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Integrating MEG, EEG and fMRI data

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<strong>MEG</strong>/<strong>EEG</strong> Brain Mapping Course<br />

HBM2006<br />

Florence, June 11, 2006<br />

<strong>Integrating</strong> <strong>MEG</strong>, <strong>EEG</strong> <strong>and</strong> <strong>fMRI</strong> <strong>data</strong><br />

Gian Luca Romani<br />

Institute of Advanced Biomedical Technologies – ITAB<br />

“G. D’Annunzio University” Foundation<br />

<strong>and</strong><br />

Department of Clinical Sciences <strong>and</strong> Bioimaging<br />

“G. D’Annunzio” University,<br />

Chieti, ITALY


Outline<br />

• <strong>MEG</strong> - <strong>EEG</strong> – <strong>fMRI</strong> integration: respective<br />

advantages <strong>and</strong> limitations<br />

• Basic methods<br />

• Examples of integration in the study of primary<br />

areas, in cognitive neuroscience, <strong>and</strong> in the<br />

clinical field<br />

– Somatosensory system: pain vs. no-pain activations <strong>and</strong><br />

somatotopic properties<br />

– Passive listening to sounds from different locations<br />

– Functional reorganization in cases of malformation of<br />

cortical development<br />

• Some critical remarks<br />

• Conclusions <strong>and</strong> perspectives


<strong>MEG</strong> <strong>and</strong> <strong>fMRI</strong> equipment<br />

at ITAB – University of Chieti<br />

<strong>MEG</strong><br />

<strong>fMRI</strong><br />

165-channel wholehead<br />

system<br />

(by end 2006, a new<br />

500-channel system)<br />

1.5T Siemens Vision<br />

(by end 2006, a new<br />

3T Philips Achieva)


<strong>MEG</strong> - <strong>EEG</strong> – <strong>fMRI</strong> integration:<br />

respective advantages <strong>and</strong><br />

limitations


<strong>fMRI</strong> – <strong>MEG</strong> (<strong>EEG</strong>) relationship<br />

<strong>fMRI</strong><br />

Generated by oxygenated<br />

hemoglobin in the blood<br />

Functional images are<br />

directly related to<br />

structural images<br />

No source model required<br />

High spatial resolution (but<br />

depends on vascularization)<br />

Low time resolution (limited<br />

by hemodynamic response)<br />

Resolution independent of<br />

source depth<br />

<strong>MEG</strong> (<strong>EEG</strong>)<br />

Generated by intracellular<br />

currents<br />

Functional images are not<br />

directly related to<br />

structural images<br />

Imaging depends on source<br />

<strong>and</strong> head models (<strong>and</strong><br />

conductivity, for <strong>EEG</strong>)<br />

Low spatial resolution<br />

(related to source type)<br />

High time resolution (better<br />

than 1 ms)<br />

Poor resolution for deep<br />

sources


<strong>MEG</strong>, <strong>EEG</strong>, <strong>fMRI</strong> spatio-temporal<br />

properties<br />

Spatial resolution (mm)<br />

10<br />

8<br />

6<br />

4<br />

2<br />

<strong>EEG</strong><br />

<strong>MEG</strong><br />

<strong>fMRI</strong><br />

0<br />

10 -3 10 -2 10 -1 10 0 10 1 10 2<br />

Temporal resolution (s)<br />

10 3


Basic methods


How can we integrate <strong>MEG</strong>, <strong>EEG</strong>, <strong>and</strong> <strong>fMRI</strong> ?<br />

a. Simple superposition of the equivalent current<br />

dipoles (ECDs) <strong>and</strong> the <strong>fMRI</strong> active areas<br />

b. Dipole seeding, i.e. utilize <strong>fMRI</strong> activation<br />

maps to constrain <strong>MEG</strong> inverse solutions<br />

(Ahlfors et al., J Neurophysiol 1999)<br />

c. Use of distributed sources, <strong>and</strong> regularization<br />

of Linear inverse Estimation (LE) for <strong>EEG</strong><br />

<strong>and</strong>/or <strong>MEG</strong> <strong>data</strong>, with inclusion of <strong>fMRI</strong><br />

constraints (Liu et al., PNAS 1998; Babiloni et al.,<br />

Int J Bioelectromagnetism 1999; etc.)


