1. Introduction to fMRI 2. Basic fMRI Physics 3. Data Analysis 4. Localisation 5. Cortical Anatomy 1 1. Introduction to fMRI 2 MRI vs. fMRI MRI studies brain anatomy. Functional MRI (fMRI) studies brain function. 3 Brain Imaging: Anatomy CAT Brain Imaging: Anatomy Photography PET MRI 4 Source: modified from Posner & Raichle, Images of Mind MRI vs. fMRI high resolution (1 mm) MRI fMRI low resolution (~3 mm but can be better) one image fMRI Blood Oxygenation Level Dependent (BOLD) signal indirect measure of neural activity: active neurons shed oxygen and become more magnetic increasing the fMRI signal neural activity many images (e.g., every 2 sec for 5 mins) blood oxygen fMRI signal5 fMRI Activation Flickering Checkerboard OFF (60 s) - ON (60 s) -OFF (60 s) - ON (60 s) - OFF (60 s) Brain Activity 6 Time Source: Kwong et al., 1992 PET and fMRI Activation 7 Source: Posner & Raichle, Images of Mind fMRI Setup 8 fMRI Experiment Stages: Prep 1) Prepare subject • Consent form • Safety screening • Instructions 2) Shimming • putting body in magnetic field makes it non-uniform • adjust 3 orthogonal weak magnets to make magnetic field as homogenous as possible 3) Sagittals Note: That’s one g, two t’s Take images along the midline to use to plan slices 9 fMRI Experiment Stages: Anatomicals 4) Take anatomical (T1) images • high-resolution images (e.g., 1x1x2.5 mm) • 3D data: 3 spatial dimensions, sampled at one point in time • 64 anatomical slices takes ~5 minutes 10 Slice Terminology VOXEL (Volumetric Pixel) Slice Thickness e.g., 6 mm In-plane resolution e.g., 192 mm / 64 = 3 mm 3 mm 6 mm SAGITTAL SLICE IN-PLANE SLICE 3 mm Number of Slices e.g., 10 Matrix Size e.g., 64 x 64 Field of View (FOV) e.g., 19.2 cm 11 fMRI Experiment Stages: Functionals 5) Take functional (T2*) images • images are indirectly related to neural activity • usually low resolution images (3x3x5 mm) • all slices at one time = a volume (sometimes also called an image) • sample many volumes (time points) (e.g., 1 volume every 2 seconds for 150 volumes = 300 sec = 5 minutes) • 4D data: 3 spatial, 1 temporal … first volume (2 sec to acquire) 12 Activation Statistics Functional images ~2s ROI Time Course fMRI Signal (% change) Time Condition Statistical Map superimposed on anatomical MRI image Time Region of interest (ROI) ~ 5 min 13 Statistical Maps & Time Courses Use stat maps to pick regions Then extract the time course 14 2D 3D 15 Design Jargon: Runs session: all of the scans collected from one subject in one day run (or scan): one continuous period of fMRI scanning (~5-7 min) experiment: a set of conditions you want to compare to each other condition: one set of stimuli or one task Note: Terminology can vary from one fMRI site to another (e.g., some places use “scan” to refer to what we’ve called a volume). 4 stimulus conditions + 1 baseline condition (fixation) A session consists of one or more experiments. Each experiment consists of several (e.g., 1-8) runs More runs/expt are needed when signal:noise is low or the effect is weak. Thus each session consists of numerous (e.g., 5-20) runs (e.g., 0.5 – 3 hours) 16 Design Jargon: Paradigm paradigm (or protocol): the set of conditions and their order used in a particular run run epoch: one instance of a condition first “objects right” epoch second “objects right” epoch volume #1 (time = 0) Time epoch 8 vol x 2 sec/vol = 16 sec volume #105 (time = 105 vol x 2 sec/vol = 210 sec = 3:30) 17 2. Basic fMRI Physics 18 Recipe for MRI 1) Put subject in big magnetic field (leave him there) 2) Transmit radio waves into subject [about 3 ms] 3) Turn off radio wave transmitter 4) Receive radio waves re-transmitted by subject – Manipulate re-transmission with magnetic fields during this readout interval [10-100 ms: MRI is not a snapshot] 5) Store measured radio wave data vs. time – Now go back to 2) to get some more data 6) Process raw data to reconstruct images 7) Allow subject to leave scanner (this is optional) 19 Source: Robert Cox’s web slides History of NMR NMR = nuclear magnetic resonance Felix Block and Edward Purcell 1946: atomic nuclei absorb and reemit radio frequency energy 1952: Nobel prize in physics nuclear: properties of nuclei of atoms magnetic: magnetic field required resonance: interaction between magnetic field and radio frequency Bloch Purcell NMR MRI: Why the name change? most likely explanation: nuclear has bad connotations less likely but more amusing explanation: 20 NMR subjects got nervous when fast-talking doctors suggested an History of fMRI MRI -1971: MRI Tumor detection (Damadian) -1973: Lauterbur suggests NMR could be used to form images -1977: clinical MRI scanner patented -1977: Mansfield proposes echo-planar imaging (EPI) to acquire images faster