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

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.