Functional Magnetic Resonance Imaging ; What is it and what can it do? Heather Rupp Common Themes in Reproductive Diversity Kinsey Institute Indiana University Note- Most slides were taken from Jody Culham’s fMRI for Dummies web site

MSNBC.com Is Hysteria Real? Brain Images Say Yes New York Times September 26, 2006 Is Hysteria Real? Brain Images Say Yes By ERIKA KINETZ Hysteria is a 4,000-year-old diagnosis that has been applied to no mean parade of witches, saints and, of course, Anna O. But over the last 50 years, the word has been spoken less and less. The disappearance of hysteria has been heralded at least since the 1960’s. What had been a Victorian catch-all splintered into many different diagnoses. Hysteria seemed to be a vanished 19th-century extravagance useful for literary analysis but surely out of place in the serious reaches of contemporary science. … New York Times September 10, 2006, Sunday The Basics; An Image of Consciousness Creates a Stir By BENEDICT CAREY (NYT) ABSTRACT - Neuroscientists were anxious as well as exuberant over the report last week that doctors in England had found clearsigns of awareness in a brain-damaged woman who was in a vegetative state. They insisted that the breathtaking finding -- that a brain thought to be all but dark flared with ... Imaging studies are very popular in the media- Evidence of brain activation equated with biological diffs and something being ‘real’ People talk about brain areas ‘lighting up’- but what does this mean? What does fMRI really measure and DO?       MSNBC.com May 8, 2006 Research finds differences in lesbian brains p.m. ET May 8, 2006 WASHINGTON - Lesbians’ brains react differently to sex hormones than those of heterosexual women. An earlier study of gay men also showed their brain response was different from straight men — an even stronger difference than has now been found in lesbians…..

Today’s Goals I. What does brain imaging actually measure? MRI fMRI II. Experimental Design Basics Some Considerations III. Data Units of measurement Basic Analysis

Measuring Brain Function Phrenology Lesions EEG/ERP Electrophysiology Need to balance considerations of spatial resolution, temporal resolution, and invasiveness. High resolution pictures of anatomy Take advantage of the fact that human tissue is primarily made up of water- you can image any tissue brain or clitoris 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

Magnetic Resonance Imaging (MRI) High resolution pictures of anatomy Take advantage of the fact that human tissue is primarily made up of water- you can image any tissue brain or clitoris 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

History of NMR NMR = nuclear magnetic resonance Felix Block and Edward Purcell 1946: atomic nuclei absorb and re-emit 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

How do you take a ‘picture’ of a brain? Take advantage of the high (and variable) water composition of human tissue. Hydrogen protons align with magnetic field. Disrupt field and measure return (T1)- different brain regions vary.

The Big Magnet B0 x 80,000 = Very strong 1 Tesla (T) = 10,000 Gauss Source: www.spacedaily.com 1 Tesla (T) = 10,000 Gauss Earth’s magnetic field = 0.5 Gauss x 80,000 = 4 Tesla = 4 x 10,000  0.5 = 80,000X Earth’s magnetic field Robarts Research Institute 4T Continuously on Main field = B0 B0

Protons align with field Outside magnetic field Protons align with field randomly oriented Inside magnetic field 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 M longitudinal axis Longitudinal magnetization transverse plane M = 0 Source: Mark Cohen’s web slides Source: Robert Cox’s web slides

RF Excitation Excite Radio Frequency (RF) field transmission coil: apply magnetic field along B1 (perpendicular to B0) for ~3 ms oscillating field at Larmor frequency frequencies in range of radio transmissions B1 is small: ~1/10,000 T tips M to transverse plane – spirals down analogies: guitar string (Noll), swing (Cox) final angle between B0 and B1 is the flip angle Transverse magnetization B1 B0 Source: Robert Cox’s web slides

T1 and TR T1 = recovery of longitudinal (B0) magnetization used in anatomical images ~500-1000 msec (longer with bigger B0) TR (repetition time) = time to wait after excitation before sampling T1 Source: Mark Cohen’s web slides

T2 and TE T2 = decay of transverse magnetization TE (time to echo) = time to wait to measure T2 or T2* (after refocusing with spin echo or gradient echo) So not recovery to alignment, but how long it takes to relax to other plane Source: Mark Cohen’s web slides

T1 T2

How do you take a ‘picture’ of a brain? 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) Felix Bloch and Edward Purcell, both of whom were awarded the Nobel Prize in 1952, discovered the magnetic resonance phenomenon independently in 1946. In the period between 1950 and 1970, NMR was developed and used for chemical and physical molecular analysis. In 1971 Raymond Damadian showed that the nuclear magnetic relaxation times of tissues and tumors differed, thus motivating scientists to consider magnetic resonance for the detection of disease. Source: Mark Cohen’s web slides