fMRI -1990: Ogawa observes BOLD effect with T2* blood vessels became more visible as blood oxygen decreased -1991: Belliveau observes first functional images using a contrast agent -1992: Ogawa et al. and Kwong et al. publish first functional images using BOLD signal Ogawa 21 Necessary Equipment 4T magnet RF Coil gradient coil (inside) Magnet Gradient Coil RF Coil 22 Source: Joe Gati, photos The Big Magnet Very strong 1 Tesla (T) = 10,000 Gauss Earth’s magnetic field = 0.5 Gauss 4 Tesla = 4 x 10,000 0.5 = 80,000X Earth’s magnetic field Continuously on Main field = B0 Robarts Research Institute 4T x 80,000 = Source: www.spacedaily.com B0 23 Magnet Safety The whopping strength of the magnet makes safety essential. Things fly – Even big things! Source: www.howstuffworks.com Screen subjects carefully Make sure you and all your students & staff are aware of hazzards Develop stratetgies for screening yourself every time you enter the magnet Source: http://www.simplyphysics.com/ flying_objects.html 24 Subject Safety Anyone going near the magnet – subjects, staff and visitors – must be thoroughly screened: Subjects must have no metal in their bodies: • pacemaker • aneurysm clips • metal implants (e.g., cochlear implants) • interuterine devices (IUDs) • some dental work (fillings okay) This subject was wearing a hair band with a ~2 mm Subjects must remove metal from their bodies copper clamp. Left: with hair band. Right: without. • jewellery, watch, piercings Source: Jorge Jovicich • coins, etc. • wallet • any metal that may distort the field (e.g., underwire bra) Subjects must be given ear plugs (acoustic noise can reach 120 dB) 25 Outside magnetic field Protons align with field • randomly oriented Inside magnetic field M • spins tend to align parallel or anti-parallel to B0 • net magnetization (M) along B0 • spins precess with random phase • no net magnetization in transverse plane • only 0.0003% of protons/T align with field longitudinal axis Longitudinal magnetization M=0 Source: Mark Cohen’s web slides Source: Robert Cox’s web slides transverse plane 26 fMRI Basics – The functional magnetic resonance imaging technique measures the amount of oxygen in the blood in small regions of the brain. These regions are called voxels. Neural activity uses up oxygen and the vasculature responds by providing more highly oxygenated blood to local brain regions. Thus a change in amount of oxygen in the blood is measured, and this is taken as a proxy for the amount of local neural activity. The measured signal is often called the BOLD signal (Blood Oxygen Level Dependent). Because neural activity is not measured directly, one needs to think about what the indirect signal really tells us, and how it’s spatial and temporal resolution are limited. Certainly, however,the BOLD signal tells us something about localization of neural activity in the brain. 27 BOLD signal Blood Oxygen Level Dependent signal neural activity blood flow oxyhemoglobin T2* MR signal Mxy Signal Mo sin T2* task T2* control Stask Scontrol S TEoptimum Source: fMRIB Brief Introduction to fMRI time Source: Jorge Jovicich 28 BOLD signal 29 Source: Doug Noll’s primer 3. DATA ANALYSIS 30 Hypotheses vs. Data Hypothesis-driven Examples: t-tests, correlations, general linear model (GLM) • a priori model of activation is suggested • data is checked to see how closely it matches components of the model • most commonly used approach Data-driven Independent Component Analysis (ICA) • no prior hypotheses are necessary • multivariate techniques determine the patterns in the data that account for the most variance across all voxels • can be used to validate a model (see if the math comes up with the components you would’ve predicted) • can be inspected to see if there are things happening in your data that you didn’t predict • can be used to identify confounds (e.g., head motion) • need a way to organize the many possible components • new and upcoming 31 Comparing the two approaches Region of Interest (ROI) Analyses • • • • • • Gives you more statistical power because you do not have to correct for the number of comparisons Hypothesis-driven ROI is not smeared due to intersubject averaging Easy to analyze and interpret Neglects other areas which may play a fundamental role Popular in North America Whole Brain Analysis • • • • • • Requires no prior hypotheses about areas involved Includes entire brain Can lose spatial resolution with intersubject averaging Can produce meaningless “laundry lists of areas” that are difficult to interpret Depends highly on statistics and threshold selected Popular in Europe NOTE: Though different experimenters tend to prefer one method over the other, they are NOT mutually exclusive. You can check ROIs you predicted and then check the data for other areas. 