epileptiform patterns on scalp eeg and meg: physiologic ... · inhibitory synapse gaba synaptic...
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Epileptiform Patterns on Scalp EEG and MEG: Physiologic Basis and Principles of Localization
Richard C. Burgess, MD, PhD
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Epileptiform Patterns on Scalp EEG and MEG: Physiologic Basis and Principles of Localization
Richard C. Burgess, MD, PhD
OVERALL OBJECTIVES
• Understand the physiologic basis of the neurophysiological signals recorded from the brain
• Appreciate the basic physics and technical principles underlyng the recording instrumentation
• Become familiar with the fundamentals of source localization
• Understand the advantages and disadvantages of EEG and MEG for source localization
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Definitions
Electroencephalography – EEG, recording of the brain’s electrical activity
Magnetoencephalography – MEG, recording of the brain’s magnetic activity
Source Imaging – pinpointing the location of the brain activity in three-dimensional space– ESI: electrical source imaging– MSI: magnetic source imaging These two are neurophysiological techniques; they are not imaging methods, despite the names !
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From where do the EEG and MEG signals originate?
Richard Caton Hans Berger
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What is EEG?
The EEG is a measure of cerebral electrical activity in the cortex
The summated post-synaptic potentials are the main generators of the recorded scalp EEG
The electrical potentials reach the surface through volume conduction, a process of:– Origination,– Spread through a conductive
medium, and– Pickup by a distant
recording electrode.
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What is MEG?
Based on recording of incredibly small magnetic fields (10 -12 T).
Easy acquisition of very high density (100-300 channels)wideband (DC – 2000 Hz) recordings of currents within the brain.
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What is MEG?MEG is a Localization Tool Based on solid theoretical reasons, MEG has
localization accuracy better than scalp EEG– Greater number of sensors typically employed– Simpler source modeling and calculation– Anatomical co-registration with 3D-MRI
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EEG and MEG Waveforms
EEG
MEG
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Origin of signals recorded by EEG and MEG:
Main source is current flow from long apical dendrites of cortical pyramidal cells which are created from: 1. Gray matter synaptic potentials 2. Propagated action potentials in white
matter fiber tracts (minimal contribution)
Consist primarily of: Extracellular current resulting from
summated IPSPs and EPSPs
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Excitatory Postsynaptic Potential (EPSP)
Presynaptic action potential
Release of glutamate
Postsynaptic depolarization
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Pyramidal neuron excitation
Intracellularcurrent
Extracellularcurrent
Part of illustration adapted from Hansen PC, Kringelbach ML, Salmelin R (eds). MEG: An Introduction to Methods.
Excitatory synapse are distal. Positive ions flow inward. Induces current flow towards
the soma. Measured extracellularly as
negative.
Depolarization
Depolarization
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Inhibitory Postsynaptic Potential (IPSP)
Presynaptic action potential
Release of GABA
Postsynaptic hyperpolarization
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Pyramidal neuron inhibition
Intracellularcurrent
Extracellularcurrent
Part of illustration adapted from Hansen PC, Kringelbach ML, Salmelin R (eds). MEG: An Introduction to Methods.
Inhibitory synapses are proximal.
Negative ions flow inward. Induces current flow towards
the soma. Measures positive
extracellularly down at the synapse, but this is also negative at the surface.
Hyperpolarization
Hyperpolarization
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Inhibitory SynapseGABA
Synaptic Summary
Excitatory synapseGlutamate
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Non-Invasive recording of PSPs
Tiny signals:– Signal from a single post-synaptic potential
(PSP) lasts ~10 msec.– Too brief and too small to be detected non-
invasively. Net effect of summated activity:
– Thousands of adjacent pyramidal neurons.– Activated within more or less the same
time window.
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EEG and MEG Signals
A current dipole creates a magnetic field
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Pyramidal Cells Act as Sheets of Dipoles in the Cortex
Cortical macrocolumn of diameter 3-4 mm contains:106 neurons, 1010 synapses.
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Presurgical Epilepsy Evaluation Goals
– Locate the epileptogenic zone.– Assess whether it can be resected to achieve seizure freedom.
Multi-modality investigative tools:– Video-EEG monitoring +/- sphenoidals– MRI– PET/SPECT– Neuropsychology– Wada/fMRI– EEG and/or MEG source localization– Invasive Monitoring
Additional hopes for source localization:– Avoidance of invasive recording if possible OR– Better placement of invasive electrodes
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What is the Electroencephalographer or Magnetoencephalographer’s Task?