How can we integrate <strong>MEG</strong>, <strong>EEG</strong>, <strong>and</strong> <strong>fMRI</strong> ?<br />

a. Simple superposition of the equivalent current<br />

dipoles (ECDs) <strong>and</strong> the <strong>fMRI</strong> active areas<br />

• Data from <strong>MEG</strong> <strong>and</strong> <strong>fMRI</strong> are independently<br />

analyzed<br />

• The active regions identified by the two<br />

techniques are merged in a common reference<br />

system (MRI) using fiducial markers<br />

• <strong>MEG</strong> sources (ECDs) are additionally<br />

transformed into the Talairach space


How can we integrate <strong>MEG</strong>, <strong>EEG</strong>, <strong>and</strong> <strong>fMRI</strong> ?<br />

b. Dipole seeding, i.e. utilize <strong>fMRI</strong> activation maps<br />

to constrain <strong>MEG</strong> inverse solution<br />

• The brain areas identified as active by <strong>fMRI</strong><br />

during a specific task are used to guide the <strong>MEG</strong><br />

inverse solution<br />

• It is not possible to simply position the <strong>MEG</strong><br />

source in a fixed location, since <strong>fMRI</strong> <strong>and</strong> <strong>MEG</strong><br />

detect different physical phenomena<br />

• The ECDs are let free to move inside a small<br />

volume, their orientation is let free as well, <strong>and</strong><br />

a figure of merit is optimized, in order to obtain<br />

the time course of each source


How can we integrate <strong>MEG</strong>, <strong>EEG</strong>, <strong>and</strong> <strong>fMRI</strong> ?<br />

c. Use of distributed sources <strong>and</strong> regularization of<br />

Linear inverse Estimation (LE)<br />

• The solution of the <strong>MEG</strong> (<strong>EEG</strong>) inverse problem<br />

with a distributed source model requires the<br />

solution of a linear equation such as:<br />

Ax – b = 0<br />

where A is the lead field matrix:<br />

# rows = # field (or potential) measurements (knowns)<br />

# columns = # dipole components (unknowns)<br />

x is a column vector of dipole components<br />

b is a column vector of measured field components<br />

(for a review, see: Del Gratta et al., Reports on Progress in Physics, 2001)


How can we integrate <strong>MEG</strong>, <strong>EEG</strong>, <strong>and</strong> <strong>fMRI</strong> ?<br />

d. Use of distributed sources <strong>and</strong> regularization of<br />

Linear inverse Estimation (LE)<br />

• since the number of dipole components (5,000-10,000) is<br />

much larger than the number of measurements (150-500),<br />

we must minimize the following expression (cost<br />

function):<br />

⎜⎜Ax - b⎜⎜ + λ 2 ⎜⎜Cx ⎜⎜<br />

where λ is the so-called regularization parameter <strong>and</strong> C is<br />

simply a weight matrix that depends on the head model.<br />

• By appropriately shaping C we can take into account the<br />

possible constraints used in various LE analysis methods<br />

(Minimum Norm, SLORETA, etc.), but also the <strong>fMRI</strong><br />

constraints


How can we integrate <strong>MEG</strong>, <strong>EEG</strong>, <strong>and</strong> <strong>fMRI</strong> ?<br />

