The publication of this manuscript has been partially supported by the SFI FutureNeruro-Funded Investigator grant to DT.

<ol>
	<li>Rosenow, F., Klein, K. M., Hamer, H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-invasive+EEG+evaluation+in+epilepsy+diagnosis.">Non-invasive EEG evaluation in epilepsy diagnosis.</a> Expert Review of Neurotherapeutics. 15 (4), 425-444 (2015).</li><li>Sharmila, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epilepsy+detection+from+EEG+signals:+a+review.">Epilepsy detection from EEG signals: a review.</a> Journal of Medical Engineering &amp; Technology. 42 (5), 368-380 (2018).</li><li>Nunez, P., Srinivasan, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Electric Fields of the Brain: The Neurophysics of EEG. , (2006).</li><li>Glover, G. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overview+of+functional+magnetic+resonance+imaging.">Overview of functional magnetic resonance imaging.</a> Neurosurgery Clinics of North America. 22 (2), 133-vii (2011).</li><li>Lin, E., Alessio, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+are+the+basic+concepts+of+temporal,+contrast,+and+spatial+resolution+in+cardiac+CT?.">What are the basic concepts of temporal, contrast, and spatial resolution in cardiac CT?.</a> Journal of Cardiovascular Computed Tomography. 3 (6), 403-408 (2009).</li><li>Kim, S., Richter, W., U&#487;urbil, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Limitations+of+temporal+resolution+in+functional+MRI.">Limitations of temporal resolution in functional MRI.</a> Magnetic Resonance in Medicine. 37, 631-636 (1997).</li><li>Fox, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mapping+Symptoms+to+Brain+Networks+with+the+Human+Connectome.">Mapping Symptoms to Brain Networks with the Human Connectome.</a> New England Journal of Medicine. 379, 2237-2245 (2018).</li><li>Makeig, S., Bell, A., Jung, T. P., Sejnowski, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Independent+component+analysis+of+electroencephalographic+data.">Independent component analysis of electroencephalographic data.</a> Advances in neural information processing systems. 8, 145-151 (1996).</li><li>Bowyer, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coherence+a+measure+of+the+brain+networks:+past+and+present.">Coherence a measure of the brain networks: past and present.</a> Neuropsychiatric Electrophysiology. , (2016).</li><li>Srinivasan, R., Winter, W. R., Ding, J., Nunez, P. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EEG+and+MEG+coherence:+measures+of+functional+connectivity+at+distinct+spatial+scales+of+neocortical+dynamics.">EEG and MEG coherence: measures of functional connectivity at distinct spatial scales of neocortical dynamics.</a> Journal of Neuroscience Methods. 166 (1), 41-52 (2007).</li><li>Bullmore, E., Sporns, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complex+brain+networks:+graph+theoretical+analysis+of+structural+and+functional+systems.">Complex brain networks: graph theoretical analysis of structural and functional systems.</a> Nature Reviews Neuroscience. 10, 186-198 (2009).</li><li>Baccal&#225;, L., Sameshima, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Partial+directed+coherence:+a+new+concept+in+neural+structure+determination.">Partial directed coherence: a new concept in neural structure determination.</a> Biological Cybernetics. 84, 463-474 (2001).</li><li>Sameshima, K., Baccal&#225;, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+partial+directed+coherence+to+describe+neuronal+ensemble+interactions.">Using partial directed coherence to describe neuronal ensemble interactions.</a> Journal of Neuroscience Methods. 94, 93-103 (1999).</li><li>Seth, A., Barrett, A. B., Barnett, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Granger+causality+analysis+in+neuroscience+and+neuroimaging.">Granger causality analysis in neuroscience and neuroimaging.</a> Journal of Neuroscience. 35, 3293-3297 (2015).</li><li>Hesse, W., M&#246;ller, E., Arnold, M., Schack, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+time-variant+EEG+Granger+causality+for+inspecting+directed+interdependencies+of+neural+assemblies.">The use of time-variant EEG Granger causality for inspecting directed interdependencies of neural assemblies.</a> Journal of Neuroscience Methods. 124, 27-44 (2003).</li><li>Nunez, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EEG+coherency.+I:+Statistics,+reference+electrode,+volume+conduction,+Laplacians,+cortical+imaging,+and+interpretation+at+multiple+scales.">EEG coherency. I: Statistics, reference electrode, volume conduction, Laplacians, cortical imaging, and interpretation at multiple scales.</a> Electroencephalography and Clinical Neurophysiology. 103, 499-515 (1997).</li><li>Nunez, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EEG+coherency+II:+experimental+comparisons+of+multiple+measures.">EEG coherency II: experimental comparisons of multiple measures.</a> Clinical Neurophysiology. 110, 469-486 (1999).</li><li>Keogh, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+and+genetic+Rett+syndrome+variants+are+defined+by+stable+electrophysiological+profiles.">Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles.</a> BMC Pediatrics. 18 (1), 333 (2018).</li><li>Peters, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+functional+networks+in+syndromic+and+non-syndromic+autism:+a+graph+theoretical+study+of+EEG+connectivity.">Brain functional networks in syndromic and non-syndromic autism: a graph theoretical study of EEG connectivity.</a> BMC Medicine. 11, 54 (2013).</li><li>Jie, B., Wee, C., Shen, D., Zhang, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyper-connectivity+of+functional+networks+for+brain+disease+diagnosis.">Hyper-connectivity of functional networks for brain disease diagnosis.</a> Medical Image Analysis. 32, 84-100 (2016).</li><li>Zhang, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topographical+Information-Based+High-Order+Functional+Connectivity+and+Its+Application+in+Abnormality+Detection+for+Mild+Cognitive+Impairment.">Topographical Information-Based High-Order Functional Connectivity and Its Application in Abnormality Detection for Mild Cognitive Impairment.</a> Journal of Alzheimer's Disease. 54, 1095-1112 (2016).</li><li>Delorme, A., Scott, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EEGLAB:+an+open+source+toolbox+for+analysis+of+single-trial+EEG+dynamics+including+independent+component+analysis.">EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis.</a> Journal of Neuroscience Methods. 134, 1 (2004).</li><li>Calabrese, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Encyclopedia of Bioinformatics and Computational Biology. , (2019).</li><li>Colic, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Support+Vector+Machines+Using+EEG+Features+of+Cross-Frequency+Coupling+Can+Predict+Treatment+Outcome+in+Mecp2-Deficient+Mice.">Support Vector Machines Using EEG Features of Cross-Frequency Coupling Can Predict Treatment Outcome in Mecp2-Deficient Mice.</a> Conference Proceedings of the IEEE Engineering in Medicine and Biology Society. , 5606-5609 (2015).</li></ol>