Examining the surface evidence of electrical currents, estimate the:
Magnitude, Location, and Distribution
Of the underlying source(s) producing the recorded field.
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Topographic Mapping: Amplitude vs Time
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Source Localization is Based on Computerized Modeling
Source model– number – type – location
Head model– homogeneity – number of layers– shape
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Models of the Brain Electrical Activity Sources
Equivalent Current Dipole Model (Simpler)
– Examples: Single Equivalent Dipole– Multiple Signal Classification (MUSIC)
Distributed Model / Current Density Reconstruction Model (Computationally Intensive)
– Examples: Minimum Norm Estimate– LORETA (Low resolution electromagnetic tomography)
– FOCUSS (Focal undetermined system solver)
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Electric fields and magnetic fields generated by a current dipole.
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What is an “Equivalent Dipole” ?
It is not the “centroid” of the electrical activity.
(In fact, it is frequently found in white matter below the spiking cortex.)
It is a device which, if it existed, couldproduce the field distribution of the activity under study.
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Dipolar Representation in MEG and EEG The signals picked up by scalp electrodes or MEG sensors are generated by
synchronized activity from many neurons:– Postsynaptic potentials produce intracellular laminar currents– Neocortical pyramidal neurons arranged in a palisade structure– Typically seen as a current dipole perpendicular to the cortical surface
Dipolar models are based on the assumption that: – Coherent activation of a large number of pyramidal cells can be represented by a
point source– A small number of current sources (multiple dipoles, sheets of dipoles) in the
brain can adequately model surface measurements
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Current Dipole ModelCurrent dipole:
• Representation of an electric current travelling from – to +over a short distance (Ohm’s law)
• Has a strength and orientation
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Magnetic Field Produced by a Current Dipole
Magnetic fields produced by current dipole:– Follow the “Right-hand rule”:
• When the right hand thumb points to direction of the current, the fingers curl in the direction of the magnetic fields.
– Biot-Savart’s law:• Forward solution• Field strength decreases
in proportion to the square of the distance from the dipole
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Radial & Tangential Sources
RadialDipole
Tangential Dipole
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Differences Between EEG and MEG inSensitivity to Current Dipole Orientation
Scalp EEG is relatively sensitive to vertical dipoles MEG is exclusively sensitive to tangential dipoles
(neglects the vertical component of the dipole vector)
Tangential dipole Vertical dipole
** **
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Determining the Best Model
In fact, many sources are not dipolar, but rather are extended or complex.
Therefore this becomes an even more difficult and elaborate ▬ but educated ▬ estimation, which draws on an extensive body of mathematical work on the inverse problem.
The solutions are usually constrained in some rational way, therefore the sources found will depend on the assumptions used.
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Source Localization: Linear Models
– Minimum norm estimation• Predetermined set of dipoles (usually 1000 to 10,000)• All have fixed positions and orientations (usually constrained to the cortical mantle• Calculate a combination of dipole strengths to explain the measured fields.
– Distributed results• Looks realistic
– Requires no initial guess• No bias by human interpretation
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Models of the Head
Sphere Model Concentric spheres (most common)Multiple spheres
Realistic Head ModelBEM (boundary element method)FEM (finite element method)Head shape from MRIImage segmentation in 3D
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Head Models
Single Sphere Multiple Spheres
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EEG: Complicated Concentric Sphere Model
Layers:Head consists of series of roughly concentric layers separating brain from scalp surface, each of which presents different electrical characteristics to the currents which conduct the EEG to the surface: CSF meninges bone skin
Effects: smearing and blurring attenuation
Model:3- or 4-layer compartment head model necessary in EEG to take inhomogeneous conductivity into account
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MEG: Simple Single Sphere Model
MEG requires a simple conductor (head) model and therefore a lower calculation burden than EEG for computerized source modeling.
Magnetic fields are conveyed transparently through all of the cranial tissues.
Effects on the magnetic fields of volume conduction and skull defects are negligible or small.
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With models for both the source and the head, we can carry out source localization
Iteratively search possible dipoles for best fit to the actual field distribution
= +
Measurement Model Residual
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How Does MEG Recording Work?
