Differential mechanisms of continuous theta burst stimulation and low-frequency repetitive transcranial magnetic stimulation for chronic tinnitus: preliminary efficacy dissociation by local focalization vs. network dispersion

Abstract

Objective This study aimed to preliminarily compare clinical efficacy and neural mechanisms of continuous theta-burst stimulation (cTBS) and low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the auditory cortex in chronic subjective tinnitus. Differential effects on tinnitus loudness and distress, as well as the moderating role of disease duration, were explored. Methods Twenty-nine patients were randomly assigned to cTBS (n = 16) or rTMS (n = 13) groups. Neuronavigation-guided stimulation was applied to the individualized auditory cortex peak activation site. Outcome measures included the Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS) at baseline, post-treatment, 1-month, and 3-month follow-ups. Resting-state fMRI was used to analyze amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Functional connectivity (FC) analysis was performed to explore the network-level changes. Results Clinically, cTBS was associated with a rapid reduction in VAS-rated tinnitus loudness (p = 0.004), while low-frequency rTMS demonstrated sustained improvements in THI scores up to the 3-month follow-up (p = 0.007). Mixed-model ANCOVA yielded significant time-by-group interactions for THI and VAS, verifying different therapeutic profiles between cTBS and rTMS. Resting-state fMRI uncovered separable brain plasticity: cTBS induced focal changes in left auditory cortex, whereas rTMS remodeled extensive limbic-cognitive networks. Two-way ANCOVA confirmed shared left prefrontal interaction signals, supporting stronger prefrontal suppression by cTBS. Baseline tinnitus duration was negatively correlated with 3-month THI improvement rates. Collectively, clinical and dual resting-state imaging results identified separable therapeutic and neuromodulatory signatures of cTBS and low-frequency rTMS. Conclusion Our exploratory results suggest that cTBS may facilitate a rapid reduction in tinnitus loudness possibly through focal auditory modulation, while low-frequency rTMS eases persistent tinnitus distress through large-scale network remodeling. Our findings provide preliminary evidence for the divergent prefrontal inhibitory profiles of the two inhibitory protocols. Shorter tinnitus duration predicts better therapeutic outcomes, highlighting the value of early intervention. These exploratory results provide evidence for personalized TMS-based neuromodulation in chronic tinnitus.