32 Source: Tootell et al., 1995 Why do we need statistics? MR Signal intensities are arbitrary -vary from magnet to magnet, coil to coil, within a coil (especially surface coil), day to day, even run to run -may also vary from area to area (some areas may be more metabolically active) We must always have a comparison condition within the same run We need to know whether the “eyeball tests of significance” are real. Because we do so many comparisons, we need a way to compensate. 33 Two approaches: ROI A. ROI approach 1. 2. 3. Do (a) localizer run(s) to find a region (e.g., show moving rings to find MT) Extract time course information from that region in separate independent runs See if the trends in that region are statistically significant Because the runs that are used to generate the area are independent from those used to test the hypothesis, liberal statistics can be used Example study: Tootell et al, 1995, Motion Aftereffect Localize “motion area” MT in a run comparing moving vs. stationary rings Extract time courses from MT in subsequent runs while subjects see illusory motion (motion aftereffect) MT 34 Source: Tootell et al., 1995 4. LOCALISATION 35 BRAIN LOCALIZATION AND ANATOMY with an emphasis on cortical areas Why so corticocentric? •cortex forms the bulk of the brain •subcortical structures are hard to image (more vulnerable to motion artifacts) and resolve with fMRI •cortex is relevant to many cognitive processes •neuroanatomy texts typically devote very little information to cortex Caveats of corticocentrism: •other structures like the cerebellum are undoubtedly very important (contrary to popular belief it not only helps you “walk and chew gum at the same time” but also has many cognitive functions) but unfortunately are poorly understood as yet •need to remember there may be lots of subcortical regions we’re neglecting 36 How can we define regions? 1. Talairach coordinates 2. Anatomical localization 3. Functional localization • Region of interest (ROI) analyses 37 Talairach Coordinate System Individual brains are different shapes and sizes… How can we compare or average brains? Talairach & Tournoux, 1988 • squish or stretch brain into “shoe box” • extract 3D coordinate (x, y, z) for each activation focus Note: That’s TalAIRach, not TAILarach! Source: Brain Voyager course slides 38 Rotate brain into ACPC plane Corpus Callosum Fornix Find anterior commisure (AC) Find posterior commisure (PC) ACPC line = horizontal axis Note: official Tal sez use top of AC and bottom of PC Pineal Body “bent asparagus” Source: Duvernoy, 1999 39 Deform brain into Talairach space Mark 8 points in the brain: • anterior commisure • posterior commisure • front • back • top • bottom (of temporal lobe) • left • right Squish or stretch brain to fit in “shoebox” of Tal system y<0 AC=0 y y>0 z y>0 Extract 3 coordinates ACPC=0 y<0 40 x Left is what?!!! Neurologic (i.e. sensible) convention • left is left, right is right L R - Note: Make sure you know what your magnet and software are doing before publishing left/right info! + x=0 Radiologic (i.e. stupid) convention • left is right, right is left R L + x=0 Note: If you’re really unsure which side is which, tape a vitamin E capsule to the one side of the subject’s head. It will show up on the anatomical image. 41 How to Talairach For each subject: • • • Rotate the brain to the ACPC Plane (anatomical) Deform the brain into the shoebox (anatomical) Perform the same transformations on the functional data For the group: Either a) Average all of the functionals together and perform stats on that b) Perform the stats on all of the data (GLM) and superimpose the statmaps on an averaged anatomical (or for SPM, a reference brain) Averaged anatomical for 6 subjects Averaged functional for 7 subjects 42 Talairach Atlas 43 Brodmann’s Areas Brodmann (1905): Based on cytoarchitectonics: study of differences in cortical layers between areas Most common delineation of cortical areas More recent schemes subdivide Brodmann’s areas into many smaller regions Monkey and human Brodmann’s areas not necessarily homologous 44 Talairach Pros and Cons Advantages • widespread system • allows averaging of fMRI data between subjects • allows researchers to compare activation foci • easy to use Disadvantages • based on the squished brain of an elderly alcoholic woman (how representative is that?!) • not appropriate for all brains (e.g., Japanese brains don’t fit well) • activation foci can vary considerably – other landmarks like sulci may be more reliable 45 Anatomical Localization Sulci and Gyri gray matter (dendrites & synapses) BANK white matter (axons) FISSURE FUNDUS Source: Ludwig & Klingler, 1956 in Tamraz & Comair, 