fMRI-compatible TMS stimulation equipment for concurrent brain stimulation and measurement

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One of the great mysteries of our time is how human cognition - our ability to perceive, think, remember, reason, imagine and feel - arises from our brain physiology. Non-invasive brain imaging techniques like functional magnetic resonance imaging (fMRI) allow us to observe the brain in action, examining how blood flow to different parts of the brain changes when participants perform task. This has been important for understanding which brain regions are involved in different tasks, and advanced analysis methods now also allow us to examine the types of stimulus and task distinctions that activity in these brain regions encodes. However, the inference from fMRI is limited in an important way: we cannot tell whether the activity we observe is causally involved in generating thought and behaviour. For example, if a particular brain region is active when a stimulus is shown, this region may be necessary for perception of that stimulus (i.e. the task could not be done without it), or it may just reflect superfluous activation (e.g. a copy of information) that is not critical for perception. Using traditional techniques, we cannot examine whether activity in one brain region is causally linked to activity in another, or whether activity in any brain region is actually necessary for behaviour. The proposed research uses transcranial magnetic stimulation (TMS) concurrent with fMRI to overcome this limitation. TMS is an established technique which temporarily perturbs activity in a targeted brain region. If TMS to a brain region changes performance on a cognitive task, we know that the brain region must be causally involved. Typically, the inference stops there. However, this is again limited because we cannot observe the hidden effects that the TMS is having on local and distant brain regions, meaning that we cannot unpick the mechanisms by which performance was affected. We propose to invest in new cutting-edge TMS machinery that can be used simultaneously with fMRI, so that we can perturb activity in a targeted brain region with TMS and simultaneously read of the effects of the perturbation throughout the brain, while also recording any changes in behaviour. This will allow us to trace the local and distant, immediate and sustained physiological effects of the TMS stimulation, and thus to link neural activity in the targeted brain region with information processing throughout the brain, and behaviour. In this way we will finally begin to understand the causal role of different brain regions in giving rise to thought and action. This is a critical insight that has been missing from the majority of previous brain imaging studies.This proposal brings together experts in neuroimaging and cognition from across the University of Cambridge in the Departments of Psychology, Psychiatry and the MRC Cognition and Brain Sciences unit, in a new cross-departmental collaboration that will transform the University to a centre of excellence in this field and bring the UK to the forefront of research into the causal biological mechanisms underpinning cognition. We will use the technology to discover the casual biological mechanisms underpinning a wide range of cognitive processes, including how we pay attention, perceive the visual world, understand speech, derive meaning of concepts, learn, and remember. Contributing to a global endeavour to understand the human brain, this will significantly enhance the UK research base in the physiology of cognition, provide outstanding training opportunities for PhD students and early career researchers, and advance our understanding of brain function with implications for human health and well-being including healthy ageing.