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Experimental Design Experimental Design Christian Ruff Christian Ruff With thanks to: Rik Henson Daniel Glaser

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Page 1: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Experimental DesignExperimental DesignExperimental DesignExperimental Design

Christian RuffChristian Ruff

With thanks to: Rik Henson

Daniel Glaser

Christian RuffChristian Ruff

With thanks to: Rik Henson

Daniel Glaser

Page 2: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

RealignmentRealignment SmoothingSmoothing

NormalisationNormalisation

General linear modelGeneral linear model

Statistical parametric map (SPM)Statistical parametric map (SPM)Image time-seriesImage time-series

Parameter estimatesParameter estimates

Design matrixDesign matrix

TemplateTemplate

KernelKernel

Gaussian Gaussian field theoryfield theory

p <0.05p <0.05

StatisticalStatisticalinferenceinference

Page 3: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

OverviewOverviewOverviewOverview

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

Page 4: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

• Aim: Aim: – Neuronal structures underlying process Neuronal structures underlying process PP? ?

• Procedure: Procedure: – Contrast: [Task with Contrast: [Task with PP] – [control task without ] – [control task without P P ] = ] = PP the critical assumption of „pure insertion“the critical assumption of „pure insertion“

• Aim: Aim: – Neuronal structures underlying process Neuronal structures underlying process PP? ?

• Procedure: Procedure: – Contrast: [Task with Contrast: [Task with PP] – [control task without ] – [control task without P P ] = ] = PP the critical assumption of „pure insertion“the critical assumption of „pure insertion“

Cognitive SubtractionCognitive SubtractionCognitive SubtractionCognitive Subtraction

- - Neuronal structures Neuronal structures computing face recognition? computing face recognition?

- - Neuronal structures Neuronal structures computing face recognition? computing face recognition?

• ExampleExample: : – Neuronal structures underlying Neuronal structures underlying face recognitionface recognition? ?

• ExampleExample: : – Neuronal structures underlying Neuronal structures underlying face recognitionface recognition? ?

Page 5: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Cognitive Subtraction: Baseline-Cognitive Subtraction: Baseline-problemsproblems

Cognitive Subtraction: Baseline-Cognitive Subtraction: Baseline-problemsproblems

-- PP implicit in control task ? implicit in control task ?-- PP implicit in control task ? implicit in control task ?

„ „Queen!“ „Aunt Jenny?“Queen!“ „Aunt Jenny?“ „ „Queen!“ „Aunt Jenny?“Queen!“ „Aunt Jenny?“

• „ „Related“ stimuliRelated“ stimuli• „ „Related“ stimuliRelated“ stimuli

-- Several components differ !Several components differ ! -- Several components differ !Several components differ !

• „ „Distant“ stimuli Distant“ stimuli • „ „Distant“ stimuli Distant“ stimuli

Name Person! Name Gender!Name Person! Name Gender!Name Person! Name Gender!Name Person! Name Gender!

-- Interaction of process and taskInteraction of process and task ?? -- Interaction of process and taskInteraction of process and task ??

• Same stimuli, different taskSame stimuli, different task• Same stimuli, different taskSame stimuli, different task

Page 6: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Differential event-related fMRIDifferential event-related fMRIDifferential event-related fMRIDifferential event-related fMRI

Parahippocampal responses to wordsParahippocampal

responses to words

BOLD EPI fMRI at 2T, BOLD EPI fMRI at 2T, TR 3.2sec. Words TR 3.2sec. Words presented every 16 presented every 16

secs; (i) studied words secs; (i) studied words or (ii) new wordsor (ii) new words

BOLD EPI fMRI at 2T, BOLD EPI fMRI at 2T, TR 3.2sec. Words TR 3.2sec. Words presented every 16 presented every 16

secs; (i) studied words secs; (i) studied words or (ii) new wordsor (ii) new words

