Why does ultrasound change brain function? The cellular and molecular mechanisms of neuromodulation by transcranial focused ultrasound stimulation (tFUS)

About the Project

Transcranial focused ultrasound stimulation (tFUS) is as a major non-invasive neuromodulator used for experimental (Folloni et al., 2019; Yaakub et al, 2023) and therapeutic (Jeong et al., 2021; Lee et al., 2022) purposes. It enables the targeted stimulation of discrete brain regions, with a range of applications from cognitive mapping through to therapies for neurodegenerative disease. But how exactly does FUS exert its effects?

Our work centres on understanding the cellular and molecular mechanisms that underpin neuromodulation by ultrasound. In our two recent publications (Clennell et al., 2021; Clennell et al., 2023), we described how transient ultrasound exposure leads to rapid changes in the intrinsic excitability properties of cortical neurons, and that these effects are initiated at the synapse. In our recent unpublished work, we now find that these effects extend beyond single cells, with consequences for neural circuitry that may have important implications in using tFUS to modulate cognition, in healthy and disease states.

Aims

This PhD will therefore focus on understanding the underlying cellular and molecular mechanisms that are responsible for neuromodulation by ultrasound, using a range of cutting-edge electrophysiology and cell imaging techniques.

• Aim 1: Determine the relationships between focused ultrasound stimulation parameters and neurophysiological effects.
• Aim 2: Determine the consequences of tFUS-induced neuromodulation for cognitive function in vivo.

Methods

We will stimulate brain slice tissue in vitro and explore the effects of specific stimulation protocols on neuronal and neural circuitry physiology. Neuronal function will be assessed by utilising electrophysiological and ion imaging techniques. We will then apply our developed understanding in vivo, determining how specific changes to neural physiology affect cognitive performance in rodents. The project will also involve characterising and defining the ultrasound waveform characteristics using hydrophone measurement and modelling approaches. This project is therefore highly interdisciplinary and will equip the candidate with cutting-edge and highly desirable experimental and analysis techniques.

How to apply for this project

This project will be based in Bristol Medical School – Translational Health Sciences in the Faculty of Health Sciences at the University of Bristol. Use this information to search for the relevant programme in our online application system. Applicants should include the names of two supervisors (with their agreement after discussion of the research proposal). If you have secured your own sponsorship or can self-fund this PhD please visit our information page here for further information on the department of Translational Health Science and how to apply.