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MEG Instrumentation
SQUID
Flux transformers
Shielded room
Head position indicator
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Relative Magnetic Field StrengthBRAIN SOURCESEvoked cortical fields: 10 fTAlpha rhythm: 1000 fT
NOISE SOURCESEarth’s magnetic field: ~50 µTField from home appliances and wiring: <10 µTUrban environmental noise: 108 fT
(fT = femto Tesla or 10-15 Tesla)
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Passive magnetic shielding using Mu-metal (alloy)
May employ coils for active noise cancellation
External magnetic field is guided around the boundaries of the magnetically-shielded room
Magnetically Shielded Room
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SQUID & Flux Transformer
Superconducting Quantum Interference Device,i.e. requires liquid helium
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SQUID Sensors Arrayed Around Head
Axial Gradiometers
Planar Gradiometers
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Gradiometers vs Magnetometers
Tanzer, PhD Thesis, Helsinki
Measuring gradients (relative differences), rather than absolute magnetic field, helps subtract background noise
Requires two coils oriented to subtract overall global field, with the difference representing local gradients
Magnetometer Axial Gradiometer
Planar Gradiometer
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Source Analysis
Forward problem:–Has a unique analytic solution–Poisson’s equation 2 Φ = – /
(von Helmholtz H. Bereinige Gesetze der Vertheilung elektrischer Stroeme in koeperlichen Leitern, mit Anwendung auf die thierisch-elektrischen Versuche. Ann Phys Chem 89:211-33, 353-77. 1853.)
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Source Analysis
Forward problem:–Has a unique analytic solution–Poisson’s equation 2 Φ = – /
Inverse problem:–Has a theoretically infinite number of solutions–Impossible to find a unique solution–THIS IS THE EEGer or MEGer’s ACTUAL PROBLEM
(von Helmholtz H. Bereinige Gesetze der Vertheilung elektrischer Stroeme in koeperlichen Leitern, mit Anwendung auf die thierisch-elektrischen Versuche. Ann Phys Chem 89:211-33, 353-77. 1853.)
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Source Localization Parallels: MEG and EEG
Both EEG and MEG can employ similar models (e.g. equivalent current source dipole).
Substrate– MEG: 3.5 cm2
– EEG: 6 cm2 or20-30 cm2 depending on location (lateral convexity vs anterior temporal) and consideration of background
Both can utilize patient-specific anatomic models (CT, MRI).
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Differences and Similarities:EEG and MEG
Similarity– Record the same phenomenon
• Same time-resolution• Spontaneous activities (epileptic spikes, non-epileptiform physiological),
evoked responses (SEP, VEP, AEP)– Sensitivity to brain volume and depth
Differences– Sensitivity to the current dipole orientation
• Tangential or vertical to the scalp surface– Complexity of the forward model
• Feasibility of the computerized source estimation– Analysis– MEG is reference-free– Number of sensors– Duration of the recording– Different sensitivity to external noises– Cost– Established knowledge
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Differences and Similarities:EEG and MEG
Similarity– Record the same phenomenon
• Same time-resolution• Spontaneous activities (epileptic spikes, non-epileptiform physiological),
evoked responses (SEP, VEP, AEP)– Sensitivity to brain volume and depth
Differences– Sensitivity to the current dipole orientation
• Tangential or vertical to the scalp surface– Complexity of the forward model
• Feasibility of the computerized source estimation– Analysis– MEG is reference-free– Number of sensors– Duration of the recording– Different sensitivity to external noises– Cost– Established knowledge
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Differences and Similarities:EEG and MEG
Similarity– Record the same phenomenon
• Same time-resolution• Spontaneous activities (epileptic spikes, non-epileptiform physiological),
evoked responses (SEP, VEP, AEP)– Sensitivity to brain volume and depth
Differences– Sensitivity to the current dipole orientation
• Tangential or vertical to the scalp surface– Complexity of the forward model
• Feasibility of the computerized source estimation– Analysis– MEG is reference-free– Number of sensors– Duration of the recording– Different sensitivity to external noises– Cost– Established knowledge
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Differences and Similarities:EEG and MEG
Similarity– Record the same phenomenon
• Same time-resolution• Spontaneous activities (epileptic spikes, non-epileptiform physiological),
evoked responses (SEP, VEP, AEP)– Sensitivity to brain volume and depth
Differences– Sensitivity to the current dipole orientation
• Tangential or vertical to the scalp surface– Complexity of the forward model
• Feasibility of the computerized source estimation– Analysis– MEG is reference-free– Number of sensors– Duration of the recording– Different sensitivity to external noises– Cost– Established knowledge
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1. Inherently higher source resolution and accuracy.
