EXPERIMENTAL TASK DESIGN: Good Rules… ! and When to Break … · 2001. 10. 17. · Experimental Design: Parameters and Paradigms Key Ideas • E.D. is not as systematic as other

! EXPERIMENTAL TASK DESIGN: Good Rules…! and When to Break Them

Robert L. Savoy, Ph.D.The Athinoula A. Martinos Center for Biomedical Imaging

HyperVision, Inc.http://www.HyperVision.US

e-mail: [email protected]

Functional MRI WorkshopsExperimental Design

Thanks and Acknowledgements

Randy L. Buckner Washington University, St. Louis, MO

Peter A. Bandettini National Institute of Mental Health, Bethesda, MD

Kathleen OʼCraven Rotman Institute, Toronto, Ontario

Jennifer Melcher Massachusetts Eye and Ear Infirmary, Boston, MA

Michael Beauchamp National Institute of Mental Health, Bethesda, MD

Randy Gollub Massachusetts General Hospital, Charlestown, MA

Tom Zeffiro Georgetown University, Georgetown, VA

Nouchine Hadjikhani Massachusetts General Hospital, Charlestown, MA

Larry Wald Massachusetts General Hospital, Charlestown, MA

… and numerous others

Experimental Design: General Issues

Key IdeasExperimental Design is not as systematic as other aspects of Functional MRIPhysics, Technology, and Physiology interact with Experimental DesignImaging Parameters and Experimental Paradigms are not the same thing, though they also interact

Messages from the SpeakerIt is very difficult, in 2011, to be a “dilettante” or “dabbler” and do good fMRI experimentsThe greatest challenge we face is integration of neuroimaging data in a manner based on theory

Examples

Experimental Design: Parameters and Paradigms

Key Ideas• E.D. is not as systematic as other parts of fMRI• Physics, Technology, Physiology interact with E.D.Imaging Parameters and Experimental Paradigms are not the same thing, though they also interact

• Messages from the Speaker• It is no longer possible to be a “dilettante” and do good fMRI experiments• The greatest challenge we face is integration of neuroimaging data in a manner based on theory

Examples

Overview: Experiment as the Subject Experiences It

Blocked versus Mixed-Trial Paradigm

BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:

SLOW EVENT RELATED:

RAPID EVENT RELATED:

Overview: Experiment as the Scanner Acquires Data

TR (single slice)

TR (brain volume; evenly spaced; continuous)

TR (brain volume; clustered; continuous)

TR (brain volume; clustered; widely spaced)

Place Kensington, Montreal Robert Savoy

July 01, 2011Psychology and Behavior Meet the Living Brain

What can you image with NMR?

Structure (MRI)Gross Chemistry (MRS)Grey Matter Activity (fMRI)White Matter Connectivity (DTI/DSI)

Structure (MRI), fMRI, & DTI: Work of Marlene Behrmann in Congenital Prospagnosia



Congenital Prosopagnosia

What is Prosopagnosia?

What is Congenital Prosopagnosia?



Congenital ProsopagnosiaILF

Congenital Prospagnosics

Matched Control Individuals



Congenital ProsopagnosiaIFOF

Congenital Prospagnosics

Matched Control Individuals



Examples

From Social PsychologyBystander Effect

From Cognitive PsychologyMoral Dilemmas

From me (for fun)From YOU



Examples from Social Psychology

John Darley Bibb Latené

“Bystander Effect” (Kitty Genovese, 1964)

How do we study it?



“Bystander Effect”

How do we study it?How would you approach it?Latené and Darley

Dropped pencilSmokeEpileptic attack

Smoke data: after 4 minutes, 75% vs 12%

Consequences of Latené and Darley studies

Just being aware of such studies helps...



Example from Cognitive Psychology

The Neuroscience of Moral Decision-Making

Joshua Greene, Harvard Psychology Dept.

June, 2007

The Dilemma: Blame“Don’t blame him. Blame his brain!”

“Don’t blame his brain. Blame him!”

