Sedley William, Parikh Jehill, Edden Richard A E, Tait Valerie, Blamire Andrew, Griffiths Timothy D
Institute of Neuroscience and
Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle Upon Tyne, NE1 7RU, United Kingdom.
J Neurosci. 2015 Nov 4;35(44):14822-8. doi: 10.1523/JNEUROSCI.2695-15.2015.
It is not known why tinnitus occurs in some cases of hearing damage but not others. Abnormalities of excitation-inhibition balance could influence whether tinnitus develops and its severity if it does. Animal models of hearing damage, which also produce tinnitus based on behavioral evidence, have identified abnormalities of GABAergic inhibition, both cortically and subcortically. However, the precise relationships of GABA inhibitory changes to tinnitus itself, as opposed to other consequences of hearing damage, remain uncertain. Here, we used magnetic resonance spectroscopy to non-invasively quantify GABA in the left (LAC) and right (RAC) auditory cortices of a group of 14 patients with lateralized tinnitus (eight left ear) and 14 controls matched for age, sex, and hearing. We also explored the potential relationships with other brain metabolites (i.e., choline, N-acetylaspartate, and creatine). The presence of tinnitus was associated with a reduction in auditory cortex GABA concentration. Regardless of tinnitus laterality, post hoc testing indicated reductions that were significant in RAC and nonsignificant in LAC. Tinnitus severity and hearing loss were correlated positively with RAC choline but not GABA. We discuss the results in the context of current models of tinnitus and methodological constraints.
Permanently affecting one in seven adults, tinnitus lacks both widely effective treatments and adequate understanding of its brain mechanisms. Existing animal models represent tinnitus that may not be distinguishable from homeostatic responses to the auditory insults used to induce it. Human studies can be well controlled in this regard but are usually not (with few even matching control subjects for hearing loss) and are limited in scope as a result of relying solely on non-invasive recording techniques. Here, we exploit recent advances in non-invasive spectroscopic techniques to establish, in a human study tightly controlled for hearing loss and hyperacusis, that tinnitus is associated with a significant reduction in auditory cortex GABA concentration, which has implications for understanding and treatment of the condition.
目前尚不清楚为什么听力受损的某些病例会出现耳鸣而其他病例却不会。兴奋 - 抑制平衡异常可能会影响耳鸣是否会发生及其严重程度（如果发生的话）。基于行为证据也会产生耳鸣的听力损伤动物模型，已经确定了皮质和皮质下GABA能抑制的异常。然而，与听力损伤的其他后果相反，GABA抑制变化与耳鸣本身的确切关系仍不确定。在这里，我们使用磁共振波谱对一组14名患有单侧耳鸣（8名左耳）的患者和14名年龄、性别和听力相匹配的对照者的左（LAC）、右（RAC）听觉皮层中的GABA进行无创定量。我们还探讨了与其他脑代谢物（即胆碱、N - 乙酰天门冬氨酸和肌酸）的潜在关系。耳鸣的存在与听觉皮层GABA浓度降低有关。无论耳鸣的单侧性如何，事后检验表明RAC中的降低是显著的，而LAC中的降低不显著。耳鸣严重程度和听力损失与RAC胆碱呈正相关，但与GABA无关。我们在当前耳鸣模型和方法学限制的背景下讨论了这些结果。
耳鸣永久性地影响着七分之一的成年人，既缺乏广泛有效的治疗方法，也缺乏对其脑机制的充分了解。现有的动物模型所代表的耳鸣可能无法与对用于诱导耳鸣的听觉损伤的稳态反应区分开来。人类研究在这方面可以得到很好的控制，但通常并非如此（很少有研究为听力损失匹配对照受试者），并且由于仅依赖非侵入性记录技术，其范围有限。在这里，我们利用非侵入性光谱技术的最新进展，在一项对听力损失和听觉过敏进行严格控制的人体研究中确定，耳鸣与听觉皮层GABA浓度的显著降低有关，这对理解和治疗该病症具有重要意义。
