Functional Magnetic Resonance Imaging ; What is it and what can it do?

Functional Magnetic Resonance Imaging ;Functional Magnetic Resonance Imaging ;What is it and what can it do?What is it and what can it do?

Heather RuppCommon Themes in Reproductive Diversity

Kinsey InstituteIndiana University

Note- Most slides were taken from Jody Culham’s fMRI for Dummies web site

May 8, 2006Research finds differences in lesbian brains

p.m. ET May 8, 2006WASHINGTON - 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…..

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 ...

MSNBC.com

Today’s Goals

I. What does brain imaging actually measure?MRIfMRI

II. Experimental DesignBasicsSome Considerations

III. Data Units of measurementBasic Analysis

Measuring Brain Function

• Phrenology

• Lesions

• EEG/ERP

• Electrophysiology

• Need to balance considerations of spatial resolution, temporal resolution, and invasiveness.

Magnetic Resonance Imaging (MRI)

History of NMRNMR = nuclear magnetic resonance

Felix Block and Edward Purcell1946: atomic nuclei absorb and re-emit radio frequency energy1952: Nobel prize in physics

nuclear: properties of nuclei of atomsmagnetic: magnetic field requiredresonance: interaction between magnetic field and radio frequency

Bloch PurcellNMR MRI: Why the name change?

most likely explanation: nuclear has bad connotations

• 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.

How do you take a ‘picture’ of a brain?

x 80,000 =

4 Tesla = 4 x 10,000 0.5 = 80,000X Earth’s magnetic field

Robarts Research Institute 4T

The Big MagnetVery strong

Continuously on

Source: www.spacedaily.com

1 Tesla (T) = 10,000 Gauss

Earth’s magnetic field = 0.5 Gauss

Main field = B0

B0

http://www.spacedaily.com/images/earth-magnetic-strings-bg.jpg

Protons align with fieldOutside magnetic field

Inside magnetic field

• randomly oriented

• 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

Source: Mark Cohen’s web slides

M

M = 0Source: Robert Cox’s web slides

longitudinalaxis

transverseplane

Longitudinalmagnetization

http://porkpie.loni.ucla.edu/BMD_HTML/SharedCode/slides/BasicMRPhysics/ppframe.htm

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

B1

B0

Source: Robert Cox’s web slides

Transversemagnetization

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


T2 and TE


T2 = decay of transverse magnetizationTE (time to echo) = time to wait to measure T2 or T2* (after refocusing with spin echo or gradient echo)

T1 T2

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)

How do you take a ‘picture’ of a brain?



How do you take a ‘picture’ of the body?

MRI studies brain anatomy.Functional MRI (fMRI) studies brain function.

MRI vs. fMRI

Source: Jody Culham’s fMRI for Dummies web site

http://defiant.ssc.uwo.ca/Jody_web/fmri4dummies.htm

Functional Magnetic Resonance Imaging (fMRI)

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

Source: Kwong et al., 1992

Flickering CheckerboardOFF (60 s) - ON (60 s) -OFF (60 s) - ON (60 s) - OFF (60 s)

1) Don’t look at T1 (recovery to magnetic field orientation), look at relaxation away from field T2, T2*

2) Relaxation differs locally and with changes in blood flow

How do you make a ‘movie’ brain function?

BOLD signal

Source: fMRIB Brief Introduction to fMRI

neural activity blood flow oxyhemoglobin T2* MR signal

Blood Oxygen Level Dependent signal

http://www.fmrib.ox.ac.uk/fmri_intro/

http://www.fmrib.ox.ac.uk/fmri_intro/

Hemodynamic Response Function

% signal change = (point – baseline)/baselineusually 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 peaksignal peaks 4-6 sec after stimulus begins

post stimulus undershootsignal 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)

Summary:MRI vs. fMRI

neural activity blood oxygen fMRI signal

MRI fMRI

one image

many images (e.g., every 2 sec for 5 mins)

high resolution(1 mm)

low resolution(~3 mm but can be better)

fMRI Blood Oxygenation Level Dependent (BOLD) signal

indirect measure of neural activity

…



Today’s Goals




fMRI Experiment Stages: Prep1) 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) SagittalsTake images along the midline to use to plan slices

Note: That’s one g, two t’s



fMRI Experiment Stages: Anatomicals4) 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



fMRI Experiment Stages: Functionals5) 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)

…



Subtraction LogicCognitive 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.

Assumption of pure insertion: You can insert a component process into a task without disrupting the other components.

Widely criticized

Example:

T1: Hit a button when you see a lightT2: Hit a button when the light is green but not redT3: 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

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?

i) Manipulate the stimulus• works best for automatic mental processes

ii) 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.

Add an attentional requirement to all stimuli or tasks.

How can you ensure that activation is not simply due to an attentional confound?

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

Assumption: Because the hemodynamic response delays and blurs the response to activation, the temporal resolution of fMRI is limited.

= trial of one type (e.g., face image)

= trial of another type (e.g., place image)

WRONG!!!!!

Blocked Design

Blocked vs. Event-related

Source: Buckner 1998

Some Considerations

Source: Doug Noll’s online tutorial

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

Use many trials to average out variability

Some ConsiderationsAverage cost of performing an fMRI experiment in 1998:

CONCLUSION: Unless you are Bill Gates or Michael Jordan, a thought experiment is much more efficient!

Your Salary

Average cost of performing a thought experiment:

Magnet SafetyThe 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


Subject SafetyAnyone 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


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




Slice Thicknesse.g., 6 mm

Number of Slicese.g., 10

SAGITTAL SLICE IN-PLANE SLICE

Field of View (FOV)e.g., 19.2 cm

VOXEL(Volumetric Pixel)

3 mm

3 mm6 mm

The Data Unit

Matrix Sizee.g., 64 x 64

In-plane resolutione.g., 192 mm / 64

= 3 mm



Statistical Mapsuperimposed on

anatomical MRI image

~2s

Functional images

Time

Condition 1

Condition 2 ...

~ 5 min

Time

fMRISignal

(% change)

ROI Time Course

Condition

Data Unit

Region of interest (ROI)



Averaged Over TrialsSingle trials

Average of all trials from 2 runs

Activation is Averaged

Source: Posner & Raichle, Images of Mind

Brain Averaging

Source: Brain Voyager course slidesNote: That’s TalAIRach, not TAILarach!

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

What do the pretty pictures mean?


Careful!

Source: Nancy Kanwisher

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.

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

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Functional Magnetic Resonance Imaging ; What is it and what can it do?