If he’s rational, blame him.If he’s not rational, blame his brain.

Assumption of the Neuroscientist: Whatever responsibility is, it’s NOT a matter of blaming you instead of your brain.

“Blame him? Blame his brain?It’s all the same!”

Moral Judgment in relation to Physical Brain Processes

John Stuart MillUtilitarianism:

The greatest good for the greatest number

Immanuel KantCategorical Imperative:

Act according to maxims that could serve as a universal law

The Trolley Problem

The Trolley Problem

John Stuart Mill

Utilitarianism:The greatest good for the

greatest number

The Footbridge Problem

The Footbridge Problem

Immanuel KantCategorical Imperative:

Act according to maxims that could

serve as a universal law

stimulus

controlled, conscious “cognitive” response

unconscious appraisal

emotional response

conflict monitor

cognitive control

judgment

A “Dual Process” Model

Posner and Snyder (1975)

Shiffrin and Schneider (1977)

Metcalfe and Mischel (1999)

Chaiken and Trope (1999)

Lieberman et al. (2002)

Kahneman (2003)

Medial Frontal Cortex

DorsolateralPrefrontal

Cortex(PFC)

Superior Temporal Sulcus

PosteriorCingulate/Precuneus

Personal MoralDilemmas

Impersonal MoralDilemmas

Non-moralDilemmasB

rain

Act

ivity

% c

hang

e M

R s

igna

lPersonal vs. Impersonal Moral Judgment

Inferior Parietal Lobe(Bilateral; Not shown)

Emotion/Social Cognition Areas

“Cognitive” Areas

Greene et al., Science, 2001

(Bilateral)

More recently…

Mendez et al., Cogn Behav Neurol

Valdesolo and DeSteno, Psych Sci (2006)

Koenigs et al. (2007)

Greene et al., Science 2001

Frontotemporal Dementia and Moral Judgment

Mendez et al., 2005 FTD patients known for “emotional blunting,” damage to medial frontal and temporal lobes

Okay to do? (Yes/No) FTD AD Normal ControlsTrolley 21/5 23/3 26/0Footbridge 15/11 6/20 5/21

Adventures in Trolleyology

87% “yes”

Standard Switch Standard Footbridge

Public sample, between-subject design, N = 1,855

31% “yes”

Cf. Petrinovich et al. (1993, 1996, 1998)

“Up Close and Personal”

31% “yes”

mean rating: 3.92

63% “yes”

mean rating: 5.27

Footbridge Remote Footbridge

Distance or Contact?Cf. Cushman et al., Psych Science 2006

31% “yes” 63% “yes”

Footbridge Remote FootbridgeFootbridge Switch

59% “yes”

*p < .0001 ns

Contact or “Personal Force?”

31% “yes”

Footbridge Footbridge Switch

59% “yes”

*p = .006ns

Footbridge Pole

33% “yes”

Why is this story here?(Why did Savoy include it?)

• What is the “model” being tested?

• What did Prof. Greene the philosopher have to do to become Prof. Greene the Psychologist and Neuroscientist?

• A psychologists prejudice: Behavioral studies drive good functional brain imaging science.

“Is it morally acceptable for the person to throw the switch?”



Example from Social Cognitive Neuroscience

Social Pain



Example from Social Cognitive Neuroscience

Social Pain

[Switch, now, to PowerPoint]

Examples• Change task or stimuli; not both

• N-back tasks for “Faces” versus “Location”• OʼCraven Example• Beauchamp Example• Post-Hoc Image Grouping

• General Rules versus Special Cases• Runs should be short … but: Cocaine study: Breiter, Gollub, et al. … but: Steady-State study: Bandettini … but: Migraine Aura: Hadjikhaniet al.• Subjects should not move … but: Beauchamp Study• Donʼt introduce variable TR! … but: Melcher and Guimaraes example

• Baseline activity: Gusnard and Raichle• Zeffiro versus Cheng

• Whole Brain Coverage vs a few slices• Standard Imaging parameter vs special











Method 1:! Keep Stimuli Identical;! Vary the Task

For example:n-back task: Is it the same face?n-back task: Is it in the same place?

