Investigating the mechanisms of focused ultrasound mediated neural plasticity using magnetic resonance spectroscopy

Transcranial ultrasound stimulation to target specific types of activity in the brain
Simulated focused ultrasound beam (red/blue) and location of magnetic resonance spectroscopy measurement (white square) overlaid on a structural magnetic resonance image (MRI)
Led by University of Plymouth: Siti Nurbaya Yaakub, Tristan A. White, Professor Elsa Fouragnan - P
Link to Staffmember: Professor Elsa Fouragnan
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Link to Staffmember: Professor Stephen Hall
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Partners: University Hospitals Plymouth NHS Trust; University College London; Radboud University Nijmegen, Netherlands; University of Oxford
Dates: 2023
 

Combining magnectic resonance spectroscopy (MRS) with transcranial focused ultrasound (TUS)

MRS is a technique that non-invasively measures molecular metabolite concentrations in the brain. MRS has been shown to be able to detect changes in excitatory and inhibitory neurotransmitter levels following the application of neuromodulatory techniques that target superficial regions of the brain like transcranial magnetic or electric stimulation. 
TUS is an emerging technique that can modulate brain activity in deep brain regions with high spatial specificity. The biomechanisms by which TUS induces excitatory or inhibitory activity are still poorly understood. Combining TUS with MRS can shed light on how TUS affects measures of neurotransmission and help us understand the effects of TUS on cognition and behaviour in deep brain regions.

Exploring the impacts of TUS

Exploring the impacts of transcranial ultrasound stimulation (TUS), this study involved 24 healthy adults in which two deep cortical regions were separately stimulated and the effects of theta-burst TUS were investigated. This protocol is shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity.
Researchers found theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex in the brain. The findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect – both mechanisms increasingly recognized to influence the brain’s response to neuromodulation.
Levels of excitatory (GIx) and inhibitory (GABA) neurotransmitters
Levels of excitatory (Glx) and inhibitory (GABA) neurotransmitters
Location of MRS measurement (white square) shown on a structural MRI scan
Location of MRS measurement (white square) shown on structural MRI scan

TUS and ‘online’ and ‘offline’ effects

Unlike other non-invasive neuromodulatory techniques, TUS can target both cortical and deep brain regions with high spatial specificity. Dependent on the sonification paradigm (the ultrasound model or pattern) used, the effects can be limited to the period during or immediately after the stimulation (online) or can last several minutes or hours after stimulation (offline).
Offline effects may represent the ability for long-term effects and potential therapeutic applications. 
It is widely thought that TUS induced neuromodulation through mechanical interactions of the ultrasound wave as it passes through cells at the target location. But the mechanism and its effects on large scale human brain connectivity was unclear.

Transcranial ultrasound stimulation in two deep cortical regions

This study confirms that TUS can induce offline changes in two deep cortical regions of the brain: the dorsal anterior cingulate cortex (dACC), part of the salience network and the posterior cingulate cortex (PCC). Aberrant functional connectivity in these networks has been implicated in several neurological and psychiatric disorders, making these regions potential targets for therapeutic TUS applications.
The results demonstrate GABA changes modulated by TUS and functional connectivity changes evolving over time and lasting at least 50 minutes. 
This represents an important first step in the generation of clinical applications that could use TUS to treat mental health disorders.

Publication

Yaakub SN, White TA, Roberts J, Martin E, Verhagen L, Stagg CJ, Hall S & Fouragnan EF (2023) 'Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans' Nature Communications 14, (1) , DOI Open access 

'Targeted ultrasound can change brain functions for up to an hour after intervention'

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Future plans

Based on our findings, we are currently investigating how TUS might affect decision making in humans by applying TUS neuromodulation to key regions involved in decision-making (the anterior cingulate cortex and nucleus accumbens). 

Get involved 

Our research would not be possible without the contribution of time and effort from volunteers. We are currently seeking participants for:
Volunteer with CENTUS: transcranial ultrasound stimulation - P
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Centre for Therapeutic Ultrasound 

One of the most advanced and comprehensive transcranial ultrasound stimulation (TUS) research centres in the world, led by Professor Elsa Fouragnan – a leading authority on brain stimulation research in the UK and recognised internationally.
The only centre that is investigating TUS safety, biomechanics and undertaking clinical studies, our multidisciplinary approach combined with working across several research labs and patient facilities is truly unique.
Discover more about transcranial ultrasound research
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