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### The General Linear Model (for dummies…)

Carmen Tur and Ashwani Jha 2009

Statistical parametric map (SPM)

Design matrix

Image time-series

Kernel

Realignment

Smoothing

General linear model

Gaussian

field theory

Statistical

inference

Normalisation

p <0.05

Template

Parameter estimates

What is the GLM?

- It is a model (ie equation)
- It provides a framework that allows us to make refined statistical inferences taking into account:
- the (preprocessed) 3D MRI images
- time information (BOLD time series)
- user defined experimental conditions
- neurobiologically based priors (HRF)
- technical / noise corrections

Collect Data

å

2

e

= minimum

t

=

t

1

Generate model

Fit model

How does work?- By creating a linear model:

Data

Y

e

X

Y=0.99x + 12 + e

GLM matrix format

- But GLM works with lists of numbers (matrices)

Y = 0.99x + 12 + e

Y = β1X1 + C + e

5.9 1 2

15.0 2 0

18.4 3 5

12.3 4 4

24.7 5 8

23.2 6 8

19.3 7 0

13.6 8 9

26.1 9 1

21.6 10 5

31.7 11 2

GLM matrix format

- But GLM works with lists of numbers (matrices)

Y = 0.99x + 12 + e

Y = β1X1 + β2X2 + C + e

5.9 1 2

15.0 2 2

18.4 3 5

12.3 4 5

24.7 5 5

23.2 6 2

19.3 7 2

13.6 8 5

26.1 9 5

21.6 10 5

31.7 11 2

sphericity assumption

We need to put this in… (data Y, and design matrix Xs)

‘non-linear’

One session

Passive word listening

versus rest

7 cycles of

rest and listening

Blocks of 6 scans

with 7 sec TR

Stimulus function

Question: Is there a change in the BOLD response between listening and rest?

…easy!

- How to solve the model (parameter estimation)
- Assumptions (sphericity of error)

å

2

e

= minimum

t

=

t

1

Solving the GLM (finding )- Actually try to estimate
- ‘best’ has lowest overall error ie the sum of squares of the error:
- But how does this apply to GLM, where X is a matrix…

^

^

e

Y=0.99x + 12 + e

…need to geometrically visualise the GLM

y

x1 x2

^

+

=

N=3

x2

Design space defined by y = X

What about the actual data y?

^

^

x1

=

b

ˆ

y

X

Once again in 3D..- The design (X) can predict the data values (y) in the design space.
- The actual data y, usually lies outside this space.
- The ‘error’ is difference.

y

^

e

x2

x1

Design space defined by X

å

2

e

= minimum

t

=

t

1

ˆ

=

b

ˆ

y

X

Solving the GLM (finding ) – ordinary least squares (OLS)- To find minimum error:
- e has to be orthogonal to design space (X). “Project data onto model”
- ie: XTe = 0

XT(y - X) = 0

XTy = XTX

y

e

x2

x1

Design space defined by X

Assuming sphericity

- We assume that the error has:
- a mean of 0,
- is normally distributed
- is independent (does not correlate with itself)

=

Assuming sphericity

- We assume that the error has:
- a mean of 0,
- is normally distributed
- is independent (does not correlate with itself)

=

x

HRF

Neural stimulus

time

Neural stimulus hemodynamic response

I. BOLD responses have a delayed and dispersed form

expected BOLD response

Hemodynamic Response Function:

This is the expected BOLD signal if a neural stimulus takes place

expected BOLD response

= input function impulse response function (HRF)

Solution: CONVOLUTION

I. BOLD responses have a delayed and dispersed form

HRF

Transform neural stimuli function into a expected BOLD signal with a canonical hemodynamic response function (HRF)

II. The BOLD signal includes substantial amounts of low-frequency noise

WHY? Multifactorial: biorhythms, coil heating, etc…

HOW MAY OUR DATA LOOK LIKE?

Real data

Predicted response, NOT taking into account low-frequency drift

Intensity

Of BOLD signal

Time

II. The BOLD signal includes substantial amounts of low-frequency noise

Solution: HIGH PASS FILTERING

discrete cosine transform (DCT) set

- Acquisition of our data (Y)
- Design our matrix (X)
- Assumptions of GLM
- Correction for BOLD signal shape: convolution
- Cleaning of our data of low-frequency noise
- Estimation of βs
- But our βs may still be wrong! Why?
- Checkup of the error…
- Are all the assumptions of the error satisfied?