Time

stimulus 1

stimulus 2

stimulus 3

stimulus 4

stimulus 6

stimulus 5

Method 1: Stimuli Identical; Vary Task As before, but with words...

For example with words, Y/N tasks:Is it the noun ABSTRACT (like “LOVE” or “ thought”) or CONCRETE (like “table” or “CHAIR”)?Is the noun presented in “UPPER CASE” or “lower case”?

LOVEtable

thoughtCHAIR






The Critical Visual Stimulus

The stimulus consists of both moving dots and stationary dots.

+

Experiment One: Pure Attention (Constant Stimulus; Varying Task)

Instructions: "Fixate and attend to the dots in the color named."

Absolutely identical visual stimuluscontinues throughout entire scan!

+VISUAL

STIMULUS:

O’CravenRowland Institute for Science & MGH-NMR Center

"White""Black"

"White""Black"

"White""Black"

"White""Black" "Black"

"White""Black"

AUDITORYSTIMULUS:

The “Castle” Paradigm(several advantages)

(constant task (sort of); varying stimuli)Instructions: "Fixate and attend to the black dots."

+++ +

++++

+

20 sec20 sec

20 sec 20 sec 20 sec20 sec

20 sec 20 sec 20 sec


A

B

C

A B A C A B A C A

fMRI Activation in Area MT/MST(Average of 5 Subjects, 6 runs each)

Stimulus

AttendStationary

AttendStationary

StationaryDots

Stationary& Moving

Dots

Task

0 40 80 120 160 200

% S

igna

l Cha

nge

Stationary& Moving

Dots

AttendMoving

Time (seconds)

-0.5

0

0.5

1

1.5

2






Areas Important for Color Processing

• Beauchamp MS, Haxby JV, Jennings J, DeYoe EA (1999) Multiple Color-Selective Areas in Human Ventral Occipital Cortex. Cerebral Cortex 9(3) 257-263.

Farnsworth-Munsell 100-Hue Experiment

An FMRI adaptation of the test

Response: CORRECT

An FMRI adaptation of the test

Response: INCORRECT

An FMRI adaptation of the F-M test: Control

Response: CORRECT

An FMRI adaptation of the F-M test: Control

Response: INCORRECT

fMRI 100-Hue Test: Three conditions

fMRI test: Stimulus Alternation

MR Parameters

Whole brain (21-25 4 or 5 mm slices, 64x64 in-plane resolution) EPI

TR = 3000 ms, TE = 40 ms

C A C A C AF F F F FF F






Memory and fMRI

Building Memories: Remembering and Forgetting of Verbal Experiences as Predicted by Brain Activity

Science (1998) Vol 281, 1188-1191.Wagner, A.D., Schacter, D.L., Rotte, M., Koustaal, W.,

Maril, A., Dale, A.M., Rosen, B. R., Buckner, R.L.!

Making Memories: Brain Activity That Predicts How Well Visual Experience Will Be Remembered

Science (1998) Vol 281, 1185-1187.Brewer, J.B., Zhao, Z., Desmond, J.E., Glover, G.H.,

Gabrieli, J.D.E. !

Memory; Data from Wagner et al.

Robert Savoy

Memory and ƒMRI: Wagner, et al.

Types of fMRI Design

Block

100-Hue Test Head Movements Human and Object Motion

SlowEvent-Related

RapidEvent-Related

Slow Event-Related: Practical Example

• Eye Movements Only• Gaze “Movements” Only• Head Movements Only

Hemodynamic Response to Single Stimulus

| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |

15 seconds

Hemodynamic Response to Single Stimulus

| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |X X | | | | | | | | | | | | | | | | | | | | | | |






Baseline activity: Gusnard and RaichleReference: ! “Searching for a baseline: Functional Imaging and the Resting

Human Brain”! Debra A. Gusnard and Marcus Raichle! Nature Reviews Neuroscience, 2 (October 2001) 685-694.Abstract:! “Functional brain imaging in humans has revealed task-specific

increases in activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive [sic!] state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.






