Reorganization of Topological Features in Brain Functional Networks in Patients with Chronic Tinnitus

Academic Background

Tinnitus is the perception of sound in the absence of any external acoustic stimuli or internal sources of auditory perception, with a global prevalence ranging from 11.9% to 30.3%. Patients with tinnitus experience not only auditory symptoms, such as hyperacusis and hearing difficulties, but also psychological symptoms, including anxiety, depression, insomnia, and inattention. These symptoms are closely related to the severity of tinnitus. According to the 2014 US Clinical Practice Guidelines, tinnitus is classified as recent-onset tinnitus (duration months) and persistent tinnitus (duration ≥6 months). Recent-onset and persistent tinnitus often exhibit different clinical features, such as variations in loudness, frequency, and mood disturbances associated with tinnitus. However, the precise mechanism underlying the chronicity of tinnitus remains unclear.

The pathophysiology of tinnitus is complex and multifactorial, involving both peripheral and central systems. Initially, tinnitus was thought to originate from aberrant neural activity localized to the peripheral auditory system. However, recent studies indicate that tinnitus is associated with abnormal neural activity across widely distributed brain networks, including both the auditory network and extra-auditory structures, such as the frontal cortex, parahippocampus, cingulate cortex, insula, and cerebellum. These abnormal neural activities span multiple brain networks. Although extensive research has explored the neural mechanisms of tinnitus, studies on the neuronal changes during the progression from recent-onset to persistent tinnitus remain limited.

Source of the Paper

This paper was co-authored by Shuting Han, Yongcong Shen, Xiaojuan Wu, Hui Dai, Yonggang Li, Jisheng Liu, and Duo-Duo Tao, affiliated with the Department of Radiology and Department of Ear, Nose, and Throat at the First Affiliated Hospital of Soochow University. The study was published in 2025 in the European Journal of Neuroscience, titled “Topological features of brain functional networks are reorganized during chronic tinnitus: a graph-theoretical study.”

Research Process

Subjects and Grouping

The study recruited 51 tinnitus patients (divided into recent-onset tinnitus and persistent tinnitus groups) and 27 healthy controls (HC). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and audiological assessments. Graph theory was used to examine the topological properties of brain networks.

Data Acquisition and Preprocessing

MRI scans were conducted using a Philips 3.0T Ingenia MRI scanner, acquiring T1-weighted images and resting-state functional magnetic resonance imaging (rs-fMRI) data. Data preprocessing included format conversion, removal of the first 10 time points, slice timing correction, motion correction, co-registration, spatial normalization, detrending, and filtering.

Construction and Analysis of Brain Functional Networks

The study used the Gretna toolbox and the AAL atlas to segment the brain into 90 regions of interest (ROIs). Pearson correlation coefficients between nodes were calculated to construct a 90x90 connectivity matrix. By applying a sparsity threshold, the study ensured that all networks had an equivalent number of nodes and edges. Network analysis included the calculation of global and nodal parameters, such as characteristic path length (LP), clustering coefficient (CP), normalized clustering coefficient (gamma), normalized characteristic path length (lambda), small-world coefficient (sigma), and brain network efficiency (including global efficiency (Eglob) and local efficiency (Eloc)).

Modular Analysis

The 90 ROIs were divided into six submodules: frontal, prefrontal, parietal, temporal, occipital, and subcortical modules. The strength of intra- and inter-module connections was calculated for the recent-onset tinnitus group, persistent tinnitus group, and healthy controls.

Key Findings

Comparison of Global Parameters

The results showed that the recent-onset tinnitus group (ROT) had significantly lower clustering coefficient (CP), normalized clustering coefficient (gamma), and local efficiency (Eloc) compared to the healthy control group (HC) and the persistent tinnitus group (PT). This indicates that patients with recent-onset tinnitus have reduced local connectivity in brain networks, but these changes gradually recover as tinnitus persists.

Comparison of Nodal Parameters

In the nodal analysis, the recent-onset tinnitus group exhibited significantly lower nodal clustering coefficient (NCP) and local efficiency (NLE) in the left caudate nucleus and left olfactory cortex, while nodal centrality increased in the left orbital middle frontal gyrus and left postcentral gyrus. Additionally, the recent-onset tinnitus group showed reduced nodal clustering in the right lenticular putamen and reduced nodal efficiency in the left olfactory cortex.

Modular Analysis Results

Modular analysis revealed that the connection strength between the subcortical module and the occipital module, as well as between the prefrontal module and the prefrontal module, was significantly stronger in the recent-onset tinnitus group compared to the persistent tinnitus group and healthy controls. In contrast, the intra-module connection strength of the subcortical module was significantly stronger in the persistent tinnitus group than in the healthy controls.

Correlation Analysis

In the tinnitus patient group, the duration of tinnitus was positively correlated with the nodal local efficiency in the right olfactory cortex.

Conclusions and Significance

This study, through graph-theoretical analysis, revealed changes in the topological properties of brain functional networks in tinnitus patients at different stages of the disease. The findings indicate that patients with recent-onset tinnitus experience a decline in local connectivity and global information transfer efficiency in brain networks, but these changes gradually recover as tinnitus persists. Additionally, functional abnormalities were observed in several key nodes, such as the left orbital middle frontal gyrus, left caudate nucleus, and bilateral olfactory cortex. These alterations may reflect a central compensatory response to tinnitus.

Scientific and Practical Value

This study not only expands our understanding of the reorganization of brain functional connectivity in tinnitus patients but also provides evidence for the reorganization of brain network topology during the chronic progression of tinnitus. These findings may offer new biomarkers and therapeutic targets for the diagnosis and treatment of tinnitus.

Highlights of the Study

1. Novel Research Methodology: This study is the first to systematically analyze changes in the topological properties of brain functional networks in tinnitus patients at different disease stages using graph theory.
2. Significant Findings: The study found that patients with recent-onset tinnitus exhibit reduced local connectivity and global information transfer efficiency in brain networks, but these changes gradually recover as tinnitus persists.
3. Potential Applications: The results provide new insights for the diagnosis and treatment of tinnitus, particularly by assessing the chronic progression of tinnitus through changes in brain network topology.

Additional Valuable Information

Despite the significant progress made in this study, there are some limitations, such as the relatively small sample size and the lack of structural MRI data analysis. Future research could expand the sample size and incorporate structural MRI data to further explore the mechanisms of brain network reorganization during the chronic progression of tinnitus.