Neuroscience 2005 Functional Brain Imaging Joy Hirsch Ph

Neuroscience 2005 Functional Brain Imaging Joy Hirsch, Ph. D. , Professor Director, f. MRI Research Center Columbia University Medical Center NI Basement www. fmri. org Columbia f. MRI Hirsch, J. , et al

A Brief Outline I. The Principle of functional specificity A. Single Areas B. Multiple Areas II. Brain Mapping Techniques A. Lesion- Based Methods 1. 2. 3. Visual field loss Aphasia Personality Changes B. Cardiovascular Based Methods 1. 2. Positron Emission Tomography, PET Functional Magnetic Resonance Imaging, f. MRI C. Electromagnetic-Based Methods 1. 2. 3. 4. SSEP Somatosensory Potentials Cortical Stimulation Magnetoencephalography, MEG Electroencephalography, EEG III. Future Directions of Brain Mapping Columbia f. MRI Hirsch, J. , et al

I. The principle of functional specificity A. Specializations of single brain areas Columbia f. MRI Hirsch, J. , et al

Homunculus: Map of Sensory/Motor Function Columbia f. MRI Hirsch, J. , et al

7 7 6 Primary Visual Cortex 6 5 5 4 4 Columbia f. MRI Flashing LED Display Calcarine Sulcus Hirsch, J. , et al

FUNCTIONAL SPECIFCITY BASED ON RETINOTOPY Columbia f. MRI Hirsch, J. , et al

Rotation Eccentricity V 1, V 2 Boundary Columbia f. MRI Hirsch, J. , et al

I. Principle of functional specificity A. Specializations of single brain areas B. Specializations of multiple brain areas Columbia f. MRI Hirsch, J. , et al

Functional Organization of Visual Cortex Columbia f. MRI Hirsch, J. , et al

BRAIN MAP OF OBJECT NAMING (MANY SUBJECTS) Anatomical Region Superior Temporal Gyrus Inferior Frontal Gyrus Medial Frontal Gyrus Hemis L L Area Centers of mass x y z Wernicke 57 Broca 49 Broca 40 Sup. Motor 9 -26 10 25 -6 9 25 8 53 Connectivity Principle: Neural circuits in the brain connect working parts to execute complex tasks. Hirsch, R-Moreno, Kim, Interconnected large-scale systems for three fundamental cognitive tasks revealed by functional MRI. Journal of Cognitive Neuroscience, 13(3), 389 -405, 2001. Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques A. Lesion-Based Methods Columbia f. MRI Hirsch, J. , et al

1. Visual Field Loss Harrington, 1964 v R lesion Previous Surgical lesion Visual Field Left Eye Right Eye Columbia f. MRI BINOCULAR FLASHING LIGHTS Hirsch, J. , et al

THE BRAIN IS ORGANIZED BY DEDICATING SPECIFIC AREAS TO SPECIFIC FUNCTIONS 2. Aphasia Neuroscience and Medicine Year BROCA 1841 Aphasia and lesions in GFi HARLOW Phineas Gage 1861 WERNICKE Aphasia and lesions in GTs Columbia f. MRI 1874 Hirsch, J. , et al

3. Personality Changes Phineas Gage Damasio, H. , et al; Science 264: 1102 -1105, 20 May 1994 Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques B. Cardiovascular Based Methods 1. Positron Emission Tomography, PET Columbia f. MRI Hirsch, J. , et al

TECHNICAL MILESTONES IN IMAGING DAMADIAN 1971 Discovery that biological tissues have different relaxation rates HOUNSFIELD CORMACK Invention of Computed Tomography 1972 LAUTERBUR First MR image 1976 MANSFIELD First MRI of a body part invention of EPI (scans whole brain in secs. ) TER-POGOSSOAN SOKOLOFF 1977 Columbia f. MRI First PET studies of brain metabolism Hirsch, J. , et al

Source of Signal Positron Emission Tomography Radionuclides that emit positrons such as 15 O and 18 F are introduced into the brain. H 215 O behaves like H 216 O and indicates blood flow (r. CBF) (half life = 123 seconds) integration time ≈ 60 seconds. 18 F – deoxyglucose behaves like deoxyglucose and indicates metabolic activity (half-life = 110 minutes) integration time ≈ 20 minutes Columbia f. MRI PET SCANNER From: www. epub. org. br/cm/n 011 pet/pet. htm Hirsch, J. , et al

