMHC variability had potential value for accurately and specifically distinguishing patients with TAO from HCs. The new findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.

Keywords: functional connectivity; functional magnetic resonance imaging; support vector machine; thyroid-associated ophthalmopathy; voxel-mirrored homotopic connectivity.

Figure 1

One-sample t-test results of VMHC maps within TAO group (A) and HC group (B). TAO, thyroid-associated ophthalmopathy; VMHC, voxel-mirrored homotopic connectivity; HC, healthy control.

Figure 2

Significant VMHC differences in the TAO and HC group (A); The mean of altered VMHC values between patients with TAO and HCs (B). TAO, thyroid-associated ophthalmopathy; HC, healthy control; VMHC, voxel-mirrored homotopic connectivity; PostCG, postcentral gyrus; LING, lingual gyrus; CAL, calcarine; MTG, middle temporal gyrus; MOG, middle occipital gyrus; ANG, angular gyrus.

Figure 3

(A) Significant FC differences between the right PostCG/LING/CAL and left LING/CUN/SOG. (B) Significant FC differences between the left PostCG/LING/CAL and right LING/MTG. (C) Significant FC differences between the right MTG and left CER-8/LING/MOG/SMA. (D) Significant FC differences between the left MTG and right MOG. (E) Significant FC differences between the right MOG/ANG and left MTP. TAO, thyroid-associated ophthalmopathy; FC, functional connectivity; PostCG, postcentral gyrus; LING, lingual gyrus; CAL, calcarine; MTG, middle temporal gyrus; MOG, middle occipital gyrus; ANG, angular gyrus; CUN, cuneus; SOG, superior occipital gyrus; CER, cerebellum; SMA, supplementary motor area; MTP, middle temporal pole.

Figure 4

Classification results using machine learning analysis based on VMHC values. (A) Function values of two groups (class 1: TAO group; class 2: HC group); (B) Function values of two groups (class 1: TAO group; class 2: HC group); (C) The ROC curve of the SVM classifier with an AUC value of 0.79. (D) Weight maps for SVM models. TAO, thyroid-associated ophthalmopathy; HC, healthy control; VMHC, voxel-mirrored homotopic connectivity; ROC, receiver operating characteristic; SVM, Support vector machine; AUC, area under the curve.