EEG and epilepsy

Authors: Francois Tadel, Elizabeth Bock, Marcel Heers & John Mosher.

This tutorial introduces some concepts that are specific to the management of EEG recordings in the Brainstorm environment. It also describes a standard pipeline for analyzing epilepsy recordings. It is based on a clinical case from the Epilepsy Center at the University Hospital of Freiburg, Germany. The anonymized dataset can be downloaded directly from the Brainstorm download page.

License

This tutorial dataset (EEG and MRI data) remains proprietary of the Epilepsy Centre, University Hospital Freiburg, Germany. Its use and transfer outside the Brainstorm tutorial, e.g. for research purposes, is prohibited without written consent from the Epilepsy Center in Freiburg. For questions please contact A. Schulze-Bonhage, MD, PhD: andreas.schulze-bonhage@uniklinik-freiburg.de

Presentation of the clinical case

This tutorial dataset was acquired in a patient who suffered from focal epilepsy with focal sensory, dyscognitive and secondarily generalized seizures since the age of eight years. He does not have any typical risk factors for epilepsy. The high resolution 3T epilepsy MRI including postprocessing was found to be normal. FDG-PET of the brain did not show any pathological changes in the glucose metabolism. Non-invasive telemetry revealed left fronto-central sharp waves, polyspikes and bursts of beta band activity (max. amplitude FC1, Cz) especially during sleep. The tutorial dataset was acquired during one night of the non-invasive telemetry recording at the Epilepsy Center Freiburg, Germany.

Afterwards the patient underwent invasive EEG to identify the epileptogenic area and to map functionally important cortex. Details about invasive EEG and source localization from invasive EEG in this patient are reported in Dümpelmann, et al. (2011). Subsequently a left frontal tailored resection was performed. The histological analysis revealed a focal cortical dysplasia type IIB according to the classification of Palmini, et al. (2004). The postsurgical outcome is Engel 1A with a follow-up of 5 years.

The EEG data distributed here was recorded at 1024Hz, using a Neurofile NT digital video-EEG system with 128 channels and a 16-bit A/D converter. The signal was filtered in the recording system with a high-pass filter with a time constant of 1 second and a low-pass filter with a cutoff frequency of 344 Hz. The spikes were marked in the Deltamed Coherence Viewer.

Overview of the data processing

The proper identification of epileptiform discharges ("spikes") is a complicated topic beyond the scope of this tutorial. Neurology students train intensively on how to identify true interictal and ictal discharges, particularly as distinct from so-called "normal variants" that can be abundant. Sleep and drowsy states of the brain can generate "vertex waves," "K-complexes," "positive occipital sharp transients of sleep" (POSTS), and "wickets," to name a few variants, none of which are epileptic. A good overview of terminology and application can be found, for example, on the Medscape website, Epileptiform Discharges.

With this caveat, we nonetheless give an overview of the processing approach. Although automation has been proposed for decades, "spike hunting" is often done by manual inspection of the recorded EEG waveforms (whether scalp, subdural, or depths). The classic scalp sensor arrangement is the International 10-20 System (Wikipedia Site, Bioelectromagnetism Book, Chapter 13.3) arranged at 10 percent and 20 percent distances about the circumference of the head. Each of these 21 electrodes is acquired with respect to some reference (as all potentials must be). In reviewing the recordings, however, several "montages" are traditionally recommended that digitally "re-reference" the original recordings into new linear combinations of electrodes.

A classic montage is the "double banana" (Google Search) which emphasizes local changes in the scalp EEG by forming sequential bipolar pairs, such as "Fp1-F3", "F3-C3." Because F3 is found twice in this montage and of opposite sign, then an epileptic spike centered under F3 will appear as a reversed polarity in these two channels, a visual cue the trained epileptologist seeks when rapidly scanning through hours of recordings. This montage is more formally known as "LB-18.3" or "Longitudinal Bipolar 3" in the nomenclature of the American Clinical Neurophysiology Society Guidelines (see References Below).

ACNS guidelines suggest using both "longitudinal" and "transversal" bipolar montages to survey your data. For temporal epilepsy cases, you may also add a "temporal ring" montage. European neurologists often prefer to review the recordings using an average reference montage. Brainstorm provides several variations of all these montages, allows the users full flexibility in creating their own and different montages can run simultaneously in multiple windows.

