连续θ爆发刺激与低频重复经颅磁刺激治疗慢性耳鸣的差异机制：局部聚焦与网络弥散之间的初步疗效分离

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中文摘要

目的： 本研究旨在初步比较针对慢性主观性耳鸣听觉皮层的连续θ爆发刺激（cTBS）与低频重复经颅磁刺激（rTMS）的临床疗效和神经机制。探讨了对耳鸣响度和痛苦的不同影响，以及病程的调节作用。
方法： 29例患者被随机分配到cTBS组（n=16）或rTMS组（n=13）。在个体化听觉皮层峰值激活位点应用神经导航引导刺激。结局指标包括基线、治疗后、1个月和3个月随访时的耳鸣残疾量表（THI）和视觉模拟量表（VAS）。使用静息态fMRI分析低频波动振幅（ALFF）和局部一致性（ReHo）。进行功能连接（FC）分析以探索网络层面的变化。
结果： 临床上，cTBS与VAS评定的耳鸣响度快速降低相关（p=0.004），而低频rTMS在3个月随访中显示出THI评分的持续改善（p=0.007）。混合模型ANCOVA对THI和VAS产生了显著的时间×组别交互作用，验证了cTBS和rTMS之间不同的治疗特征。静息态fMRI揭示了可分离的脑可塑性：cTBS诱导左侧听觉皮层的局灶性变化，而rTMS重塑了广泛的边缘-认知网络。双向ANCOVA确认了共享的左侧前额叶交互信号，支持cTBS具有更强的前额叶抑制。基线耳鸣病程与3个月THI改善率呈负相关。总体而言，临床和双重静息态成像结果确定了cTBS和低频rTMS可分离的治疗和神经调控特征。
结论： 我们的探索性结果提示，cTBS可能通过局灶性听觉调制促进耳鸣响度的快速降低，而低频rTMS通过大规模网络重塑缓解持续性耳鸣痛苦。我们的发现为两种抑制性方案的不同前额叶抑制特征提供了初步证据。较短的耳鸣病程预示更好的治疗结局，凸显了早期干预的价值。这些探索性结果为慢性耳鸣的个性化TMS神经调控提供了证据。

英文摘要

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.