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

图雷特综合征（TS）是一种儿童期发病的神经系统疾病，其特征是运动和发声抽搐。许多（~90%）TS患者报告说，他们的抽搐之前有一个“先兆冲动”（PU），被描述为不舒服的身体感觉，这是一个强烈的冲动抽搐的经验。经历PU的人经常报告说，如果他们没有经历PU，他们就不会表现出抽搐。基于这些原因，我们认为利用脑成像技术，如功能性磁共振成像（fMRI）和脑磁图（MEG）来研究TS患者产生抽搐冲动的脑机制是及时和非常重要的。不幸的是，由于TS患者不想要的运动，使用传统的功能性磁共振成像和脑磁图方法扫描TS患者是非常困难的，这通常导致非常高（50-75%）的数据丢失。如果个体实际上被要求在被扫描时表达他们的抽搐（即，在传统的fMRI分析中，抽搐必须实际发生，以便可以模拟与产生抽搐相关的大脑活动的时间过程）。然而，大多数TS患者可以非常有效地抑制他们的抽搐：尽管抽搐抑制与不适程度的增加有关，这是一种强烈的抽搐冲动。这表明，如果我们要求TS患者在整个扫描过程中抑制抽搐，我们可能会成功地扫描许多TS患者。本项目的目的是开发新的方法来成像PU和抽搐的神经前因TS。一种方法是基于一种替代的，数据驱动的，框架的功能磁共振成像（fMRI）数据的分析，称为“多回波稀疏范式自由映射”（ME-SPFM），在其中，我们获得与PU发生在TS没有必要抽搐表达相关的fMRI测量。使用这种方法，我们将准确可靠地识别与有效抑制抽搐的情况下（即没有抽搐可用作外部定时事件）PU发生相关的功能性大脑活动。第二种方法涉及我们使用一种全新形式的可穿戴MEG设备，该设备由诺丁汉大学开发。脑磁图是一种非侵入性的脑成像技术，它比功能磁共振成像有优势：不仅可以测量毫秒级的持续脑活动。使用这种设备将使我们能够记录与PU相关的大脑活动，以及TS患者抽搐之前的大脑活动，即使他们正在执行大的头部或身体运动。我们将进行的MEG研究的一个关键重点是，它们将使我们能够研究瞬时同步的大脑网络是如何组装的，将与行动冲动体验相关的大脑区域与参与行动启动的大脑网络连接起来。再次，这些分析将使用新颖的，最先进的，数据驱动的方法来调查大脑区域之间功能连接的变化。

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.