what are we measuring with m/eeg? · pdf filebiophysical basisinstrumentationradial and deep...

32

Upload: duongdien

Post on 06-Mar-2018

215 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

What are we measuring with M/EEG?(And what are we measuring with?)

Saskia Helbling

Goethe University Frankfurt

SPM course, May 12, 2014

Saskia Helbling | M/EEG origins 1/32

Page 2: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Outline

1 Biophysical basis

2 Instrumentation

3 Radial and deep sources

4 Forward models

Saskia Helbling | M/EEG origins 2/32

Page 3: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

MEG and EEG are di�erent views of the same neuralsources

• Both record synchronized neural activity at a very high temporal resolution

• EEG ⇒ di�erences in electric potential at the skalp

• MEG ⇒ magnetix �ux density outside the head

Saskia Helbling | M/EEG origins 3/32

Page 4: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Origin of M/EEG signal

• Synaptic input leads to ionic currents across the postsynaptic membrane

• EPSP (often at apical dendrites): in�ux of positive Na+ ions• IPSP (often at the soma): in�ux of negative Cl− ions

Lopes da Silva, Mag. Res. Imag., 2004

Saskia Helbling | M/EEG origins 4/32

Page 5: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Origin of M/EEG signal

• Intracellular currents �ow from the apical dendrite to the soma

• Extracellular volume currents complete the loop of ionic �ow so that there is nobuild-up of charge

Lopes da Silva, Mag. Res. Imag., 2004

Saskia Helbling | M/EEG origins 5/32

Page 6: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

From a single neuron to a neural assembly

• A large number of simultaneously active neurons are needed to generate ameasurable M/EEG signal

Churchill, BMC Neuroscience 2004/Häusser and Cuntz (Wellcome Images)

Saskia Helbling | M/EEG origins 6/32

Page 7: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

High local lateral connectivity means that near by cellsshare similar excitation patterns

Holmgren et al. 2003

The current dipoles across a small cortical area are often summarised to an EquivalentCurrent Dipole (ECD).

Saskia Helbling | M/EEG origins 7/32

Page 8: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Realistic modelling of current sources

• Neuronal models of detailed morphologywere excited by virtually injecting current

• ECD moment was estimated bysumming elementary dipoles acrossneural segments

• 50 000 cells su�cient to generate adipolar source of 10nAm

• Sodic spikes with large current densities⇒ about 10 000 synchronous neuronscould yield an MEG measurable signal

S. Murakami et al., J. Physiol, 2006

Saskia Helbling | M/EEG origins 8/32

Page 9: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Primary intracellular currents give rise to volume currentsand a magnetic �eld

• Volume currents yield potential di�erences on the scalp that can be measured byEEG (Ohm`s law: J = σE)

• MEG measures magnetic �elds induced mainly by primary currents based onexcitatory activity (Okada et al. 1997)

Baillet: MEG consortium

Saskia Helbling | M/EEG origins 9/32

Page 10: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Mini Summary I

• M/EEG signal originates from postsynapic potentials, typically at the apicaldendrites of pyramidal cells

• The primary intracellular currents give rise to both volume currents and amagnetic �eld

• About 50 000 simultaneously pyramidal cells give rise to a measurable M/EEGsignal

Saskia Helbling | M/EEG origins 10/32

Page 11: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

1 Biophysical basis

2 Instrumentation

3 Radial and deep sources

4 Forward models

Saskia Helbling | M/EEG origins 11/32

Page 12: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Measuring potential di�erences with EEG

• The representation of the EEG channels is referred to as a montage

• Bipolar ⇒ represents di�erence between adjacent electrodes• Unipolar/Referential ⇒ potential di�erence between electrode and

designated reference

• The potential di�erences are then ampli�ed and �ltered

McFarland et al., 1997

Saskia Helbling | M/EEG origins 12/32

Page 13: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Laplacian montages are most sensitive to super�cialsources in EEG

Srinivasan et al., Prog Brain Res, 2007

Saskia Helbling | M/EEG origins 13/32

Page 14: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Measuring tiny magnetic �elds: the SQUID

• SQUIDs are ultrasensitive detectors of magnetic �ux made of a superconductingring interrupted by one or two Josephson junctions

• SQUIDs can measure �eld changes of the order of 10−15 (femto) Tesla (compareto the earth's �eld of 10−4Tesla)

• Cooling achieved by liquid Helium

• Output signal is a magnetic �ux dependent voltage

Adapted from J Clarke, Scienti�c American 1994

Saskia Helbling | M/EEG origins 14/32

Page 15: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

The high sensitivity means we also record a lot of noise

Hämälainen 1993

Saskia Helbling | M/EEG origins 15/32

Page 16: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Flux converters can enhance the sensitivity of the SQUIDsto magnetic �elds