The user has to step along through the data, look for abnormal brain activity, then use Brainstorm's event markers to tag suspect intervals.With the suspected events marked and saved, the user can return later to perform source analyses on these intervals. With this brief overview, we detail below an exercise with the sample epilepsy data.

Note that the aim of this tutorial is not to not train you to the spike recognition itself, but rather to illustrate how to manipulate the Brainstorm interface to build a an environment adapted to this task. The data reviewing should be done by clinical neurophysiologists or experienced persons with special training only.

References

Dümpelmann M, Ball T, Schulze-Bonhage A (2011)
sLORETA allows reliable distributed source reconstruction based on subdural strip and grid recordings. Human Brain Mapping.

Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldvary-Schaefer N, Jackson G, Luders HO, Prayson R, Spreafico R, Vinters HV (2004) Terminology and classification of the cortical dysplasias.
Neurology, 62:S2-8.

Standard montages recommended by the American Clinical Neurophysiology Society:

• American Clinical Neurophysiology Society Guidelines

• Guidelines for Standard Electrode Position Nomenclature #5

• A Proposal for Standard Montages to Be Used in Clinical EEG #6

Download and installation

• Requirements: You have already followed all the introduction tutorials and you have a working copy of Brainstorm installed on your computer.

• Go to the Download page of this website, and download the file: sample_epilepsy.zip

• Unzip it in a folder that is not in any of the Brainstorm folders (program folder or database folder)

• Start Brainstorm (Matlab scripts or stand-alone version)

• Select the menu File > Create new protocol. Name it "TutorialEpilepsy" and select the options:

  • "No, use individual anatomy",

  • "Yes, use one channel file per subject".

Import the anatomy

• Right-click on the TutorialEpilepsy folder > New subject > sepi01

  • Leave the default options you set for the protocol

• Right-click on the subject node > Import anatomy folder:

  • Set the file format: "FreeSurfer folder"

  • Select the folder: sample_epilepsy/anatomy

  • Number of vertices of the cortex surface: 15000 (default value)
• Set the 6 required fiducial points (indicated in MRI coordinates):
  • NAS: x=135, y=222, z=75
  • LPA: x=57, y=118, z=68
  • RPA: x=204, y=119, z=76
  • AC: x=131, y=145, z=110
  • PC: x=130, y=119, z=111
  • IH: x=128, y=134, z=170 (anywhere on the midsagittal plane)

• At the end of the process, make sur the file "cortex_15000V" is selected (downsampled pial surface, that will use for the source estimation). If it is not, double-click on it to select it as the default cortex surface.
  
  

Without the individual MRI

If you do not have access to an individual MR scan of the subject (or if its quality is too low to be processed with FreeSurfer), but if you have digitized the head shape of the subject using a tracking system, you have an alternative: deform one of the Brainstorm templates (Colin27 or ICBM152) to match the shape of the subject's head.
For more information, read the following tutorial: Warping default anatomy

Access the recordings

Link the recordings

• Switch to the "functional data" view.

• Right-click on the subject folder > Review raw file:

  • Select the file format: "EEG: Deltamed Neurofile-Coherence (*.bin)"

  • Select the file: sample_epilepsy/data/tutorial_EEG.bin

  • The new file "Link to raw file" lets you access directly the contents of the EEG recordings
  • The channel file "Deltamed channels" in the (Common files) folder contains the name of the channels, but not their positions. We need to overwrite this file and import manually the positions of the electrodes (either a standard cap or accurate positions digitized with a Polhemus device).

Prepare the channel file

• Right-click on the subject folder > Import channel file:

  • Select the file format: "EEG: ANT Xensor (*.elc)"

  • Select the file: sample_epilepsy/data/tutorial.elc

  • Confirm that you want to overwrite the existing channel file.
  • This file contains the default electrodes positions from the ASA software (ANT)
• The recordings contain signals coming from different types of electrodes:
  • 29 EEG electrodes
  • EOG1, EOG2: Electrooculograms
  • EMG, ECG: Electromyogram and electrocardiogram
  • SP1, SP2: Sphenoidal electrodes
  • RS: Electrode on the right shoulder
  • PHO: Photo stimulation channel
  • DELR, DELL, QR, QL: Additional
• The file format for the electrodes positions does not describe the type of the channels correctly, therefore all the signals saved in the files are classified as EEG. We need to redefine this manually to get correct groups of sensors, we want to have only real EEG electrodes in the "EEG" category and put everything that we are not going to use a "MISC" category.