SPM{F} testing for SPM{F} testing for evoked responsesevoked responsesSPM{F} testing for SPM{F} testing for evoked responsesevoked responses

Evoked responsesEvoked responsesEvoked responsesEvoked responses

• “ “Baseline” here corresponds to session mean Baseline” here corresponds to session mean (and thus processing during “rest”) (and thus processing during “rest”)

• Null events or long SOAs essential for estimationNull events or long SOAs essential for estimation

• “ “Cognitive” interpretation hardly possible, Cognitive” interpretation hardly possible, but useful to define regions generally involved in the but useful to define regions generally involved in the tasktask

• “ “Baseline” here corresponds to session mean Baseline” here corresponds to session mean (and thus processing during “rest”) (and thus processing during “rest”)

• Null events or long SOAs essential for estimationNull events or long SOAs essential for estimation

• “ “Cognitive” interpretation hardly possible, Cognitive” interpretation hardly possible, but useful to define regions generally involved in the but useful to define regions generally involved in the tasktask

Page 7: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Differential event-related fMRIDifferential event-related fMRIDifferential event-related fMRIDifferential event-related fMRI

Parahippocampal responses to wordsParahippocampal

responses to words

BOLD EPI fMRI at 2T, BOLD EPI fMRI at 2T, TR 3.2sec. Words TR 3.2sec. Words presented every 16 presented every 16

secs; (i) studied words secs; (i) studied words or (ii) new wordsor (ii) new words

BOLD EPI fMRI at 2T, BOLD EPI fMRI at 2T, TR 3.2sec. Words TR 3.2sec. Words presented every 16 presented every 16

secs; (i) studied words secs; (i) studied words or (ii) new wordsor (ii) new words

SPM{F} testing for SPM{F} testing for evoked responsesevoked responsesSPM{F} testing for SPM{F} testing for evoked responsesevoked responses

Differential responsesDifferential responsesDifferential responsesDifferential responses

Peri-stimulus time {secs}Peri-stimulus time {secs}Peri-stimulus time {secs}Peri-stimulus time {secs}

SPM{F} testing SPM{F} testing for differencesfor differences

SPM{F} testing SPM{F} testing for differencesfor differences

studied wordsstudied wordsstudied wordsstudied words

new wordsnew wordsnew wordsnew words

Page 8: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Experimental designExperimental design

Word generationWord generation GGWord repetitionWord repetition RR

R G R G R G R G R G R GR G R G R G R G R G R G

Experimental designExperimental design

Word generationWord generation GGWord repetitionWord repetition RR

R G R G R G R G R G R GR G R G R G R G R G R G

G - R = Intrinsic word generationG - R = Intrinsic word generation

……under assumption of under assumption of pure insertionpure insertion

G - R = Intrinsic word generationG - R = Intrinsic word generation

……under assumption of under assumption of pure insertionpure insertion

A categorical analysisA categorical analysisA categorical analysisA categorical analysis

Page 9: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

OverviewOverviewOverviewOverview

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

Page 10: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

• One way to minimise the baseline/pure insertion problem is to isolate the One way to minimise the baseline/pure insertion problem is to isolate the same process by two or more separate comparisons, and inspect the same process by two or more separate comparisons, and inspect the resulting simple effects for commonalitiesresulting simple effects for commonalities

• A test for such activation common to several independent contrasts is A test for such activation common to several independent contrasts is called “called “Conjunction”Conjunction”

• Conjunctions can be conducted across a whole variety of different Conjunctions can be conducted across a whole variety of different contexts:contexts:

• taskstasks• stimulistimuli• senses (vision, audition)senses (vision, audition)• etc.etc.

• But the contrasts entering a conjunction have to be truly independent!But the contrasts entering a conjunction have to be truly independent!