Thomas A. Zeffiro, M.D., Ph.D.

Former Director of a Neuroimaging Laboratory at Georgetown University, Virgina, USA

Has studied hundreds of children, with colleaguesUses a single, standard set of imaging parameters for

essentially ALL studies (on a given scanner):• isotropic voxels• whole-head coverage• fixed acquisition orientation (coronal, I believe)• fixed TR• clustered volume acquisition

Kang Cheng and Ocular Dominance Columns

Human Ocular Dominance Columns as Revealed by High-Field Functional Magnetic Resonance imaging

Neuron, Vol 32, 350-374, October 25, 2001.


Figure 1. Orientation of human ODC stripes and optimal ways for prescribing slices

(A) An MR image shows the medial view of the right hemisphere. The medial occipital lobe around V1 (green rectangles) is schematicallly shown in (B) [on the next slide].


Figure 1. (B) A Cartoon diagram depicts the relationship betwen the orientation of human ODC stripes and the geometry of the calcarine V1 based on the observation by Horton et al. (1990). The opercular V1, which curves out toward the occipital pole, is not shown. OCD

stripes run perpendicular to the the V1/V2 border (arrows) and the lipss of the calcarine sulcus (CS).


Kang Cheng: Imaging Parameters

• Bitebar or Head Vice• Pressure sensors to measure movement directly• Physiological monitoring of heartbeat and respiration ! (for later correction during data analysis)

• Multi-excitation (several segments per slice)• Surface coil for rf excitation and readout• Matrix: 512 x 512; in-plane resolution of .47x.47 mm• TE = 15msec• TR = 300 msec (between segments of slice acquisition)• Flip Angle = 40°• Slice Thickness = 3mm (no gap).

Kang Cheng: ResultsReproducibility across sessions

Outlines of the Ocular Dominance Columns from data in (A)

Above outlines from data in (A) [see “(B)”]

overlaid on data from the separate second run (C)

Imaging Data for Ocular Dominance Columns; data from first session

Imaging Data for Ocular Dominance Columns; data from second session.

Figure 8.8 from Functional Magnetic Resonance Imaging by Huettel, et al.

Ocular Dominance Columns: Enlarged ViewTest

and OutlineRetest

with Same Outlines

Other Issues• How many subjects are needed for your study?

• “Fixed Effects” model• “Random Effects” model• Paper by Friston, Holmes and Worsley (1999):

How Many Subjects Constitute a Study?NeuroImage, 10, 1-5

• Contrast Mechanisms to push spatial ! ! ! and/or temporal resolution

• Bandettini chapters and articles

Themes (in the systematic presentation of basic

issues in experimental design)• Task Comparison• Importance of a Neuro-anatomical Hypothesis • The Behavioral Response• Look at Your Data• Averaging is (generally) Good • Hemodynamics & Alternative Task Designs

Themes

• Task Comparisons• The reference task is an important player• “Tight” versus “Loose” task comparisons• More than one task is essential; more than

two for interpretation

The task comparison

STIPRE

DOG

+ + + +

GRE

STIPRE

PAINT STR

STIPRE

EGGTASK 1

TASK 2

The tight task comparisonTry to hold all variables constant including:

! (1) Stimulus display (nominally or statistically)

! (2) Order of presentation (e.g.., counterbalance!)

