A Brief Outline Neuroscience 2004 A. Single Areas .
A Brief OutlineI. Hypothesis of functional specificityNeuroscience 2004Functional Brain ImagingA. Single AreasB. Multiple AreasII. Brain Mapping TechniquesA. Lesion- Based Methods1.2.Positron Emission Tomography, PETFunctional Magnetic Resonance Imaging, fMRIB. Cardiovascular Based MethodsJoy Hirsch, Ph.D., ProfessorDirector, fMRI Research CenterColumbia University Health SciencesNI Basement1.2.Positron Emission Tomography, PETFunctional Magnetic Resonance Imaging, fMRIC. Electromagnetic-Based Methods1.2.3.4.www.fmri.orgSSEP Somatosensory PotentialsCortical StimulationMagnetoencephalography, MEGElectroencephalography, EEGIII. Integration of Brain Mapping TechniquesColumbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et al776PrimaryVisual Cortex65544I. Hypothesis of functional specificitySpecializations of single brain areasFlashingLED DisplayCalcarine SulcusColumbia fMRIColumbia fMRIHirsch, J., et alI. Hypothesis of functional specificityHirsch, J., et alFunctional Organization of Visual CortexSpecializations of single brain areasSpecializations of multiple brain areasColumbia fMRIColumbia fMRIHirsch, J., et alPage 1Hirsch, J., et al
Harrington, 1964II. Brain Mapping TechniquesRlesionA. Lesion-Based MethodsPreviousSurgicallesionVisual FieldBINOCULARFLASHINGLIGHTSLeft EyeColumbia fMRIRight EyeColumbia fMRIHirsch, J., et alHISTORICAL MILESTONESFUNCTIONAL SPECIFICITY AND NEUROIMAGINGNeuroscience and MedicineBROCAAphasia and lesions in GFiHARLOWHirsch, J., et alPhineas GagePhysics and Engineering18411845FARADAYMagnetic properties of blood1861Phineas GageWERNICKEAphasia and lesions in GTs1874MOSSOBlood flow and cognitiveeventsPAULING18811890ROY & SHERRINGTONRelationship between neuralactivity and vascular changesBRODMANNCytoarchitectonic regionsof cortex19091936Change of magnetic state ofhemoglobin with oxygenationRABIDiscovery of MagneticResonancePURCELL / BLOCK1945Demonstration of NMR incondensed matterPENFIELD1949HAHNIntraoperative cortical maps1950Discoverer of spin echophenomenonColumbia fMRIDamasio, H., et al; Science 264: 1102-1105, 20 May 1994Columbia fMRIHirsch, J., et alHirsch, J., et alHISTORICAL MILESTONESFUNCTIONAL SPECIFICITY AND NEUROIMAGINGII. Brain Mapping TechniquesNeuroscience and MedicinePhysics and EngineeringDAMADIANB. Cardiovascular Based Methods1971Discovery that biological tissues havedifferent relaxation ratesHOUNSFIELD CORMACK1. Positron Emission Tomography, PETInvention of Computed TomographyLAUTERBUR1972TER-POGOSSOAN SOKOLOFFFirst PET studies of brain metabolism, bloodflow, and correlates of human behavior1976MANSFIELD1977First MRI of a body partinvention of EPI(scans whole brain in secs.)1981PETERSON/FOX POSNER/RAICHLEFirst MR image1984PET study of human languageHILALRadiolabeled blood flow and neural eventsFirst clinical MRI scannerOGAWA1990Blood Oxygen dependent signalEPI/MRI and neural eventsBELLIVEAUColumbia fMRICortical map of the human visual system: fMRIHirsch, J., et alPage 21992Columbia fMRIHirsch, J., et al
