BasicBasic PrinciplesPrinciples ofof ElectroencephalographyElectroencephalography && MagnetoencephalographyMagnetoencephalography

Po-Lei Lee, PhD Department of Electrical Engineering, National Central University, TAIWAN

Yung-Yang Lin, MD, PhD National Yang-Ming University Taipei Veterans General Hospital, TAIWAN Brain, Body, & Mind

Introduction Mentality

Structure Function Presurgical Mapping of Vital Areas in the Brain fMRI + MEG/EEG

Introduction

Tumor

Epileptic foci Visualization & Modulation of Human Brain Information Processing

Introduction Integrated Brain Research Unit (IBRU)

MEG (Magnetoencephalography) EEG (Electroencephalography) 3T MRI Introduction

(a) (d)

(b)

(c)

Multimodality

Top Top •MEG/EEG source localization Back Right •Structure MRI LeftLeft FrontFront •Functional MRI

Front 12 Front •Brain computer interface (BCI) Right nAm Right LeftLeft

LeftLeft •MEG/EEG rhythm analyis 0 •Clinical studies BasicsBasics ofof electroencephalographyelectroencephalography z InIn 1875,1875, RichardRichard CatonCaton discovereddiscovered thethe EEGEEG fromfrom thethe exposedexposed brainsbrains ofof rabbitsrabbits andand monkeys.monkeys.

By courtesy of Prof. Yong-Yang Lin z InIn 1925,1925, HansHans BergerBerger measuredmeasured humanhuman brainbrain’’ss electricalelectrical activityactivity onon thethe scalp.scalp.

By courtesy of Prof. Yong-Yang Lin NeuroelectricNeuroelectric potentialspotentials

Electroencephalogram (EEG) Evoked potential (EP) Event-related potential (ERP)

Recording site: scalp cortex within the depth of the brain

By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin OverviewOverview ofof signalingsignaling betweenbetween neuronsneurons

z PostPost--synapticsynaptic ((dendriticdendritic)) potentialspotentials vs.vs. axonalaxonal actionaction potentials.potentials.

By courtesy of Prof. Yong-Yang Lin NeuralNeural electricalelectrical activityactivity

z CurrentsCurrents ofof thethe actionaction potentialpotential z PostsynapticPostsynaptic cellularcellular currentscurrents

By courtesy of Prof. Yong-Yang Lin Action potential

overshoot

K x

+ u l f e n i f

f + l u a x

N

resting potential

By courtesy of Prof. Yong-Yang Lin PostsynapticPostsynaptic cellularcellular currentcurrent

By courtesy of Prof. Yong-Yang Lin CurrentCurrent dipoledipole

By courtesy of Prof. Yong-Yang Lin ActionAction potentialpotential vsvs PostsynapticPostsynaptic currentcurrent

By courtesy of Prof. Yong-Yang Lin DipolesDipoles z The dipoles make the major contribution to the scalp potential. z When neurons are activated, local currents are produced. z EEG measures the currents that flow during the excitations of the dendrites of many pyramidal neurons in the cerebral cortex. z Potential differences are caused by summed postsynaptic potentials from pyramidal cells that create dipoles between soma and apical dendrites. By courtesy of Prof. Yong-Yang Lin NecessaryNecessary conditions:conditions: AlignedAligned neuronsneurons andand synchronoussynchronous activityactivity z Neurons which are radially z Neurons which are non-radially symmetric, randomly oriented or symmetric, spatially aligned and asynchronously activated do not synchronously activated add up produce externally observable to produce externally observable electric or magnetic fields. electric or magnetic fields.

By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin RadialRadial equivalentequivalent dipoledipole

By courtesy of Prof. Yong-Yang Lin TangentialTangential equivalentequivalent dipoledipole

By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin InternationalInternational 1010--2020 systemsystem

By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin By courtesy of Prof. Yong-Yang Lin EEGEEG analysisanalysis z VisualVisual analysisanalysis ofof spontaneousspontaneous waveformswaveforms z Epilepsy, infectious diseases, metabolic disorders, stroke, degenerative diseases z SpectralSpectral analysisanalysis z TopographicTopographic mapping,mapping, dipoledipole modelingmodeling z AEP,AEP, VEP,VEP, SEPSEP z ERD,ERD, ERSERS z P300P300 z PolysomnographyPolysomnography