2. Better detection yield.
3. Reference – free.
4. Signals not attenuated or distorted by bone and scalp, or other inhomogeneities that exist between brain and surface.
5. Therefore for source analysis, the head modelling problem is significantly simpler.
6. Easy to obtain multichannel, whole-head, high spatial-density recordings.
7. No exposure to radiation, magnetic field, or other active device.
Advantages of MEG
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Authors Year EEG MEGCohen D and Cuffin BN2 1991 10 mm 8 mmLeahy RM, Mosher JC, Spencer ME, Huang MX, and Lewine JD3 1998 7-8 mm 3 mm
1 A Bayesian Approach to Introducing Anatomo-Functional Priors in the EEG/MEG Inverse Problem. Baillet S, Garnero L: IEEE Transactions on Biomedical Engineering 1997, 44(5):374-385.
2 EEG versus MEG localization accuracy: Theory and experiment Brain Topography Springer Netherlands Vol 4, No 2; December 1991.
3 A study of dipole localization accuracy for MEG and EEG using a human skull phantom. Electroencephalogr Clin Neurophysiol 1998;107:159-173.
What is clinically acceptable? In 1997, Baillet recommended a spatial accuracy of better than
5 mm. Source localization accuracy is higher for MEG than for EEG. ..
Source Localization Accuracy
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Cortex inflated
(Adapted from Hillebrand A and Barnes GR, NeuroImage 16, 638-650, 2002)
MEG Sensitivity: Geographic detection probability
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(Adapted from Hillebrand A and Barnes GR, NeuroImage 16, 638-650, 2002)
MEG Sensitivity: Required source strength
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What do we know about MEG in Epilepsy?
The yield of MEG is higher than scalp EEG.– (Yoshinaga et al, 2002; Iwasaki et al, 2005;
Ossenblok et al, 2007; Goldenholz et al, 2009) MEG provides additional localizing
information.– (Wheless et al, 1999; Stefan et al, 2003; Pataraia et
al, 2004) MEG results change the electrode coverage
decisions for intracranial EEG.– (Knowlton et al, 2009)
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Burgess, Richard C.; Barkley, Gregory L.; Bagic, Anto I.; Turning a New Page in Clinical Magnetoencephalography: Practicing According to the First Clinical Practice Guidelines. Journal of Clinical Neurophysiology. 28(4):339-340, August 2011.
Bagic, Anto I.; Barkley, Gregory L.; Rose, Douglas F.; Ebersole, John S.; American Clinical Magnetoencephalography Society Clinical Practice Guideline 4: Qualifications of MEG–EEG Personnel. Journal of Clinical Neurophysiology. 28(4):364-365, August 2011.
ACMEGS Clinical Practice Guidelines
Bagic, Anto I.; Knowlton, Robert C.; Rose, Douglas F.; Ebersole, John S.; American Clinical Magnetoencephalography Society Clinical Practice Guideline 1: Recording and Analysis of Spontaneous Cerebral Activity. Journal of Clinical Neurophysiology. 28(4):348-354, August 2011.
Burgess, Richard C.; Funke, Michael E.; Bowyer, Susan M.; Lewine, Jeffrey D.; Kirsch, Heidi E.; Bagic, Anto I.; American Clinical Magnetoencephalography Society Clinical Practice Guideline 2: Presurgical Functional Brain Mapping Using Magnetic Evoked Fields. Journal of Clinical Neurophysiology. 28(4):355-361, August 2011.
Bagic, Anto I.; Knowlton, Robert C.; Rose, Douglas F.; Ebersole, John S.; American Clinical Magnetoencephalography Society Clinical Practice Guideline 3: MEG–EEG Reporting. Journal of Clinical Neurophysiology. 28(4):362-365, August 2011.1
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What Should the Referring Physician Expect from a MEG Report?
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Run I EEG
EEG dipole #1: Spike regional right posterior quadrant
Fp1-F7
F7-T7
T7-P7
P7-O1
Fp2-F8
F8-T8
T8-P8
P8-O2
Fp1-F3
F3-C3
C3-P3
P3-O1
Fp2-F4
F4-C4
C4-P4
P4-O2
Fz-Cz
Cz-Pz
300 uV1 sec #1
Example Waveforms Showing the EEG Correlate to the MEG Discharge
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MEG dipole #1: Poly spikes maximum in the right temporal > occipital sensors
1 sec 500 fT/cm Right temporal
Right occipital
#1
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Ictal and dipoles with SEF and MEF dipoles
RIGHT
Summary Slide Showing Epileptic and Functional Results
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Magnetoencephalography LabCCF Epilepsy Center, Neurological Institute