STEPS so far…

e

0

0

t

It should be…

III. The data are serially correlated

Temporal autocorrelation:

in y = Xβ + e over time

e

e in time t is correlated with e in time t-1

t

It is…

III. The data are serially correlated

Temporal autocorrelation:

in y = Xβ + e over time

WHY? Multifactorial…

III. The data are serially correlated

Temporal autocorrelation:

in y = Xβ + e over time

et= aet-1 + ε (assuming ε ~ N(0,σ2I))

Autoregressive model

autocovariance function

in other words:

the covariance of error at time t (et) and error at time t-1 (et-1) is not zero

III. The data are serially correlated

Temporal autocorrelation:

in y = Xβ + e over time

et= aet-1 + ε (assuming ε ~ N(0,σ2I))

Autoregressive model

et -1= aet-2 + ε

et -2= aet-3 + ε

…

et= aet-1 + ε

et=a (aet-2 + ε) + ε

et=a2et-2 + aε + ε

et=a2(aet-3 + ε) + aε + ε

et=a3et-3 + a2ε + aε + ε

…

But ais a number between 0 and 1

in other words:

the covariance of error at time t (et) and error at time t-1 (et-1) is not zero

time (scans)

ERROR:

Covariance matrix

1 2 3 4 5 6 7 8 9 10

1

2

3

4

5

6

7

8

9

10

time

(scans)

III. The data are serially correlated

Temporal autocorrelation:

in y = Xβ + e over time

et= aet-1 + ε (assuming ε ~ N(0,σ2I))

Autoregressive model

autocovariance function

in other words:

the covariance of error at time t (et) and error at time t-1 (et-1) is not zero

This violates the assumption of the error

e ~ N (0, σ2I)

III. The data are serially correlated

Solution:

1. Use an enhanced noise model with hyperparameters for multiple error covariance components

It should be…

It is…

et= ε

et= aet-1 + ε

et= aet-1 + ε

?

Or, if you wish

et= ε

a ≠ 0

But…a?

a = 0

III. The data are serially correlated

Solution:

1. Use an enhanced noise model with hyperparameters for multiple error covariance components

We would like to know covariance (a, autocovariance) of error

But we can only estimate it: V V = ΣλiQ i

V = λ1Q1 + λ2Q 2

λ1 and λ2: hyperparameters

Q1 and Q2: multiple error covariance components

It should be…

It is…

et= aet-1 + ε

et= aet-1 + ε

?

et= ε

a = 0

a ≠ 0

But…a?

III. The data are serially correlated

Solution:

1. Use an enhanced noise model with hyperparameters for multiple error covariance components

2. Use estimated autocorrelation to specify filter matrix W for whitening the data

et= aet-1 + ε(assuming ε ~ N(0,σ2I))

WY = WXβ + We

Other problems – Physiological confounds

- head movements
- arterial pulsations (particularly bad in brain stem)
- breathing
- eye blinks (visual cortex)
- adaptation affects, fatigue, fluctuations in concentration, etc.

Other problems – Correlated regressors

Example: y = x1β1 + x2β2 + e

When there is high (but not perfect) correlation between regressors, parameters can be estimated… But the estimates will be inefficiently estimated (ie highly variable)

Other problems – Variability in the HRF

- HRF varies substantially across voxels and subjects
- For example, latency can differ by ± 1 second
- Solution: MULTIPLE BASIS FUNCTIONS (another talk)

HRF could be understood as a linear combination of A, B and C

A

B

C

Model everything

globalactivity or movement

Important to model all known variables, even if not experimentally interesting:

effects-of-interest (the regressors we are actually interested in)

+

head movement, block and subject effects…

conditions:

effects of interest

subjects

- Minimise residual error variance

REMEMBER!!

- The aim of modelling the measured data was to make inferences about effects of interest
- Contrasts allow us to make such inferences
- How? T-tests and F-tests

Another talk!!!

Using an easy example...

Y= X. β+ ε

Fitting our models into our data (estimation of parameters, β)

HOW?

Y= X. β+ ε

Minimising residual error variance

Minimising residual error variance

Minimising the Sums of Squares of the Error differences between your predicted model and the observed data

Fitting our models into our data (estimation of parameters, β)

Y= X. β+ ε

y = x1β1 + x2β2 + x3β3 + x4β4 + x5β5 + x6β6 + e

y = x16 + x23+ x31+ x42+ x51+ x636 + e

We must pay attention to the problems that the GLM has…

GENERAL LINEAR MODEL – Methods for Dummies 2009-2010

REFERENCES

- Talks from previous years
- Human brain function

THANKS TO GUILLAUME FLANDIN

Many thanks for your attention

London 4th Nov 2009

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