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國立交通大學生物科技系暨研究所 黃植懋老師 1 Chapter 4 The Imaged Brain March 10, 2016 5707 Brain and Cognitive Science Methods for Brain and Cognitive Science Electrophysiology: Electroencephalography (EEG) Magnetoencephalography (MEG) Transcranial magnetic stimulation (TMS) Neuroimaging: Magnetic Resonance Imaging (MRI) functional MRI (fMRI) Positron emission tomography (PET) Chapter 3 Electrophysiological Brain Chapter 4 Imaged Brain

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  • 1

    Chapter4TheImagedBrain

    March10,2016

    5707BrainandCognitiveScience

    MethodsforBrainandCognitiveScience

    Electrophysiology:Electroencephalography(EEG)Magnetoencephalography (MEG)Transcranial magneticstimulation(TMS)

    Neuroimaging:MagneticResonanceImaging(MRI)functionalMRI(fMRI)Positronemissiontomography(PET)

    Chapter3ElectrophysiologicalBrain

    Chapter4ImagedBrain

  • 2

    PaulBroca (1824 1880):Tansbrain

    Apatient,withlossofspeechwastransferredtoPaulBrocas care LosttheabilitytospeakexceptforTan. Goodcomprehension Braindamagetothelefthemisphere.

    CarlWernicke (1848 1904)

    Reported acaseofawomanwithdisruptedbutfluentspeech (1874)Fluentbutmeaningless speechComprehension isimpairedBraindamagetothelefthemisphere

  • 3

    Leftsideofthebrain

    Arcuatefasciculus:connectionbetweenBrocas areaandWernickesarea

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    6

  • 4

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    7

    Thebasicconceptofimages

    Beforeanyimageprocessing,weneedtounderstandtheformatoftheimage.

    Neuralimagesaredigitalimages.

  • 5

    Resolutionofanimage

    lowresolution highresolution

    Thebasicconceptofimages

    Whatistheformatoftheimage? digitalimages

    Adigitalimage=Amatrixofnumbers,w/onenumberrepresentsonepixel

    Pixel =Pictureelement Adigitalimage=Amathematicalmatrix

    222 220 200 146 103

    200 158 127 96 73

    207 131 103 82 86

    202 126 112 124 133

    PixelValues(p)

  • 6

    Columns(j)

    Rows(i)

    Pixel Datap(i,j)

    Thebasicconceptofimages

    PixelsandImageMatrices numbersofpixels=numberofrows* numberofcolumns

    Frommathematicstophysics

    Adigitalimage=amathematicalmatrix Apixelinthematrixhasaphysicaldimension(e.g.mm)

    1024x1024 64x64 32x32 16x16

  • 7

    Frommathematicstophysics

    Adigitalimage=amathematicalmatrix Apixelinthematrixhasaphysicaldimension(e.g.mm)

    8mm 4mm 2mm 1.5mm 1mm

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    14

  • 8

    Computedtomography(CT)

    ProjectionoftheXrayfrommultipleangles 3Dimagesbasedontissuedensity

    15

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    16

  • 9

    Necessaryequipment:3TeslaMRIscanner

    Magnet

    Gradientcoil

    RFcoil

    http://www.magnet.fsu.edu/education/tutorials/magnetacademy/mri/fullarticle.html

  • 10

    WhatdoesanMRIscansoundlike

    HighresolutionT1structuralMRIimages

    graymatter(morewater)

    whitematter(morefat)

  • 11

    3TMRIscandemohttps://www.youtube.com/watch?v=Gs3onhjuKio

    Magnet

    Earthsmagneticfield=0.5Gauss

    1Tesla=10,000Gauss 3Tesla(T)=

    3X10,000/0.5=60,000Earthsmagneticfield

    Permanent Superconducting Activeshielding

  • 12

    Review:Magneticfield

    GradientCoil

    Gradientstrength Activeshielding Shimming

  • 13

    Radiofrequency(RF)coil

    Transmission Receiving Severalkindsofcoils:

    ActivecoilsPassivecoilsBirdcagecoils

    MRIsafety

  • 14

    MRIsafetyvideoIhttp://www.youtube.com/watch?v=6BBx8BwLhqg&feature=related

    MRIsafetyvideoII

    28

    https://www.youtube.com/watch?v=5KuzTyn45og

  • 15

    Subjectsafety

    Anyonegoingnearthemagnet subjects,staffandvisitors mustbethoroughlyscreened

    Subjectsmusthavenometalintheirbodies:pacemaker aneurysmclipsmetalimplants(e.g.,cochlearimplants) somedentalwork(fillingsokay)

    Subjectsmustremovemetalfromtheirbodies jewellery,watch,piercings,coins,etc.wallet anymetalthatmaydistortthefield

    29

    fmri

    30

  • 16

    MagneticResonanceImaging(MRI)

    MRI=NMR+Imaging Magnetic:Magnetizationinducedbymagneticfield

    Resonance:Exciteandreceiveofmagnetization

    Imaging:Spatialencodingofmagnetization()

    MRImeasures

    Differenttissueinthebrain(e.g.,graymatter,whitematter)

    Differenttissuehasdifferentwatercontent Watercontainshydrogenatoms(H20)

  • 17

    Magnetizationinducedbymagneticfield

    + =()(spin)

  • 18

    MRIsignalvariesacrosstissue

    Time

    Signalintensity

    TissueA(e.g.,fat)

    TissueB(e.g.,water)

    HighresolutionT1structuralMRIimages

    graymatter(morewater)

    whitematter(morefat)

  • 19

    Structuralimaging

    CT T1MRIimage T2MRIimage

    Howtomeasurethedifferencesbetweengroups?

    Normalyoungadult(mid20s)

    Normalolderadult(late70s)

  • 20

    Voxelbasedmorphometry analysis(VBM)

    voxelwisecomparisonofthelocalvolumeofgraymatterandwhitematterbetweentwogroupsofsubjects

    StructuralMRI:Voxelbasedmorphometry analysis(VBM)

  • 21

    StructuralMRIapplication:IQandcorticaldevelopment

    StructuralMRIapplication:IQandcorticaldevelopment

    Moreintelligentchildrendemonstrateaparticularlyplasticcortex,withaninitialacceleratedandprolongedphaseofcorticalincrease:theneuroanatomicalexpressionofintelligenceinchildrenisdynamic

  • 22

    StructuralMRIapplication:Learningandmemory

    Changesingraymatterinducedbytraining: StudentsinexperienceatjugglingDividedintotwogroups(scanthem)Onegroupspracticesjugglingfor3months,andtheotherdoesnt(scanagain)

    Wait3months,noonejuggles(scanagain)

    43

    StructuralMRIapplication:Learningandmemory

    LargerposteriorhippocampusinLondontaxidrivers:LondontaxidriverisbetteronspatialnavigationOver26,000streetswithinasixmileradiusofCharing Crossand1,400differentplacesofinterests.

  • 23

    StructuralMRIapplication:Learningandmemory

    LargerposteriorhippocampusinLondontaxidrivers: StructureMRIscan:16licensedLondontaxidriversand50nontaxidrivers.

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    46

  • 24

    Restricteddiffusion:AnisotropicdiffusionFractionalAnisotrophy (FA)~1

    Freediffusion:IsotropicdiffusionFractionalAnisotrophy (FA)~0

    47

    DiffusionMRI:Diffusiontensorimaging(DTI)

    12

    NeuralfiberreconstructionCalculationofthediffusiontensor

  • 25

    DiffusionMRI:Diffusiontensorimaging(DTI)

    50

    DTIapplications:sexdifferences

    Malebrain Femalebrain

  • 26

    DTIapplicationsEvolutionofthearcuatefasciculus

    51

    10invivohuman1invivochimpanzee3postmortemchimpanzee1invivomacaque2postmortemmacaque

    52

  • 27

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    53

    MRIvs.fMRI

    MRI studiesbrainanatomy Functional MRI(fMRI)studiesbrainfunction

  • 28

    MRIscannerandfMRIscan

    ThefirstBrainImagingexperiment

  • 29

    Vasculatureofhumanbrain

    Cerebralmetabolism:neuronalenergyconsumption

    fMRIindirectlymeasurebrainfunction

    Functionalbrainmaps:mapsofneuralactivity Mapsofneuralactivity:

    Imagingthechangeinbloodflow(hemodynamicresponse)relatedtoenergyusebyneurons.