Saskia Helbling | M/EEG origins 16/32

Page 17: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Axial and planar gradiometers have di�erent depth pro�les

• Axial gradiometers are aligned orthogonally to the scalp and record gradient ofmagnetic �eld along the radial direction

• Planar gradiometers consist of two detector coils on the same plane

• The gradiometer con�guration is important for the interpretation of the data

Vrba 2001, Hämälainen 1993

Saskia Helbling | M/EEG origins 17/32

Page 18: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

1 Biophysical basis

2 Instrumentation

3 Radial and deep sources

4 Forward models

Saskia Helbling | M/EEG origins 18/32

Page 19: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Given a spherical conductor, radial source do not give riseto an external magnetic �eld

• Biot-Savart`s law can be used to describe the magnetic �eld generated by anelectric current

• In the special case of a spherically symmetric volume conductor MEG is onlysensitive to the tangential component of the primary current

• The tangential component can be computed without knowing the conductivitypro�le

From D. CohenSaskia Helbling | M/EEG origins 19/32

Page 20: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Gyral sources remain partly visible

Hillebrand and Barnes 2002

• Pyramidal cells are aligned perpendicularly to the cortex surface ⇒ gryral sourcesare most radial

• But they are very close to the sensors and are surrounded by non-radial cortex towhich MEG is highly sensitive

Saskia Helbling | M/EEG origins 20/32

Page 21: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Depth is a limiting factor in MEG measurements

Hillebrand and Barnes 2002

• Magnetic �eld strength decreases steeply with distance ( 1

r2 )

• Deeper sources are more radial

Saskia Helbling | M/EEG origins 21/32

Page 22: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

But we can see deep sources, can't we?

Parkkonen et al. 2009

Saskia Helbling | M/EEG origins 22/32

Page 23: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

But we can see deep sources, can't we?

• Increase the signal-to-noise ratio and incorporate previous knowledge!

• Increasing number of papers published in recent years, e.g.:

• Thalamus (Tesche, Brain Res 1994, Roux, J Neurosc 2013)• Cerebellum and Thalamus (Timmermann, Brain 2002)• Hippocampus (Riggs, Neuroimage 2008)• ...

Saskia Helbling | M/EEG origins 23/32

Page 24: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

What are the deep brain neural generators of M/EEGsignals?

Attal et al., 2007

Saskia Helbling | M/EEG origins 24/32

Page 25: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Using realistic models fascilitates the detection of thalamicalpha band activity

Attal et al., 2013

Saskia Helbling | M/EEG origins 25/32

Page 26: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Mini Summary II

• MEG is less sensitive, but not blind to radial sources

• Sensitivity decreases steeply with depth, but accumulating evidence that we canmeasure the activity of deep sources

• Ability to detect deep sources depends on several factors, e.g. the signal to noiseratio, the cytoarchitecture of the deep structures, the forward model applied ...

Saskia Helbling | M/EEG origins 26/32

Page 27: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

1 Biophysical basis

2 Instrumentation

3 Radial and deep sources

4 Forward models

Saskia Helbling | M/EEG origins 27/32

Page 28: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Forward models predict the M/EEG surface signals tocurrent dipoles in the brain

Saskia Helbling | M/EEG origins 28/32

Page 29: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Headmodels show di�erent degrees of complexity

• The simpler models are not su�cient to predict the electric potential di�erencesat the scalp

• Complex models are (1) computationally more expensive and (2) require moreprior knowledge about the anatomy and conductivity values

Saskia Helbling | M/EEG origins 29/32

Page 30: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

MEG also may bene�t from using more complexheadmodels

Stenroos, Neuroimage 2014

Saskia Helbling | M/EEG origins 30/32

Page 31: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

EEG is strongly a�ected by skull anisotropy

• Finite element head models with skull or white matter anisotropy wereinvestigated for EEG and MEG simulations

• WM anisotropy had a signi�cant e�ect on both methods

• While MEG was hardly a�ected by skull anisotropy, potential di�erences on thescalp as measured by EEG are severely smeared

Wolters et al. 2006

Saskia Helbling | M/EEG origins 31/32

Page 32: What are we measuring with M/EEG? · PDF fileBiophysical basisInstrumentationRadial and deep sourcesrwForda models What are we measuring with M/EEG? (And what are we measuring with?)

Biophysical basis Instrumentation Radial and deep sources Forward models

Summary

• Electromagnetic signals predominantely based on aggregate post-synapticcurrents of tens of thousands of pyramidal cells

• MEG is most sensitive to tangential sources, while EEG 'sees' both components

• EEG has a higher sensitivity to deep sources, but is limited by head modelaccuracy

• Forward models describe how primary currents in the brain give rise to electricpotentials or magnetic �elds at the head surface

Saskia Helbling | M/EEG origins 32/32