a. Source of SignalPositron Emission TomographyPrinciple of PETRadionuclides that emit positronssuch as 15O and 18F areintroduced into the brain.PET is based on the radioactivedecay of positrons from the nucleusof the unstable atoms (15O has 8protons and 7 neutrons)H2behaves like H2andindicates blood flow (rCBF) (halflife 123 seconds) integrationtime 60 seconds.15O16O– deoxyglucose behaves likedeoxyglucose and indicatesmetabolic activity (half-life 110minutes) integration time 20minutesA1 Positron emissionin the brain18FA2 Positron and electron annihilationand emission of gamma raysGamma raySite of positronannihilation(imaged olutionlimitGamma rayphotonPET SCANNERFrom: Principles of Neural Science (4th. Ed.) Kandel, Schwartz, & Jessell, p. 377.From: www.epub.org.br/cm/n011pet/pet.htmColumbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et alGamma Ray Detections to Location of FunctionII. Brain Mapping TechniquesB. Cardiovascular Based Methods1. Positron Emission Tomography, PETa. Source of signalb. Measurement techniquesFrom: Principles of Neural Science (4th. Ed.) Kandel,Schwartz, & Jessell, p. 377.Columbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et alInjection of radioactive-labeled water for PET scanningII. Brain Mapping TechniquesB. Cardiovascular Based Methods1. Positron Emission Tomography, PETa. Source of signalb. Measurement techniquesc. Computation for analysisColumbia fMRIColumbia fMRIHirsch, J., et alPage 3Hirsch, J., et al
Analysis of PET ResultsStimulationFixationII. Brain Mapping TechniquesDifferenceFlashingCheckerboardB. Cardiovascular Based MethodsFixation1. Positron Emission Tomography, PETIndividual difference images2. Functional Magnetic Resonance Imaging, fMRIMean difference imageFrom: Images of Mind by Posner, M. and Raichle, M. Scientific American Library, 1994, p. 24Columbia fMRIColumbia fMRIHirsch, J., et alII. Brain Mapping TechniquesHISTORICAL MILESTONES199019771992First PET studies of brainmetabolism, blood flow, andcorrelates of human behavior1971DAMADIANDiscovered thatbiological tissueshave differentrelaxation ratesfMRIBlood Oxygendependent signal19761972BELLIVEAUa. Source of signalCortical Map:human visualsystemEPI / MRIBehaviorLAUTERBUR MANSFIELDFirst MR image1. Functional Magnetic Resonance Imaging, fMRIOGAWATER-POGOSSIANSOKOLOFFHirsch, J., et alFirst MRI of a body partInvented EPI (scans wholebrain in secs.)Columbia fMRIa. Source of SignalColumbia fMRIHirsch, J., et alPrinciples of fMRIVision-related cortical effectsThe MR Signal and 4 Magnetic FieldsMAGNETIC FIELD 1:Hirsch, J., et alSagittalMAGNETIC FIELD 2:Coronal Created when a radio frequency pulseScanner Environment [1.5] TProtons align along an axis(63.3 mgHz) is applied Protons precess around the axis and createa small current (MRI signal) Protons return to aligned state when radiofrequency pulse is turned offAxialMAGNETIC FIELD 3:MAGNETIC FIELD 4: Location of the MR signal Local signal change at a single voxel isdue to change in proportions ofoxyhemoglobin/deoxyhemoglobin A detectable radio frequency is emitted by theprotons as they relax into their aligned state The frequency is dependent upon field strength Application of magnetic field gradient (mT) issufficient to convert detected frequencies tolocationQuickTime and a Video decompressor are needed to see this picture. Deoxyhemoglobin is paramagentic andreduces the uniformity of the precessing andtherefore the signal intensity This change is called BOLDColumbia fMRIColumbia fMRIPage 4Hirsch, J., et al
