Summary Neuroscience has an essential requirement for large-scale perturbation tools. Such tools would be transformative in the mapping of brain function and the diagnosis and treatment of neurological disorders. The proposed project is aimed at uncovering a potential therapeutic role for US neuromodulation (USNM) in Alzheimer’s disease, following up on early phenomenological observations that focused US may have such an impact. Our project’s goal is to use state-of-the-art in vivo imaging techniques to understand how US could be used to study and manipulate cerebrospinal fluid (CSF) flow in the brain, with applications focused on Alzheimer’s disease, using combined US and simultaneous fluorescence microscopy of amyloid-β and tau. We will study if USNM effects in the brain can lead to changes in blood and CSF flow, and whether USNM induced flow effect amyloid-β or tau clearance in the brain.

Narrative The high tissue penetrability of ultrasound (US) waves presents untapped and exciting opportunities for accessing structures throughout the mammalian brain for therapeutic purposes. In this project, we will investigate the effects of US on cerebrospinal fluid (CSF) blow in the brain building upon unique experimental tools developed in our lab. We will examine whether the impact of US on CSF or vascular flow is potentially coupled to the progression of Alzheimer’s disease.