Project Summary/Abstract Anxiety disorders represent a significant mental health disease burden in the United States today, with roughly 1 in 3 Americans expected to be diagnosed with an anxiety disorder in their lifetimes. Current treatment strategies include psychotherapy and psychopharmacology, which are better than nothing, but still are insufficient. Novel brain stimulation techniques have emerged as putative alternatives, but these have drawbacks, namely imprecision and lack of ability to stimulate deep brain structures. Transcranial focused ultrasound (tFUS) suppression of the amygdala has the potential as an ideal therapeutic due to the combination of depth and precision. Today, unfortunately, it lacks validation of the focality of stimulation. Magnetic resonance acoustic radiation force impulse (MR-ARFI) imaging is a technique that can accurately image the tFUS focus by visualizing the micrometer displacement of tissue due to ultrasound. However, MR-ARFI has never before been shown in-vivo in the human brain. This proposal will show for the first time MR-ARFI imaging in humans. Therefore, in Specific Aim 1, MR-ARFI imaging will be acquired in an anthropomorphic phantom. These MR sequence parameters and ultrasound parameters will form the basis of Specific Aim 2, which will show in-vivo amygdala targeting that the location of the ultrasonic focus as predicted by MR-ARFI imaging will be in the area predicted by modeling software. In Specific Aim 3A and 3B, we will show that the more accurately the ultrasound targets the amygdala, the greater the reduction in amygdalar perfusion and anxiety rating scores will be. The described research will form part of the fellowship training plan, providing the fellow with training in MR sequence design, ultrasound parameter design, phantom MR imaging, human subjects imaging, and analysis of human imaging and behavioral data.. The entirety of the fellowship training plan (including the proposed research project) will take place at UCLA. It will supplement the fellow’s training as part of the UCLA-Caltech MSTP. The training plan will be jointly supervised by Drs. Susan Bookheimer and Martin Monti, forming the basis of the fellow’s dissertation. It will give him the skills and training to be an outstanding clinician-scientist.