Multi-site and state-dependent effects of Transcranial Ultrasound Stimulation on brain function and cognition

Brain Stimulation Lab

Principal Investigator: Dr Elsa Fouragnan

Co-investigators: Dr Sam Hughes – University of Exeter, Dr Matthew Howard – Kings College London, Dr Nils Kolling – University of Oxford, Professor Kim Butts Pauly – Stanford University, Dr Jerome Sallet – French Institute of Health and Medical Research

Funded by: Biotechnology and Biological Sciences Research Council, part of UK Research and Innovation

2023–2025

Brain or neuroplasticity – the ability of the nervous system to change its activity in response to stimuli

Brain plasticity plays a crucial part in response to a large range of brain disorders, as well as healthy ageing. Measures of neuroplasticity can improve our understanding of diseases, treatments and strategies to improve health outcomes and also in understanding of the brain in general health.

Current methods to change brain function, and promote neuroplasticity are invasive and require surgery, such as deep brain stimulation.

Other methods suffer from low spatial resolution – like magnetic stimulation and can only reach superficial areas of the brain – and so cannot be used to investigate small structures of the brain, particularly the deep cortex or the subcortex.

Transcranial ultrasound stimulation (TUS) can be used to safely induce neuroplasticity in deep brain regions with millimetric resolution up to an hour after intervention, using acoustic energy to affect neuronal activity.

This research aims to examine whether the state of targeted brain regions interact with TUS-induced plasticity and therefore optimise designs of TUS therapies.

Is TUS ‘state’-dependent?

At the University of Plymouth, we have demonstrated that TUS can be employed to perturb brain activity in specific brain areas, revealing causal relationships between distinct brain areas and their functions. But how do variations in physiological and task demands – ‘states’ – alter the effects of TUS on neural activity and behaviour? E.g. awake or sleeping (physiological state) or resting or focusing on a task (cognitive state).

We will investigate for the first time the relationships between brain states and TUS and whether recruitment of targeted brain regions improves TUS-induced plasticity. This is crucial for optimizing future treatment designs, particularly those leveraging cognitive-behavioural tasks during TUS therapies. We will focus on the effects of the same TUS intervention on different states:

different states of consciousness (manipulated with different depths of anaesthesia)
different states of pain sensitivity (manipulated through experimental manipulation of pain development)
different cognitive load (manipulated through complex versus simple learning tasks).

Better refining the relationship between TUS and states will be vital to pave the way for effective clinical interventions, particularly those combining cognitive-behavioural therapy and brain stimulation.

Does concurrent multi-site TUS improve outcome measures?

In earlier studies, we showed that TUS specifically affects the targeted brain area, including its connections to other brain circuits. We tested how specific these effects are by examining whether changes in one brain region influence its related functions.

While this method showed that certain brain areas are important for specific functions, it still provides limited information about how brain networks work together.

TUS can reach any region in the brain – in the order of millimetres – even deep in the brain, unlike more traditional methods that remain superficial and not spatially accurate. This is important when trying to assess the role of specific nuclei in the brain or specific regions.

Some regions of the brain have specific functions, for example, a brain region A can be linked to a function A, while another brain region B can be linked to a function B. By modulating regions A and B on different days, one can assess the role of these regions.

However, sometimes a function is linked to the way regions communicate with one other and not solely on the region themselves. In theory, this could be assessed through concurrent brain stimulation of the two regions.

In this new line of research, we will also pursue the idea that TUS can be used at different locations of the brain at the same time, in order to change communication between brain regions.

We want to show that concurrent multisite TUS is safe and can increase outcome measures by providing additional ways of intervening in the brain. This will increase the potential of TUS applications and open a new avenue for thinking about non-invasive brain stimulation which considers the dynamism of brain networks.

Leading the way in transcranial ultrasound stimulation

The University of Plymouth's pioneering research in transcranial ultrasound stimulation has the potential to improve the lives of millions of people with mental health conditions as well as neurological disorders like Parkinson’s disease.

Dr Elsa Fouragnan is a leading authority on transcranial ultrasound stimulation research in the UK, and is recognised internationally. Her lab is one of the few in the UK to apply TUS in humans.

This research is hosted at the University’s Brain Research & Imaging Centre (BRIC) – the most advanced multi-modal brain research facility in the South West.

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