The authors have nothing to disclose.

The described method allows the derivation of statistical maps of cortical network dynamics from non-invasive EEG data. This allows the investigation of phenomena not readily apparent on examination of simple time series data through assessment of how the recorded regions are interacting with each other, rather than evaluating what is happening in each individual location in isolation. This can reveal important insights into disease pathology18.
The essential aspect of ...

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.

<table><tbody><tr><td>Electrode cap</td><td>ElectroCap International</td><td></td><td>Or any suitable cap</td></tr><tr><td>Conductive gel</td><td>SignaGel</td><td></td><td>Or any suitable gel</td></tr><tr><td>Pin-type electrodes</td><td>BioSemi</td><td></td><td>Or any suitable electrode</td></tr><tr><td>BioSemi Active Two recording system</td><td>BioSemi</td><td></td><td></td></tr><tr><td>ActiView recording environment</td><td>BioSemi</td><td></td><td></td></tr><tr><td>MATLAB software</td><td>Mathworks</td><td></td><td></td></tr></tbody></table>

statistical modelling of cortical connectivity using non-invasive electroencephalograms

Non-invasive electrophysiological recordings are useful for the evaluation of nervous system function. These techniques are inexpensive, fast, replicable, and less resource-intensive than imaging. Further, the functional data produced have excellent temporal resolution, which is not achievable with structural imaging.
Current applications of electroencephalograms (EEG) are limited by data processing methods. Standard analysis techniques using raw time series data at individual channels are very limited methods of interrogating nervous system activity. More detailed information about cortical function can be achieved by examining relationships between channels and deriving statistical models of how areas are interacting, allowing visualization of connectivity between networks.
This manuscript describes a method for deriving statistical models of cortical network activity by recording EEG in a standard manner, then examining the interelectrode coherence measures to assess relationships between the recorded areas. Higher order interactions can be further examined by assessing the covariance between the coherence pairs, producing high-dimensional &#34;maps&#34; of network interactions. These data constructs can be examined to assess cortical network function and its relationship to pathology in ways not achievable with traditional techniques.
This approach offers greater sensitivity to network level interactions than is achievable with raw time series analysis. It is, however, limited by the complexity of drawing specific mechanistic conclusions about the underlying neural populations and the high volumes of data generated, requiring more advanced statistical techniques for evaluation, including dimensionality reduction and classifier-based approaches.

Measurements of the spectral power will produce n measures for each frequency band measured, where n is the number of channels recorded. These measures will be in decibels for the overall power. Measures of power within individual frequency bands should be expressed as relative power (i.e., the proportion of overall power represented by power within that band) to allow accurate comparisons between groups and conditions.
An example of visualiza...

Watch this Scientific Journal Video about Statistical Modelling of Cortical Connectivity Using Non-invasive Electroencephalograms at JoVE.com

Statistical Modelling of Cortical Connectivity Using Non-invasive Electroencephalograms

Standard EEG analysis techniques offer limited insight into nervous system function. Deriving statistical models of cortical connectivity offers far greater ability to investigate underlying network dynamics. Improved functional assessment opens new possibilities for diagnosis, prognostication, and outcome prediction in nervous system diseases.

Non-invasive electrophysiological recordings are useful for the evaluation of nervous system function. These techniques are inexpensive, fast, replicable, ...

statistical-modelling-cortical-connectivity-using-non-invasive

Research

JoVE Journal

Neuroscience

5.6K Views.  University Hospital Limerick. Standard EEG analysis techniques offer limited insight into nervous system function. Deriving statistical models of cortical connectivity offers far greater ability to investigate underlying network dynamics. Improved functional assessment opens new possibilities for diagnosis, prognostication, and outcome prediction in nervous system diseases.

Video: Statistical Modelling of Cortical Connectivity Using Non-invasive Electroencephalograms

Cortical Source Analysis of High-Density EEG Recordings in Children

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2, because the composition and spatial configuration of head tissues changes dramatically over development3.&#160;
In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how&#160;EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.&#160;

In recent years, there has been increasing interest in estimating the cortical sources of scalp measured electrical activity for cognitive neuroscience experiments. This article describes how high density EEG is acquired and how recordings are processed for cortical source estimation in children from the age of 2 years at the London Baby Lab.

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and ...

Behavior

Recording Human Electrocorticographic (ECoG) Signals for Neuroscientific Research and Real-time Functional Cortical Mapping

Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), magnetoencephalography or functional magnetic-resonance imaging. These techniques have either inherently low temporal or low spatial resolution, and suffer from low signal-to-noise ratio and/or poor high-frequency sensitivity. Thus, they are suboptimal for exploring the short-lived spatio-temporal dynamics of many of the underlying brain processes. In contrast, the invasive technique of electrocorticography (ECoG) provides brain signals that have an exceptionally high signal-to-noise ratio, less susceptibility to artifacts than EEG, and a high spatial and temporal resolution (i.e., &lt;1 cm/&lt;1 millisecond, respectively). ECoG involves measurement of electrical brain signals using electrodes that are implanted subdurally on the surface of the brain. Recent studies have shown that ECoG amplitudes in certain frequency bands carry substantial information about task-related activity, such as motor execution and planning1, auditory processing2 and visual-spatial attention3. Most of this information is captured in the high gamma range (around 70-110 Hz). Thus, gamma activity has been proposed as a robust and general indicator of local cortical function1-5. ECoG can also reveal functional connectivity and resolve finer task-related spatial-temporal dynamics, thereby advancing our understanding of large-scale cortical processes. It has especially proven useful for advancing brain-computer interfacing (BCI) technology for decoding a user's intentions to enhance or improve communication6 and control7. Nevertheless, human ECoG data are often hard to obtain because of the risks and limitations of the invasive procedures involved, and the need to record within the constraints of clinical settings. Still, clinical monitoring to localize epileptic foci offers a unique and valuable opportunity to collect human ECoG data. We describe our methods for collecting recording ECoG, and demonstrate how to use these signals for important real-time applications such as clinical mapping and brain-computer interfacing. Our example uses the BCI2000 software platform8,9 and the SIGFRIED10 method, an application for real-time mapping of brain functions. This procedure yields information that clinicians can subsequently use to guide the complex and laborious process of functional mapping by electrical stimulation.
Prerequisites and Planning:
Patients with drug-resistant partial epilepsy may be candidates for resective surgery of an epileptic focus to minimize the frequency of seizures. Prior to resection, the patients undergo monitoring using subdural electrodes for two purposes: first, to localize the epileptic focus, and second, to identify nearby critical brain areas (i.e., eloquent cortex) where resection could result in long-term functional deficits. To implant electrodes, a craniotomy is performed to open the skull. Then, electrode grids and/or strips are placed on the cortex, usually beneath the dura. A typical grid has a set of 8 x 8 platinum-iridium electrodes of 4 mm diameter (2.3 mm exposed surface) embedded in silicon with an inter-electrode distance of 1cm. A strip typically contains 4 or 6 such electrodes in a single line. The locations for these grids/strips are planned by a team of neurologists and neurosurgeons, and are based on previous EEG monitoring, on a structural MRI of the patient's brain, and on relevant factors of the patient's history. Continuous recording over a period of 5-12 days serves to localize epileptic foci, and electrical stimulation via the implanted electrodes allows clinicians to map eloquent cortex. At the end of the monitoring period, explantation of the electrodes and therapeutic resection are performed together in one procedure.
In addition to its primary clinical purpose, invasive monitoring also provides a unique opportunity to acquire human ECoG data for neuroscientific research. The decision to include a prospective patient in the research is based on the planned location of their electrodes, on the patient's performance scores on neuropsychological assessments, and on their informed consent, which is predicated on their understanding that participation in research is optional and is not related to their treatment. As with all research involving human subjects, the research protocol must be approved by the hospital's institutional review board. The decision to perform individual experimental tasks is made day-by-day, and is contingent on the patient's endurance and willingness to participate. Some or all of the experiments may be prevented by problems with the clinical state of the patient, such as post-operative facial swelling, temporary aphasia, frequent seizures, post-ictal fatigue and confusion, and more general pain or discomfort.