Principle of PET is based on the radioactive decay of positrons from the nucleus of the unstable atoms (15 O has 8 protons and 7 neutrons) A 1 Positron emission in the brain A 2 Positron and electron annihilation and emission of gamma rays Gamma ray Site of positron annihilation (imaged point) Electron Unstable radionuclide Positron 0 -9 mm resolution limit Gamma ray photon From: Principles of Neural Science (4 th. Ed. ) Kandel, Schwartz, & Jessell, p. 377. Columbia f. MRI Hirsch, J. , et al

Cerebral Blood Flow is Coupled to Neural Activity Year 1881 Blood flow and cognitive events ROY & SHERRINGTON Relationship between neural activity and vascular changes Columbia f. MRI 1890 Blood Flow MOSSO Neural Activity Hirsch, J. , et al

NEUROIMAGING: PET Year STRUCTURAL IMAGING: MRI HILAL 1981 First clinical MRI scanner PETERSON/FOX POSNER/RAICHLE PET study of human language 1984 Radiolabeled blood flow and neural events Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques B. Cardiovascular Based Methods 1. Positron Emission Tomography, PET 1. Source of signal and principles • Measurement techniques Columbia f. MRI Hirsch, J. , et al

Gamma Ray Detections to Location of Function From: Principles of Neural Science (4 th. Ed. ) Kandel, Schwartz, & Jessell, p. 377. Columbia f. MRI Hirsch, J. , et al

Injection of radioactive-labeled water Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques B. Cardiovascular Based Methods 1. Positron Emission Tomography, PET 1. Source of signal and principles 2. Measurement techniques • Computation for analysis Columbia f. MRI Hirsch, J. , et al

Analysis of PET Results Stimulation Fixation Difference Flashing Checkerboard Fixation Individual difference images Mean difference image From: Images of Mind by Posner, M. and Raichle, M. Scientific American Library, 1994, p. 24 Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques B. Cardiovascular Based Methods 1. Positron Emission Tomography, PET 2. Functional Magnetic Resonance Imaging, f. MRI Columbia f. MRI Hirsch, J. , et al

FUNCTIONAL MRI: f. MRI OGAWA 1990 Blood Oxygen dependent signal EPI/MRI and neural events BELLIVEAU 1992 Cortical map of the human visual system: f. MRI Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques 1. Functional Magnetic Resonance Imaging, f. MRI 1. Source of signal and principles Columbia f. MRI Hirsch, J. , et al

MAGNETIC FIELD 1: Scanner Environment [1. 5] T Protons align along an axis Columbia f. MRI Protons Outside Field Protons Inside Field (scattered) (aligned) Hirsch, J. , et al

MAGNETIC FIELD 2: Created when a radio frequency pulse (63. 3 mg. Hz) is applied to RFi aligned protons Protons precess around the axis and create a small current (MRI signal) (precess) (wobble) Columbia f. MRI Hirsch, J. , et al

MAGNETIC FIELD 3: A detectable radio frequency is emitted by the protons as they relax RFo into their aligned state The Radio frequency (RFo) is dependent upon field strength and therefore indicates location of origin uniform field Application of magnetic field gradient (m. T) Location of signa are recorded gradient field Columbia f. MRI Hirsch, J. , et al

MAGNETIC FIELD 4: Local signal change of a single voxel over time is due to change in proportions of oxyhemoglobin/deoxyhemoglobin PHYSIOLOGY NEURAL ACTIVATION IS ASSOCIATED WITH AN INCREASE IN BLOOD FLOW (Roy & Sherrington, 1890) RESULT: REDUCTION IN THE PROPORTION OF DEOXY HGB IN THE LOCAL VASCULATURE Columbia f. MRI Signal Intensity Change in MR Signal over time REST TASK - 40 s - REST - 40 s - PHYSICS DEOXY HGB IS PARAMAGNETIC (Linus Pauling, 1936) AND DISTORTS THE LOCAL MAGNETIC FIELD CAUSING SIGNAL LOSS RESULT: LESS DISTORTION OF THE MAGNETIC FIELD RESULTS IN LOCAL MR SIGNAL INCREASE Hirsch, J. , et al