• One way to minimise the baseline/pure insertion problem is to isolate the One way to minimise the baseline/pure insertion problem is to isolate the same process by two or more separate comparisons, and inspect the same process by two or more separate comparisons, and inspect the resulting simple effects for commonalitiesresulting simple effects for commonalities

• A test for such activation common to several independent contrasts is A test for such activation common to several independent contrasts is called “called “Conjunction”Conjunction”

• Conjunctions can be conducted across a whole variety of different Conjunctions can be conducted across a whole variety of different contexts:contexts:

• taskstasks• stimulistimuli• senses (vision, audition)senses (vision, audition)• etc.etc.

• But the contrasts entering a conjunction have to be truly independent!But the contrasts entering a conjunction have to be truly independent!

ConjunctionsConjunctionsConjunctionsConjunctions

Page 11: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Example: Example:

Which neural structures support object recognition, Which neural structures support object recognition,

independent of task (naming vs viewing)?independent of task (naming vs viewing)?

Example: Example:

Which neural structures support object recognition, Which neural structures support object recognition,

independent of task (naming vs viewing)?independent of task (naming vs viewing)? A1A1A1A1 A2A2A2A2

B2B2B2B2B1B1B1B1

Task (1/2)Task (1/2)Task (1/2)Task (1/2)

NamingNaming ViewingViewingNamingNaming ViewingViewing

Stim

uli (

A/B

)S

timul

i (A

/B)

Stim

uli (

A/B

)S

timul

i (A

/B)

Col

ours

O

bjec

tsC

olou

rs

Obj

ects

C

olou

rs

Obj

ects

Col

ours

O

bjec

ts

Visual Processing Visual Processing V V Object Recognition Object Recognition RRPhonological Retrieval Phonological Retrieval PP

(Object - Colour viewing) & (Object - Colour naming)(Object - Colour viewing) & (Object - Colour naming)

[1 -1 0 0] & [0 0 1 -1][1 -1 0 0] & [0 0 1 -1]

[ R,V - V ] & [ P,R,V - P,V ][ R,V - V ] & [ P,R,V - P,V ]

= = R & R R & R = R= R

(assuming no interaction (assuming no interaction RxPRxP; see later); see later)

Visual Processing Visual Processing V V Object Recognition Object Recognition RRPhonological Retrieval Phonological Retrieval PP

(Object - Colour viewing) & (Object - Colour naming)(Object - Colour viewing) & (Object - Colour naming)

[1 -1 0 0] & [0 0 1 -1][1 -1 0 0] & [0 0 1 -1]

[ R,V - V ] & [ P,R,V - P,V ][ R,V - V ] & [ P,R,V - P,V ]

= = R & R R & R = R= R

(assuming no interaction (assuming no interaction RxPRxP; see later); see later)

ConjunctionsConjunctionsConjunctionsConjunctions

Price et al, 1997Price et al, 1997Common object Common object

recognition response (Rrecognition response (R))Common object Common object

recognition response (Rrecognition response (R))

Page 12: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

ConjunctionsConjunctionsConjunctionsConjunctions

Page 13: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

SPM8 offers two general ways to test the SPM8 offers two general ways to test the significance of conjunctions: significance of conjunctions:

• Test of global null hypothesis: Test of global null hypothesis: Significant set of consistent effectsSignificant set of consistent effects

“ “which voxels show effects of similar which voxels show effects of similar direction (but not necessarily direction (but not necessarily individual significance) across contrasts?” individual significance) across contrasts?”

• Test of conjunction null hypothesis: Test of conjunction null hypothesis: Set of consistently significant effectsSet of consistently significant effects

“ “which voxels show, for each specified which voxels show, for each specified contrast, effects > threshold?” contrast, effects > threshold?”

• Choice of test depends on hypothesis and Choice of test depends on hypothesis and congruence of contrasts; the global null test congruence of contrasts; the global null test is more sensitive (i.e., when direction of is more sensitive (i.e., when direction of effects hypothesised)effects hypothesised)

SPM8 offers two general ways to test the SPM8 offers two general ways to test the significance of conjunctions: significance of conjunctions:

• Test of global null hypothesis: Test of global null hypothesis: Significant set of consistent effectsSignificant set of consistent effects

“ “which voxels show effects of similar which voxels show effects of similar direction (but not necessarily direction (but not necessarily individual significance) across contrasts?” individual significance) across contrasts?”