At the Epilepsy Monitoring Unit at Albany Medical Center in Albany, New York, clinical monitoring is implemented around the clock using a 192-channel Nihon-Kohden Neurofax monitoring system. Research recordings are made in collaboration with the Wadsworth Center of the New York State Department of Health in Albany. Signals from the ECoG electrodes are fed simultaneously to the research and the clinical systems via splitter connectors. To ensure that the clinical and research systems do not interfere with each other, the two systems typically use separate grounds. In fact, an epidural strip of electrodes is sometimes implanted to provide a ground for the clinical system. Whether research or clinical recording system, the grounding electrode is chosen to be distant from the predicted epileptic focus and from cortical areas of interest for the research. Our research system consists of eight synchronized 16-channel g.USBamp amplifier/digitizer units (g.tec, Graz, Austria). These were chosen because they are safety-rated and FDA-approved for invasive recordings, they have a very low noise-floor in the high-frequency range in which the signals of interest are found, and they come with an SDK that allows them to be integrated with custom-written research software. In order to capture the high-gamma signal accurately, we acquire signals at 1200Hz sampling rate-considerably higher than that of the typical EEG experiment or that of many clinical monitoring systems. A built-in low-pass filter automatically prevents aliasing of signals higher than the digitizer can capture. The patient's eye gaze is tracked using a monitor with a built-in Tobii T-60 eye-tracking system (Tobii Tech., Stockholm, Sweden). Additional accessories such as joystick, bluetooth Wiimote (Nintendo Co.), data-glove (5th Dimension Technologies), keyboard, microphone, headphones, or video camera are connected depending on the requirements of the particular experiment.
Data collection, stimulus presentation, synchronization with the different input/output accessories, and real-time analysis and visualization are accomplished using our BCI2000 software8,9. BCI2000 is a freely available general-purpose software system for real-time biosignal data acquisition, processing and feedback. It includes an array of pre-built modules that can be flexibly configured for many different purposes, and that can be extended by researchers' own code in C++, MATLAB or Python. BCI2000 consists of four modules that communicate with each other via a network-capable protocol: a Source module that handles the acquisition of brain signals from one of 19 different hardware systems from different manufacturers; a Signal Processing module that extracts relevant ECoG features and translates them into output signals; an Application module that delivers stimuli and feedback to the subject; and the Operator module that provides a graphical interface to the investigator.
A number of different experiments may be conducted with any given patient. The priority of experiments will be determined by the location of the particular patient's electrodes. However, we usually begin our experimentation using the SIGFRIED (SIGnal modeling For Realtime Identification and Event Detection) mapping method, which detects and displays significant task-related activity in real time. The resulting functional map allows us to further tailor subsequent experimental protocols and may also prove as a useful starting point for traditional mapping by electrocortical stimulation (ECS).
Although ECS mapping remains the gold standard for predicting the clinical outcome of resection, the process of ECS mapping is time consuming and also has other problems, such as after-discharges or seizures. Thus, a passive functional mapping technique may prove valuable in providing an initial estimate of the locus of eloquent cortex, which may then be confirmed and refined by ECS. The results from our passive SIGFRIED mapping technique have been shown to exhibit substantial concurrence with the results derived using ECS mapping10.
The protocol described in this paper establishes a general methodology for gathering human ECoG data, before proceeding to illustrate how experiments can be initiated using the BCI2000 software platform. Finally, as a specific example, we describe how to perform passive functional mapping using the BCI2000-based SIGFRIED system.

