Mapping Regional Homogeneity and Functional Connectivity of the Visual Cortex in Resting-State fMRI

Summary

We present a protocol for analyzing functional magnetic resonance imaging data to investigate spontaneous neural activity alterations in retinitis pigmentosa patient using a combined regional homogeneity and functional connectivity method.

Abstract

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.

Introduction

Functional magnetic resonance imaging (fMRI) is a noninvasive method that can be used to investigate alterations in brain function and structure in vivo. Regional homogeneity (ReHo) and functional connectivity (FC) are often used to assess intra-and interregional synchronizations of brain activity. ReHo, a resting-state fMRI methodology, is used to calculate similarity between the time series of a given voxel and its nearest neighbors, which reflects the local synchronization of brain activities¹. FC is used to investigate the similarity between spatially remote regional time series².

fMRI technology can offer an objective assessment of visual function in the context of eye disease management. Here, we present a methodological protocol that combines ReHo and FC methods to share this experience and support the dissemination of our expertise. In the present work, we used the ReHo and FC protocol in retinitis pigmentosa (RP) subjects and healthy controls (HCs) to elaborate the details of the procedure. RP is a serious hereditary eye disease characterized by impaired night vision and the progressive loss of vision^3,4. Genetic mutation is the main risk factor for RP. The death of rod and cone photoreceptor cells leads to the loss of peripheral vision and finally blindness in RP patients. Previous neuroimaging studies have shown structural and functional abnormalities in the visual cortex and visual pathway of RP patients^5,6,7. Moreover, diffusion tensor imaging was used to investigate the integrity of white matter fiber bundles. RP patients showed significantly higher apparent diffusion coefficient, principal eigenvalue, and orthogonal eigenvalue, as well as significantly lower fractional anisotropy in the optic nerves, relative to HCs⁸.

Here, our aim was the exploration of intra- and interregional synchronizations of neuronal activity. We investigated whether the mean ReHo values and mean FC values were correlated with clinical variables in RP patients. Our method might enable researchers to obtain important insights into the neural mechanism of peripheral vision loss in RP patients.

Protocol

The research protocol was approved by the medical ethics committee of the Renmin Hospital of Wuhan University. All participants completed a written consent form. 1. Participant classification and screening Enroll RP subjects and HCs closely matched in age, gender, and education. Ensure that all participants meet the following criteria: 1) able to be scanned with an MRI scanner (e.g., no cardiac pacemakers or implanted metal devices); 2) no claustrophobia; 3) no heart dise…

Representative Results

In our study, 16 RP individuals and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. ReHo and FC methods were used to explore the intra-and intersynchronous neuronal activity in RP individuals. Significant differences in BCVA were observed between the right eye (P < 0.001) and the left eye (P < 0.001), but the difference in gender, age, or weight between the groups was not significant. The RP and HCs show similar…

Discussion

This report describes a protocol for computing ReHo and FC values for RP and HC groups and showed significantly different ReHo and FC values between the two groups. Notably, an important step in this process is the classification and screening of samples before the experiment. When we applied this protocol for our own analysis, all RP subjects were diagnosed by two experienced ophthalmologists. We excluded RP patients with other eye diseases such as glaucoma, cataracts, and optic atrophy. In addition, HCs enrolled in our…

Materials

BrainNet Viewer software	National Key Laboratory of Cognition Neuroscience and Learning, BNU	BrainNet Viwer 2013	BrainNet Viewer is a brain network visualization tool to visualize structural and functional connectivity patterns
DPABI software	Institute of Psychology, CAS, Beijing, China	DPABI 4.3	DPABI is a toolbox for data processing and analysis of brain imaging.
MATLAB	MathWorks, Natick, MA, USA	2013a	MATLAB is a high-level technical computing language and interactive environment for algorithm development, data visualization, data analysis, and numeric computation.
MRI scanner	GE Healthcare, Milwaukee	MRI 3.0
SPM software	Wellcome Centre for Human Neuroimaging, UCL	SPM8	SPM8 is a major update to the SPM software, containing substantial theoretical, algorithmic, structural and interface enhancements over previous versions.
SPSS	IBM, Chicago, IL, USA	SPSS version 20.0	SPSS software platform offers advanced statistical analysis, text analysis, open-source extensibility, integration with big data and seamless deployment into applications.