经颅超声刺激(TUS)作为一种有前途的非侵入性神经调节技术正在迅速兴起。TUS在动物模型中已经很成熟,为现在优化人类应用的神经调节功效提供基础。在多项研究中,一个有希望的协议,1000Hz脉冲,一直导致人类运动皮层抑制(Fomenko等人。,2020)。同时,一项平行研究线强调了由可听频率的TUS脉冲引起的周围听觉刺激的潜在混杂影响.在这项研究中,我们将直接的神经调节和间接的听觉对TUS的运动抑制作用的贡献分开。为此,我们在四个实验中包括紧密匹配的控制条件,一个预先注册的,在三个机构独立进行。我们采用了经颅超声和磁刺激相结合的范例,其中TMS引起的运动诱发电位(MEPs)是皮质脊髓兴奋性的指标。首先,我们复制了TUS的运动抑制作用,但通过严格控制和操纵刺激强度,持续时间,和听觉掩蔽条件,这种抑制是由周围听觉刺激驱动的,不是直接的神经调节.此外,我们认为神经调节超出了驱动整体兴奋/抑制的范围,并显示了TUS可能与正在进行的神经动力学相互作用的初步证据.首先,这项研究强调了在考虑先前TUS-TMS工作中的听觉混淆方面的重大缺陷,在这些工作中,仅使用了翻转假操作而没有使用主动对照.鉴于已证明的外围矛盾的影响,该领域必须严格地重新评估以前的发现。此外,在未来的TUS研究中,需要通过(在)主动控制条件进行严格的实验设计,才能提出有证据的主张。只有当直接效应与周围混淆驱动的效应分离时,TUS才能充分发挥其研究和临床应用的潜力。
Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where
TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-
TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.