How do you take a ‘picture’ of the body?                                             Remember- T1 images

MRI vs. fMRI Functional MRI (fMRI) studies brain function. MRI studies brain anatomy. Source: Jody Culham’s fMRI for Dummies web site

Functional Magnetic Resonance Imaging (fMRI) High resolution pictures of anatomy Take advantage of the fact that human tissue is primarily made up of water- you can image any tissue brain or clitoris 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

History of fMRI 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

First Functional Images Flickering Checkerboard OFF (60 s) - ON (60 s) -OFF (60 s) - ON (60 s) - OFF (60 s) Finger tapping Source: Kwong et al., 1992

How do you make a ‘movie’ brain function? Don’t look at T1 (recovery to magnetic field orientation), look at relaxation away from field T2, T2* Relaxation differs locally and with changes in blood flow

BOLD signal Blood Oxygen Level Dependent signal neural activity   blood flow   oxyhemoglobin   T2*   MR signal Source: fMRIB Brief Introduction to fMRI

Hemodynamic Response Function % signal change = (point – baseline)/baseline usually 0.5-3% initial dip -more focal and potentially a better measure -somewhat elusive so far, not everyone can find it time to rise signal begins to rise soon after stimulus begins time to peak signal peaks 4-6 sec after stimulus begins post stimulus undershoot signal suppressed after stimulation ends

Summary: What Does fMRI Measure? Big magnetic field protons (hydrogen molecules) in body become aligned to field RF (radio frequency) coil radio frequency pulse knocks protons over as protons realign with field, they emit energy that coil receives (like an antenna) Gradient coils make it possible to encode spatial information MR signal differs depending on concentration of hydrogen in an area (anatomical MRI) amount of oxy- vs. deoxyhemoglobin in an area (fMRI)

 neural activity   blood oxygen   fMRI signal Summary: MRI vs. fMRI MRI fMRI high resolution (1 mm) low resolution (~3 mm but can be better) one image fMRI Blood Oxygenation Level Dependent (BOLD) signal indirect measure of neural activity … many images (e.g., every 2 sec for 5 mins)  neural activity   blood oxygen   fMRI signal Source: Jody Culham’s fMRI for Dummies web site

Today’s Goals I. What does brain imaging actually measure? MRI fMRI II. Experimental Design Basics Some Considerations III. Data Units of measurement Basic Analysis High resolution pictures of anatomy Take advantage of the fact that human tissue is primarily made up of water- you can image any tissue brain or clitoris 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

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 Take images along the midline to use to plan slices Note: That’s one g, two t’s Source: Jody Culham’s fMRI for Dummies web site

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 Source: Jody Culham’s fMRI for Dummies web site

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) … Source: Jody Culham’s fMRI for Dummies web site

Subtraction Logic Cognitive subtraction originated with reaction time experiments (F. C. Donders, a Dutch physiologist). Measure the time for a process to occur by comparing two reaction times, one which has the same components as the other + the process of interest. Example: T1: Hit a button when you see a light T2: Hit a button when the light is green but not red T3: Hit the left button when the light is green and the right button when the light is red T2 – T1 = time to make discrimination between light color T3 – T2 = time to make a decision Assumption of pure insertion: You can insert a component process into a task without disrupting the other components. Widely criticized

You Must Have a Baseline!

Change only one thing between conditions! Two paired conditions should differ by the inclusion/exclusion of a single mental process How do we control the mental operations that subjects carry out in the scanner? Manipulate the stimulus works best for automatic mental processes Manipulate the task works best for controlled mental processes DON’T DO BOTH AT ONCE!!! Source: Nancy Kanwisher

Dealing with Attentional Confounds fMRI data seem highly susceptible to the amount of attention drawn to the stimulus or devoted to the task. How can you ensure that activation is not simply due to an attentional confound? Add an attentional requirement to all stimuli or tasks. Time Add a “one back” task subject must hit a button whenever a stimulus repeats the repetition detection is much harder for the scrambled shapes any activation for the intact shapes cannot be due only to attention Other common confounds that reviewers love to hate: eye movements motor movements

Block Designs Blocked Design = trial of one type (e.g., face image) = trial of another type (e.g., place image) Assumption: Because the hemodynamic response delays and blurs the response to activation, the temporal resolution of fMRI is limited. WRONG!!!!!

