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Learning objectives:at the end of this lecture, students will be able to• explain the biophysical basis of MEG and EEG• understand the principles of MEG measurement• differentiate strengths and weaknesses of MEG• compare MEG with other methods• grasp implications for experimental design

Electrophysiology I

Magnetoencephalography (MEG)

http://www.psychology.nottingham.ac.uk/staff/mxs/MScCognNeurosciNeuroimaging/

Martin Schürmann, martin.schuermann@nottingham.ac.uk

MEG and EEG record neuronal electrical activity directly• as opposed to hemodynamic by-effects in functional MRI• with excellent temporal resolution (milliseconds)• with good spatial resolution in the case of MEG

Electrophysiology I: MEG vs EEG

MEG, magnetoencephalographyEEG, electroencephalographyen * kephale * graphein-graphy is the method-gram is the result

MEG and EEG as methods for cognitive neuroscience• study the brain basis of sensory and cognitive processes• in many cases single-subject data can be evaluated in MEG

MEG measuresmagnetic field

around the head

EEG measuresvoltage changes

on the scalpdifferent signal,but same

biophysical basis

Brain imaging methods: spatial and temporal resolution

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Particular advantage of MEG: activation sequences

Nishitani and Hari Neuron 2002

120ms

320ms

Observation, imitation, and execution of orofacial gestures

Neuromag VVLTL, HUT, Helsinki102 x 3 sensors

Principle of MEG measurement:what kind of brain activity is measured?

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CTF, 275-channels(axial gradiometers)

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same biophysical basis for MEG and EEG

EEG and MEG measure electrical activity in pyramidal cells

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Membrane potential for potassium (K+):-- concentration gradient from intra- to extracellular space;-- electrical gradient from extra- to intracellular space;

Membrane potential for sodium (Na+)-- in opposite direction

maintained by proteins that pump ionsagainst gradient

Changes of membrane potentials over time(=information processing in neurons)

1. action potentials2. postsynaptic potentials

What gives rise to signals in MEG and EEG –action potentials or postsynaptic potentials?

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Neuronal activity: dynamics of membrane potentials

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presynaptic action potentialliberates neurotransmittersinto synaptic cleft

neurotransmitters interact withpostsynaptic receptors

postsynaptic depolarization orhyperpolarization (excitationor inhibition)

strength ofexcitationreflected infrequency

strength ofexcitationreflected inamplitude

temporal summation

postsynapticpotentials

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postsynaptic potentials (PSPs)• either excitatatory (EPSP)• or inhibitory (IPSP)• temporal and spatial summation

Action potentials not visible in EEG/MEG

Reason 1: AP generates 2 current dipoles =quadrupole: antiparallel and equalintensity, so cancel out

Reason 2: Quadrupolar field decreases withdistance as 1/r³ (compared with 1/r² in thecase of dipolar field)

Reason 3: Duration of AP ~ 1 ms, sotemporal summation unlikely

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Neuronal activity measurable outside the head?

Wikswo 1989

generate ~ one current dipoledipolar fields decrease with

distance as 1/r²duration: tens of ms, so temporal

summation possible

current dipole produced by singleEPSP ~ 20 fAm, too small to bemeasured in EEG/MEG

femto 10-15 pico 10-12

Hämäläinen et al Rev Mod Phys 1993 * Zlobinski/de Tiege http://www.fil.ion.ucl.ac.uk “What are we measuring with EEG and MEG”

Neuronal activity measurable outside the head?

Postsynaptic potentials visible in EEG/MEG

Primary current source: movement of ions due toconcentration gradients (also: impressed current)Passive currents in the surrounding mediumcomplete the loop of ionic flow (i.e. no buildup ofcharge): volume currents

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MEG requires source strength onthe order of 10 nAm

nano 10-9, 6 orders of magnitude larger than single dipole

In many regions of cerebral cortex,dendrites of pyramidal cells areperpendicular to the corticalsurface, so they are parallel withone another, and PSPs summatein practice, synaptic activity is shadowed by cancellation due to thesignal is attenuated due to spatiotemporal misalignment

MEG signals mainly reflectPSP generated at apical dendritesof pyramidal cells in the cortex

Zlobinski/de Tiege http://www.fil.ion.ucl.ac.uk “What are we measuring with EEG and MEG”

Neuronal activity measurable outside the head?

http://thebrain.mcgill.ca/flash/i/i_02/i_02_cl/i_02_cl_vis/i_02_cl_vis.html

Spatial summation: Dendrites in parallel

http://www.brain.riken.jp/en/aware/neurons.html

Principle of MEG measurement:how is brain activity manifest outside the head?

