Background Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways. Objective We aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal. Methods In 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were <0.5 °C at the target and <3 °C in the skull. To test for non-specific auditory activation, TUS (500 kHz, 300 ms burst, modulated at 1 kHz with 50% duty cycle) was applied to primary visual cortex and participants were asked to distinguish stimulation from non-stimulation trials. EEG was recorded throughout the task. Furthermore, ex-vivo skull experiments tested for the presence of skull vibrations during TUS. Results We found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound. Conclusion Future studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.

中文翻译：

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人体经颅超声刺激与可以有效掩盖的听觉混淆有关

背景经颅超声刺激 (TUS) 正在成为一种潜在的强大的、非侵入性的局灶性脑刺激技术。然而，最近的动物研究表明，TUS 效应可能会被早期听觉通路的间接刺激所混淆。目标 我们旨在调查人类参与者 TUS 是否会引发可听见的声音，以及这些声音是否可以被音频信号掩盖。方法 在 18 名健康参与者中，获得 T1 加权磁共振脑成像以进行 3D 超声模拟，以确定最佳换能器放置和源振幅。热模拟确保目标处的温升<0.5°C，头骨处的温升<3°C。为了测试非特异性听觉激活，TUS（500 kHz，300 ms 突发，以 1 kHz 调制，占空比为 50%）应用于初级视觉皮层，并要求参与者区分刺激与非刺激试验。在整个任务过程中记录脑电图。此外，体外颅骨实验测试了 TUS 期间颅骨振动的存在。结果 我们发现参与者可以在 TUS 期间听到声音，并且可以区分刺激和非刺激试验。表明与 TUS 相关的听觉激活的 EEG 记录证实了这一点。在应用 TUS 的同时通过耳机向参与者提供音频波形将检测率降低到机会水平，并消除了 TUS 引起的听觉脑电图信号。体外颅骨实验表明，声音以超声波的脉冲重复频率通过颅骨传导。