BOLD Impulse Response Model • Function of blood oxygenation, flow, volume (Buxton et al, 1998) • Peak (max. oxygenation) 4 -6 s poststimulus; baseline after 20 -30 s • Initial undershoot can be observed (Malonek & Grinvald, 1996) Peak Brief Stimulus Undershoot • Similar across V 1, A 1, S 1… • … but differences across: other regions (Schacter et al 1997) individuals (Aguirre et al, 1998) Columbia f. MRI Initial Undershoot Hirsch, J. , et al

BOLD ORIGIN BOLD Signal corresponds to local field potential (LFP) Logothetis, N. K. , Pauls, , Augath, M, Torsten, T, Oeltermann, A, (2001) Neurophysiological investigation of the basis of the f. MRI signal. Nature 412 150 -157 Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques B. Cardiovascular Based Methods 1. Positron Emission Tomography, PET 2. Functional Magnetic Resonance Imaging, f. MRI 1. Source of signal and principles 1. Measurement techniques Columbia f. MRI Hirsch, J. , et al

Imaging While Naming Objects Scanner acquires the whole brain every [4] secs: [26] axial slices Resolution [1. 5 x 4. 5] mm Each voxel is analyzed seperately Columbia f. MRI Hirsch, J. , et al

COMPUTATIONS FOR f. UNCTIONAL IMAGE PROCESSING Acquisition RECONSTRUCTION ALIGNMENT VOXEL BY VOXEL ANALYSIS GRAPHICAL REPRESENTATION Columbia f. MRI Functional Brain Map from Nature 388, 171 -174 (1997) Kim, Relkin, Lee, & Hirsch

Brain Map of Object Naming (Single Subject) Columbia f. MRI Hirsch, J. , et al

Block Design Columbia f. MRI Event-Related Design Hirsch, J. , et al

One voxel = One test (t, F, . . . ) amplitude General Linear Model Üfitting Üstatistical analysis tim e Voxel Location Temporal series f. MRI voxel time course Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques B. Cardiovascular Based Methods 1. Positron Emission Tomography, PET 2. Functional Magnetic Resonance Imaging, f. MRI 1. Source of signal and principles 2. Measurement techniques 1. Computations for analysis Columbia f. MRI Hirsch, J. , et al

Voxel statistics… • parametric • • • one sample t-test two sample t-test paired t-test Anova An. Cova correlation linear regression multiple regression F-tests etc… Columbia f. MRI all cases of the General Linear Model assume normality to account for serial correlations: Hirsch, J. , et al

two-sample t-test Image intensity ¢standard t-test assumes independence ignores temporal autocorrelation! Columbia f. MRI Columbia voxel time series t-statistic image SPM{t} compares size of effect to its error standard deviation Hirsch, J. , et al

Regression 90 100 110 -10 0 10 90 100 110 + = a a=1 voxel time series box-car reference function m -2 0 2 + m = 100 Mean value Fit the GLM Columbia f. MRI

II. Brain Mapping Techniques B. Cardiovascular Based Methods 1. Positron Emission Tomography, PET 2. Functional Magnetic Resonance Imaging, f. MRI 1. Source of signal and principles 2. Measuremnet techniques 3. Computation for analysis 1. Individual brain maps Columbia f. MRI Hirsch, J. , et al

Standard Brain Mapping Tasks SENSORY MOTOR Touch Finger Thumb Tapping (passive) (active) GPo. C GPr. C LANGUAGE Picture Naming (active) GOi VISION Listening to Words Reversing Checkerboard (passive) GTT GFi GTs From Hirsch, J. , et al; Neurosurgery 47: 711 -722, 2000 Columbia f. MRI Hirsch, J. , et al Ca. S

Conventional Imaging Tumor Functional Imaging Before Surgery After Surgery Tumor R Left Hand: Sensory/Motor Columbia f. MRI Left Hand Movement Hirsch, J. , et al CC 23 (AB)