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Model of neural sources: equivalent current dipole

http://de.wikipedia.org http://hyperphysics.phy-astr.gsu.edu/hbase/magnetic

Magnetic fields outside the head

recording surface

neuronal source

Magnetic fields outside the head

recordingsurface

neuronalsource

Skull is “transparent” to magnetic fields (i.e. no distortion) whereas electric fields aredistorted (important consequences for spatial reolution of EEG vs MEG)

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Primary currents

Volume currents

Induced magnetic field

Magnetic fields outside the head

skull is transparent to magnetic fields whereasit distorts electric potential maps

therefore optimal MEG source reconstructionneeds a realistic model of the brain only

in contrast, optimal EEG source reconstructionneeds multi-compartment model with knownconductivities and shapes for brain,cerebrospinal fluid, skull, and scalp

low conductivity of the skull: ~1/100 of brain's conductivity, therefore95% of current associated with brain activity limited to teh brain

so in practice MEG has better spatial resolutionthan EEG (notice also MEG specificity forfissural sources)

Magnetic fields outside the head

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MEG localization inaccuracy for dipoles:direction transverse to dipole orientation< direction of dipole orientation < depth

Sylvain Baillet HBM 2006

EEG

MEG

Tangential currents: magnetic fields that can be recorded outside the head

Radial currents: no magnetic fields outside the head

MEG (with magnetometers or gradiometers) only detects tangential currentsprimary sensory areas are located in sulci = fissural cortex

EEG detects tangential and adial sources and to some extent also deep sources

Zlobinski/de Tiege http://www.fil.ion.ucl.ac.uk “What are we measuring with EEG and MEG”

Magnetic fields outside the head

Magneticfieldsoutsidethe head

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Head approximated as a spherically symmetric conductor:• only currents with component tangential to the surface produce magnetic

field outside,• radial sources are externally silent (fissures vs gyral crowns)• source localization? “inverse problem” without unique solution (Hermann von

Helmholtz 1853)• headshape approximation not equally precise in all areas• when used for source analysis, sphere model gives good results even if

conductor is not a perfect sphere (as long as curvature is fitted locally toarea of interest -- difficult for frontal areas)

• given that only superficial tangential dipoles contribute to MEG, 3D sourcelocalization can be replaced with 2D source localization

• in a sphere model, the magnetic field of a dipole can be calculated withoutknowing how conductive and how thick the different layers are (not possiblefor electric potential)

• therefore sphere model allows simple forward models for fast computation• realistic head models: * due to low conductivity of the skull most of the

current associated with brain activity is limited to intracranial space,therefore skull's inner surface needs to be modelled with boundary elementmethod or finite element method * very complex forward model

Some methods of MEGsource localization rely onrepeated comparison of theforward model with the actualsource distributionso a simple forward modelspeeds up source analysis

Magneticfieldsoutsidethe head

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Perfectly radial currents: no magnetic fields outside the head (but even 10° deviation from radial orientation may makesources detectable, given that gyral crowns are close to sensors) - Hillebrand and Barnes, Neuroimage 2002

Deep sources?

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Principle of MEG measurement:what’s inside the helmet?