• Test of conjunction null hypothesis: Test of conjunction null hypothesis: Set of consistently significant effectsSet of consistently significant effects

“ “which voxels show, for each specified which voxels show, for each specified contrast, effects > threshold?” contrast, effects > threshold?”

• Choice of test depends on hypothesis and Choice of test depends on hypothesis and congruence of contrasts; the global null test congruence of contrasts; the global null test is more sensitive (i.e., when direction of is more sensitive (i.e., when direction of effects hypothesised)effects hypothesised)

Two flavours of inference about Two flavours of inference about conjunctionsconjunctions

Two flavours of inference about Two flavours of inference about conjunctionsconjunctions

A1-A2 A1-A2

B

1-B

2

B1-

B2 p(A1=A2)<pp(A1=A2)<p

++p(B1=B2)<pp(B1=B2)<p

++

Friston et al.Friston et al. (2005). Neuroimage, Neuroimage, 25:661-7.25:661-7.

Nichols et al. (2005). Nichols et al. (2005). Neuroimage, Neuroimage, 25:653-60.25:653-60.

Friston et al.Friston et al. (2005). Neuroimage, Neuroimage, 25:661-7.25:661-7.

Nichols et al. (2005). Nichols et al. (2005). Neuroimage, Neuroimage, 25:653-60.25:653-60.

Page 14: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

OverviewOverviewOverviewOverview

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

Page 15: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Parametric Designs: General Parametric Designs: General ApproachApproach

Parametric Designs: General Parametric Designs: General ApproachApproach

• Parametric designs approach the baseline problem by:Parametric designs approach the baseline problem by:

– Varying a stimulus-parameter of interest on a continuum, Varying a stimulus-parameter of interest on a continuum, in multiple (n>2) steps...in multiple (n>2) steps...

– ... and relating blood-flow to this parameter... and relating blood-flow to this parameter

• Flexible choice of tests for such relations :Flexible choice of tests for such relations :• LinearLinear• Nonlinear: Quadratic/cubic/etc.Nonlinear: Quadratic/cubic/etc.• „„Data-driven“ (e.g., neurometric functions)Data-driven“ (e.g., neurometric functions)• Model-basedModel-based

Page 16: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Linear effect Linear effect of time of time

Linear effect Linear effect of time of time

A linear parametric contrastA linear parametric contrastA linear parametric contrastA linear parametric contrast

Page 17: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

The nonlinear effect of time The nonlinear effect of time assessed with the SPM{T}assessed with the SPM{T}

The nonlinear effect of time The nonlinear effect of time assessed with the SPM{T}assessed with the SPM{T}

A nonlinear parametric contrastA nonlinear parametric contrastA nonlinear parametric contrastA nonlinear parametric contrast

Page 18: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Inverted ‘U’ response toInverted ‘U’ response toincreasing word presentationincreasing word presentation

rate in the DLPFCrate in the DLPFC

Inverted ‘U’ response toInverted ‘U’ response toincreasing word presentationincreasing word presentation

rate in the DLPFCrate in the DLPFCSPM{F}SPM{F}SPM{F}SPM{F}

Polynomial expansion:Polynomial expansion:f(x) ~ f(x) ~ b1 x + b2 x2 + ...

…up to (N-1)th order for N levels

Polynomial expansion:Polynomial expansion:f(x) ~ f(x) ~ b1 x + b2 x2 + ...

