Pre-treatment structural brain biomarkers predict response to repetitive transcranial magnetic stimulation in subjective tinnitus.

Overview

1. Department of Otorhinolaryngology, The First Affiliated Hospital of Soochow University, Suzhou, China
2. Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China
3. Suzhou Medical College of Soochow University, Suzhou, China

Abstract

Background: Variable efficacy of repetitive transcranial magnetic stimulation (rTMS) for tinnitus necessitates predictive biomarkers. Pre-treatment brain structural features may predict rTMS outcomes, given that tinnitus involves structural brain alterations and rTMS can induce neuroplastic changes.

Objective: To identify pre-treatment brain structural biomarkers predictive of rTMS efficacy in subjective tinnitus.

Methods: We prospectively enrolled 64 patients with subjective tinnitus and 18 healthy controls (HCs). Patients underwent a 2-week course of rTMS. High-resolution T1-weighted structural MRI (sMRI) was acquired, and 242 whole-brain morphometric features were extracted. Univariate analysis identified features differing between responders and non-responders, which subsequently were used to construct a machine learning model evaluated via 5-fold cross-validation and SHapley Additive exPlanations (SHAP) analysis. Feature significance was further interpreted through three-group comparisons among responders, non-responders, and HCs. Spearman correlation analyses were performed between structural features and clinical improvement scores (ΔVAS, ΔTHI) as well as baseline clinical measures.

Results: Thirty-six patients (56.25%) were classified as responders. Ten regional features distinguished responders from non-responders, encompassing prefrontal, limbic, sensorimotor, and parietal networks. The predictive model (ExtraTreesGini_BAG_L1) achieved optimal performance (AUC = 0.85; accuracy = 0.77; precision = 0.71; recall = 0.97; F1-score = 0.82). SHAP analysis identified right pars triangularis of the inferior frontal gyrus (IFGtriang-R) gray matter volume (GMV) as the top predictor (positive influence). Three-group comparison revealed that IFGtriang-R GMV was significantly larger in responders (0.90 ± 0.08) than in both HCs (0.86 ± 0.06) and non-responders (0.86 ± 0.07), indicating a specific structural signature associated with positive treatment outcome. Spearman correlation analyses revealed that IFGtriang-R volume did not significantly correlate with ΔVAS or ΔTHI, and no structural feature showed a robust association with baseline clinical measures after Bonferroni correction.

Conclusion: Responders were characterized by relative enlargement of the IFGtriang-R, suggesting a threshold effect of neuroplastic reserve conducive to rTMS efficacy. Pre-treatment sMRI assessment of this region may facilitate patient stratification for rTMS treatment, advancing precision neuromodulation for tinnitus.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• doi:10.17632/cj3j8cwnc8.1, at the source; found in “Data availability statement”

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: Mendeley Data (https://doi.org/10.17632/cj3j8cwnc8.1).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Recorded: type, language, journal, volume, pages, dates, 11 authors, 6 keywords, 3 funders, 69 references.

Cite

This paper

Ding, Z., Peng, B., Gong, M., Qiu, H., He, Q., Zhu, X., Kang, S., Sheng, X., Liu, J., Dai, Y., & Tao, D.-D. (2026). Pre-treatment structural brain biomarkers predict response to repetitive transcranial magnetic stimulation in subjective tinnitus. Frontiers in neurology, 17, 1808769. https://doi.org/10.3389/fneur.2026.1808769

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