Transcranial focused ultrasound platform for noninvasive neuromodulation

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Project Summary This S10 grant application requests funds to purchase a transcranial focused ultrasound (FUS) instrument platform for translational neuroscience studies in human and nonhuman primates. FUS is a means of non- invasively modulating neural activity, similar to transcranial magnetic stimulation (TMS) and electrical stimulation, through the application of ultrasonic acoustic vibrations, and can be implemented safely across a variety of species. Importantly, FUS has a number of important advantages over magnetic and electrical neuromodulation, including better spatial resolution (as small as .5 mm), and true three-dimensional targeting. Additionally, FUS technology has novel applications beyond direct stimulation, such as the ability to fenestrate the blood brain barrier for defined periods of time, with high spatial precision, opening new avenues for inducing noninvasive chemogenetic and optogenetic receptor expression. These strengths make FUS an ideal translational neuromodulatory technology for testing the causal relationship between neural functioning and behavior in a variety of species. Here we are requesting the funds to outfit the Center for Biomedical Imaging and Neuromodulation (C-BIN) at the Nathan Kline Institute with state-of-the-art, MRI compatible ultrasound instrumentation that is integrated with neuronavigation. This instrument system will complement our current TMS and transcranial electrical stimulation instruments. C-BIN has a long history of implementing novel neuroscientific techniques, and the integration of FUS would complement a number of mental health research projects that are ongoing and proposed within the institute. As a form of noninvasive neuromodulation, the proposed instruments would provide a benefit to current mental health research investigating the therapeutic effects of neuromodulation in major depressive disorder and Alzheimer’s Disease, schizophrenia, and post- traumatic stress disorder, and the neural underpinning of functional resting-state in nonhuman primates and humans. The addition of FUS as a translational neuromodulatory technique also opens the door to a large variety of new mental health related projects.