Targeted, noninvasive neuromodulation of the brain of an otherwise awake subject could revolutionize both basic and clinical neuroscience. Towards this goal, the JHU scientists have developed nanoparticles that allow noninvasive uncaging of a neuromodulatory drug upon the application of focused ultrasound. These nanoparticles are composed of biodegradable and biocompatible constituents and are activated using sonication parameters that are readily achievable by current clinical transcranial focused ultrasound systems. These particles are potent enough that their activation can silence seizures in an acute rat seizure model. Notably, there is no evidence of brain parenchymal damage or blood-brain barrier opening with their use. Further development of these particles promises noninvasive, focal, and image-guided clinical neuromodulation along a variety of pharmacological axes.