By courtesy of Prof. Yong-Yang Lin ResearchResearch andand clinicalclinical applicationsapplications ofof thethe EEGEEG z The greatest advantage of EEG is speed. EEG can determine the relative strengths and positions of electrical activity in different brain regions. z Monitor alertness, coma and brain death z Locate areas of damage following head injury, stroke, tumor, etc. z Test afferent pathways (by evoked potentials) z Monitor cognitive engagement z Produce biofeedback situations z Control anesthesia depth z Investigate epilepsy and locate seizure origin z Test epilepsy drug effects z Assist in experimental cortical excision of epileptic focus z Monitor human and animal brain development z Test drugs for convulsive effects z Investigate sleep disorder and physiology

By courtesy of Prof. Yong-Yang Lin BasicsBasics ofof magnetoencephalographymagnetoencephalography BasicsBasics ofof magnetoencephalographymagnetoencephalography

By courtesy of Prof. Yong-Yang Lin “MEG” is short for… Magnetoencephalography

MEG Stands for... ● Magnetoencephalography – Magneto = magnetic – Encephalo = brain – Graphy = writing ● MEG = the magnetic signals from the brain

By courtesy of Prof. Yong-Yang Lin NeuromagneticNeuromagnetic fieldsfields

MagnetoencephalogramMagnetoencephalogram (MEG)(MEG) EvokedEvoked fieldsfields (EF)(EF) EventEvent--relatedrelated fieldsfields (ERF)(ERF)

By courtesy of Prof. Yong-Yang Lin Overview

● Part 1: Introduction to MEG – What it measures – How it works – MEG recording procedure – Ways to interpret

● Part 2: Clinical and research applications

By courtesy of Prof. Yong-Yang Lin Part 1 • What MEG measures –Neuroscience – Physics behind MEG • How does MEG work? – S.Q.U.I.D. technology – Shielded room • MEG recording procedure • Ways to interpret MEG – Dipole models – Distributed models – Other techniques

By courtesy of Prof. Yong-Yang Lin Your body and brain are full of nerves which transmit and receive information electrically, producing “magnetic fields”that provide a window into their function

By courtesy of Prof. Yong-Yang Lin What MEG measures : Neuroscience Origin of MEG signal

The axon has bidirectional The post-synapse has currents and therefore two unidirectional current and opposing dipoles whose therefore only has one dipole. magnetic fields effectively The magnetic field is not cancel each other canceled in this case

By courtesy of Prof. Yong-Yang Lin What MEG measures : Neuroscience What MEG measures...

zTheory: – MEG measures groups of post-synaptic currents of layer 5 cortical neurons firing synchronously zPractical: – MEG provides maps of where and when groups of certain types of neurons fire – This is a FUNCTIONAL measurement

Layer V

Gray matter of cat cortex

By courtesy of Prof. Yong-Yang Lin What MEG measures : Neuroscience Structure and function

By courtesy of Prof. Yong-Yang Lin What MEG measures : Physics Current dipole

A current dipole can be thought of as a battery that has a positive and a negative pole. Electrical current flows from positive to negative. Because there are two poles, - + we call dipole. It sets up… - Electric field - Magnetic field

By courtesy of Prof. Yong-Yang Lin What MEG measures : Physics Magnetic field and right hand rule

z Electrical currents generate magnetic fields

z The magnetic field lines make a ring around the direction of the current flow

Point right thumb in direction of current, and fingers curl around direction of magnetic field

By courtesy of Prof. Yong-Yang Lin What MEG measures : Physics Dipole in a sphere Image your head was a sphere. Put a dipole in it. Partly radial The dipole can be: Radial Tangential Partly tangential

MEG will see the tangential dipoles in the brain. But not the radial ones

By courtesy of Prof. Yong-Yang Lin What MEG measures : Physics MEG is blind to…

z Tangential dipoles are tangential to the SKULL; NOT necessarily to the brain

z Thus dipoles which are radial to brain surface can be seen if they are tangential to skull

By courtesy of Prof. Yong-Yang Lin MEGMEG v.s.v.s. EEGEEG inin signalsignal detectiondetection

z TheThe scalpscalp andand skull,skull, whichwhich distortdistort thethe electricelectric potentials,potentials, areare transparenttransparent forfor magneticmagnetic fields.fields. Thus,Thus, MEGMEG cancan pickpick upup neuronalneuronal activitiesactivities ‘‘directlydirectly throughthrough thethe skullskull’’.. z MEGMEG isis mainlymainly sensitivesensitive toto tangentialtangential sourcessources,, whereaswhereas EEGEEG reflectsreflects allall intracranialintracranial currents.currents.