• Right-click on the channel file > Edit channel file:

  • Note that the EOG, EMG and ECG channels already have a different type
  • Select all the other non-EEG channels: SP1, SP2, RS, PHO, DELR, DELL, QR, QL

  • Right-click in the window > Set channel type: type MISC

  • Close the figure and accept to save the modifications

  

Register electrodes with MRI

• The channel file we imported contains generic electrodes positions, hence it cannot be properly aligned properly with the head surface coming from the MRI. We need to register manually these electrodes positions with the subject anatomy.

• Right-click on the channel file > MRI registration > Edit...

• The default positions are already quite good, and the head shape is correct, there not much manual registration to do. You can click on the Label button in the toolbar to show the electrodes names.
• Click on the button "Refine registration with the head points" to find a better registration between the head shape defined by the electrodes and the head surface coming from the MRI. To get the legend of a button, leave your mouse for a few seconds over it.
• Click on the button "Project electrodes on the scalp surfaces", to ensure all the electrodes touch the skin surface.

• Click on "OK" to save the modifications.
  
  

Review EEG recordings

Display the recordings in one montage

• For basic information on how to manipulate the montages in Brainstorm: read this tutorial.

• Open a time series figure with the "Average reference" montage

  • Right-click on the "Link to raw file" > EEG > Display time series.

  • In the Record tab, select the first button in the toolbar (Display mode for time series) to view the signals in columns.
  • Select the "Average reference" in the drop-down list. This menu allows you to set a predefined montages to linearly re-arranging the waveforms. Note the keyboard shortcuts in the menus.

  • In the Record tab, change the default duration that is reviewed to 10s.

  • In the figure, click on the [Flip +/-] button to have the negative values pointing up (convention used by most neurologists)

• Open a 2D Sensor cap map of the EEG sensor values as well:

  • Right-click on "Link to raw file" again > EEG > 2D Sensor cap

  • In the Record tab, set the Montage to this view to "Average reference"

• Open the ECG and EOG traces as well, to avoid confusing spikes with cardiac or ocular artifacts:
  

  • Right-click on the Link to raw file > ECG > Display time series

  • Right-click on the Link to raw file > EOG > Display time series

  • The ECG is almost mandatory. The EOG is optional: it can be helpful for beginners but an experienced reviewer will easily recognize the eye movements directly in the EEG data.

• Re-arrange the figures in a convenient way, for example as illustrated below, and disable the automatic positioning of the figures you the figure arrangement doesn't get lost when you open a new figure (Window layout menu at the top-right of the Brainstorm figure > None)

• Having a lot of windows open may slow down significantly the display because each time you change the current time, all the figures have to be updated. A lot of space is also wasted on the screen due to window frames. The number of windows to open has to be a balance between the amount of information to display and the ease of use.
• Review a few existing SPIKE events, to get the feeling of how this reviewing environment works.

Frequency filters

Go to the Filter tab to enable some display frequency filters. General recommendations are:

• High-pass filter: 0.5 Hz

• Low-pass filter: 70 Hz
  
  

Time and amplitude resolution

The resolutions of the time and amplitude axes has a lot of importance for the visual detection of epileptic spikes. The shapes we are looking for are altered by the horizontal and vertical scaling. The distance unit on a screen is the pixel, we can set how much time is represented by one pixel horizontally and how much amplitude is represented by one pixel vertically.

In the Brainstorm interface, this resolution is usually set implicitly: you can set the size of the window, the duration or recordings reviewed at once (text box "duration" in tab Record) and the maximum amplitude to show in the figure (buttons [...] and [AS] on the right of the time series figure). From there, you can also zoom in time ([<], [>], mouse wheel) or amplitude ([^], [v], Shift+mouse wheel). Those parameters are convenient to explore the recordings interactively but don't allow us to have reproducible displays with constant time and amplitude resolutions.

To set the figure resolution explicitly: right-click on the figure > Figure > Set axes resolution. Note that this interface does not store the input values, it just modifies the other parameters (figure size, time window, max amplitude) to fit the resolution objectives. Then if you modify those parameters (resize the figure, leave the button [AS] selected and scroll in time, etc) the resolution is lost, you have to set it again manually.

