The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus induced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. We delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-inducing bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-inducing bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that induces LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide.

耳蜗背核是哺乳动物听觉通路中多感觉汇聚的第一个部位。主要输出神经元，即梭形细胞，将来自耳蜗的听觉神经输入与来自头部和颈部的体感输入整合起来。在之前的工作中，我们开发了由噪声暴露引起的耳鸣的豚鼠模型，并表明这些动物的梭状细胞表现出自发活动和跨单位同步性的增加，这是耳鸣的生理相关性。我们对患有耳鸣的豚鼠的耳蜗背核进行重复的双模式听觉体感刺激，选择已知会诱发长期抑郁（LTD）的刺激间隔。每天 20 分钟的 LTD 诱导双峰（而非单峰）刺激可在 25 天后减少豚鼠耳鸣的生理和行为证据。接下来，我们通过双盲、假对照、交叉研究对 20 名患有耳鸣的人类受试者应用了相同的双模式治疗。 28 天的 LTD 诱导双峰刺激降低了耳鸣响度和干扰性。单峰听觉刺激没有带来任何好处。在耳蜗背核中诱导 LTD 的双模式听觉体感刺激可能有望抑制慢性耳鸣，因为慢性耳鸣降低了全球数百万耳鸣患者的生活质量。