  • 30

    Oxygenated BloodDeoxygenated Blood

    Resting

    Active

    fMRI:BOLDsignal

    BloodOxygenationLevelDependent(BOLD)signal

    MRI

    Neural

    Metabolic

    Hemodynamic

  • 31

    CategoriesoffunctionalMRI

    TaskrelatedfMRISpecificexperimentaldesigntoexaminethebrainfunctionsassociatedwithperception,attention,language,learningandmemory,decisionmaking,andemotion.Brainduringwork

    RestingstatefMRINospecificexperimentaldesign Brainatrest

    CategoriesoffunctionalMRI

    TaskrelatedfMRISpecificexperimentaldesigntoexaminethebrainfunctionsassociatedwithperception,attention,language,learningandmemory,decisionmaking,andemotion.Brainduringwork

    RestingstatefMRINospecificexperimentaldesign Brainatrest

  • 32

    taskrelatedfMRI(taskfMRI):Physicaltask

    +

    1000ms500ms 4 9

    +

    1000ms500ms 3 3

    +Time

    ...1000ms500ms 2 7

    TaskfMRIDatatransformations

    Motioncorrection Smoothing

    kernel

    Spatialnormalization

    Standardtemplate

    fMRItimeseries

    GeneralLinearModel

    Designmatrix

    Parameterestimates

    Gaussianfieldtheory

    p

  • 33

    TaskfMRIresults

    TasksfMRIbasic:orientation

    Sliceorientation:AP:anteriorposterior()SI:superiorinferior()LR:leftright()

  • 34

    TaskfMRIbasic:orientation

    NeurologicalconventionLeftisleft,rightisright

    Radiologicalconvention Leftisright,rightisleft

    Makesurehowyoursoftwaredoingwithleft/right Ifyourereallyunsure,tapeavitaminEoroilcapsuletotheonesideofthesubjectshead.Itwillshowupontheanatomicalimage

    left

    left

    right

    right

    IntroductiontotaskfMRIhttps://www.youtube.com/watch?v=BmQR57V5TVU

  • 35

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    69

    Experimentaldesigns

    BetweensubjectdesignDifferentconditionsareassignedtodifferentsubjectgroupse.g.malevs.female;drugabuservs.abstainers;youngvs.olderadults.

    WithinsubjectdesignEachsubjectparticipantsinallexperimentalconditions

  • 36

    Essentialcomponentsinanexperimentaldesign

    IndependentvariablesManipulatedbytheexperimenterse.g.stimulus(face,words,pictures)

    DependentvariableQuantitiesthatmeasuredbyexperimenters

    e.g.,heartrate,bloodpressure,cortisollevel,BOLDsignal

    e.g.,accuracy,reactiontimes

    Variables:

    Anterior

    PosteriorLOCLOC

    Experimentaldesigns Experimentalconditions Containsthestimuliortask

    thatismostrelevanttoresearchhypothesis

    Taskcondition

    Controlconditions Baselinecondition Nontask condition

    Experimentalcondition

    Controlcondition

  • 37

    Experimentaldesigns:fMRI

    Experimentalconditions Controlconditions

    faces Scrambledpicturesw/samespatialfrequency

    =

    TaskfMRIstudies:theoreticallydriven

    Welldefinedproblem

    TheoryA PredictionATheoryB PredictionB

    Experiment

    TheoryAorBstandsorrevisedtheory

  • 38

    TaskfMRIstudies:theoreticallydriven

    Anterior

    PosteriorLOCLOC

    Differentstimuluscategorieselicitdifferentpatternsofactivityinventralvisualcortex.

    Predictions: Facerecognitiontaskleadtoactivationinfusiformfacearea Animacy judgmenttaskleadtoactivationinlateraloccipitalcomplex

    Place/HouseAreas(Parahippocampal gyrus)

    ObjectAreas(Lateraloccipitalcomplex)

    FaceAreas(FusiformFaceArea)

    ThreedistinctlevelsofresearchhypothesisintaskfMRIstudies

    Hemodynamic

    Neuronal

    Psychological(Cognitive)

  • 39

    Confoundingfactors

    Anypropertythatcovarieswiththeindependentvariablewithintheconductedexperiment

    Couldbedistinguishedfromtheindependentvariablesusingadifferentexperimentaldesign

    ExampleofconfoundingCleverHans

  • 40

    CleverHanseffect:Observerexpectancy

    WhenHansisclever WhenHansisnotclever

    Confoundingfactors

    Anypropertythatcovarieswiththeindependentvariablewithintheconductedexperiment

    Couldbedistinguishedfromtheindependentvariablesusingadifferentexperimentaldesign

    Evidenceofglobalwarming?

