Study on Structural and Functional Network Connectivity Changes in Patients with Traumatic Brain Injury

Background Introduction

Traumatic Brain Injury (TBI) is a common neurological disorder that can lead to long-term cognitive, emotional, and physical symptoms. Although many patients experience symptom relief within months after the injury, a significant proportion continue to exhibit symptoms for years or even decades. To better understand the impact of TBI on the brain, researchers have begun to focus on the relationship between Structural Connectivity (SC) and Functional Connectivity (FC) in the brain. SC is typically assessed using Diffusion Tensor Imaging (DTI) to evaluate the integrity of white matter, while FC is studied through Functional Magnetic Resonance Imaging (fMRI) to examine the functional correlations between different brain regions.

This study aims to explore changes in SC and FC in TBI patients, particularly those with chronic symptoms, and compare them with a healthy control group. By combining SC and FC analyses, researchers hope to gain a more comprehensive understanding of the impact of TBI on brain networks and provide new biomarkers for future diagnosis and treatment.

Source of the Paper

This paper was authored by Xiaojian Kang, Emily Grossner, Byung C. Yoon, and Maheen M. Adamson, among others, from the VA Palo Alto Health Care System and Stanford University School of Medicine. The study was published in 2025 in the European Journal of Neuroscience under the title “Relationship between structural and functional network connectivity changes for patients with traumatic brain injury and chronic health symptoms.”

Research Process

Study Participants and Grouping

The study included 46 participants divided into three groups: 1. Healthy Control Group (CG): 13 healthy individuals with no history of TBI. 2. TBI Patients Without Chronic Symptoms (TBI-NCS): 16 TBI patients who reported no chronic symptoms at the time of testing. 3. TBI Patients With Chronic Symptoms (TBI-CS): 17 TBI patients who developed chronic symptoms after the injury.

All participants underwent comprehensive physical, neurological, neuropsychological, and psychiatric evaluations, as well as MRI scans.

Data Acquisition and Preprocessing

The study used a GE 3T Discovery MR750 scanner for MRI, acquiring high-resolution T1-weighted images, T2-weighted images, Diffusion-Weighted Images (DWI), and resting-state functional MRI (rsfMRI) data. T1-weighted images were preprocessed using FreeSurfer software, including intensity normalization, image segmentation, inflation of gray matter (GM) and white matter (WM) surfaces, and parcellation of brain regions. DWI data were processed using MRtrix3 software, including denoising, Gibbs artifact removal, EPI distortion correction, b0 field inhomogeneity correction, eddy current and motion distortion correction, and finally registration and resampling using FSL software.

Structural Connectivity (SC) Analysis

SC was constructed using MRtrix3 software, generating 10 million streamlines using the Anatomically Constrained Tractography (ACT) method and filtering them to 1 million streamlines using the Spherical Deconvolution Informed Filtering of Tracts (SIFT) algorithm. The SC matrix was based on 68 Desikan-Killiany (DK) brain regions, with connectivity strength calculated as the sum of streamline weighting factors between node pairs.

Functional Connectivity (FC) Analysis

rsfMRI data were processed using the CONN toolbox, including loading structural surface data, DK atlas, and rsfMRI data, followed by preprocessing. FC was generated through first-level analysis, with signal time series linearly detrended and bandpass filtered (0.008–0.09 Hz). The FC matrix was based on 68 DK brain regions.

Correlation Analysis Between SC and FC

The study calculated the global correlation between SC and FC and compared the differences among the three groups. The results showed that the correlation between SC and FC was significantly higher in TBI patient groups compared to the healthy control group.

Key Findings

Correlation Between SC and FC

The study found that the correlation between SC and FC was significantly higher in TBI patient groups compared to the healthy control group. The SC-FC correlation was 11.5% and 11.9% higher in the TBI-NCS and TBI-CS groups, respectively, than in the control group.

Cluster Analysis of SC

Compared to the healthy control group, the TBI-CS group showed significant reductions in SC across multiple brain regions, particularly in the Default Mode Network (DMN) and Language Network (LAN). The TBI-NCS group showed SC reductions only in the left DMN and LAN networks.

Cluster Analysis of FC

The TBI-NCS group showed reduced FC in bilateral DMN, left CON, bilateral LAN, bilateral SMN, and bilateral VMM networks. The TBI-CS group showed reduced FC in bilateral DMN, FPN, SMN, and VS2 networks. Compared to the TBI-NCS group, the TBI-CS group showed reduced FC in bilateral DMN and CON networks.

ROI Analysis

In the TBI-CS group, the rostral anterior cingulate gyrus (RACG) in the left DMN showed increased SC, while four other ROIs showed reduced SC. The TBI-NCS group showed increased FC in the right VS2’s cuneus cortex (CU) and reduced FC in the left DMN’s lateral orbital frontal gyrus (LOFG). Compared to the TBI-NCS group, the TBI-CS group showed increased FC in the right DMN’s temporal pole (TP) and reduced FC in the left DMN’s medial orbital frontal gyrus (MOFG) and right CON’s posterior cingulate gyrus (PCG).

Conclusion

By combining SC and FC analyses, this study revealed changes in brain network connectivity in TBI patients. The findings indicate that TBI patients, particularly those with chronic symptoms, exhibit significantly higher SC-FC correlations compared to healthy controls. Additionally, the TBI-CS group showed widespread reductions in SC across multiple brain regions, while the TBI-NCS group showed reductions in FC. These results suggest that the presence of chronic symptoms is associated with specific patterns of changes in brain structural and functional networks, potentially providing new biomarkers for the diagnosis and treatment of TBI.

Research Highlights

1. Multimodal Neuroimaging Analysis: This study combined SC and FC analyses, offering a more comprehensive perspective on changes in brain network connectivity.
2. Impact of Chronic Symptoms: The study found that the presence of chronic symptoms is associated with specific patterns of changes in brain structural and functional networks, providing new insights into the long-term effects of TBI.
3. Potential Biomarkers: The findings suggest that changes in SC and FC could serve as biomarkers for TBI diagnosis and prognosis, with significant clinical applications.

Additional Valuable Information

Although this study provides important findings, it has some limitations, such as a small sample size and imbalanced gender ratios. Future research should validate these findings in larger, more diverse samples and further explore the long-term effects of TBI and their underlying neural mechanisms.