Developing novel neuroimaging approaches to investigate the neural antecedents of tics and brain correlates of premonitory urges in Tourette syndrome

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Tourette syndrome (TS) is a neurological condition of childhood onset that is characterised by motor and vocal tics. Many (~90%) people with TS report that their tics are preceded by a 'premonitory urge' (PU) that is described as uncomfortable bodily sensations that is experienced as a strong urge-to-tic. People who experience PU often report that they would not exhibit tics if they did not experience PU. For these reasons, we consider it timely and highly important to investigate the brain mechanisms that give rise to the urge to tic in TS using brain imaging techniques such as functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG).Unfortunately, scanning individuals with TS using conventional fMRI and MEG methods is extremely difficult due to their unwanted movements, which often lead to a very high (50-75%) loss of data. This problem is exacerbated if the individual is actually required to express their tic while being scanned (i.e., in conventional fMRI analyses it is necessary that tics actually occur so that the time course of the brain activity associated with producing the tic can be modelled). However, most TS patients can suppress their tics quite effectively: although tic suppression is associated with increasing levels of discomfort which is experienced as a strong urge-to-tic. This suggests that we might successfully scan many TS patients if we asked them to suppress their tics throughout the period they were being scanned. The objective of this project is to develop new approaches to imaging PU and the neural antecedents of tics in TS. One approach is based upon an alternative, data-driven, framework for the analysis of functional magnetic resonance imaging (fMRI) data, termed 'Multi-echo Sparse Paradigm Free Mapping' (ME-SPFM), in which we obtain fMRI measurements associated with PU that occur in TS without the necessity for tic expression. Using this approach, we will accurately and reliably identify functional brain activity that is associated with the occurrence of PU in circumstances where tics are effectively suppressed (i.e. there is no tic to use as an external timing event). The second approach involves our using an entirely novel form of wearable MEG device, developed at the University of Nottingham. MEG is a non-invasive brain imaging technique that has advantages over fMRI: not least it allows the measurement of ongoing brain activity at the millisecond scale. Using this device will allow us to record brain activity associated with PU, and the brain activity that precedes a tic, in patients with TS even when they are executing large head or body movements. A key focus of the MEG studies that we will carry out are that they will allow us to investigate how transiently-synchronising brain networks are assembled linking brain regions associated with the experience of the urge-for-action with brain networks involved in the initiation of action. Once again, these analyses will be conducted using novel, state-of-the-art, data-driven approaches to investigating changes in functional connectivity between brain areas.