! (3) Response and response selection characteristics

! (4) Performance level

! (5) Eye movements






! (5) Eye movements






! (5) Eye movements

Columbia Color Vision Test

Protonopic Match

Deuteronopic Match

Tritonopic Match

Target in Center

Trichromatic Match(i.e, = Target)

Columbia Color Vision Test

The loose task comparisonDoes not hold all variables constant BUT:

! (1) Uses a low level reference task

! (2) Allows the more extensive activation pattern to! ! be observed

! (3) Allows the data to be examined for expected! ! stimulus or response driven activations

! (4) Particularly important at early stages of study

B minus ATASK A TASK B

BRAIN AREAS THAT DIFFER

ALL ACTIVE BRAIN AREAS

Semantic vs Perceptual Word Categorization

PERCEPTUALSEMANTIC

LEFT

SEMANTICminus

PERCEPTUAL

A Set of Tasks

FIXATION

BOOK

READING ALOUD

“book”

PASSIVE READING

GENERATION ALOUD

BOOK

BOOK

DOG

DOG

DOG

“dog”

“read”

“walk”

What if...

FIXATION

BOOK

DOG

READING ALOUD

“dog”

“book”

BOOK

DOG

PASSIVE READING

BOOK

DOG

GENERATION ALOUD

“walk”

“read”

BOOK

DOG

READING ALOUD

“dog”

“book”

BOOK

DOG

GENERATION ALOUD

“walk”

“read”

BOOK

DOG

READING ALOUD

“dog”

“book”

BOOK

DOG

GENERATION ALOUD

“walk”

“read”

G R

G R

OR OR

G R

G R

FIXATION

BOOK

DOG

GENERATION ALOUD

“walk”

“read”

G R

G R G R

G R

OR OR

FIXATION

BOOK

DOG

READING ALOUD

“dog”

“book”

G R

G R G R

G R

OR OR

Themes

• Task Comparisons• The reference task is an important player

• And see recent work from Marcus Raichle and colleagues on defining a “physiological baseline”

• “Tight” versus “Loose” task comparisons• More than one task is essential; more than

two for interpretation• Importance of a neuroanatomical hypothesis

Themes

• Importance of a neuroanatomical hypothesis:• Do you know where you are looking?

Do you need to image the whole brain?• Can you detect it?

• Some benefits of small voxels (at high field)• Can you constrain the search? (And thus

minimize or eliminate Bonferroni or other corrections for multiple comparisons.)

Themes• Task Comparison• Importance of a Neuro-anatomical Hypothesis • The Behavioral Response

Themes

• The Behavioral Response• Three Quotes• Some Data

Differing Views...“Ideally, a concurrent, observable and measurable behavioral response, such as a yes or no bar-press response, measuring accuracy or reaction time, should verify task performance”

! ! -- Mark Cohen & Susan Bookheimer, TINS 1994

Differing Views...“I wonder whether PET research so far has taken the methods of experimental psychology too seriously. In standard psychology we need to have the subject do some task with an externalizable yes-or-no answer so that we have some reaction times and error rates to analyze -- those are our only data. But with neuroimaging youʼre looking at the brain directly so you literally donʼt need the button-press or the overt blurting. I wonder whether we can be more clever in figuring out how to get subjects to think certain kinds of thoughts silently, without forcing them to do some arbitrary classification task as well. I suspect that when you have people do some artificial task and look at their brains, the strongest activity youʼll see is in the parts of the brain that are responsible for doing the artificial tasks.”

! ! -- Steve Pinker, J. Cog. Neuro. Interview 1994

Differing Views...“I make my subjects do something when theyʼre in the scanner so they donʼt fall asleep.”

! ! -- Anonymous fMRI researcher

More Universal ViewsIt is a lot harder to get an experiment published if there is no behavioral measure associated with it.

Even contexts where it is difficult, at first blush, to obtain objective behavioral measures (e.g., imagery, hallucinations) can be often be addressed. (Example: mental rotation a la Shepard and Meltzer)


MGH Visiting Fellowship Program - June, 1996

The “Castle” ParadigmInstructions: "Fixate and attend to the black dots."

+++ +

++++

+

20 sec 20 sec 20 sec 20 sec 20 sec 20 sec 20 sec 20 sec 20 sec


The early MT/Attention paper was an exception, for a number of

reasons. It has since been replicated with behavioral

measures by people from several other laboratories.

And there remained a related question about eye-movements!