…up to (N-1)th order for N levels

Lin

ear

Lin

ear

Qu

adr

atic

Qu

adr

atic

E.g, F-contrast [0 1 0] on E.g, F-contrast [0 1 0] on Quadratic Parameter =>Quadratic Parameter =>E.g, F-contrast [0 1 0] on E.g, F-contrast [0 1 0] on Quadratic Parameter =>Quadratic Parameter =>

Nonlinear parametric design matrixNonlinear parametric design matrixNonlinear parametric design matrixNonlinear parametric design matrix

(SPM8 GUI offers polynomial (SPM8 GUI offers polynomial expansion as option during creation expansion as option during creation of parametric modulation regressors)of parametric modulation regressors)

(SPM8 GUI offers polynomial (SPM8 GUI offers polynomial expansion as option during creation expansion as option during creation of parametric modulation regressors)of parametric modulation regressors)

Page 19: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Parametric Designs: Neurometric Parametric Designs: Neurometric functionsfunctions

Parametric Designs: Neurometric Parametric Designs: Neurometric functionsfunctions

Rees, G., et al. (1997). Rees, G., et al. (1997). Neuroimage, 6Neuroimage, 6: 27-78: 27-78Rees, G., et al. (1997). Rees, G., et al. (1997). Neuroimage, 6Neuroimage, 6: 27-78: 27-78

versusversusversusversus

Inverted ‘U’ response toInverted ‘U’ response toincreasing word presentationincreasing word presentation

rate in the DLPFCrate in the DLPFC

Inverted ‘U’ response toInverted ‘U’ response toincreasing word presentationincreasing word presentation

rate in the DLPFCrate in the DLPFCRees, G., et al. (1997). Rees, G., et al. (1997). Neuroimage, 6Neuroimage, 6: 27-78: 27-78Rees, G., et al. (1997). Rees, G., et al. (1997). Neuroimage, 6Neuroimage, 6: 27-78: 27-78

Page 20: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Parametric Designs: Neurometric Parametric Designs: Neurometric functionsfunctions

Parametric Designs: Neurometric Parametric Designs: Neurometric functionsfunctions

Coding of tactile stimuli in Anterior Cingulate Cortex:Stimulus (a) presence, (b) intensity, and (c) pain intensity

– Variation of intensity of a heat stimulus applied to the right hand(300, 400, 500, and 600 mJ)

Büchel et al. (2002). Büchel et al. (2002). The Journal of Neuroscience, 22The Journal of Neuroscience, 22: 970-6: 970-6

– Assumptions::

Page 21: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Parametric Designs: Neurometric Parametric Designs: Neurometric functionsfunctions

Parametric Designs: Neurometric Parametric Designs: Neurometric functionsfunctions

Büchel et al. (2002). Büchel et al. (2002). The Journal of Neuroscience, 22The Journal of Neuroscience, 22: 970-6: 970-6Büchel et al. (2002). Büchel et al. (2002). The Journal of Neuroscience, 22The Journal of Neuroscience, 22: 970-6: 970-6

Stimulus presenceStimulus presence Stimulus presenceStimulus presence

Pain intensityPain intensity Pain intensityPain intensity

Stimulus intensityStimulus intensity Stimulus intensityStimulus intensity

Page 22: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Parametric Designs: Model-based Parametric Designs: Model-based regressorsregressors

Parametric Designs: Model-based Parametric Designs: Model-based regressorsregressors

Seymour, O‘Doherty, et al. (2004). Seymour, O‘Doherty, et al. (2004). Nature.Nature.Seymour, O‘Doherty, et al. (2004). Seymour, O‘Doherty, et al. (2004). Nature.Nature.