Recommendations for this dataset are:

• Time axis: 170 pixels/sec (~55 mm/sec)

• Amplitude: 15 μV/pixels (~45 μV/mm)
  
  

User setups

This preparation of the reviewing environment requires a large number of operations, and would become quickly annoying if you have to repeat it every time you open a file. This is a good time to use the menu "User setups" to save this window configuration, to reload it in one click later. In the menu "Window layout", at the top-right of the Brainstorm window, select User setup > New setup. Enter a name of your choice for this particular window arrangement.

This operation will also disable the automatic window arrangement (Window layout > None). To reload it later, open one figure on the dataset you want to review and then select your new entry in the User setup menu.

• 

Multiple montages

It may be interesting for some cases to display different groups of sensors in multiple windows (eg. with an MEG system with 300 sensors), or some complicated epilepsy cases where you would like to review at the same time multiple montages (eg. longitudinal and transversal bipolar montages). Brainstorm offers a flexible way of doing this.

• Open your full reviewing environment as described before, where the EEG signals are displayed with the "Average reference" montage.

• Open another view on the same data with the "Longitudinal 3" montage ("double-banana" LB-18.3)

  • Right-click on the "Link to raw file" again > EEG > Display time series

  • Alternatively, you can right-click on the existing figure > Figure > Clone figure.

  • Then set the montage for this new figure to "Longitudinal 3"
  • Redimension all the figures to make room for the new window
  • Save this as a new "User setup"
• If you don't see the "Longitudinal 3" menu, it is probably because you have using Brainstorm before those predefined montages were made available in the software distribution. To add them manually:
  • In the Record tab, select "Edit montages" in the drop-down menu
  • Click on the "Load montage" button
  • Go to the folder "brainstorm3/toolbox/sensors/private/", and select the first file
  • Note that a new entry (probably "Longitudinal 1") is added to the list of available montages
  • Repeat the operation with all the files in the folder "brainstorm3/toolbox/sensors/private/"

  • Click on "Save" to close the montage editor and now select "Longitudinal 3"
    
    

Mark spikes

In the dataset, the spikes have already been identified by experts at the University Hospital of Freiburg. You can see that 177 SPIKE events are available in the Record tab. Click on a few of them a try to identify the shape of the spike.

The procedure if you are marking the events by yourself is the following:

• Close all the current figures ("Close all" button at the top-right corner of the Brainstorm window)
• Double-click on the "Link to raw file" to open a continuous file viewer, and load your reviewing environment (menu User setups)

• Start by creating a group of events (Events > Add group), and select it in the list of events.

• Make sure that the time and amplitude resolutions are what you are used to
  (right-click on the figure > Figure > Set axes resolution)

• Scroll through the recordings using the [<<<] and [>>>] buttons or shortcuts such as F3 or F4 (complete list and descriptions available when you leave your mouse over those buttons).

• You can adjust the gain of the electrodes to observe better an event with the buttons [^] and [v] or the shortcut [Shift+mouse wheel].

• When you identify a spike, click in a white area of the figure in order to place the time cursor at the peak of the spike. If you click on the signal itself, it selects the corresponding channel, but you can use the shortcut Shift+Click to prevent this behavior and force the time cursor to be moved instead.
• Press Ctrl+E to add a marker where the time cursor is.

• If you are marking multiple types of events, it is convenient to set up some additional keyboard shortcuts. Using the menu Events > Edit keyboard shortcuts, you can associate custom events to the key 1 to 9 of the keyboard. Define the name of the event type to create for each key, and then simply press the corresponding key to add/delete a marker at the current time position.

• To jump to the next/previous event in the current category: use the keyboard shortcuts [Shift+arrow right] and [Shift+arrow left]

• More information on the data viewer, see tutorial: ?Review continuous recordings.

Pre-process recordings

We would like to apply a 0.5Hz high-pass filter to the entire file in order to get rid of the long amplitude fluctuations (longer than 2s). With some MEG file formats, Brainstorm supports the creation of new filtered files in native formats, which means that you can drag and grop directly the "Link to raw file" to the Process1 tab and run the band-pass filter process. Unfortunately, this is currently not supported for the file format we are currently working on (Deltamed Neurofile-Coherence). There is an alternative option which consists in importing the entire continuous file in the database in one single block, then run the filter on it. This approach works is possible only on rather small files (4 * file size < memory on the computer). Here the file size is less than 80 Mb, so it can be easily processed this way.