HousesFacesChairs

MedialFusiformGyrus

LateralFusiformGyrus

InferiorTemporalGyrus

Perc

ent I

ncre

ase

in M

R S

igna

l

Passive Viewing versus

Delayed Match to SampleActiveTasks

IncreaseActivations

Ishai, et al. (1999)Proc. Nat. Acad. Sci.USA 96, 9379-9384.

Passive Viewing versus

Delayed Match to Sample

ActiveTasks

IncreaseActivations

Ishai, et al. (1999)Proc. Nat. Acad. Sci.USA 96, 9379-9384.

BUT....Even my favorite rule can be wrong in special cases...Emotional responses normally seen in the amygdala

have been reported to be lost with a behavioral task...(e.g. Lieberman, et al., Putting Feelings Into Words Affect Labeling Disrupts Amygdala Activity in Response to Affective Stimuli. (2007) Psychological Science, 18(5): 421-428)

Themes• Task Comparison• Importance of a Neuro-anatomical Hypothesis • The Behavioral Response• Look at Your Data

Themes• Task Comparison• Importance of a Neuro-anatomical Hypothesis • The Behavioral Response• Look at Your Data• Averaging is (generally) Good

Within-subject Averaging: Activation Maps

1 RUN 3 RUNS 7 RUNS

(threshold = p<.001)

Averaging: Time Course Data

1 RUN 3 RUNS 7 RUNS

390

395

400

405

410

385

390

395

400

405

385

390

395

400

438

440

442

444

446

4488 SUBJECTS

Themes• Task Comparison• Importance of a Neuro-anatomical Hypothesis • The Behavioral Response• Look at Your Data• Averaging is (generally) Good• Hemodynamics & Alternative Task Designs

Themes• Hemodynamics & Alternative Task Designs

The MGH/MIT/HMS Athinoula A. Martinos Center Robert SavoyHyperVision, Inc.

Basic Time Course of theHemodynamic Response

Hemodynamic Delay and Dispersion

Neuronal Response

Time

Stimulus

1 sec

6-8 sec

Hemodynamic Response


Neuronal ResponseTime

Stimulus

14-18 sec


10 sec

Buckner: Blocked/Spaced/Rapid


BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:

SLOW EVENT RELATED:


MIXED BLOCKED/EVENT-RELATED:

Further Design Options

SELF-PACED:

SUB-SECOND TEMPORAL ESTIMATION:



BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:

Youʼve seen plenty of these.

But you should keep in mind that it is still a very good design. It is also the one that is most

commonly used in clinical applications.Also, for detecting a weak effect, it is the optimal

design.



BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:

However, it is limited in a number of ways thatare best addressed through randomization of

stimulus presentations.

For example ...

Blocked designs may trigger expectations and cognitive sets

…

Pleasant (P)Unpleasant (U)

Intermixed designs can minimise this by stimulus randomisation

… … ………

(slide from Christian Ruff, Zurich 2008 SPM5 Course)

Unpleasant (U)

Unpleasant (U)

Unpleasant (U)

Pleasant (P) Pleasant (P)



BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:Youʼve may have seen this before, but the next few

slides will refresh your memory.It turns out that this is rarely the best design, if one is

grouping like trials. It is probably essential for individual trial detection. But boredom is a non-trivial drawback.

SLOW EVENT RELATED:

Basic Time Course of the Hemodynamic Response


Neuronal Response

Time

Stimulus

1 sec

6-8 sec


b

a

“Blocked” Paradigm for Word-Stem Completion

STIPRE

COU

+ + + +

0 30 60 90 120 150 180 210

GRE

STIPRE

PRE STR

STIPRE

ABS

TIME (SEC)

“Single-Trial” fMRI Paradigm for Word-Stem Completion

COU

TIME (SEC)

0 32 64 96 128 160 192 228 256

PRE TRA AFT PEL STA FRADRI EST TOU BLA BES NAR FEL POI JUN

“Single-Trial” Response Across a Run

375

376

377

378

379

380

381

TIME (SEC)

0 32 64 96 128 160 192 228 256

MeanNMR

Signal

Average Time-Course of Response for a“Single-Trial”

.