Recording Human Electrocorticographic ECoG Signals for Neuroscientific Research and Real-time Functional Cortical Mapping

We present a method for collecting electrocorticographic signals for research purposes from humans who are undergoing invasive epilepsy monitoring. We show how to use the BCI2000 software platform for data collection, signal processing and stimulus presentation. Specifically, we demonstrate SIGFRIED, a BCI2000-based tool for real-time functional brain mapping.

Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), ...

Mapping Cortical Dynamics Using Simultaneous MEG/EEG and Anatomically-constrained Minimum-norm Estimates: an Auditory Attention Example

Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the cortical networks involved in dynamical perceptual and cognitive tasks, such as attending to different sounds in a cocktail party. Many past studies have employed data recorded at the sensor level only, i.e., the magnetic fields or the electric potentials recorded outside and on the scalp, and have usually focused on activity that is time-locked to the stimulus presentation. This type of event-related field / potential analysis is particularly useful when there are only a small number of distinct dipolar patterns that can be isolated and identified in space and time. Alternatively, by utilizing anatomical information, these distinct field patterns can be localized as current sources on the cortex. However, for a more sustained response that may not be time-locked to a specific stimulus (e.g., in preparation for listening to one of the two simultaneously presented spoken digits based on the cued auditory feature) or may be distributed across multiple spatial locations unknown a priori, the recruitment of a distributed cortical network may not be adequately captured by using a limited number of focal sources.
Here, we describe a procedure that employs individual anatomical MRI data to establish a relationship between the sensor information and the dipole activation on the cortex through the use of minimum-norm estimates (MNE). This inverse imaging approach provides us a tool for distributed source analysis. For illustrative purposes, we will describe all procedures using FreeSurfer and MNE software, both freely available. We will summarize the MRI sequences and analysis steps required to produce a forward model that enables us to relate the expected field pattern caused by the dipoles distributed on the cortex onto the M/EEG sensors. Next, we will step through the necessary processes that facilitate us in denoising the sensor data from environmental and physiological contaminants. We will then outline the procedure for combining and mapping MEG/EEG sensor data onto the cortical space, thereby producing a family of time-series of cortical dipole activation on the brain surface (or "brain movies") related to each experimental condition. Finally, we will highlight a few statistical techniques that enable us to make scientific inference across a subject population (i.e., perform group-level analysis) based on a common cortical coordinate space.

