Spontaneous changes in brain network centrality in patients with pathological myopia: A voxel‐wise degree centrality analysis

Abstract Background Myopia has become a worldwide problem that endangers public health and adds a serious socioeconomic burden. Current research has focused on the pathogenesis and manifestations of pathological myopia (PM). However, few studies have been conducted on the spontaneous activity of the patient's brain. Purpose To study the potential brain network activity in patients with PM by the degree centrality (DC) method. Materials and Methods This experiment included 15 PM patients and 15 healthy controls (HCs). Every participant experienced a resting‐state functional magnetic resonance imaging (rs‐fMRI) scan. Receiver operating characteristic (ROC) curve analysis was used to distinguish between PM patients and HCs. Correlation analysis was used to explore the relationships between mean DC values and clinical performance in different brain regions. Results It showed that patients with PM had lower DC values in the right fusiform gyrus (FR) and right cingulate (CAR). The ROC curve was used to indicate the accuracy of the correlation. It showed that in PM group, left best corrected visual acuity (BCVA‐L) and right best corrected visual acuity (BCVA‐R) were negatively correlated with the DC value of FR. Conclusion The occurrence of PM is mainly related to the abnormal activity of the fusiform and cingulum. DC value might be used as a biological marker of abnormal brain activity in PM patients.

Most studies conducted thus far mainly focused on the pathogenesis and manifestations of PM. However, there are few studies on the spontaneous activity of the patient's brain. Nowadays, functional magnetic resonance imaging (fMRI) can be used to assess various brain activities, and studies utilizing this approach have shown that myopia reduces the activity of the visual cortex of the brain. 5 In the resting state, spontaneous activities of the brain are formed by the transfer between neurons. 6 Currently, resting state-fMRI is used for the investigation of eye and brain diseases, such as optic neuritis, primary angle-closure glaucoma, Alzheimer's disease, and epilepsy. [7][8][9] Previous studies 10 have found that compared with normal people, the visual function of HM patients is abnormal, even if the corrected vision is the same, the results also showed lower functional connectivity in the posterior cingulate cortex/precuneus. Moreover, another research 11 found that in the HM groups, the cortical surface thickness of the right primary visual area 1 (V1) decreased, while the thickness of the parietal operculum (OP4) increased. Although there are many studies on the visual and brain functions of HM patients, there are few studies on the brain functions of visual impairment caused by PM.
The voxel-based degree centrality (DC) method is a data analysis method derived from the graph theory approach that allows direct assessment of whole brain network connectivity without a priori assumptions. 12  We illustrate the results of these diseases in Figure 1. This study aimed to explore the whole-brain functional connectivity changes in PM patients and the relationships between mean DC values and clinical performance in different brain regions.

| Patients
Fifteen patients with PM and 15 healthy controls (HCs) were selected. This study was approved by the Human Research Ethics

| MRI data collection
We used a 3-Tesla MR scanner to perform an MRI scan. And the 3-Tesla MR scanner (Trio, Siemens) was for MRI scanning. Wholebrain T1 weights with different gradient recall echo sequences were obtained using the following parameters: repetition time, 1900 ms; echo time, 2.26 ms; thickness, 1.0 mm; gap, 0.5 mm; acquisition matrix, 256 × 256; field of view, 250 × 250 mm; and turning angle, 9°.

| Data processing for fMRI
First, we used MRIcro (www.MRIcro.com) to check the original data and remove unqualified data, then, pre-processing of fMRI data based on Matlab2014a platform Statistical Parameter Mapping 8 (http://www.fil.ion.ucl.ac.uk/spm) software packages for format conversion (DICOM to NIFTI), removal of the first 10 time points, time layer correction, head movement correction (<3 mm), linear regression analysis, spatial normalization, and lowfrequency filtering.

| Analysis of DC
For binary graphs, DC is the number of edges connecting to a node. For a weighted tabulation, it is adjusted as the total of the weights distance from the peakish joint to the mass. It represents the wealthiest inborn and momentarily quantifiable centrality routine. 20

| Statistical analysis
We used the SPSS 22.0 software (IBM) to perform two independent sample t tests on the difference between the clinical manifestations of PM and HCs. DC differences between the two groups were evaluated by the SPM8 toolkit, which includes a general linear model. We also used Gaussian random field (GRF) theory for calibration, and set p < 0.001 as the level of statistically significant difference. Subsequently, we used correlation analysis to evaluate the relationship between the DC value and clinical performance.
F I G U R E 2 Typical fundus photographs of (A) healthy controls and (B) pathological myopia patients.

| Demographics and visual measurements
There were no significant differences observed in sex, age, and weight between patients with PM and HCs (p > 0.05). The BCVA values of the left and right eyes of the PM group were 0.11 ± 0.11 and 0.22 ± 0.16, respectively, while those of the intraocular lens were 14.39 ± 2.23 and 12.27 ± 3.19, respectively. Table 1 shows more information.

| DC differences
DC values in the right fusiform (Fusiform_R) and right cingulum ant (Cingulum_Ant_R) were decreased among patients with PM compared with HCs ( Figure 3 and Table 2). The

| Receiver operating characteristic curve
We used the receiver operating characteristic curve (ROC) to determine the DC average value of each region of the brain which can be used as markers to distinguish PM and HCs. The area under the curve values were as follows: right cingulum ant (0.973) (PM < HCs) and right fusiform (1.000) (PM < HCs). Figure 4 shows the result of ROC.

| Correlation analysis
In the PM group, both left and right best-corrected visual acuity (BCVA) were negatively correlated with the DC signal value of the right fusiform. Figure 5 shows the relationship between BCVA and DC value through a scatter plot ( Figure 6).

| DISCUSS ION
There are still limitations in the understanding of pathological myopia by the majority of researchers, and the pathogenesis, degree of correlation with various factors, and pathophysiological processes of pathological myopia still need to be continued to be explored. DC, as a non-invasive method of functional brain imaging, has been applied by several researchers to investigate the pathogenesis of ocular diseases. In the present study, we found that DC values in PM patients showed abnormalities in two brain regions, right fusiform and right cingulum ant, compared to normal controls ( Figure 7).
The fusiform gyrus is a functional area in the ventral side of the visual cortex, which may be related to the priority of face recognition. 22 Some brain imaging studies have found that blind people can perceive 3D faces through touch to generate selective activation of faces in the lateral fusiform area, which is evidence of highly functional-specific brain area independent of modal processing. 23 Rizzo et al. 24  In conclusion, we propose that dysfunction of the fusiform and cingulum may lead to VI. We hypothesize that the development of PM leads to changes in fMRI signals in the above two brain areas, or that the signal changes further affect the occurrence of PM, or that both mechanisms exist. Our results may provide new breakthroughs to explore the related neural mechanisms of PM and provide new directions for its treatment.

ACK N OWLED G M ENTS
This work was financially supported by the National Natural

CO N FLI C T O F I NTE R E S T S TATE M E NT
This study did not receive any industrial support. The authors have no competing interests to declare regarding this study.

DATA AVA I L A B I L I T Y S TAT E M E N T
The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

CO N S E NT TO PA RTI CI PATE
Informed consent was obtained from legal guardians.