0

.5

0 1 2 3 4 5 6 7 8 9 101112131415

PercentSignal

Change

Time (sec)

375

376

377

378

379

380

381

MeanNMR

Signal


SLOW EVENT RELATED:



BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:

SLOW EVENT RELATED:


Boynton et al., J. Neuroscience, 1996

Visual Activation Paradigm

20 sec0 sec

1 secon

Dale and Buckner, Hum. Brain Map., 1997

Response to Averaged Single Trials: Subject JM

-1

0

1

2

3

4

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19TIME (SEC)

PER

CEN

T M

R S

IGN

AL

Visual Activation Paradigm: 1 versus 2 Trials

20 sec0 sec

20 sec0 sec 5 sec

Response to Averaged Double Trials: Subject JM

-1

0

1

2

3

4

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19TIME (SEC)

PER

CEN

T M

R S

IGN

AL

Response to Averaged Double Trials: Subject JM

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19TIME (SEC)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19TIME (SEC)

Separation of Responses: Subject JM

-1

0

1

2

3

4

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19TIME (SEC)

R AESTIMATED

SECOND T I L

FIRST TRIAL

Visual Activation Paradigm: 1 , 2, & 3 Trials

20 sec0 sec

0 sec 2 sec 20 sec

0 sec 2 sec 20 sec4 sec

-1

0

1

2

3

4

5

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

ONE-TRIAL

TWO-TRIAL

THREE-TRIAL

-1

0

1

2

3

4

5

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

RAW DATA ESTIMATED RESPONSES

Response to Multiple Trials: Subject RW

TIME (SEC) TIME (SEC)

Fixed Interval Between Trials

INDIVIDUALBOLD

RESPONSE

h7 + h4 + h1h6 + h3h5 + h2h4 + h1 + h7h3 + h6h2 + h5h1 + h4 + h7

MEASUREDBOLD

RESPONSE

Seven unknownsOnly three independent equations

TIME

Variable (“Jittered”) Interval between like trial types

h7 + h5 + h3h6 + h4 + h2h5 + h3 + h1h4 + h2h3 + h1 + h7h2 + h6h1 + h5h7 + h4h6 + h3

Seven unknownsMore than seven independent equations

INDIVIDUALBOLD

RESPONSE

MEASUREDBOLD

RESPONSE

TIME

Fixed Interval

INDIVIDUALBOLD

RESPONSE

h7 + h4 + h1h6 + h3h5 + h2h4 + h1 + h7h3 + h6h2 + h5h1 + h4 + h7

MEASUREDBOLD

RESPONSE

Seven unknownsOnly three independent equations

TIME

Recall Algebra

y = 3x + 4! y = 3x + 4! y = 3x + 4! y = 3x + 4 y = 5x + 2! y = 5x + 2! y = 3x + 2! y = 3x + 4 y = 4x + 7! !! ! y = 6x + 8

Least Squares! Unique Solution! (no solution) Many solutions

Variable Intervals

h7 + h5 + h3h6 + h4 + h2h5 + h3 + h1h4 + h2h3 + h1 + h7h2 + h6h1 + h5h7 + h4h6 + h3

Seven unknownsMore than seven independent equations

INDIVIDUALBOLD

RESPONSE

MEASUREDBOLD

RESPONSE

TIME

Themes• Hemodynamics & Alternative Task Designs

• Benefits of Rapid Stimulus Presentation• Randomized stimulus presentation (more analogous to EEG/MEG)• More trials per unit time• Less time spent imaging “rest”• Keeps subject much more engaged (Comment about chidren, here)

• Price of Rapid Stimulus Presentation• More complex experimental design: Must randomize in a special way• More complex data analysis• Less sensitivity

• Distinguish from “Individual Trial” designs



BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:

For INDIVIDUAL Trials, must use spaced trials

SLOW EVENT RELATED:


fractionalsignal change

(%)

finger pressure

Kim et al. CMRRUniv. of Minn., 4T

fMRI Signal vs. Finger Movements(a single subject, a single trial)

Presentation Contemplation Decision

Instruction

Behavior

time

Mental Rotation Task

displayed until decision is made

Richter & Kim et al. CMRRUniv. of Minn., 4T

Functional Maps of Single-Trial Mental Rotation

(Single-trial, Single-subject)

Superior Parietal Area

Supplementary Motor Area

Lateral Premotor Area

Central Sulcus

0 200 400 6000.98

1.00

1.02

1.04

1.06

1.08

Time (seconds)

Time Course in SMA during 16 Single Mental Rotation Trials

Rel

ativ

e B

OLD

sig

nal i

nten

sity

(Single Subject) Richter & Kim et al. CMRRUniv. of Minn., 4T

-10 -5 0 5 10 15

1%Re

lativ

e fM

RI in

tens

ity

Time from button press (sec)

Response Time-locked Time Courses in M1 and SMA

SMA

M1


201510500.98

0.99

1.00

1.01

1.02

1.03

time (s)

inte

nsity

(arb

. uni

ts)

Execution

Comparison of two tasks with different reaction times in the superior parietal area

(single trial data without averaging)


Event-Related fMRI Design Options

BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:

SLOW EVENT RELATED:


MIXED BLOCKED/EVENT-RELATED:

Further Design Options

SELF-PACED:

SUB-SECOND TEMPORAL ESTIMATION:

Experimental Design:Closing Reminder...

E.D. is not as systematic as other parts of fMRI.

One consequence of the above is that there are many ways to present and organize this topic.

Because my emphasis is on creativity in experimental design, I have chosen the style of presentation you have seen—with an emphasis on general ideas and examples.

A good alternative (which would require a very different lecture and emphasis) is captured in a slide set from Christian Ruff (with slides from Rik Henson and Daniel Glaser). The organizing principles are shown in the next slide.

• Categorical designs Subtraction - Pure insertion, evoked / differential responses Conjunction - Testing multiple hypotheses

• Parametric designs Linear - Adaptation, cognitive dimensions Nonlinear - Polynomial expansions, neurometric functions

• Factorial designs Categorical - Interactions and pure insertion Parametric - Linear and nonlinear interactions - Psychophysiological Interactions

Overview of Experimental Designa la Christian Ruff, et al. (Zurich SPM course)

• Categorical Designs (Subtraction; Conjunction)• Parametric designs (Linear; Non-linear)• Factorial Designs (Categorical; Parametric)


• Connection of each to the “design matrix”

• Categorical Designs (Subtraction; Conjunction)• Parametric designs (Linear; Non-linear)• Factorial Designs (Categorical; Parametric)


• Connection of each to the “design matrix”

Key theme: Connect experimental design more tightly, from the beginning, to the mechanisms of data analysis that you will eventually use.

This theme is, eventually, critical. But there are weaknesses with starting with this approach.

Experimental Design:Closing reminder...

• E.D. is not as systematic as other parts of fMRI.• Physics, Technology, Physiology interact with E.D.• Imaging Parameters and Experimental Paradigms are

not the same thing, though they also interact.• There are a variety of ways to take advantage of timing

and design techniques.• It is okay to break rules if you can justify it.

Other:• It is no longer possible to be a “dilettante” and do good

fMRI experiments.• The greatest challenge we face is integration of

neuroimaging data in a manner based on theory.

! EXPERIMENTAL DESIGN: Good Rules…! and When to Break Them

Robert L. Savoy, Ph.D.The Athinoula A. Martinos Center for Biomedical Imaging

HyperVision, Inc.http://www.HyperVision.US

e-mail: [email protected]

Functional MRI WorkshopsExperimental Design

Documents

EXPERIMENTAL TASK DESIGN: Good Rules… ! and When to Break … · 2001. 10. 17. · Experimental Design: Parameters and Paradigms Key Ideas • E.D. is not as systematic as other