Step 1 in Designing Appropriate Shams and Controls in Human TUS

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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.