 Current non-invasive neuromodulatory approaches like transcranial magnetic stimulation TMS and transcranial direct current stimulation tDCS have proven efficacious for inducing transient plastic changes in the human cortex. However, these technologies have poor spatial resolution, suffer from a depth focality tradeoff and experience significant attenuation at depth. Thus, they cannot effectively target neural tissue below the surface of the cortex. Transcranial focused ultrasound tFUS is a new and very promising non-surgical low-energy technique for inducing transient plasticity with high spatial resolution, adjustable focus and low tissue attenuation. tFUS has been used safely and effectively for neural stimulation in mouse, rabbit and monkey and my research has shown tFUS to also be a safe and effective method of transient cortical stimulation in humans. Having demonstrated its efficacy in humans for cortical stimulation, the next step is to take advantage of tFUS high spatial resolution and deep focal lengths to stimulate sub-cortical neural structures. Currently, the only way to stimulate sub-cortical structures involves expensive and risky surgery. It is the purpose of this proposal to test tFUS for sub-cortical stimulation. The ability to individually stimulate small neural structures deep to the cortex without invasive surgery would have broad application in basic neuroscience for the investigation of brain structure and function as well as for the potential diagnosis and therapy of many neurological and psychiatric diseases. 