Control of focal brain stimulation with high-precision robotic aid

New technologies have allowed us to look at the healthy human brain in action with remarkable clarity. A somewhat surprising observation, however, has been that different brain regions often show the same patterns of activity as each other. For example, in a study where you are asked to categorise a sound as either a word or non-word, lots of brain regions may show more activity for the word vs non-word. Do all these brain regions truly do the same thing?
One way to solve this problem is to see what happens when typical brain function is disrupted. There is a long history of neuroscientists working with patients groups to find out which brain regions make critical contributions to domains of psychological function. For example, damage to the prefrontal cortex may lead to challenges in making good decisions, suggesting this brain regions is important for decision making. However, studying patients groups has drawbacks. We often don't know exactly how much brain damage there has been, making localisation difficult. We also don't get to choose where and how patients come to have brain injury. However, methods for non-invasive brain stimulation are able to address some of these limitations and open up the possibility of testing the non-damaged brain.
One such method is transcranial magnetic stimulation (TMS), which is well-established as a safe and effective form of brain stimulation. TMS uses brief magnetic pulses to perturb brain activity in a localised region (~5mm). We can apply this stimulation and see how the behaviour of participants change during or after TMS. TMS can also be combined with measurements of brain activity, to help us understand how individual brain regions may modulate the activity of whole networks of brain regions.
TMS is therefore an exciting method for contemporary cognitive neuroscience. However, there are some severe practical constraints on TMS that limit the method. The key practical limitation is the consistency of the stimulation position relative to the participant's head. The stimulator is either held manually in place by an experimenter or by a specialised mechanical arm, after manual placement. As experiments frequently last for over 60 minutes, maintaining the same stimulator position consistently is almost impossible. Small movements by either the experimenter or the participants can mean that much larger regions of the brain are stimulated than intended. Also, it is difficult to test two brain regions that are very close to each other.
To solve these problems, we propose to purchase an Axilum TMS-robot (ATR). This equipment automates the placement of the stimulator, relying on a brain scan (MRI) to ensure accuracy. Importantly, the ATR will be able to compensate for any head movements from the participant, moving automatically to make sure the stimulation target is maintained. There are several further advantages of the ATR, such as the ability to prepare the stimulation session in advance. This can help to reduce the amount of time participants have to spend in the lab and increase the efficiency with which we can run the whole experiment.
We aim to take advantage of the ATR to answer a broad range of research questions: 1) Can we use brain stimulation to reveal the neural mechanisms that help us learn to cope with challenging sensory environments? 2) How does the prefrontal cortex help us attend to relevant information and ignore irrelevant information? Here, TMS will help us differentiate between different regions of the prefrontal cortex in tasks that require you to attend to different parts of a visual scene. 3) Can TMS be used as an effective intervention for depression and other psychiatric conditions? 4) What is the sequence of brain activity that supports accurate speech perception and production?

Contemporary research into the biological basis of human cognition is often limited by an inability to make causal inferences about the necessity of neural activity for healthy cognition, or the significance of atypical activity for treating clinical disorders. To open this avenue of research, we can use methods that temporarily perturb neural activity in localised regions of brain tissue. Transcranial magnetic stimulation is a safe and well-established method for doing so, but is often critically limited by the accuracy of the placement of the stimulator coil on the surface of the scalp. Currently, a researcher will typically manually adjust (or even hold) the coil to target the brain region of interest. This is suboptimal due to the almost certainty of movement by either the participant or the researcher.
To overcome this limitation, we propose to acquire an Axilum TMS-robot (ATR). This is a fully automated coil placement system, which spatially targets the stimulation based on an individual participant's anatomy (i.e. structural MRI scan). The ATR will track any participant head motion throughout the experimental session. This ensures high-precision stimulation, even for long (e.g. >60 minutes) sessions and sessions can be easily replicated exactly. The ATR therefore removes any variability that arises from manual placement and/or static positioning of the stimulation coil. The ATR system will also be used in conjunction with neuroimaging (EEG). This combination of methods means that we can both validate the neural impact of TMS and track the TMS-induced neural activity. We have also recently invested in a new NIBS method, transcranial ultrasound stimulation (TFUS), which can used with the ATR.
The ATR is a solution to a practical limitation for many TMS/TFUS studies and therefore the research that will benefit from its technical advances are very broad, covering several MRC priority areas (Mental Health, Precision Medicine, Advanced Therapies).