• The functional information is used to force the linear inverse<br />

estimation weighting the minimization procedure with respect to<br />

the bold activation.<br />

• Anatomical <strong>and</strong> functional information can be used to delimit the<br />

source space to a given ROI. The activity of this specific ROI<br />

during time can be estimated using a linear inverse estimation.<br />

• λ (regularization parameter): by choosing the correct value for λ<br />

an equilibrium between goodness of fit <strong>and</strong> closeness to the model<br />

term ⎜⎜Cx ⎜⎜ is achieved.<br />

A possible method to calculate λ is the L-<br />

λ ≈ 0.0001<br />

curve criterion: if the model term ⎜⎜Cx ⎜⎜<br />

10<br />

is plotted vs. the <strong>data</strong> term ⎜⎜Ax - b⎜⎜ as<br />

3<br />

λ ≈ 0.001<br />

a curve parametrized by λ,an L-shaped<br />

10 2<br />

λ ≈ 0.01<br />

curve is obtained. The corner of L can be<br />

λ ≈ 0.1<br />

10<br />

seen as an equilibrium point between the<br />

1<br />

<strong>data</strong> term <strong>and</strong> the model term. (see<br />

10 -3 10 -2 10<br />

schematic <strong>and</strong> the reference: Hansen, P.C., SIAM<br />

-1<br />

⎜⎜Ax - b⎜⎜<br />

Rev. 34, 1992)<br />

⎜⎜Cx ⎜⎜


Sensorimotor <strong>EEG</strong>-<strong>MEG</strong> <strong>data</strong> can be<br />

“fused” in a finger movement<br />

paradigm, using the LE approach<br />

Regularization of LE permits to infer the time<br />

course of the source current density <strong>and</strong> to<br />

better discriminate the contribution from<br />

different neural districts in the pre- <strong>and</strong> postmotor<br />

period (Babiloni et al., Human Brain<br />

Mapping 2001)


Integration of <strong>fMRI</strong>-<strong>EEG</strong> (MRP) with regularization of LE<br />

allows better identification of the active areas, if we add the<br />

<strong>fMRI</strong> constraints<br />

Right index finger movement


Somatosensory system:<br />

pain vs. no-pain activations<br />

<strong>and</strong><br />

somatotopic properties


Exp.1 - Effect of stimulus intensity from motor<br />

to weak painful, <strong>MEG</strong> study I<br />

(Torquati et al., NeuroReport 2002)<br />

• Median nerve stimulation in 8 healthy subjects<br />

• Ten different levels of current intensity.<br />

Sensory Motor Weak painful<br />

I 0 I 1 I 2 I 3 I 4 I 5 I 6<br />

4.2 7.5 11 14 17 21 24<br />

I 7 I 8 I 9<br />

31 45 59 mA


Results<br />

motor strong motor weak painful<br />

I 1 I 5<br />

I 9<br />

SI - increase in amplitude from I1 to I5, then saturation: increasing<br />

synchronization mechanism of post-synaptic potentials, then “ceiling” effect on the<br />

involved myelinated Aβ fibers (nociceptive innervation in SI mainly represented by<br />

much slower Aδ <strong>and</strong> C unmyelinated fibres)<br />

SII - decrease for strong motor stimulation: “gating” effect due to the poor<br />

nociceptive specificity of the electrical stimulation involving possible interference<br />

in the evoked activation of the “non painful” <strong>and</strong> “painful” populations; increase for<br />

weak painful stim.: stronger attention to the stimulus, <strong>and</strong> amount of activated “non<br />

painful” neurons decreasing with the “gating” effect<br />

•Possible existence of two adjacent neuronal pools indistinguishable by <strong>MEG</strong>