Page 23: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

OverviewOverviewOverviewOverview

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

Page 24: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

A1A1A1A1 A2A2A2A2

B2B2B2B2B1B1B1B1

Task (1/2)Task (1/2)Task (1/2)Task (1/2)

NamingNaming Viewing Viewing NamingNaming Viewing Viewing

Stim

uli (

A/B

)S

timul

i (A

/B)

Stim

uli (

A/B

)S

timul

i (A

/B)

Col

ours

C

olou

rs O

bjec

tsO

bjec

ts

Col

ours

C

olou

rs O

bjec

tsO

bjec

ts

Colours Objects Colours ObjectsColours Objects Colours Objects Colours Objects Colours ObjectsColours Objects Colours Objects

interaction effectinteraction effect (Task x Stimuli)(Task x Stimuli)interaction effectinteraction effect (Task x Stimuli)(Task x Stimuli)

ViewingViewingViewingViewing NamingNamingNamingNaming

Factorial designs: Main effects and Factorial designs: Main effects and InteractionsInteractions

Factorial designs: Main effects and Factorial designs: Main effects and InteractionsInteractions

• Main effect of task:Main effect of task: (A1 + B1) – (A2 + (A1 + B1) – (A2 + B2)B2)

• Main effect of stimuli: Main effect of stimuli: (A1 + A2) – (B1 + (A1 + A2) – (B1 + B2)B2)

• Interaction of task and stimuli: Interaction of task and stimuli: Can show a failure of pure insertionCan show a failure of pure insertion

(A1 – B1) – (A2 – (A1 – B1) – (A2 – B2)B2)

• Main effect of task:Main effect of task: (A1 + B1) – (A2 + (A1 + B1) – (A2 + B2)B2)

• Main effect of stimuli: Main effect of stimuli: (A1 + A2) – (B1 + (A1 + A2) – (B1 + B2)B2)

• Interaction of task and stimuli: Interaction of task and stimuli: Can show a failure of pure insertionCan show a failure of pure insertion

(A1 – B1) – (A2 – (A1 – B1) – (A2 – B2)B2)

Page 25: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Interactions and pure insertionInteractions and pure insertionInteractions and pure insertionInteractions and pure insertion

Object-naming-specific activationsObject-naming-specific activationsObject-naming-specific activationsObject-naming-specific activations

Context: Context: no naming namingno naming namingContext: Context: no naming namingno naming namingad

just

ed r

CB

Fad

just

ed r

CB

Fad

just

ed r

CB

Fad

just

ed r

CB

F

ComponentsComponentsVisual processingVisual processing VVObject recognition Object recognition RRPhonological retrievalPhonological retrieval PPInteractionInteraction RxPRxP

InteractionInteraction(name object - colour) - (view object - colour)(name object - colour) - (view object - colour)

[1 -1 0 0] [1 -1 0 0] - - [0 0 1 -1] [0 0 1 -1]

= = [ P,R,V + RxP[ P,R,V + RxP - P,V ] - [ R,V - V ] - P,V ] - [ R,V - V ]

= = RxPRxP

ComponentsComponentsVisual processingVisual processing VVObject recognition Object recognition RRPhonological retrievalPhonological retrieval PPInteractionInteraction RxPRxP

InteractionInteraction(name object - colour) - (view object - colour)(name object - colour) - (view object - colour)

[1 -1 0 0] [1 -1 0 0] - - [0 0 1 -1] [0 0 1 -1]

= = [ P,R,V + RxP[ P,R,V + RxP - P,V ] - [ R,V - V ] - P,V ] - [ R,V - V ]

= = RxPRxP

Page 26: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Interactions and pure insertionInteractions and pure insertionInteractions and pure insertionInteractions and pure insertion

Interactions: Interactions:

cross-over cross-over

and and

simplesimple

We can selectively We can selectively inspect our data for one inspect our data for one or the other by masking or the other by masking during inferenceduring inference

Interactions: Interactions:

cross-over cross-over

and and

simplesimple

We can selectively We can selectively inspect our data for one inspect our data for one or the other by masking or the other by masking during inferenceduring inference

A1 A2A1 A2 B1 B2B1 B2

A1 A2A1 A2 B1 B2B1 B2

Page 27: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

OverviewOverviewOverviewOverview

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

Page 28: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

A (Linear) A (Linear) Time-by-ConditionTime-by-Condition

InteractionInteraction(“Generation strategy”?) (“Generation strategy”?)

