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This method aims to produce statistical maps of cortical networks based on non-invasive electrode recordings using a clinically viable setup, to allow for investigation of nervous system pathology, the impact of novel treatments, and the development of novel electrophysiological biomarkers.
EEG offers great potential for the investigation of nervous system function and disease1,2. This technology is inexpensive, readily available in research and clinical settings, and generally well tolerated. The simple, non-invasive nature of recordings make clinical use straightforward, and the existing framework of clinical EEG departments allows for easy access to the technology for clinicians.
From a technical perspective, EEG offers excellent time domain resolution3. This is of great importance when investigating nervous system function due to the rapid timescales of nervous system interactions and network dynamics. While imaging methods such as functional MRI offer greater spatial resolution and easily interpretable images, they are far more limited in their ability to interrogate nervous system function on the fine time scales offered by electrophysiological recordings4,5,6.
There is a growing need for the ability to interrogate nervous system function to inform diagnosis, treatment, and prognostication of nervous system diseases. The role of cortical network dynamics in nervous system pathology is increasingly recognized7. Many pathologies of the nervous system produce no macroscopic structural lesions visible with traditional imaging, but the abnormalities produced at the network level may be apparent with appropriate functional analysis methods.
Unfortunately, current EEG analysis methods are greatly limited in this regard. Traditional methods involve the analysis of simple time series data from individual electrodes. These signals represent the summation of field potentials in large cortical areas3,8. Analysis of data from individual channels in isolation using either visual inspection or simple statistical methods limits the usefulness of these recordings to detecting gross electrophysiological abnormalities in discrete, individual locations. With the increasing recognition of the importance of network-level effects to nervous system function and pathology, these simple analysis methods are clearly deficient in that they will fail to detect subtle relationships between signals, representing abnormalities in how cortical areas are interacting with one another at the network level.
A method of deriving statistical maps of cortical network connectivity from low-dimensional electrode recordings is demonstrated. This method allows investigation of the dynamics of interactions between varying brain regions in a way that is not possible with traditional analysis techniques, as well as visualization of these network interactions. This opens the possibility for non-invasive investigation of network level effects at high time domain resolutions in ways not previously possible. This method is based on the derivation of measures of interelectrode coherence9,10. These measures allow the investigation of how two recorded regions are interacting by evaluating the statistical relationships between the recordings of these areas11. By assessing how each recorded area interacts with every other recorded area, a statistical map of electrophysiological networks within the recorded areas can be made. This allows for the discovery of functional relationships that are not apparent on evaluation of individual channel data in isolation.
The focus of this manuscript is on the use of coherence on neural time series. Currently, there are a number of techniques for investigating the relationships between time series data that can be applied to channels in a pairwise fashion to derive models of cortical connectivity. Some methods, such as the related partial directed coherence12,13, aim to infer the direction of influence of the pair of signals investigated in order to better characterize the structure of the underlying networks, while other methods, such as Granger causality14,15, attempt to infer functional relationships through the ability of one signal to predict the data in another. Methods such as these can be applied in similar ways to generate high-dimensional models of cortical networks. However, the advantages of coherence as a means of investigating relationships between neural signals lies in its lack of assumptions. It is possible to investigate statistical relationships between recordings at two sites without making statements about the functional basis of these relationships and to build up a model of cortical connectivity based purely on statistical relationships with minimal assumptions about the cortical networks generating these signals.
Due to the purely mathematical nature of these measures, the relationship between the coherence measures of electrode recordings at the scalp and the underlying neural activity is complex16,17. While these methods allow the derivation of statistical constructs describing relationships between the electrode recordings for comparison, making direct causal inferences about the activity of the specific underlying neural populations is not straightforward3,8,16,17. These approaches allow for comparison of the network-level activity between groups to identify potentially useful biomarkers but are limited in terms of drawing specific conclusions regarding the relationship of these markers to specific neural mechanisms. This is due to the large number of confounding factors influencing the recorded activity3, as well as issues with estimating the specific cortical source of electrical signals recorded at the level of the scalp8. Rather, these approaches can produce statistical models of activity that can be interrogated and compared between groups to determine that differences exist at the network level18 and can be leveraged to produce novel biomarkers based on these constructs. However, these methods alone have a limited capacity to relate the differences seen to specific mechanisms and neural activities due to the complexity of the underlying system.
The use of network measures such as coherence is well established in systems neuroscience16,17. The full potential of these approaches for modelling and investigating cortical function has been limited by a lack of exploitation of these high-dimensional data structures. This work demonstrates that it is possible to apply these measures to EEG channels in a pairwise fashion in order to map data onto a high-dimensional feature space based purely on the statistical relationships between the electrical activity in cortical regions. It also demonstrates that, using modern statistical techniques, it is possible to use the generated models of cortical function to investigate these models without losing the information gained in the modelling process.
This method is potentially valuable in expanding the scope of applications of existing EEG technologies, improving the ability to derive useful functional measures without requiring adaptations to existing recording equipment18,19. By improving the ability to model cortical function and interrogate these models, the questions that can be investigated using EEG data are expanded. This further opens the possibility of greater integration of functional and structural evaluations for investigation of neurological disease20,21. This approach, using technology that is already widely available clinically, would allow investigation of cortical pathologies with both high temporal and spatial resolution.