Advancing the state-of-the-art through multimodal Focused Ultrasound Stimulation (FUS)

Non-invasive brain stimulation equipment is a fundamental tool in neuroscience that allows activity in specific brain regions to be temporally altered. This is important for both basic neuroscience (i.e., understanding the role of a brain region during behaviour by temporally altering its activity) and in the clinical treatments of neurological/psychiatric conditions (i.e., rebalancing the activity of a brain region which is affected by disease). However, existing non-invasive techniques are restricted to brain areas close to the scalp and are unable to target critical deep (subcortical) brain structures. Given the essential role these areas play within behaviour and neural disorders, it is vital for new equipment to be developed that bridges this technological gap. Transcranial focused ultrasound stimulation (FUS) has recently revolutionised the field by allowing, for the first time, the accurate and safe non-invasive stimulation of deep brain structures. Whilst FUS is now an established technique, combining it with neuroimaging techniques (i.e., magnetic resonance imaging), is not. The ability to perform FUS concurrently with neuroimaging opens an exciting window of opportunity to casually map human brain function during behaviour/cognition at a level of detail never previously achieved in health and disease. In addition, it will allow novel interventions to be developed for clinical populations. For example, ongoing brain activity (measured by neuroimaging) could be used as a signal to deliver temporally specific FUS (i.e., closed-loop stimulation) in order to restore normal brain activity/function. This application sets out the case for the purchase of the first commercially available system that enables FUS to be combined with neuroimaging techniques. The state-of-the-art combination of FUS-brain imaging promises novel insight across a large range of scientific areas (learning, memory, consciousness, attention) and neural disorders (Depression, Parkinson's disease, Disorders of Consciousness, Dystonia, Autism). The new equipment will be placed in a specialist facility in the University of Birmingham that is dedicated to the study of human brain health. This facility houses 5 separate brain imaging modalities/techniques alongside specialist trained staff. This will ensure that the equipment will be used rapidly and by the largest possible number of researchers in order to make the greatest possible advances in science and medicine.

The ability to alter activity in specific brain regions is fundamental to both basic neuroscience and in the clinical treatments of neurological conditions. Whilst existing non-invasive techniques are restricted to brain areas close to the scalp, a new form of stimulation -transcranial focused ultrasound stimulation (FUS)- has revolutionised the field. FUS uses sound waves to temporarily alter brain activity with unprecedented resolution and depth of stimulation, allowing the accurate non-invasive stimulation of subcortical brain structures for the first time. Whilst FUS is now an established technique, combining it with neuroimaging techniques (i.e., magnetic resonance imaging) is not. The ability to perform FUS concurrently with neuroimaging opens an exciting window of opportunity in which we can casually examine the role of these subcortical brain areas across a wide range of behaviours in health and disease, and for developing novel personalised stimulation protocols in clinical populations (i.e., closed-loop stimulation) in which these regions are maladaptively affected. This application sets out the case for the purchase of the first commercially available system that enables FUS to be combined with neuroimaging techniques. This cutting-edge combination of techniques, currently unavailable in the UK, will ensure the University of Birmingham is at the forefront of human neuroscience research. The equipment will be housed within a large multiuser centre with 5 different brain imaging modalities and a strong support team. This will enable FUS to be combined with a large range of imaging techniques, ensure the long-term sustainability for the equipment and maximise its userbase. The need for a multimodal FUS platform and our capacity to deliver research excellence is highlighted by a diverse set of planned projects that cover MRC strategic priorities (mental health/precision medicine) and areas of continued investment (neuroscience/methods).