Current Developments in MR are focusedon the structure/function problemPHYSIOLOGYTHE BOLD SIGNALRMRI Signal IntensityLREST TASK REST- 40 s - - 40 s - - 40 s -REST TASK REST- 40 s - - 40 s - - 40 s -2 minutes 24 seconds2 minutes 24 secondsTIMEColumbia fMRINEURAL ACTIVATIONIS ASSOCIATED WITH ANINCREASE IN BLOOD FLOWDEOXY HGBIS PARAMAGNETICO2 EXTRACTION ISRELATIVELY UNCHANGEDAND DISTORTS THE LOCALMAGNETIC FIELD CAUSINGSIGNAL LOSSRESULT:REDUCTION IN THEPROPORTION OF DEOXY HGBIN THE LOCAL VASCULATURERESULT:LESS DISTORTION OF THEMAGNETIC FIELD RESULTS INLOCAL SIGNAL INCREASEColumbia fMRIHirsch, J., et al Peak (max. oxygenation) 4-6spoststimulus; baseline after 20-30s Initial undershoot can be observed(Malonek & Grinvald, 1996)Hirsch, J., et alBOLD ORIGINBOLD Impulse Response Model Function of blood oxygenation,flow, volume (Buxton et al, 1998)PHYSICSPeakBOLD SignalcorrespondsBriefStimulusto local fieldrepresentation(LFP)Undershoot Similar across V1, A1, S1 but differences across:other regions (Schacter et al 1997)individuals (Aguirre et al, 1998)InitialUndershootColumbia fMRILogothetis, N.K., Pauls, , Augath, M, Torsten, T, Oeltermann, A, (2001) Neurophysiological investigation ofthe basis of the fMRI signal. Nature 412 150150-157Columbia fMRIHirsch, J., et alHirsch, J., et alImaging While Naming ObjectsII. Brain Mapping TechniquesB. Cardiovascular Based Methods1. Positron Emission Tomography, PETQuickTime and a Video decompressor are needed to see this picture.2. Functional Magnetic Resonance Imaging, fMRIa. Source of signalb. Measuremnet techniquesQuickTime and aRadius SoftDV - NTSC decompressorare needed to see this picture.Scanner acquires the whole brain every [4] secs:[26] axial slicesResolution [1.5 x 1.5 x 4.5] mmColumbia fMRIEach voxel is analyzed seperatelyColumbia fMRIHirsch, J., et alPage 5Hirsch, J., et al
Block DesignCOMPUTATIONS FOR fUNCTIONALIMAGE PROCESSINGAcquisitionEvent-Related DesignRECONSTRUCTIONALIGNMENTVOXEL BY VOXELANALYSISFunctionalBrain MapGRAPHICALREPRESENTATION“EARLY” BILINGUAL(Overlapping Language Areas)“LATE” BILINGUAL(Separate Language Areas) R R 00Native 1 (Turkish)Native 2 (English)Common Region Center-of-MassNative (English)Second (French) Center-of-MassColumbia fMRIColumbia fMRIfrom Nature 388, 171-174 (1997)Kim, Relkin, Lee, & HirschHirsch, J., et alII. Brain Mapping TechniquesOne voxel One test (t, F, .)amplitudeB. Cardiovascular Based MethodsGeneral Linear ModelÂfittingÂstatistical analysis1. Positron Emission Tomography, PET2. Functional Magnetic Resonance Imaging, fMRIa. Source of signalb. Measuremnet techniquesc. Computation for analysisetimVoxel LocationTemporal seriesfMRIvoxel time courseColumbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et altwo-sample t-testVoxel statistics parametric one sample t-testtwo sample t-testpaired t-testAnovaAnCovacorrelationlinear regressionmultiple regressionF-testsetc t all cases of theY1 Y0 σˆ 2 ( 1n 1General Linear Model1n0)assume normalityto account for serial correlations:Image intensity standard t-test assumes independence ignores temporal autocorrelation!Columbia fMRIColumbia fMRIColumbiavoxel timeseriesHirsch, J., et alPage 6t-statistic imageSPM{t}compares size of effectto its error standarddeviationHirsch, J., et al