A (Linear) A (Linear) Time-by-ConditionTime-by-Condition

InteractionInteraction(“Generation strategy”?) (“Generation strategy”?)

Contrast: Contrast:

[5 3 1 -1 -3 -5][5 3 1 -1 -3 -5] [-1 1][-1 1]

= [-5 5 -3 3 -1 1 1 -1 3 -3 5 -5]= [-5 5 -3 3 -1 1 1 -1 3 -3 5 -5]

Contrast: Contrast:

[5 3 1 -1 -3 -5][5 3 1 -1 -3 -5] [-1 1][-1 1]

= [-5 5 -3 3 -1 1 1 -1 3 -3 5 -5]= [-5 5 -3 3 -1 1 1 -1 3 -3 5 -5]

Linear Parametric InteractionLinear Parametric InteractionLinear Parametric InteractionLinear Parametric Interaction

Page 29: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

Factorial Design with 2 factors:Factorial Design with 2 factors:

1.1. Gen/Rep (Categorical, 2 levels)Gen/Rep (Categorical, 2 levels)2.2. Time (Parametric, 6 levels)Time (Parametric, 6 levels)

Time effects modelled with both linear Time effects modelled with both linear and quadratic components…and quadratic components…

Factorial Design with 2 factors:Factorial Design with 2 factors:

1.1. Gen/Rep (Categorical, 2 levels)Gen/Rep (Categorical, 2 levels)2.2. Time (Parametric, 6 levels)Time (Parametric, 6 levels)

Time effects modelled with both linear Time effects modelled with both linear and quadratic components…and quadratic components…

G-RG-R TimeLin

TimeLin

G x TLin

G x TLin

TimeQuadTimeQuad

G x TQuadG x TQuad

F-contrast tests for nonlinearF-contrast tests for nonlinearGeneration-by-Time interactionGeneration-by-Time interaction

(including both linear and (including both linear and Quadratic components)Quadratic components)

F-contrast tests for nonlinearF-contrast tests for nonlinearGeneration-by-Time interactionGeneration-by-Time interaction

(including both linear and (including both linear and Quadratic components)Quadratic components)

Nonlinear Parametric InteractionNonlinear Parametric InteractionNonlinear Parametric InteractionNonlinear Parametric Interaction

Page 30: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

OverviewOverviewOverviewOverview

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

Page 31: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

ContextContextContextContext

sourcesourcesourcesource

targettargettargettarget

XXXX

Parametric, factorial design, in which one factor is a psychological context …

...and the other is a physiological source (activity extracted from a brain region of interest)

Parametric, factorial design, in which one factor is a psychological context …

...and the other is a physiological source (activity extracted from a brain region of interest)

Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)

Page 32: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

stimulistimulistimulistimuli

Modulation of Modulation of stimulus-specific stimulus-specific

responsesresponses

Modulation of Modulation of stimulus-specific stimulus-specific

responsesresponses

sourcesourcesourcesource

targettargettargettarget

SetSetSetSet

Context-sensitiveContext-sensitiveconnectivityconnectivity

Context-sensitiveContext-sensitiveconnectivityconnectivity

sourcesourcesourcesource

targettargettargettarget

Parametric, factorial design, in which one factor is a psychological context …

...and the other is a physiological source (activity extracted from a brain region of interest)

Parametric, factorial design, in which one factor is a psychological context …

...and the other is a physiological source (activity extracted from a brain region of interest)

Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)

Page 33: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

SPM{Z}SPM{Z}

Attentional modulation ofAttentional modulation ofV1 - V5 contributionV1 - V5 contribution

Attentional modulation ofAttentional modulation ofV1 - V5 contributionV1 - V5 contribution

AttentionAttentionAttentionAttention

V1V1V1V1

V5V5V5V5

attention

no attention

V1 activityV1 activity

V5

activ

ity

timetime

V1

activ

ity

Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)