• Right-click on the "Link to raw file" > Import in database.

• Uncheck all the options and leave the default "Time window" option.
  
  

• Click on Import, it creates an integral copy of the file in the database. Do NOT try to review it: for imported file, the partial loading and the scrolling in time are disabled and it would take a lot of time to display the waveforms for the entire file. It could event result in a crash of Brainstorm or Matlab.
• Drag this new file "Raw (0s,3600s)" to the Process1

• Run the process "Pre-process > Band-pass filter", with the options:

  • Lower cutoff frequency: 0.5Hz (high-pass filter at 0.5Hz)

  • Lower cutoff frequency: 0Hz (no low-pass filter)

  • Mirror signal before flitering: On

  • Sensor types: EMPTY (to process all the signals)

  • Overwrite: On (we don't need to keep the original copy)
    
    

Epoching and averaging

Import recordings

• Now we want to extract all the spikes as 400ms windows from this filtered file.

• Right-click on the imported and filtered file "Raw (0s,3600s) | high(0.5Hz)" > Import in database
  
  

• Select the option "Use events" and select the category SPIKE, with 177 events.

• Epoch time: [-100, +300]ms around the spike events

• Uncheck "Remove DC offset": the DC offset has already been removed with the high-pass filter
  
  

• You should see a new folder "SPIKE" containing 177 epochs in your database.
  
  

Average spikes

• Drag and drop all the SPIKE files or the SPIKE folder into the Process1 tab

• Run the process "Average > Average files", with the following options:
  
  

• Double click on the new file "Avg: SPIKE" to review it, and set the "Average reference" montage.

• Open a "2D sensor cap" view on the same file, or simply press [Ctrl+T] from the time series figure.
  
  

• To have all the figures re-arrange themselves automatically again, select "Weighted" or "Tiled" in the "Window layout" menu (top-right corner).
• Explore this average in time with the left and right keyboard arrow.

• To get a synthetic view at the sensor level of the evolution of the 2D map in time, right-click on the figure > Snapshot > "Time contact sheet: Figure"
  
  

Source analysis: Cortically constrained

Head model

• We are going to use a realistice head model, this requires to calculate some additional surfaces for the subject, to represent the inner skull and outer skull surface. Go to the "Anatomy" view, right-click on the subject > Generate BEM surfaces.

• Use 2000 vertices for each layer. This value will be replaced with the closest possible value (1922). Three new surface files are created at the end of the process.
  
  

• Go back to the "Functional data" view, right-click on the channel file (or any folder containing the channel file) > Compute head model
  
  

• Select the "cortex surface option" and the "OpenMEEG BEM" forward model. Leave all the OpenMEEG options to their defaults except for one: select the option "Use adjoint formulation".
  
  

• If you can't download OpenMEEG automatically, download and install it manually (menu Help)

• If the OpenMEEG process crashes, please refer to the OpenMEEG tutorial.

• If you can compute the model but then later the source maps you get don't make any sense, it is probably because the BEM surfaces were poorly defined. When some cortex vertices are too close to the inner skull surface, the model can be unstable and after the source estimation you would typically see source maps containing zeros everywhere except for a few vertices. If this happens, delete the existing BEM surfaces and try computing new ones with a higher number of vertices for the inner and outer skull BEM surfaces.

• If you cannot get OpenMEEG to work, or if the results definitely do not make sense, try using a different forward model: "3-shell sphere". It's a spherical model, so it would perform better in the regions of the head that are close to the sphere. See the ?Head model tutorial.

Noise covariance matrix

• For minimum norm inverse models, we need to estimate first the level of noise at the level of the sensors. Defining what can be considered as "noise" in the middle of continuous brain recordings is a difficult question, discussed in the ?Noise covariance tutorial.