Surgery Before After LANGUAGE English Language Areas English R Tumor Italian Language Areas Tumor a Columbia f. MRI English Language Areas b Hirsch, J. , et al

II. Brain Mapping Techniques C. Electromagnetic - Based Methods 1. Somatosensory Evoked Potential, SSEP 2. Direct Cortical Stimulation Columbia f. MRI Hirsch, J. , et al

Sensory Motor Mapping Craniotomy SSEP Direct Cortical Stimulation Localization f. MRI “Twitching of hand, focal seizure involving arm ” Tag 3 Tag 5 “Twitching in 1 st three digits” From Hirsch, J. , et al; An Integrated Functional Magnetic Resonance Imaging Procedure for Preoperative Mapping of Cortical Areas Associated with Tactile, Motor, Language, and Visual Functions, Neurosurgery 47: 711 -722, 2000. Columbia f. MRI Tag 5 Hirsch, J. , et al

Language Mapping f. MRI Intraoperative Stimulation Response Broca’s Area Speech Arrest During Counting Wernicke’s Area Literal paraphasic speech error during picture naming From Hirsch, J. , et al; An Integrated Functional Magnetic Resonance Imaging Procedure for Preoperative Mapping of Cortical Areas Associated with Tactile, Motor, Language, and Visual Functions, Neurosurgery 47: 711 -722, 2000. Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques C. Electromagnetic - Based Methods 1. Somatasensory Evoked Potential, SSEP 2. Direct Cortical Stimulation 3. Magnetoencephalography, MEG • Source of signal and principles Columbia f. MRI Hirsch, J. , et al

Methods to Measure Electromagnetic Activity: MEG (Magnetoencephalography) - EEC (Electroencephalography) Signal Source: Electrical Activity of nerve cells. What is measured on the surface of the head is the result of mostly postsynaptic potentials (excitatory or inhibitory) Many nerve cells are aligned in palisades (e. g. pyramidal cells) and post-synaptic electrical fields sum with increasing area. Typically it is thought that 100, 000 adjacent neurons acting in temporal synchrony are required to produce a measurable change in the magnetic field Columbia f. MRI Hirsch, J. , et al

Relationship between currents in the brain and the magnetic field outside the head. Based on the discovery that electrical currents generate magnetic fields: Hans Christian Oersted, a Danish physicist (early 19 th. century) A current source with strength Q causes a current flow Jv within the brain. Columbia f. MRI The current flow produces a potential difference V on the scalp: (measured by EEG) B V Q Jv And a magnetic field B outside of the head: (measured by MEG) from: www. Aston. ac. uk/psychology/ meg/intro/magfield. htm Hirsch, J. , et al

II. Brain Mapping Techniques C. Electromagnetic - Based Methods 1. Somatasensory Evoked Potential, SSEP 2. Direct Cortical Stimulation 3. Magnetoencephalography, MEG 1. Source of signal and principle 1. Measurement techniques Columbia f. MRI Hirsch, J. , et al

Magnetoencephalography, MEG Tiny magnetic fields produced by brain activity (10 -13 Teslas) can be measured using Superconducting Quantum Interference Devices (SQUIDs). SQUIDS operate at superconducting temperatures (-269 o. C). Sensors are placed in a dewar containing liquid helium. Stimulus – evoked neuromagnetic signals are recorded by an array of detectors. The spatial location of the source is inferred by mathematical modeling of the magnetic field pattern. Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques C. Electromagnetic - Based Methods 1. Somatasensory Evoked Potential, SSEP 2. Direct Cortical Stimulation 3. Magnetoencephalography, MEG 1. Source of signal 2. Measurement techniques 1. Computation for analysis Columbia f. MRI Hirsch, J. , et al

Somatosensory evoked magnetic signals in response to tactile stimulation of the contralateral index finger Neuro magnetic response occurs about 50 msec after the stimulation. Columbia f. MRI Isofield contour maps at the time of maximal response (50 msec) to the tactile stimulation The field pattern is dipolar with clearly defined regions of entering (solid lines) and emerging (dashed lines) magnetic flux. Hirsch, J. , et al

