Secondary Histologic Analysis of TUS Studies

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 effective in animal models, without any evidence of damage from either behavioral studies, H&E stained sections, or TUNEL staining. Further, there have been millions of diagnostic imaging studies at the pressures proposed for TUS, that have appeared to be safe. As a result, it is currently under active investigation in humans. However, when it comes to safety, we are compelled to examine all existing data. In particular, we have existing data from our prior studies in which we applied TUS to the sheep brain and examined it on H&E stained sections, as well as TUNEL staining. Here in this proposal, we seek to extend this analysis to the examination of inflammatory cytokines and the examination of glial cells using immunohistochemistry. These studies will give us a more complete picture whether TUS has an inflammatory effect on the brain.