We use magneto- and electroencephalography (MEG/EEG), combined with anatomical information captured by magnetic resonance imaging (MRI), to map the dynamics of the cortical network associated with auditory attention.

Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the ...

Network Analysis of the Default Mode Network Using Functional Connectivity MRI in Temporal Lobe Epilepsy

Functional connectivity MRI (fcMRI) is an fMRI method that examines the connectivity of different brain areas based on the correlation of BOLD signal fluctuations over time. Temporal Lobe Epilepsy (TLE) is the most common type of adult epilepsy and involves multiple brain networks. The default mode network (DMN) is involved in conscious, resting state cognition and is thought to be affected in TLE where seizures cause impairment of consciousness. The DMN in epilepsy was examined using seed based fcMRI. The anterior and posterior hubs of the DMN were used as seeds in this analysis. The results show a disconnection between the anterior and posterior hubs of the DMN in TLE during the basal state. In addition, increased DMN connectivity to other brain regions in left TLE along with decreased connectivity in right TLE is revealed. The analysis demonstrates how seed-based fcMRI can be used to probe cerebral networks in brain disorders such as TLE.

The Default Mode Network (DMN) in Temporal Lobe Epilepsy (TLE) is analyzed in the resting state of the brain using seed-based functional connectivity MRI (fcMRI).

Functional connectivity MRI (fcMRI) is an fMRI method that examines the connectivity of different brain areas based on the correlation of BOLD signal ...

Medicine

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

High-density Electroencephalographic Acquisition in a Rodent Model Using Low-cost and Open-source Resources

Advanced electroencephalographic analysis techniques requiring high spatial resolution, including electrical source imaging and measures of network connectivity, are applicable to an expanding variety of questions in neuroscience. Performing these kinds of analyses in a rodent model requires higher electrode density than traditional screw electrodes can accomplish. While higher-density electroencephalographic montages for rodents exist, they are of limited availability to most researchers, are not robust enough for repeated experiments over an extended period of time, or are limited to use in anesthetized rodents.1-3 A proposed low-cost method for constructing a durable, high-count, transcranial electrode array, consisting of bilaterally implantable headpieces is investigated as a means to perform advanced electroencephalogram analyses in mice or rats.

Procedures for headpiece fabrication and surgical implantation necessary to produce high signal to noise, low-impedance electroencephalographic and electromyographic signals are presented. While the methodology is useful in both rats and mice, this manuscript focuses on the more challenging implementation for the smaller mouse skull. Freely moving mice are only tethered to cables via a common adapter during recording. One version of this electrode system that includes 26 electroencephalographic channels and 4 electromyographic channels is described below.

Instructions for the low-cost construction and surgical implantation of a chronic transcranial high-density electroencephalographic montage into mice are provided. Signal recording, extraction, and processing techniques are also described.

Advanced electroencephalographic analysis techniques requiring high spatial resolution, including electrical source imaging and measures of network ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area.

This protocol describes a procedure to track the evolution of mesial network measures in temporal lobe epilepsy (TLE) patients. It is based on the combination of intracranial recordings with a novel numerical technique for data analysis. Specifically, we present a protocol for network analyses of foramen ovale recordings.

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

Concurrent Recording of Co-localized Electroencephalography and Local Field Potential in Rodent

Although electroencephalography (EEG) is widely used as a non-invasive technique for recording neural activities of the brain, our understanding of the neurogenesis of EEG is still very limited. Local field potentials (LFPs) recorded via a multi-laminar microelectrode can provide a more detailed account of simultaneous neural activity across different cortical layers in the neocortex, but the technique is invasive. Combining EEG and LFP measurements in a pre-clinical model can greatly enhance understanding of the neural mechanisms involved in the generation of EEG signals, and facilitate the derivation of a more realistic and biologically accurate mathematical model of EEG. A simple procedure for acquiring concurrent and co-localized EEG and multi-laminar LFP signals in the anesthetized rodent is presented here. We also investigated whether EEG signals were significantly affected by a burr hole drilled in the skull for the insertion of a microelectrode. Our results suggest that the burr hole has a negligible impact on EEG recordings.