  • 41

    Topreventconfoundingfactors

    Randomizing orCounterbalancingtheorderoftheconditionsmakessurethatthepotentialeffectsaredistributedequallyacrosstheconditionsoftheexperiment. Randomized:ABC,ACB,BCA,BAC,CAB,CBA(N!)

    4conditions:24;5conditions:120;6conditions:720

    Counterbalancing:ABC,BCA,CABEaseofusage:donthavetoswitchinstructionsorequipmentveryoften

    TaskfMRIapplication:Decodingthereadingbrain

    Hearingwords:Superior/middletemporalregions

    Seeingwords:Leftoccipitotemporalregion

    Petersenetal.,1988

  • 42

    Speaking/producingwords:Motorregion

    Generatingwords:Leftinferiorfrontalregion

    TaskfMRIapplication:DecodingthereadingbrainPetersenetal.,1988

    TaskfMRIapplication:ColorwordStrooptask

    Congruent()

    Incongruent()

  • 43

    TaskfMRIapplication:consciousness?

    Awarenessinthevegetativestate 23yearoldwomansustainedaseveretraumaticbraininjury Spokeninstructionstoperformtwomentalimagerytasks: imagingplayingagameoftennis imagingvisitingalloftheromofherhouse

    Advantages&disadvantagesoffMRI

    AdvantagesNoninvasiveSpatialresolutionisgoodShowsallparticipatingareas,notjustcriticalones

    DisadvantagesPoortemporalresolutionDifficulttousewithsubjectsandtoobtaingoodmeasurementsSensitivitytoheadmotionPregnancy,obesity,metalparts,etc.

  • 44

    Aneuralportraitofthehumanmind

    87

    http://is.gd/cpNjvA

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    88

  • 45

    CategoriesoffunctionalMRI

    TaskrelatedfMRISpecificexperimentaldesigntoexaminethebrainfunctionsassociatedwithperception,attention,language,learningandmemory,decisionmaking,andemotion.Brainduringwork

    RestingstatefMRINospecificexperimentaldesign Brainatrest

    Restingstatebrainactivity

    RestingstatebrainactivityassessedbyfMRINoninvasive,bloodoxygenleveldependent(BOLD)

    Defaultmodenetwork(DMN):AsetofbrainregionsshowingincreasedfMRIactivityintaskfreestatecomparedtocognitivelydemandingtaskatrest.deactivationSuperior/middlefrontal,medialprefrontal,posteriorcingulatecortex(PCC)/precuneus,superiorparietal,hippocampalregion.

  • 46

    Defaultmodenetwork(DMN)&Taskrelatedactivationregions

    Parketal.,2010

    Young

    rsfMRIapplication:mindwandering

    92

  • 47

    rsfMRIapplication:mindwandering

    CorrelationbetweenmindwanderingfrequencyandBOLDchange

    Smallworld:Graphtheory

    94

  • 48

    Smallworld:Graphtheory

    95

    WhatisrestingstatefMRI?

    96Adaptedfrom,2015

  • 49

    Functionalneuralconnectivity:restingstatefunctionalMRI

    Stronglycorrelatedpatternsofbrainactivityamongdistantbrainregions(i.e.,functionalconnectivity)aretakenasanindicationthattheseregionscommunicate.

    Functionalconnectivityisoftenmeasuredasinterregionalcorrelationsamongspontaneousfluctuationsofhemodynamicactivityduringarestingstate whileparticipantsliepassivelyintheMRImachine,butnoactivecognitiveorbehavioraldemandsareimposed.

    Dosenbach etal.,2008

  • 50

    Outlinefortoday

    Thebasicconceptofimages Structural/anatomicalbrainimagingtechniquesCT/structuralMRI/DiffusionMRIPrincipleApplications

    Functionalbrainimagingtechniques TaskrelatedfunctionalMRI(taskfMRI)PrincipleExperimentaldesignApplications

    RestingstatefunctionalMRI(rsfMRI)andgraphtheory

    100