Principle of MEG measurement -...
Transcript of Principle of MEG measurement -...
1
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, [email protected]
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
http
://w
ww
.psy
ch.n
dsu.
noda
k.ed
u/m
ccou
rt/P
sy46
0/
fine temporal resolution coarse
fine
spat
ialr
esol
utio
nco
arse
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?
http
://ku
rage
.nim
h.ni
h.go
v
CTF, 275-channels(axial gradiometers)
Har
iR.N
ews
Phy
siol
Sci
1993
same biophysical basis for MEG and EEG
EEG and MEG measure electrical activity in pyramidal cells
Häm
äläi
nen
etal
Rev
Mod
Phy
s19
93
http
://th
ebra
in.m
cgill.
ca/fl
ash/
i/i_02
/i_02
_cl/i_
02_c
l_vi
s/i_
02_c
l_vi
s.ht
ml
2
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?
Zlo
bins
ki/d
eT
iege
http
://w
ww
.fil.i
on.u
cl.a
c.uk
Neuronal activity: dynamics of membrane potentials
http
://w
ww
.wik
iped
ia.o
rg
Neuronal activity:dynamics ofmembrane potentials
Mar
kM
cCou
rt,ht
tp://
www.
psyc
h.nd
su.n
odak
.edu
/mcc
ourt/
Psy4
60/
Neuronal activity:dynamics ofmembrane potentials
http
://co
urse
s.w
ashi
ngto
n.ed
u/co
nj/
presynaptic action potentialliberates neurotransmittersinto synaptic cleft
neurotransmitters interact withpostsynaptic receptors
postsynaptic depolarization orhyperpolarization (excitationor inhibition)
strength ofexcitationreflected infrequency
strength ofexcitationreflected inamplitude
temporal summation
postsynapticpotentials
Mar
kM
cCou
rt,ht
tp://
www.
psyc
h.nd
su.n
odak
.edu
/mcc
ourt/
Psy4
60/Neuronal activity:
dynamics ofmembrane potentials
Häm
äläi
nen
etal
Rev
Mod
Phy
s19
93
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
Zlob
insk
i/de
Tieg
eht
tp://
ww
w.fi
l.ion.
ucl.a
c.uk
“Wha
tare
we
mea
surin
gw
ithEE
Gan
dM
EG”
--
--
----
----
++++
++
++
++
++
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
3
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?
Har
iR.N
ews
Phy
siol
Sci
1993
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)
4
Syl
vain
Bai
llet
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
recording surface
neuronal source
rst.g
sfc.
nasa
.gov
/Sec
t11/
Sec
t11_
2.ht
ml
contour plot
Häm
äläi
nen
etal
Rev
Mod
Phy
s19
93
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
Har
i,Le
väne
nan
dR
aij,
Tren
dsC
ogn
Sci2
000
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
Har
i,Le
väne
nan
dR
aij,
Tren
dsC
ogn
Sci2
000
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?
5
Principle of MEG measurement:what’s inside the helmet?
Har
iR.N
ews
Phy
siol
Sci
1993
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)
Zlob
insk
i/de
Tieg
eht
tp://
ww
w.fi
l.ion.
ucl.a
c.uk
“Wha
tare
we
mea
surin
gw
ithEE
Gan
dM
EG”
flux transformer
radial component ofthe magnetic field
Sensors must detect a small signal within noisesignal-to-noise ration is critical, not just sensitivity
1 0 - 4
1 0 - 5
1 0 - 6
1 0 - 7
1 0 - 8
1 0 - 9
1 0 - 1 0
1 0 - 1 1
1 0 - 1 2
1 0 - 1 3
1 0 - 1 4
1 0 - 1 5
Earth field
Urban noise
Contamination at lung
Heart QRS
MuscleFetal heart
Spontaneous signal(-wave)
Signal from retina
Intrinsic noise of SQUID
Inte
nsity
ofm
agne
ticsi
gnal
(T)
Evoked signal
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)
Dav
idPo
eppe
l,ww
w.lin
g.um
d.ed
u/~p
oepp
el/B
SCI_
mat
eria
ls/Po
eppe
l_M
EG_P
t1.p
pt
Häm
äläi
nen
etal
Rev
Mod
Phy
s19
93
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
Dav
idPo
eppe
l,ww
w.lin
g.um
d.ed
u/~p
oepp
el/B
SCI_
mat
eria
ls/Po
eppe
l_M
EG_P
t1.p
pt
6
Häm
äläi
nen
etal
Rev
Mod
Phy
s19
93
Amplitudesof magneticsignalsdue to atangentialdipole in asphericallysymmetricconductor
Axial vs planar gradiometers
gradiometer recordingsLEFT VS RIGHT – CORRECT?
Häm
äläi
nen
etal
Rev
Mod
Phy
s19
93
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