This protocol describes a simple method for concurrent recording of co-localized electroencephalography (EEG) and multi-laminar local field potential in an anesthetized rat. A burr hole drilled in the skull for the insertion of a microelectrode is shown to produce negligible distortion of the EEG signal.

Although electroencephalography (EEG) is widely used as a non-invasive technique for recording neural activities of the brain, our understanding of the ...

Analyzing Neural Activity and Connectivity Using Intracranial EEG Data with SPM Software

Measuring neural activity and connectivity associated with cognitive functions at high spatial and temporal resolutions is an important goal in cognitive neuroscience. Intracranial electroencephalography (EEG) can directly record electrical neural activity and has the unique potential to accomplish this goal. Traditionally, averaging analysis has been applied to analyze intracranial EEG data; however, several new techniques are available for depicting neural activity and intra- and inter-regional connectivity. Here, we introduce two analytical protocols we recently applied to analyze intracranial EEG data using the Statistical Parametric Mapping (SPM) software: time-frequency SPM analysis for neural activity and dynamic causal modeling of induced responses for intra- and inter-regional connectivity. We report our analysis of intracranial EEG data during the observation of faces as representative results. The results revealed that the inferior occipital gyrus (IOG) showed gamma-band activity at very early stages (110 ms) in response to faces, and both the IOG and amygdala showed rapid intra- and inter-regional connectivity using various types of oscillations. These analytical protocols have the potential to identify the neural mechanisms underlying cognitive functions with high spatial and temporal profiles.

We present two analytical protocols that can be used to analyze intracranial electroencephalography data using the Statistical Parametric Mapping (SPM) software: time-frequency statistical parametric mapping analysis for neural activity, and dynamic causal modeling of induced responses for intra- and inter-regional connectivity.

Measuring neural activity and connectivity associated with cognitive functions at high spatial and temporal resolutions is an important goal in cognitive ...

Electroencephalography Network Indices as Biomarkers of Upper Limb Impairment in Chronic Stroke

Alteration of electroencephalography (EEG) signals during task-specific movement of the impaired limb has been reported as a potential biomarker for the severity of motor impairment and for the prediction of motor recovery in individuals with stroke. When implementing EEG experiments, detailed paradigms and well-organized experiment protocols are required to obtain robust and interpretable results. In this protocol, we illustrate a task-specific paradigm with upper limb movement and methods and techniques needed for the acquisition and analysis of EEG data. The paradigm consists of 1 min of rest followed by 10 trials comprising alternating 5 s and 3 s of resting and task (hand extension)-states, respectively, over 4 sessions. EEG signals were acquired using 32 Ag/AgCl scalp electrodes at a sampling rate of 1,000 Hz. Event-related spectral perturbation analysis associated with limb movement and functional network analyses at the global level in the low-beta (12-20 Hz) frequency band were performed. Representative results showed an alteration of the functional network of low-beta EEG frequency bands during movement of the impaired upper limb, and the altered functional network was associated with the degree of motor impairment in chronic stroke patients. The results demonstrate the feasibility of the experimental paradigm in EEG measurements during upper limb movement in individuals with stroke. Further research using this paradigm is needed to determine the potential value of EEG signals as biomarkers of motor impairment and recovery.

The experimental protocol demonstrates the paradigm for acquiring and analyzing electroencephalography (EEG) signals during upper limb movement in individuals with stroke. The alteration of the functional network of low-beta EEG frequency bands was observed during the movement of the impaired upper limb and was associated with the degree of motor impairment.

Alteration of electroencephalography (EEG) signals during task-specific movement of the impaired limb has been reported as a potential biomarker for the ...