2000 46 Variability of Sulci Variability of Sulci Source: Szikla et al., 1977 in Tamraz & Comair, 2000 47 Variability of Functional Areas Watson et al., 1995 -functional areas (e.g., MT) vary between subjects in their Talairach locations -the location relative to sulci is more consistent Source: Watson et al. 1995 48 Cortical Surfaces segment gray-white matter boundary render cortical surface inflate cortical surface sulci = concave = dark gray gyri = convex = light gray Advantages • surfaces are topologically more accurate • alignment across sessions and experiments allows task comparisons 49 Source: Jody Culham Cortical Inflation Movie Movie: unfoldorig.mpeg http://cogsci.ucsd.edu/~sereno/unfoldorig.mpg Source: Marty Sereno’s web page 50 Cortical Flattening 2) make cuts along the medial surface (Note, one cut typically goes along the fundus of the calcarine sulcus though in this example the cut was placed below) 1) inflate the brain 3) unfold the medial surface so the cortical surface lies flat 4) correct for the distortions so that the true cortical distances are preserved 51 Source: Brain Voyager Getting Started Guide Spherical Averaging Future directions of fMRI: Use cortical surface mapping coordinates Inflate the brain into a sphere Use sulci and/or functional areas to match subject’s data to template Cite “latitude” & “longitude” of spherical coordinates Source: Fischl et al., 1999 Movie: brain2ellipse.mpeg http://cogsci.ucsd.edu/~sereno/coord1.mpg52 Source: Marty Sereno’s web page Spherical Averaging 53 Source: MIT HST583 online course notes 5. CORTICAL ANATOMY 54 14 Major Sulci Main sulci are formed early in development Fissures are really deep sulci Typically continuous sulci •Interhemispheric fissure •Sylvian fissure •Parieto-occipital fissure •Collateral sulcus •Central sulcus •Calcarine Sulcus Typically discontinuous sulci •Superior frontal sulcus •Inferior frontal sulcus •Postcentral sulcus •Intraparietal sulcus •Superior temporal sulcus •Inferior temporal sulcus •Cingulate sulcus •Precentral sulcus Other minor sulci are much less reliable 55 Source: Ono, 1990 Interhemispheric Fissure -hugely deep (down to corpus callosum) -divides brain into 2 hemispheres 56 Sylvian Fissure -hugely deep -mostly horizontal -insula (purple) is buried within it -separates temporal lobe from parietal and frontal lobes Sylvian Fissure 57 Parieto-occipital Fissure and Calcarine Sulcus Parieto-occipital fissure (red) -very deep -often Y-shaped from sagittal view, X-shaped in horizontal and coronal views Calcarine sulcus (blue) -contains V1 Cuneus (pink) -visual areas on medial side above calcarine (lower visual field) Lingual gyrus (yellow) -visual areas on medial side below calcarine and above collateral sulcus (upper visual field) 58 Collateral Sulcus -divides lingual (yellow) and parahippocampal (green) gyri from fusiform gyrus (pink) 59 Cingulate Sulcus -divides cingulate gyrus (turquoise) from precuneus (purple) and paracentral lobule (gold) 60 Central, Postcentral and Precentral Sulci Central Sulcus (red) -usually freestanding (no intersections) -just anterior to ascending cingulate Postcentral Sulcus (red) -often in two parts (superior and inferior) -often intersects with intraparietal sulcus -marks posterior end of postcentral gyrus (somatosensory strip, purple) Precentral Sulcus (red) -often in two parts (superior and inferior) -intersects with superior frontal sulcus (Tjunction) -marks anterior end of precentral gyrus (motor strip, yellow) ascending band of the cingulate 61 Intraparietal Sulcus -anterior end usually intersects with inferior postcentral (some texts call inferior postcentral the ascending intraparietal sulcus) -posterior end usually forms a T-junction with the transverse occipital sulcus (just posterior to the parieto-occipital fissure) -IPS divides the superior parietal lobule from the inferior parietal lobule (angular gyrus, gold, and supramarginal gyrus, lime) POF 62 Slice Views inverted omega = hand area of motor cortex 63 Superior and Inferior Temporal Sulci Superior Temporal Sulcus (red) -divides superior temporal gyrus (peach) from middle temporal gyrus (lime) Inferior Temporal Sulcus (blue) -not usually very continuous -divides middle temporal gyrus from inferior temporal gyrus (lavender) 64 Superior and Inferior Frontal Sulci Superior Frontal Sulcus (red) -divides superior frontal gyrus (mocha) from middle frontal gyrus (pink) Inferior Frontal Sulcus (blue) -divides middle frontal gyrus from inferior frontal gyrus (gold) Frontal Eye fields lie at this junction orbital gyrus (green) and frontal pole (gray) also shown 65 Medial Frontal -superior frontal gyrus continues on medial side -frontal pole (gray) and orbital gyrus (green) also shown 66