II. Brain Mapping TechniquesRegression90 100 110-10 0 1090 100 110B. Cardiovascular Based Methods-2 0 21. Positron Emission Tomography, PET µ 100α 1voxel time seriesµ α2. Functional Magnetic Resonance Imaging, fMRIa. Source of signalb. Measuremnet techniquesc. Computation for analysisd. Individual brain mapsbox-car reference functionFit the GLMMean valueColumbia fMRIColumbia fMRIHirsch, J., et alConventionalImagingMapping Specific Functionsto Locate Specific AreasTumorBrain Mapping andNeurosurgery:R[Fixed Effects]Columbia fMRIConventionalImagingTumorCC 23 (AB)Columbia fMRIHirsch, J., et alConventionalImagingFunctional ImagingBefore SurgeryTumorTumorRHirsch, J., et alFunctional ImagingBefore SurgeryAfter SurgeryTumorRLeft Hand: Sensory/MotorLeft Hand: Sensory/MotorLeft HandMovementCC 23 (AB)Columbia fMRICC 23 (AB)Columbia fMRIHirsch, J., et alPage 7Hirsch, J., et al
Standard Brain Mapping nguageAreasSENSORYMOTORTouchFinger VISIONListeningto e)ItalianLanguageAreasTumoraGPoCbGPrCGOiGTT GFi GTsCaSFrom Hirsch, J., et al; Neurosurgery 47: 711-722, 2000Columbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et alSensory Motor MappingII. Brain Mapping TechniquesSSEPCraniotomyC. Electromagnetic - Based Methods Somatasensory Evoked Potential, SSEP Direct Cortical StimulationDirect CorticalStimulationLocalization fMRI“Twitching ofhand,focal seizureinvolving arm ”Tag 3Tag 3Tag 5“Twitching in1st threedigits”Tag 5From Hirsch, J., et al; An Integrated Functional Magnetic Resonance ImagingProcedure for Preoperative Mapping of Cortical Areas Associated with Tactile,Motor, Language, and Visual Functions, Neurosurgery 47: 711- 722, 2000.Columbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et alLanguage onseBroca’s AreaSpeech ArrestDuring CountingWernicke’s AreaLiteralparaphasicspeech errorduring picturenamingFrom Hirsch, J., et al; An Integrated Functional Magnetic Resonance Imaging Procedure for Preoperative Mapping ofCortical Areas Associated with Tactile, Motor, Language, and Visual Functions, Neurosurgery 47: 711- 722, 2000.Columbia fMRIColumbia fMRIHirsch, J., et alPage 8Hirsch, J., et al
Methods to Measure Electromagnetic Activity:II. Brain Mapping TechniquesMEG (Magnetoencephalography) - EEC (Electroencephalography)C. Electromagnetic - Based Methods Somatasensory Evoked Potential, SSEPSignal Source: Electrical Activity of nerve cells.What is measured on the surface of the head isthe result of mostly postsynaptic potentials(excitatory or inhibitory) Direct Cortical Stimulation Magnetoencephalography, MEGa. Source of signalMany nerve cells are aligned in palisades (e.g.pyramidal cells) and post-synaptic electricalfields sum with increasing area.Typically it is thought that 100,000 adjacentneurons acting in temporal synchrony arerequired to produce a measurable change in themagnetic fieldColumbia fMRIColumbia fMRIHirsch, J., et alRelationship between currents in the brain and themagnetic field outside the head.Based on the discoverythat electrical currentsgenerate magnetic fields:Hans Christian Oersted,a Danish physicist (early19th. century)A current source withstrength Q causes acurrent flow Jv withinthe brain.Columbia fMRIVQII. Brain Mapping TechniquesC. Electromagnetic - Based Methods Somatasensory Evoked Potential, SSEPThe current flowproduces a potentialdifference V on the scalp:(measured by EEG)BJv Direct Cortical Stimulation Magnetoencephalography, MEGa. Source of signalb. Measurement techniquesAnd a magnetic field Boutside of the head:(measured by magfield.htmColumbia fMRIHirsch, J., et alMagnetoencephalography, MEGTiny magnetic fieldsproduced by brainactivity (10-13 Teslas)can be measured usingSuperconductingQuantum InterferenceDevices (SQUIDs).Hirsch, J., et alII. Brain Mapping TechniquesSQUIDS operate