Predict TMS Tinnitus Relief with Brain Scans

For many with tinnitus, repetitive transcranial magnetic stimulation (rTMS) offers hope, but its effectiveness is notoriously inconsistent. Only about half of patients experience meaningful relief. New research led by Zhongling Ding, Bo Peng, and Mengfang Gong provides a potential solution: a pre-treatment brain scan that can predict a patient’s likelihood of success with remarkable accuracy. The study identifies a specific structural feature in the brain that distinguishes future responders from non-responders, moving tinnitus treatment closer to a precision medicine approach.

Pinpointing a Predictive Brain Signature

The researchers prospectively studied 64 patients with subjective tinnitus and 18 healthy controls. All patients underwent a standard two-week course of rTMS treatment. Before any treatment began, each participant received a high-resolution structural MRI (sMRI) scan. The team then extracted 242 distinct measurements of brain morphology from these scans, creating a detailed map of each brain’s architecture.

After treatment, patients were classified as responders (56.25%) or non-responders based on their improvement in tinnitus severity. The central question was whether the pre-treatment brain scans of these two groups looked different. Univariate analysis flagged ten regional brain features that distinguished responders from non-responders. These features spanned networks involved in prefrontal, limbic, sensorimotor, and parietal functions, indicating that the potential for rTMS benefit is not localized to the auditory cortex but involves a broader brain network.

Right Inferior Frontal Gyrus Emerges as Top Predictor

To build a practical predictive tool, the researchers used these ten features to train a machine learning model. The model was rigorously evaluated using 5-fold cross-validation. Its performance was strong, with an area under the curve (AUC) of 0.85, an accuracy of 77%, and a recall of 97%, meaning it was excellent at correctly identifying most future responders.

A SHAP analysis, which explains the output of the machine learning model, pinpointed the single most important predictor: the gray matter volume (GMV) of the right pars triangularis of the inferior frontal gyrus (IFGtriang-R). A larger volume in this region before treatment was associated with a positive outcome from rTMS.

To understand this finding, the team compared this brain measure across three groups: responders, non-responders, and healthy controls. The IFGtriang-R GMV was significantly larger in responders (0.90 ± 0.08) than in both healthy controls (0.86 ± 0.06) and non-responders (0.86 ± 0.07). This pattern is critical. It shows that responders possess a unique structural signature—a relative enlargement of this specific frontal brain region—compared to both healthy individuals and those who do not benefit from treatment. This work adds to a growing body of evidence that brain biomarkers can predict tinnitus treatment success.

Interpreting the Role of the Inferior Frontal Gyrus

The inferior frontal gyrus, particularly on the right side, is not primarily an auditory region. It is a key node in cognitive control, attention regulation, and salience detection networks. In the context of tinnitus, it is thought to help modulate the perceived importance and intrusiveness of the phantom sound. A larger volume in this area may indicate a greater inherent capacity for neuroplastic change—a higher “neuroplastic reserve”—within these control networks. This reserve could set a threshold, making some brains more amenable to the neuromodulatory effects of rTMS, which aims to rewire maladaptive tinnitus networks. This concept aligns with the broader framework of integrated auditory health from cochlea to cortex.

Clinical Implications and a Path to Precision Treatment

The practical implication of this study is direct. A routine structural MRI scan, assessed for the volume of the right IFG pars triangularis, could become a valuable clinical tool for patient stratification. Identifying individuals with a high probability of responding to rTMS would allow clinicians to recommend this often costly and time-intensive treatment with greater confidence. Conversely, for those predicted to be non-responders, clinicians could avoid a likely ineffective treatment and explore alternative strategies sooner, such as combined sound and tongue stimulation or cognitive behavioral approaches.

Interestingly, the study found that the IFGtriang-R volume did not linearly correlate with the degree of improvement (ΔVAS or ΔTHI scores), nor did any structural feature strongly correlate with baseline tinnitus severity after statistical correction. This supports the “threshold effect” hypothesis: having a larger volume in this region may be a necessary precondition for a positive response, but other factors then determine the exact magnitude of benefit.

Conclusion

The research by Ding, Peng, and Gong marks a shift from a trial-and-error approach to a predictive model for rTMS in tinnitus. The enlargement of the right inferior frontal gyrus pars triangularis emerges as a promising biomarker, suggesting that a brain’s structural predisposition for cognitive control influences its receptivity to neuromodulation. While further validation in larger, independent cohorts is needed, pre-treatment sMRI assessment holds clear potential to personalize neuromodulation therapy, ensuring it is offered to those most likely to benefit. You can read the full, open-access study for more details: Frontiers in Neurology (2026).