Ultrasound as a versatile tool for short- and long-term improvement and monitoring of brain function.

Treating the brain with focused ultrasound (FUS) at low intensities elicits diverse responses in neurons, astroglia, and the extracellular matrix. In combination with intravenously injected microbubbles, FUS also opens the blood-brain barrier (BBB) and facilitates focal drug delivery. However, an incompletely understood cellular specificity and a wide parameter space currently limit the optimal application of FUS in preclinical and human studies. In this perspective, we discuss how different FUS modalities can be utilized to achieve short- and long-term improvements, thereby potentially treating brain disorders. We review the ongoing efforts to determine which parameters induce neuronal inhibition versus activation and how mechanoreceptors and signaling cascades are activated to induce long-term changes, including memory improvements. We suggest that optimal FUS treatments may require different FUS modalities and devices, depending on the targeted brain area or local pathology, and will be greatly enhanced by new techniques for monitoring FUS efficacy.