Exp.2 – identification of anterior <strong>and</strong> posterior<br />

SII: spatial features, <strong>fMRI</strong> study<br />

Activation for non-painful stimuli<br />

cSI<br />

cSIIa<br />

iSIIa<br />

Ferretti et al., NeuroImage, 2003


Activation for painful stimuli<br />

cSI<br />

cSIIa<br />

iSIIa<br />

cSIIp<br />

iSIIp<br />

Ferretti et al., NeuroImage, 2003


Results<br />

• Evidence for a spatial segregation<br />

occurring in SII for neural population<br />

responding to painful stimulation with<br />

respect to that activated by non-painful<br />

stimulation<br />

• The “painful” population located more<br />

posterior than the “non-painful” area<br />

• Small distance between the two areas<br />

• No information on timing


Exp.3 - Identification of anterior <strong>and</strong> posterior<br />

SII: temporal features, <strong>MEG</strong> study II<br />

[example of dipole seeding]<br />

Torquati et al., Neuroimage 2005


Identification of anterior <strong>and</strong> posterior SII:<br />

temporal features<br />

[example of LE (MNE) with <strong>fMRI</strong> constraints]<br />

SI<br />

SIIa<br />

SIIp


Motor threshold<br />

Painful threshold<br />

SI<br />

iSII<br />

cSII


Results<br />

Mean Latencies<br />

ms<br />

90<br />

88<br />

86<br />

84<br />

82<br />

80<br />

( * p


Passive listening to sounds from different<br />

locations (<strong>fMRI</strong> <strong>and</strong> <strong>MEG</strong>)<br />

(Brunetti et al., Human Brain Mapping 2005)<br />

This study aimed at highlighting how the auditory system<br />

identifies the direction a sound is coming from. Activations of<br />

cortical areas during stimulation with sounds coming from a<br />

fixed source or, r<strong>and</strong>omly, from five different sources<br />

located in a horizontal half-space were studied with both<br />

<strong>MEG</strong> <strong>and</strong> <strong>fMRI</strong>


Passive listening to sounds from different<br />

locations (<strong>fMRI</strong> results)<br />

•Two main areas were found to be<br />

activated during auditory stimulation: the<br />

bilateral Heschl’s gyrus <strong>and</strong> the right<br />

superior temporal gyrus. Larger activation<br />

was found in the MIXED condition than in<br />

the LEFT <strong>and</strong> RIGHT conditions<br />

•Additionally, the right supramarginal<br />

gyrus was activated during the MIXED<br />

condition only<br />

•A right hemisphere specialization for<br />

auditory spatial processing seemed<br />

confirmed, as opposed to the language<br />

processing in the left hemisphere<br />

(Gazzaniga et al., 1998)<br />

•No information about timing was obtained<br />

from <strong>fMRI</strong><br />

MIXED<br />

RIGHT<br />

LEFT


Passive listening to sounds from different locations<br />

(example of simple superposition <strong>and</strong> of dipole seeding)<br />

<strong>MEG</strong> allowed identification of a bilateral activation in<br />

the Heschl’s gyrus, but no reliable localizations for the<br />

superior temporal gyrus <strong>and</strong> the supramarginal gyrus<br />

were obtained (sources too close)<br />

The last two areas were identified by constraining the<br />

sources in a cube with 4 mm side centered in the<br />

corresponding <strong>fMRI</strong> activation.


Passive listening to sounds from different<br />

locations (time course results)<br />

<strong>MEG</strong> permitted identification of<br />

the time sequence of activation for<br />

the three sources:<br />

1.Heschl’s gyrus (m. latency 138 ms)<br />

2.superior temporal gyrus (156 ms)<br />

3.supramarginal gyrus (162 ms)<br />

thus suggesting a hierarchical<br />

structure for the processing of<br />

sound localization features


Functional reorganization in cases of malformation of<br />

cortical development (MCD) - a TMS-<strong>fMRI</strong> study<br />

• Structural MRI, TMS, <strong>and</strong> <strong>fMRI</strong><br />

findings (paretic h<strong>and</strong> movement)<br />

obtained in 3 cases<br />

• A–C: Axial reconstructions from<br />

the T1-weighted 3D <strong>data</strong> sets<br />

• D–F: Results of TMS for<br />

stimulation of the affected <strong>and</strong><br />

contralesional hemispheres, with<br />

MEPs recorded simultaneously<br />

from target muscles of both the<br />

paretic h<strong>and</strong> (yellow MEPs) <strong>and</strong><br />

the non paretic h<strong>and</strong> (white<br />

MEPs).<br />

• H, J <strong>and</strong> L: <strong>fMRI</strong> activations for<br />

movement of the paretic h<strong>and</strong>.<br />

• M–O: illustration of TMS <strong>and</strong><br />

<strong>fMRI</strong> findings;<br />

(Staudt et al., J. Neurosurg., 2004)


