外周-中枢相互作用塑造衰老和噪声暴露过程中听性脑干反应波幅与听阈之间的解耦：一项计算建模研究。
Peripheral-central interactions shape the decoupling between auditory brainstem response amplitudes and auditory thresholds during aging and noise exposure: a computational modeling study.
文献信息
| PMID | 42822759 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Juan Carlos Alvarado |
| 作者单位 | Research Group on Neurodegenerative Diseases and Their Relationship with Neurosensory Alterations and Aging, Institute of Biomedicine of Castilla-La Mancha (IB UCLM), Department of Medical Sciences, School of Medicine of Albacete, University of Castilla-La Mancha, Albacete, Spain. Electronic address: juancarlos.alvarado@uclm.es. |
| 期刊 | Neuroscience |
| SCI 分区 | Q2 |
| IF | 3.2 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
背景： 年龄相关性和噪声诱导的听力损失反映了进行性耳蜗退变以及中枢听觉通路的适应性改变，但它们对听性脑干反应（ABR）波幅和听阈的联合影响仍不清楚。方法：我们开发了听觉稳态动力学模型（AHDM），这是一个三状态常微分方程模型，涵盖低、中、高频域中毛细胞感觉功能、耳蜗突触完整性和活动依赖性中枢补偿。该模型包括乘性外周门控、受限的ABR输出以及靶向外周和中枢消融。在4,096个参数集上评估了稳健性。衰老组分根据已发表数据进行校准，并在独立的纵向和噪声暴露数据集中不重新拟合进行评估。结果：中枢补偿稳健地增加了相对II波保留并减弱了阈值表达，而神经-阈值解离取决于外周区室之间的平衡。校准使平衡预测误差降低了78.2%。迁移至独立的未暴露2019队列后，I波和II波误差分别改善了65.5%和72.9%，尽管衰退被过早预测。按方案映射的模拟捕捉了2019年的累积暴露效应以及2020年的持续性阈值偏移，在未治疗动物中均方根误差为5.60 dB。结论：结果确定了参数依赖性的外周解离、稳健的下游中枢调制以及AHDM的明确经验域。
英文摘要
Age-related and noise-induced hearing loss reflect progressive cochlear degeneration and adaptive changes in central auditory pathways, yet their joint effects on auditory brainstem response (ABR) amplitudes and auditory thresholds remain unclear. We developed the Auditory Homeostatic Dynamics Model (AHDM), a three-state ordinary differential equation model of hair-cell sensory function, cochlear synaptic integrity, and activity-dependent central compensation across low-, mid-, and high-frequency domains. The model includes multiplicative peripheral gating, constrained ABR outputs, and targeted peripheral and central ablations. Robustness was assessed across 4,096 parameter sets. The aging component was calibrated to published data and evaluated without refitting in independent longitudinal and noise-exposure datasets. Central compensation robustly increased relative Wave II preservation and attenuated threshold expression, while neural-threshold dissociation depended on the balance between peripheral compartments. Calibration reduced balanced prediction error by 78.2%. Transfer to the independent non-exposed 2019 cohort improved Wave I and Wave II errors by 65.5% and 72.9%, although decline was predicted prematurely. Protocol-mapped simulations captured cumulative exposure effects in 2019, and persistent threshold shifts in 2020, with a root mean square error of 5.60 dB in untreated animals. The results identify parameter-dependent peripheral dissociation, robust downstream central modulation, and a defined empirical domain for the AHDM.