• Here we chose what is described as option 1b in the section "Noise and epilepsy" in that tutorial: we are going to calculate the noise covariance matrix using 10 seconds from the continuous file that are very "quiet", ie. that contain no apparent epileptic activity, no REM and no other special artifacts. We can use for this purpose the 10s segment between 120s and 130s.
• The file you use for the calculation of the noise covariance matrix must be pre-processed in the same way as the files for which you want to estimate the sources (the SPIKE epochs), so we need to use the imported+filtered continuous file.

• Right-click on the "Raw (0s,3600s) | high(0.5Hz)" > Noise covariance > Compute from recordings
  
  

• Select the time window [120s - 130s] and leave the other options to the default values
  
  

Inverse model

• Right-click on the head model > Compute sources.

• Leave all the default options to calculate a wMNE solution with constrained dipole orientation
  
  

• This operation creates a shared inversion kernel in the folder (Common files) and one source link for each block of recordings in subject sepi01. If you are not familiar with those concepts, please refer to the ?Source estimation tutorial.
  
  

• Double-click on the sources file for the average to open it. Configure its display: surface smoothing, amplitude threshold, colormap. For a reminder on how to manipulate the colormaps, see the tutorial Explore recordings.

• Double-click on the recordings as well to get a visual reference of the time. In the Record tab, you can click on the "Display mode" button in the toolbar to switch back to the "butterfly" view.
  
  

• You can save movies or contact sheets of the source maps with the Snapshot popup menu
  
  

• Example: Video made with three figures: Download

• Example: Contact sheet
  
  

• The inverse solutions that you calculated are all shared for all the recordings in this subject, so you can go back to your individual epochs, or even the continuous file, and look at the source maps for those files.

Regions of interest

• We can easily identify four main regions of activity in this short time window around the spike:
  • Left frontal: Starting from -80ms
  • Right frontal: Starting from -12ms
  • Left parietal: Starting from 50ms
  • Right temporal: Starting from 100ms
• With the Scout tab, create four small scouts (~7 vertices each) at the peak of each of those regions.
• Plot the overlayed scouts time series for those four scouts.

• If you need a reminder on how to manipulating scouts: see the ?Scouts tutorial
  
  

Z-score normalization

Todo

Source analysis: Full head volume

If the results you obtain are not satisfying with the surface-based source estimation, you can run again the same analysis with a different source space, sampling the entire head volume instead of being contrained to the surface. More information about this method in the Volume source estimation tutorial.

Head model

• Right-click on the channel file > Compute head model, select "MRI volume" instead of "Cortex surface". This feature is now stable, but still tagged as experimental because not all the Brainstorm features are available for volume-based source models (eg. no regions of interest, no group analysis, etc). Use the same options as before for OpenMEEG.
  
  

Inverse model

• Right-click on the head model > Compute sources. Use all the default options.
  
  

• Right-click on the unconstrained sources > Cortical activation > Display on MRI (3D).

  • To move the slices in the 3D view: right-click + move your mouse in the slice direction.

  • Use all the sliders in the Surface tab to configure the display.
    
    

• Right-click on the same file > Cortical activation > Display on MRI (MRI Viewer)

  • To smooth the display across slices: right-click on the figure > Smooth sources > "3"

  • For a glass brain view: select the option "MIP: Functional" in the MRI Viewer
    
    

Moving dipoles

See tutorial: Computing and displaying dipoles

Note: you can also load dipoles calculated with other programs.

MEM inverse solution

Coming soon...

Discussion

Distributed source models vs. ECD

Discussion about the advantages of distributed source models in the evaluation of epilepsy data compared with equivalent current dipole models (ECD):
Kobayashi K, Yoshinaga H, Ohtsuka Y, Gotman J (2005)
Dipole modeling of epileptic spikes can be accurate or misleading
Epilepsia, 2005 Mar;46(3):397-408.

Distributed source models vs. BOLD

Heers M, Hedrich T, An D, Dubeau F, Gotman J, Grova C, Kobayashi E (2014)
Spatial correlation of hemodynamic changes related to interictal epileptic discharges with electric and magnetic source imaging
Human Brain Mapping [in press].

ECD vs. BOLD

Benar CG, Grova C, Kobayashi E, Bagshaw AP, Aghakhani Y, Dubeau F, Gotman J (2006)
EEG–fMRI of epileptic spikes: Concordance with EEG source localization and intracranial EEG
NeuroImage, 30:1161-1170.

Scripting

To reproduce this entire analysis with a script, use the following processes:

Feedback

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