Blocked vs. Event-related Source: Buckner 1998

Some Considerations PHYSIOLOGICAL FACTORS SOLUTION & TRADEOFF Cardiac and respiratory noise Monitor and compensate hassle Head (and body) motion Use experienced or well-warned subjects limits useable subjects Use head-restraint system possible subject discomfort Post-processing correction often incompletely effective 2nd order effects can introduce other artifacts Single trials to avoid body motion Low frequency noise Use smart design Perform post-processing filtering BOLD noise (neural and vascular fluctuations) Use many trials to average out variability Behavioral variations Use well-controlled paradigm Source: Doug Noll’s online tutorial

Some Considerations US$463/hour!!! Average cost of performing an fMRI experiment in 1998: US$463/hour!!! Average cost of performing a thought experiment: Your Salary CONCLUSION: Unless you are Bill Gates or Michael Jordan, a thought experiment is much more efficient!

Source: http://www.simplyphysics.com/ Magnet Safety The whopping strength of the magnet makes safety essential. Things fly – Even big things! Source: www.howstuffworks.com Source: http://www.simplyphysics.com/ flying_objects.html Source: Jody Culham’s fMRI for Dummies web site

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) Subjects must remove metal from their bodies jewellery, watch, piercings 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) This subject was wearing a hair band with a ~2 mm copper clamp. Left: with hair band. Right: without. Source: Jorge Jovicich Source: Jody Culham’s fMRI for Dummies web site

Thought Experiments What do you hope to find? What would that tell you about the cognitive process involved?  Would it add anything to what is already known from other techniques?  Could the same question be asked more easily & cheaply with other techniques? Would fMRI add enough to justify the immense expense and effort?  What would be the alternative outcomes (and/or null hypothesis)?  Or is there not really any plausible alternative (in which case the experiment may not be worth doing)?  If the alternative outcome occurred, would the study still be interesting?  If the alternative outcome is not interesting, is the hoped-for outcome likely enough to justify the attempt?  What would the headline be if it worked? What are the possible confounds? Can you control for those confounds? Has the experiment already been done? 

Today’s Goals I. What does brain imaging actually measure? MRI fMRI II. Experimental Design Basics Some Considerations III. Data Units of measurement Basic Analysis High resolution pictures of anatomy Take advantage of the fact that human tissue is primarily made up of water- you can image any tissue brain or clitoris 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

The Data Unit VOXEL (Volumetric Pixel) SAGITTAL SLICE IN-PLANE SLICE Slice Thickness e.g., 6 mm Number of Slices e.g., 10 SAGITTAL SLICE VOXEL (Volumetric Pixel) 3 mm 6 mm Matrix Size e.g., 64 x 64 In-plane resolution e.g., 192 mm / 64 = 3 mm IN-PLANE SLICE Field of View (FOV) e.g., 19.2 cm Source: Jody Culham’s fMRI for Dummies web site

superimposed on anatomical MRI image Data Unit Functional images Time fMRI Signal (% change) ROI Time Course Condition ~2s Region of interest (ROI) Condition 1 Statistical Map superimposed on anatomical MRI image Condition 2 Time ... ~ 5 min Source: Jody Culham’s fMRI for Dummies web site

Averaged Over Trials Single trials Average of all trials from 2 runs

Activation is Averaged Source: Posner & Raichle, Images of Mind

Brain Averaging 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

What do the pretty pictures mean? Source: Jody Culham’s fMRI for Dummies web site

Careful! 1. "Brain Area X is activated by Task A." Compared to what? Activations are differences! 2. "Baseline". Huh?! There's a role for this, but be careful. 3. Inferring: Because Region X responded significantly more strongly in Task A than control, but didn't respond significantly more strongly in Task B than control, it is selectively activated by Task A. A difference in significances is not necessarily a significant difference. 4. Imputing a specific function to a region of cortex from a difference in only two conditions. Data always underdetermines theory, but reasonable hypotheses about function require multiple tests applied to the same region of cortex. 5. "Gyrus X was active in my comparison of tasks B and C, and in Joe Shmo's comparison of tasks D and E, so the same area must be involved in both tasks B and D." Gyri can be very big places; need within-subject data. Source: Nancy Kanwisher

Next Time Meet in Room 130 Psychology Volunteers? http://www.indiana.edu/~imaging/index.html

Top Ten Things Sex and Brain Imaging Have in Common 10. It's not how big the region is, it's what you do with it.  9. Both involve heavy PETting.  8. It's important to select regions of interest.  7. Experts agree that timing is critical.  6. Both require correction for motion.  5. Experimentation is everything.  4. You often can't get access when you need it.  3. You always hope for multiple activations.  2. Both make a lot of noise.  1. Both are better when the assumption of pure insertion is met. Source: students in the Dartmouth McPew Summer Institute