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Sensors for magnetic fields outside the head

• magnetometers are sensitive to very weak magnetic fields• in the pickup coil, the neuromagnetic field induces a current that

increases with the density of magnetic flux• SQUID Superconducting QUantum Interference Device detects the tiny

currents in the pickup coil• for minimal resistance, superconducting properties are required which are

maintained only when magnetometer is cooled to -269 °C (liquid helium)

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flux transformer

radial component ofthe magnetic field

Sensors must detect a small signal within noisesignal-to-noise ration is critical, not just sensitivity

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Earth field

Urban noise

Contamination at lung

Heart QRS

MuscleFetal heart

Spontaneous signal(-wave)

Signal from retina

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Biomagnetism

EYE (retina)Steady activityEvoked activity

LUNGSMagnetic contaminants

LIVERIron stores

FETUSCardiogram

LIMBSSteady ionic current

BRAIN (neurons)Spontaneous activityEvoked by sensory stimulation

SPINAL COLUMN (neurons)Evoked by sensory stimulation

HEARTCardiogram (muscle)Timing signals (His Purkinje system)

GI TRACKStimulus responseMagnetic contaminations

MUSCLEUnder tension

requires sensitive detectors(low noise-high gain amplification)

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discrimination of signal ofinterest along frequency axis

Sensors must detect a small signal within noise

Shielded room (several layers of metal) and coil properties

axial gradiometer(first order)

Magnetometers are most sensitive tosignals but also to artifacts

In axial gradiometers, distantdisturbances link the same magnetic fluxin pickup coil and compensation coil(they “look similar” to both coils)

A weak cortical signal, however,looks different between the twocoils because of the distancebetween the two coils

Gradiometers are, however. lesssensitive than magnetometers

Some MEG systems have additionalcompensation sensors far away from thehead

Another way to compensate for noise isby signal-space projection in software(based on a measurement of noise in theshielded room without subject)

Sensors must detect tiny signal within noise

magnetometer

single pickup coil

pickup coil

compensation coil

higher-order gradiometers

Planar type

Magnetometer

Gradiometer

Axial type

50 mm base line

NeuroMag VectorViewBTi-4D Magnes

NeuroMagVectorView

CTF SystemBTi-4D

Magnetometer

Sensitivity for deeper sourceshigher lower

Different configurations of pickup coils

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Amplitudesof magneticsignalsdue to atangentialdipole in asphericallysymmetricconductor

Axial vs planar gradiometers

gradiometer recordingsLEFT VS RIGHT – CORRECT?

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Multichannel MEG systems

How many channels?No benefit from reducingsensor-to-sensor spacingbelow sensor-to-cortexdistance of ~3 cmtherefore ~150 sensorsare enough to cover wholecortex

Summary slide at the end of lecture Magnetoencephalography II

With modern MEG systems the subjectcan be either seated or supine

Summary: MEG and EEG as complementary methods

Movement does not matter (as longas short-lived artifacts are removed)

Subject to remain immobile duringmeasurements (unless headposition is recorded continuously)

Averaging across subjects isstraightforward

Frequently permits single-subjectanalysis

Considerably less expensiveequipment

Expensive equipment, normallyneeds shielding, considerable costfor maintenance (helium)

Inverse problem applies, combinedwith distortion of signal by skull andscalp

Inverse problem applies but nodistortion of signal by skull andscalp

Sensitive to tangential and radialsources, to some exent alsosensitive to deep sources

Sensitive mainly to superficialtangential sources (cortical sulci)

EEGMEG

MEG in a nutshellas explained in Hari, Levänen and Raij Trends Cogn Sci 2000

Advantages• totally non-invasive, good for repeated measurements in healthy subjects and patients• excellent temporal resolution (millisecond range)• reflects neural activation directly (mainly postsynaptic currents), rather than blood flow or metabolism.• signals frequently evident without complicated statistical analysis (just time-locked averaging)• selective to activation of fissural cortex (tangential dipoles) which is difficult to reach with other means• skull and scalp do not distort the magnetic field patterns; this is an advantage over EEG• quantitative information about activation strengths of neuronal populations.• often conclusions possible on the basis of single subject data: individual processing strategies• subtractions between conditions are not necessary: advantage over PET and fMRI

Disadvantages• non-unique inverse problem: source modeling demanding for someone not familiar with the technique• neuromagnetometer needs magnetically silent (often shielded) environment.• subject has to cooperate and to keep the head immobile during recording (children!)• detected signals always reflect population responses (at least 1 mm2 of cortex)• most synchronous activation dominates the measured signals (functional role of this activation?)• deep and radial sources largely neglected• activations of areas less than 2 cm apart difficult to discern (but current orientation or timing may help)• cancellation of activation for adjacent symmetric dipoles of opposite direction