By courtesy of Prof. Yong-Yang Lin What MEG measures : Physics Magnetic fields

B (Teslas) 10-4 Earth’ Field 10-5 10-6 Urban Noise 10-7 10-8 Car at 50 m 10-9 Screwdriver at -10 Human heart 5 m 10 Skeletal muscles 10-11 Fetal heart Human eye Transistor, IC 10-12 Human Brain (alpha) chip at 2 m 10-13 Human Brain (evoked response) 10-14 SQUID System 10-15 Noise level

By courtesy of Prof. Yong-Yang Lin How does MEG work?

Two key technologies: - S.Q.U.I.D. Sensors - Shielded Room

Kamerlingh Onnes

By courtesy of Prof. Yong-Yang Lin How does MEG work : SQUID Faraday’s Law

• Make a loop of wire • Pass magnetic field through this loop • A current will be induced - This is a magnetic flux to current converter

The voltage on the loop changes as a function of the magnetic flux passing through it.

By courtesy of Prof. Yong-Yang Lin How does MEG work : SQUID Superconductors? Why?

• To boost sensitivity • Brain signal < 10-12 Tesla – VERY SMALL • Superconductors require extreme cold – Use liquid helium (-2700C)

By courtesy of Prof. Yong-Yang Lin How does MEG work : Shielded Room Shielded room

• Remove extraneous magnetic fields • Of interest: - Brain Response < 10-12 Tesla - VERY SMALL • Extraneous: - Earth’s Magnetic Field ≈ 5*10-5 Tesla - TOO BIG

By courtesy of Prof. Yong-Yang Lin Properties of MEG

By courtesy of Prof. Yong-Yang Lin MEG recording procedure 3D digitizer • Place 4 coils and EOG electrodes • Landmark: Nasion, RPA and LPA

By courtesy of Prof. Yong-Yang Lin MEG recording procedure MEG Recording

•Whole-scalp 306 channel neuromagnetometer (VectorviewTM, Elekta Neuromag, Helsinki, Finland) •Continuous and transient real-time data acquisition •Optional 64 EEG channels •8 trigger lines •4 order low-pass filter: 30…1000 Hz •High-pass filter: down to DC •Head Position Indicator (Polhemus Isotrak II)

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG – Dipole models – Distributed models – Other techniques

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG: Dipole models Dipole models

ForwardForward problem problem (well-posed)(well-posed) YY== K K(J(J) )+ + E E

InverseInverse problem problem (ill-posed)(ill-posed) Data Y Current density J

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG: Dipole models Auditory neuromagnetic responses Anterior

Left Right

Posterior

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG: Dipole models MEG-MRI Coordination

LPA Nasion RPA

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG: Dipole models Source modeling

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG: Dipole models 2 Dipoles model

Right dipole

Left dipole

Goodness(%)

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG: Dipole models Fitting result

latency dipole dipole goodness location strength

By courtesy of Prof. Yong-Yang Lin Ways to interpret MEG: Dipole models Noise problems

Apply SSP

1-40 Hz 2-40 Hz Bandpass Bandpass Filter Filter

External magnetic disturbances which have fairly uniform distribution but varying amplitudes can be suppressed by the signal space projection (SSP) technique. The measured signals span a signal space whose dimension equals the number of channels n being measured. By courtesy of Prof. Yong-Yang Lin Part 2

Clinical and research applications of MEG

By courtesy of Prof. Yong-Yang Lin ClinicalClinical applicationsapplications z Epilepsy z Enhanced identification of spike activity z Localization of spike focus and functional areas z Evaluation of epileptic pathogenesis z Functional evaluation before and after treatment intervention z Making a thorough evaluation possible for epilepsy patients (spike localization; relation to functional cortices; evaluation of sensorimotor, auditory, visual, and cognitive functions) z Functional mapping in patients with brain tumor z Language lateralization z Functional evaluation in various neurological diseases

By courtesy of Prof. Yong-Yang Lin