Predicting TMS Success for Tinnitus

A two-week course of repetitive transcranial magnetic stimulation (rTMS) reduced tinnitus for just over half of patients in a new study. For the other half, the treatment was ineffective. Researchers have now found a potential explanation for this split: a specific, measurable difference in brain structure visible on an MRI scan before treatment even begins.

Scientists led by Zhongling Ding, Bo Peng, and Mengfang Gong examined whether pre-treatment brain anatomy could predict which patients with subjective tinnitus would respond to rTMS. Their work, published in *Frontiers in Neurology*, identified a single brain region whose size was strongly linked to a positive outcome. This finding moves the field closer to a precision medicine approach for tinnitus neuromodulation.

### How Researchers Identified a Brain Biomarker
The study enrolled 64 patients with subjective tinnitus and 18 healthy controls for comparison. All patients underwent a high-resolution structural MRI scan. From these scans, the team extracted 242 distinct measurements of brain morphometry, covering the volume and thickness of regions across the cortex.

Patients then received a standardized two-week course of rTMS treatment. Based on their reported improvement in tinnitus severity (using Visual Analogue Scale and Tinnitus Handicap Inventory scores), they were classified as either responders (36 patients) or non-responders (28 patients).

The researchers first used univariate analysis to see which of the 242 brain features differed between responders and non-responders. Ten regional features showed significant differences. These features were then fed into a machine learning model to build a predictive tool. The model’s performance was rigorously tested using 5-fold cross-validation to avoid overfitting, and its decisions were interpreted using SHAP analysis to identify the most important predictors.

### The Right Inferior Frontal Gyrus Emerges as Top Predictor
The machine learning model achieved strong predictive performance, with an area under the curve (AUC) of 0.85, accuracy of 77%, and a recall of 97% for identifying future responders. The SHAP analysis pinpointed one feature as the most influential: the gray matter volume of the right pars triangularis, a sub-region of the inferior frontal gyrus (IFGtriang-R).

In responders, the volume of this region was significantly larger (0.90 ± 0.08) than in both healthy controls (0.86 ± 0.06) and non-responders (0.86 ± 0.07). This three-group comparison was critical. It showed that responders had a specific structural signature—not just a difference from non-responders, but also a deviation from the typical brain structure seen in people without tinnitus.

Interestingly, the size of the IFGtriang-R did not linearly correlate with the *degree* of improvement. Instead, its influence appeared to be more of a threshold effect: having a larger volume in this area made a positive response to rTMS much more likely.

The right inferior frontal gyrus is not primarily an auditory processing area. It is deeply involved in cognitive control, attention, working memory, and emotional regulation. Its involvement suggests that the brain’s capacity to benefit from rTMS may depend on a reserve of neuroplastic potential in these higher-order cognitive networks.

### What This Means for Tinnitus Treatment
The practical implication of this research is direct. A routine structural MRI scan could, in the future, be used to stratify patients. Clinicians could identify those with a high probability of benefiting from rTMS, avoiding the time, cost, and potential disappointment of an ineffective treatment for others. This aligns with a broader shift in neurology and psychiatry toward using biomarkers to guide brain stimulation therapies.

“This study provides a clear, anatomical target that can be assessed prior to treatment,” the authors note. The enlargement of the IFGtriang-R in responders may indicate a greater inherent capacity for the brain to reorganize—a neuroplastic reserve—that rTMS can effectively engage.

It is important to note that rTMS is one of several neuromodulation approaches for tinnitus. Other strategies, such as bimodal stimulation, work on different principles. The search for predictive biomarkers is a active area across all these modalities.

Furthermore, the cognitive role of the identified brain region underscores the complex nature of tinnitus, which often involves attentional and emotional components beyond mere sound perception. This complexity is why multidisciplinary approaches, including manual therapy for temporomandibular issues, can be effective for some patients, as they address different contributing factors.

The concept of predicting treatment response based on baseline characteristics is not unique to tinnitus. Similar research is exploring predictors for therapies in other sensory and cognitive conditions. For instance, in sleep medicine, studies examine how baseline depression influences outcomes of Cognitive Behavioral Therapy for Insomnia (CBT-I).

### The Path Toward Precision Neuromodulation
The study by Ding, Peng, and Gong is a step toward making rTMS a more reliable and efficient tool for tinnitus. By identifying patients who are neurologically primed to respond, clinicians can allocate resources more effectively and set realistic expectations.

Future research will need to validate this biomarker in larger, independent patient groups and determine if it is specific to rTMS or predicts response to other tinnitus treatments. The work also opens a scientific question: why does a larger right inferior frontal gyrus confer this advantage? Understanding that mechanism could lead to novel therapies designed to actively enhance this neuroplastic reserve.

For now, the evidence suggests that the brain’s own architecture holds clues to treatment success. In tinnitus care, where patient experiences and treatment responses are highly variable, such objective clues are invaluable.

**Source:** Ding Z, Peng B, Gong M. (2026). Pre-treatment brain structural biomarkers predict efficacy of repetitive transcranial magnetic stimulation for subjective tinnitus. *Front Neurol*. DOI: 10.3389/fneur.2026.1808769.