Magnetic resonance spectroscopy (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. Transcranial focused ultrasound (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.
This research project aims to further our understanding of the neurochemical effects of TUS neuromodulation at the molecular level. We first aimed to outline a framework for safe and effective TUS neuromodulation in humans, and then to investigate the spatial specificity of the TUS effect and how it affects neurotransmitter levels and brain connectivity.
In the short term, this will inform our future studies on investigating decision-making processes using neuromodulation. TUS is a relatively new technique and BRIC is one of the few places where this technique is available to use in human neuroscience research. In the longer term, TUS will potentially be used by many other groups at BRIC, with a view to becoming a leading centre for TUS in the UK. This project is thus a crucial first step to determining how to safely apply TUS neuromodulation in humans and to gain a better understanding of the mechanisms by which TUS modulates neural activity.
We found that TUS changes the concentration GABA (gamma-aminobutyric acid), the main inhibitory neurotransmitter in the brain, in the hour following exposure to TUS in a specific region of the brain called the posterior cingulate cortex. Similarly, the way this region communicates with the rest of the brain was also profoundly altered in the hour that followed TUS. Interestingly, this was not the case for another brain region called the anterior cingulate cortex. Although its connectivity with the rest of the brain was different after TUS, GABA levels did not change in that region. Importantly, these findings were observed while the brain was at rest and not actively involved in any task, suggesting that TUS may act differently on different parts of the brain depending on the underlying tissue composition or brain state.