Page 34: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

SPM{Z}SPM{Z}

attention

no attention

V1 activityV1 activity

V5

activ

ity

timetime

V1

activ

ity

V1V1 AttAtt V1 x AttV1 x Att

0 0 1 0 0 1

Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)

Page 35: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

adju

sted

rC

BF

adju

sted

rC

BF

adju

sted

rC

BF

adju

sted

rC

BF

medial parietal activitymedial parietal activitymedial parietal activitymedial parietal activity

FacesFacesFacesFaces

ObjectsObjectsObjectsObjects

Stimuli:Stimuli:Faces or objectsFaces or objects

Stimuli:Stimuli:Faces or objectsFaces or objects

PPCPPCPPCPPC

ITITITIT

SPM{Z}SPM{Z}SPM{Z}SPM{Z}

Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)

Page 36: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

• PPIs tested by a GLM with form:PPIs tested by a GLM with form:

yy = ( = (V1V1AA).b).b11 + + V1V1.b.b22 + + AA.b.b33 + + ee c = [1 0 0]c = [1 0 0]

• However, the interaction term of interest, However, the interaction term of interest, V1V1AA, is the product of V1 activity and , is the product of V1 activity and Attention block AFTER convolution with HRFAttention block AFTER convolution with HRF

• We are really interested in interaction at neural level, but:We are really interested in interaction at neural level, but:

(HRF (HRF V1) V1) (HRF (HRF A) A) HRF HRF (V1 (V1 A A) )

(unless A low frequency, e.g., blocked; mainly problem for event-related PPIs)(unless A low frequency, e.g., blocked; mainly problem for event-related PPIs)

• SPM5 can effect a SPM5 can effect a deconvolutiondeconvolution of physiological regressors (V1), before of physiological regressors (V1), before calculating interaction term and reconvolving with the HRF – the “PPI button”calculating interaction term and reconvolving with the HRF – the “PPI button”

• PPIs tested by a GLM with form:PPIs tested by a GLM with form:

yy = ( = (V1V1AA).b).b11 + + V1V1.b.b22 + + AA.b.b33 + + ee c = [1 0 0]c = [1 0 0]

• However, the interaction term of interest, However, the interaction term of interest, V1V1AA, is the product of V1 activity and , is the product of V1 activity and Attention block AFTER convolution with HRFAttention block AFTER convolution with HRF

• We are really interested in interaction at neural level, but:We are really interested in interaction at neural level, but:

(HRF (HRF V1) V1) (HRF (HRF A) A) HRF HRF (V1 (V1 A A) )

(unless A low frequency, e.g., blocked; mainly problem for event-related PPIs)(unless A low frequency, e.g., blocked; mainly problem for event-related PPIs)

• SPM5 can effect a SPM5 can effect a deconvolutiondeconvolution of physiological regressors (V1), before of physiological regressors (V1), before calculating interaction term and reconvolving with the HRF – the “PPI button”calculating interaction term and reconvolving with the HRF – the “PPI button”

Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)Psycho-physiological Interaction (PPI)

Page 37: Experimental Design Christian Ruff With thanks to: Rik Henson Daniel Glaser Christian Ruff With thanks to: Rik Henson Daniel Glaser

OverviewOverviewOverviewOverview

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions

• Categorical designsCategorical designsSubtraction Subtraction - Pure insertion, evoked / differential - Pure insertion, evoked / differential

responsesresponses

Conjunction Conjunction - Testing multiple hypotheses- Testing multiple hypotheses

• Parametric designsParametric designsLinear Linear - Adaptation, cognitive dimensions- Adaptation, cognitive dimensions

NonlinearNonlinear - Polynomial expansions, neurometric - Polynomial expansions, neurometric functionsfunctions

• Factorial designsFactorial designsCategoricalCategorical - Interactions and pure insertion- Interactions and pure insertion

ParametricParametric - Linear and nonlinear interactions- Linear and nonlinear interactions

- Psychophysiological Interactions- Psychophysiological Interactions