Step 1 in Designing Appropriate Shams and Controls in Human TUS

项目摘要 延髓核（NAc）是非侵入性脑刺激治疗物质使用的目标 疾病（SUD）。由于其位于大脑深处，经颅超声刺激（TUS）是独特的 在非侵入性脑刺激方法中，能够以高空间分辨率聚焦于NAc。个tu 已经在动物模型中被证明是安全有效的。目前正在对人类进行积极的研究。 然而，在人类研究中使用TUS的一个主要问题是脱靶听觉的可能性。 骨传导声音的刺激，使研究容易受到安慰剂和注意力的影响，这是 与大多数神经系统疾病干预研究相关。这项研究的目的是 提高TUS治疗SUD的严格性和安全性，从而提高TUS治疗SUD的成功率， 从而使真正的创新科学成为可能。我们将通过准确量化听力来做到这一点 人类TUS波形的响应，包括与颅骨形态的相关性，以及设计和测试 一个框架，用于创建波形，降低可听度，同时改善掩蔽，同时仍然提供 研究人员需要的灵活性。我们将针对刺激波形和MR-ARFI波形执行此操作， 我们在临床前数据中显示，其提供了对超声刺激的剂量响应的测量。

Project Abstract The nucleus accumbens (NAc) is a target for non-invasive brain stimulation for the treatment of substance use disorders (SUDs). Due to its location deep in the brain, transcranial ultrasound stimulation (TUS) is unique among non-invasive brain stimulation methods to be able to focus on the NAc with high spatial resolution. TUS has been shown to be safe and effective in animal models. It is currently under active investigation in humans. However, a major concern in the use of TUS in human studies is the potential for an off-target auditory stimulation by bone-conducted sound, making the study susceptible to placebo and attention effects, which are relevant in most studies of neurological disorder interventions. The purpose of this proposed research is to increase the rigor and safety, and therefore success, of TUS in the treatment of SUDs, and TUS more generally, thereby enabling truly innovative science. We will do this by accurately quantitating the hearing response from TUS waveforms in humans, including correlation to skull morphology, and designing and testing a framework for creating waveforms that reduce audibility while improving masking, all while still providing the flexibility needed by TUS researchers. We will do this for stimulation waveforms and for MR-ARFI waveforms, which we show in preclinical data provide a measure of the dose-response to the ultrasound stimulation.