atsuperconductingtemperatures (-269oC).Sensors are placed in adewar containing liquidhelium.C. Electromagnetic - Based Methods Somatasensory Evoked Potential, SSEP Direct Cortical Stimulation Magnetoencephalography, MEGa. Source of signalb. Measurement techniquesc. Computation for analysisStimulus – evokedneuromagnetic signalsare recorded by anarray of detectors.The spatial location of thesource is inferred bymathematical modeling ofthe magnetic field pattern.Columbia fMRIHirsch, J., et alColumbia fMRIHirsch, J., et alPage 9Hirsch, J., et al
Somatosensory evokedmagnetic signals inresponse to tactilestimulation of thecontralateral index fingerNeuro magnetic responseoccurs about 50 msec afterthe stimulation.Isofield contour maps atthe time of maximalresponse (50 msec) to thetactile stimulationMagnetic field strength in left hemisphere sensors over timeLooking at wordsThe field pattern is dipolarwith clearly defined regionsof entering (solid lines) andemerging (dashed lines)magnetic flux.Liina Pylkkanen, Alec Marantz, 2002Columbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et alElectroencephalographyII. Brain Mapping TechniquesC. Electromagnetic - Based Methods Somatasensory Evoked Potential, SSEP Direct Cortical Stimulation Magnetoencephalography, MEG Electroencephalography, EEGa. Source of signalb. Measurement techniquesColumbia fMRIColumbia fMRIHirsch, J., et alHirsch, J., et alElectroencephalographyII. Brain Mapping TechniquesElectrode Arrayfor EEGC. Electromagnetic - Based Methods Somatasensory Evoked Potential, SSEPAveraged Activity profiles duringbilateral finger movement Direct Cortical Stimulation Magnetoencephalography, MEG Electroencephalography, EEGa. Source of signalb. Measurement techniquesc. Computation for analysisColumbia fMRIColumbia fMRIHirsch, J., et alPage 10Hirsch, J., et al
C. Integration of Brain Mapping TechniqueMapping specific functions to understand aneural system Normalized Brain Inferences to general population[Random effects]Columbia fMRIColumbia fMRIHirsch, J., et alLabeling of Active Brain AreasFunctional BrainHirsch, J., et alMap of HumanLanguage SystemAtlas BrainAnatomical RegionMedial Frontal GyrusSuperior Temporal GyrusInferior Frontal GyrusInferior Frontal GyrusxCenter ofmassyz62244459574940- 6 53- 2691025258labelsactivitytransferColumbia ,60,a,E,60,-ab,E,60c,E,60b,G,60Hirsch, R-Moreno, Kim, Interconnected large-scalesystems for three fundamental cognitive tasks revealedby functional MRI. Journal of Cognitive Neuroscience,13(3), 389-405, 2001.Columbia fMRIHirsch, J., et alFunctional MRI Research CenterDepartment of RadiologyCenter for Neurobiology and BehaviorColumbia University Medical CenterMissionTo establish a collaborative and multi-investigatorneuroimaging research environment focused oneducation, medical applications, and the study ofbrain, behavior, and therapy-induced cortical effectsaimed at the systems of the brain that underliecognition, perception, and action.ColumbiafMRIColumbiafMRIBAHirsch, J., et alPage 11Hirsch, J., et al
Director, fMRI Research Center Columbia University Health Sciences NI Basement www.fmri.org Neuroscience 2004 Functional Brain Imaging Hirsch, J., et al Columbia fMRI I. Hypothesis of functional specificity II. Brain Mapping Techniques 1. Positron Emission Tomography, PET 2. Functional Magnetic Resonance Imaging
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