Development of Single Trial EEG-fMRI: Investigations of Dynamic Brain Function at High Temporal and Spatial Resolution

在过去的十年里，功能磁共振成像(FMRI)在理解人脑方面取得了实质性的进展。功能磁共振成像主要测量大脑活跃区域的血流变化。例如，如果受试者看着闪烁的屏幕，处理视觉信息的区域会做出反应，导致血流量增加。功能磁共振成像非常强大，因为它是完全非侵入性的，允许参与者重复研究。然而，它有两个主要缺点：它是大脑功能的间接标志，依赖于血流而不是电活动；它速度很慢，因为血流的变化需要几秒钟的时间才能发生。这比大脑本身的动态处理要慢得多，这可以通过将电极连接到头皮上并测量活动细胞激发产生的电场来看到，这项技术被称为脑电(EEG)。EEG显示，大脑在毫秒的时间尺度上改变状态。因此，尽管功能磁共振成像在定位任务中涉及的大脑区域方面非常强大，但关于它们做出反应的顺序的更详细信息并不容易揭示。解决这个问题的一种方法是将功能磁共振成像与脑电(EEG-fMRI)相结合，在扫描仪中从电极记录。只是在最近几年，才发展出安全和有效地完成这项工作的设备和分析方法。与任何一种单独的技术相比，EEG-fMRI的好处是可以获得准确的时间和空间信息，潜在地提供了对大脑功能的更全面的了解。EEG-fMRI的应用越来越广泛，但仍有许多问题需要回答，特别是关于如何最好地结合这两个数据集的问题。直到最近，EEG和fMRI数据通常是分开平均的，并在不同的实验条件下进行比较。然而，一种新的方法利用了在脑电信号中观察到的从刺激到刺激的变异性，并直接使用它来整合EEG和fMRI。初步研究表明，与标准分析相比，这有相当大的优势，这与以前在脑电中使用反应分类和分组的工作一致，后者表明，通过平均会丢失相当大量的生理有用信息。这种方法还有助于更全面地描述EEG和fMRI之间的关系，这种关系已经通过放置在麻醉动物大脑中的电极来解决，但这需要在清醒的人类中进一步验证。这项研究不仅有特定于项目的科学目标，而且还有与广泛的神经科学界相关的一般方法目标。其目的是研究EEG和fMRI对个别感觉事件的反应之间的关系，重点是开发改进的方法，以了解重复刺激反应中变化的原因，从而改进对人脑动态功能的表征。该项目将使用视觉、听觉、运动和疼痛刺激进行四个独立的实验，以表征由于感觉通道而产生的差异，利用反应的时间动力学的内在差异来约束建模方法。将应用新的分析方法，更充分地利用脑电中可用的信息，并允许在功能磁共振中检查其相关性。开发利用大脑从刺激到刺激反应的微小差异的新技术，对于准确确定大脑功能的时间和地点至关重要，未来将开辟新的研究途径，研究更复杂的认知功能，如学习和大脑疾病。该项目将奠定必要的基础，以了解两种最广泛使用的非侵入性技术之间的联系，以研究人脑，并提供对基本感觉信息处理方式的见解。

In the last decade functional MRI (fMRI) has lead to substantial progress in understanding the human brain. fMRI mainly measures changes in blood flow in active regions of the brain. For example, if a subject watches a flashing screen the areas that process visual information respond, leading to an increase in blood flow. FMRI is extremely powerful because it is completely non-invasive and allows the repeated study of participants. However, it has two main drawbacks: it is an indirect marker of brain function, reliant on blood flow rather than electrical activity, and it is slow, since the changes in blood flow take several seconds to occur. This is much slower than the dynamic processing of the brain itself, as can be seen by attaching electrodes to the scalp and measuring the electric fields produced by the firing of active cells, a technique called electroencephalography (EEG). EEG shows that that the brain changes state on a timescale of milliseconds. So although fMRI is very powerful for locating which brain regions are involved in a task, more detailed information about the order in which they respond cannot easily be revealed.One way around this problem is to combine fMRI with EEG (EEG-fMRI), recording from electrodes while in the scanner. It is only in the last few years that the equipment and methods of analysis have been developed to accomplish it safely and effectively. The benefit of EEG-fMRI, compared with either technique alone, is that accurate timing and spatial information are both available, potentially providing a much more complete view of brain function. EEG-fMRI is increasingly widely used, but many questions remain to be answered, particularly concerning the best way to combine the two data sets. Until recently, EEG and fMRI data were usually averaged separately and compared across experimental conditions. However, a new method takes advantage of the variability that is observed in the EEG signal from stimulus to stimulus and uses it directly to integrate EEG and fMRI. Initial studies have shown considerable advantages over the standard analysis, consistent with previous work in EEG using categorisation and grouping of responses which suggests that a considerable amount of physiologically useful information is lost by averaging. This approach can also help to characterise more fully the relationship between EEG and fMRI themselves, which has been addressed using electrodes placed within the brains of anaesthetised animals, but which requires further validation in awake humans. The research not only has project-specific scientific goals, but also general methodological goals, relevant to the broad neuroscience community. The aim is to examine the relationship between EEG and fMRI responses to individual sensory events, focusing on the development of improved methods to understand the causes of variability in the response to repetitive stimuli, and hence improving characterisation of the dynamic function of the human brain. The project will perform four separate experiments using visual, auditory, motor and pain stimuli in order to characterise differences due to sensory modality, capitalising on inherent differences in the temporal dynamics of responses to constrain modelling methods. New analysis methods will be applied that utilise more fully the information available in the EEG and allow examination of its correlates in fMRI. The development of new techniques to utilise small differences in the brain's response from stimulus to stimulus is crucial to pinpoint the when and where of brain function, and in the future will open up new avenues of research to study more complex cognitive functions, such as learning, and brain diseases. This project will lay the groundwork that is necessary to understand the link between the two most widely available non-invasive techniques for studying the human brain, as well as providing insights into the way in which basic sensory information is processed.