Magnetic field strength in left hemisphere sensors Looking at words Liina Pylkkanen, Alec Marantz, 2002 Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques C. Electromagnetic - Based Methods 1. Somatasensory Evoked Potential, SSEP 2. Direct Cortical Stimulation 3. Magnetoencephalography, MEG 1. 4. Electroencephalography, EEG 1. Source of signal and principles 2. Measurement techniques Columbia f. MRI Hirsch, J. , et al

Electroencephalography Columbia f. MRI Hirsch, J. , et al

II. Brain Mapping Techniques C. Electromagnetic - Based Methods 1. Somatasensory Evoked Potential, SSEP 2. Direct Cortical Stimulation 3. Magnetoencephalography, MEG 4. Electroencephalography, EEG 1. Source of signal and principles 2. Measurement techniques 3. Computation for analysis Columbia f. MRI Hirsch, J. , et al

Electroencephalography Electrode Array for EEG Columbia f. MRI Averaged Activity profiles during bilateral finger movement Hirsch, J. , et al

C. Future Directions of Brain Mapping Columbia f. MRI Hirsch, J. , et al

• NEUROCIRCUITRY FOR ANXIETY The “Fearful” Face Etkin, A. , Klemenhage, K. , Dudman, J. , Rogan, M. , Hen, R. , Kandel, E. , Hirsch, J. , Individual differences in Trait Anxiety Predict the Response of Basolateral Amygdala to Unconsciously Processed Threat, Vol 44, 1043 -1055, Neuron, 2004. Columbia f. MRI Hirsch, J. , et al

FEAR-ANXIETY SYSTEM AND INDIVIDUAL DIFFERENCES Amygdala Covariation with Trait Anxiety Dorsal Amygdala Masked threat (FN-NN) r=-0. 04, p=0. 9 trait anxiety Basolateral Amygdala Masked threat (FN-NN) r=0. 67, p=0. 003 trait anxiety amygdala Etkin, A. , Klemenhage, K. , Dudman, J. , Rogan, M. , Hen, R. , Kandel, E. , Hirsch, J. , Individual differences in Trait Anxiety Predict the Response of Basolateral Amygdala to Unconsciously Processed Threat, Vol 44, 1043 -1055, Neuron, 2004. Columbia f. MRI Hirsch, J. , et al

NEUROCIRCUITRY FOR “FALSE ANSWERS” Inferior Frontal G. Middle Frontal G. Medial Frontal G. Anterior Cingulate G. Thalamus Candate Nunez, J. M. , Casey, B. J. , Egner, T. , Hare, T. , Hirsch, J. , Intentional False Responding Shares Neural Substrates with Response Conflict and Cognitive Control, in press, Neuro. Image, 2005. Columbia f. MRI Hirsch, J. , et al

• NEUROCIRCUITRY AND DISORDERS OF CONSCIOUSNESS: LISTENING TO NARRATIVES (FORWARD AND/NOT BACKWARD) “Healthy” Volunteers Group (n=10) R GTm (21) GFi (44) GTs (22) “Healthy” Volunteer Matched Subject 29 year old male R GTm (21) “Minimally Conscious” Patient 33 year old male GFi (44) R GFi (44) GTs (22) GTm (21) GOm (18) SCa (17) Schiff, N. D. , Rodriguez-Moreno, D. , Kamal, A. , Kim, K. H. S. , Giancino, J. T. , Plum, F. , Hirsch, J. , f. MRI Reveals Large Scale Network Activation in Minimally Conscious Patients, Neurology, 64: 3, 514 -523, 2005. Columbia f. MRI Hirsch, J. , et al

• NEURAL ANATOMY OF “MORALITY” Year HARLOW Phineas Gage 2004 1861 2004 Greene, J. d. , Nystrom, L. E. , Engell, A. D. , Darley, J. M. , Cohen, J. D. , The Neural Bases of Cognitive Conflict and Control in Moral Judgement, Neuron, 44, 389 -400, 2004. Columbia f. MRI Hirsch, J. , et al

THE MOST FUNDAMENTAL GOAL OF NEUROSCIENCE TO UNDERSTAND THE RELATIONSHIP BETWEEN THE AND Neurophysiology of the brain Operation of the mind (behavior) (structure) BRAIN-TO-BEHAVIOR PRINCIPLE Columbia f. MRI Hirsch, J. , et al