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

@article{zhang2026differential,
  title = {{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}},
  author = {Mengxue Zhang and Li Qin and Enli Jin and Chaoqi Shi and Jiayu Ni and Jiaying Wang and Siqi Gao and Yiqi Ma and Xiao Li and Yuan Li},
  journal = {Frontiers in neurology},
  year = {2026},
  month = sep,
  doi = {10.3389/fneur.2026.1921227},
  url = {https://europepmc.org/article/PMC/PMC13661314},
  note = {CC BY},
}

TY  - JOUR
TI  - 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
AU  - Mengxue Zhang
AU  - Li Qin
AU  - Enli Jin
AU  - Chaoqi Shi
AU  - Jiayu Ni
AU  - Jiaying Wang
AU  - Siqi Gao
AU  - Yiqi Ma
AU  - Xiao Li
AU  - Yuan Li
PY  - 2026
DA  - 2026/09/30
JO  - Frontiers in neurology
DO  - 10.3389/fneur.2026.1921227
UR  - https://europepmc.org/article/PMC/PMC13661314
AB  - 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.
SN  - 1664-2295
ER  -