A <strong>MEG</strong> coherence study on the same grop<br />

of patients (Belardinelli et al., 2006, in preparation)<br />

Coherent brain areas with paretic h<strong>and</strong> EMG in the β frequency range<br />

during forearm contraction. The coherence 3D mapping within the<br />

brain is obtained by means of different spatial filters (Linear<br />

Constrained Minimum Variance Beamformer <strong>and</strong> Sloreta)


A further possibility: identification of coupling<br />

direction<br />

Different direction evaluators were used: a Granger causality index (Kaminski et al,<br />

Biological Cybernetics, 2001), as well as two different indexes for the detection of<br />

coupling direction in chaotic oscillators (Rosenblum et al, Phys. Rev. Lett. 2004)<br />

have shown values indicating M1 as generator of the activity which comes to the<br />

cerebellum in case of paretic h<strong>and</strong> use. The cerebellum coherent activity is not<br />

present in case of contralateral (healthy) h<strong>and</strong> use


Pyramidal neurons: only<br />

1% of these neurons (low<br />

metabolic dem<strong>and</strong>), if<br />

synchronously active<br />

produce 90% of scalp<br />

<strong>EEG</strong>/<strong>MEG</strong><br />

Some critical remarks<br />

Stellate neurons (15% of neocortical<br />

neurons): strong metabolic/rCBF dem<strong>and</strong><br />

but no scalp <strong>EEG</strong> or <strong>MEG</strong> signals (closed<br />

electromagnetic fields)<br />

Moreover, <strong>MEG</strong>/<strong>EEG</strong> <strong>and</strong> <strong>fMRI</strong> may be sensitive to different<br />

phenomena (i.e. rhythm modulations vs. regional neural<br />

activation), or be affected by different “boundary” conditions


Cognitive <strong>fMRI</strong>-<strong>EEG</strong>-<strong>MEG</strong> <strong>data</strong> could not be “fused” in a<br />

working memory (WM) paradigm, since ERD/ERS of rhythmic<br />

activity can be studied with <strong>MEG</strong>/<strong>EEG</strong> much better<br />

Alpha ERD is evaluated by LE after the 1st (T1) <strong>and</strong> 2nd (T2)<br />

second of the delay phase<br />

<strong>fMRI</strong><br />

Babiloni et al., Clin. Neurophysiol. 2004


Neural plasticity after stroke<br />

<strong>MEG</strong> ECDs were always<br />

identified in both<br />

hemispheres of all<br />

patients featuring a<br />

good clinical function<br />

recovery;<br />

BOLD-<strong>fMRI</strong> activation<br />

was seldom observed<br />

(20% of same patients<br />

only): this could be<br />

related to the<br />

significantly impaired<br />

vasomotor reactivity<br />

those patients were<br />

still featuring<br />

Rossini et al., Brain 2004


Conclusions <strong>and</strong> perspectives<br />

• A combined use of <strong>MEG</strong>, <strong>EEG</strong> <strong>and</strong> <strong>fMRI</strong> may<br />

provide a unique tool for studying brain<br />

activity with both high spatial resolution <strong>and</strong><br />

high temporal resolution<br />

• Integration requires skill <strong>and</strong> care, but can be<br />

h<strong>and</strong>led routinely<br />

• Integration makes sense only if the same kind<br />

of activity is being studied with the different<br />

techniques<br />

• Even in this case, <strong>and</strong> particularly before<br />

applying the method to the clinical field, one<br />

must be aware of some respective limitations<br />

of the three approaches in this area<br />

• Integration with TMS!

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