extracting diagnostic information from intrinsic...

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1 Comparison of multi-subject ICA methods for analysis of fMRI data: Consistency and Variability of Intrinsic Networks in the Healthy and Diseased Brain Vince D. Calhoun, Ph.D. Chief Technology Officer & Director, Image Analysis & MR Research The Mind Research Network Professor, Electrical and Computer Engineering (primary), Psychiatry, Neurosciences, & Computer Science The University of New Mexico Overview Motivation A brief review of group ICA A Testing Framework Application to large study Application to disease groups A Simulation Framework & Toolbox (simTB) Pushing the limits of Group ICA Summary 2 Prediction of Individual Responses is Important 3 E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011. 4 Extracting Diagnostic Information from Intrinsic Networks Accurate classification requires single-subject accuracy -> very stringent requirement! We cannot use knowledge of the diagnosis in the development of the classification algorithm Overview Motivation A brief review of group ICA A Testing Framework Application to large study Application to disease groups A Simulation Framework & Toolbox (simTB) Pushing the limits of Group ICA Summary 5 6 Group ICA R L V.D. Calhoun, T. Adali, G.D. Pearlson, and J.J. Pekar, "A Method for Making Group Inferences From Functional MRI Data Using Independent Component Analysis," Hum. Brain Map., vol. 14, pp. 140-151, 2001.

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1

Comparison of multi-subject ICA methods for analysis of fMRI data:

Consistency and Variability of Intrinsic Networks in the Healthy and Diseased Brain

Vince D. Calhoun, Ph.D. Chief Technology Officer &

Director, Image Analysis & MR Research The Mind Research Network

Professor, Electrical and Computer Engineering (primary),

Psychiatry, Neurosciences, & Computer Science The University of New Mexico

Overview

• Motivation

• A brief review of group ICA

• A Testing Framework

• Application to large study

• Application to disease groups

• A Simulation Framework & Toolbox (simTB)

• Pushing the limits of Group ICA

• Summary

2

Prediction of Individual Responses is Important

3

E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011. 4

Extracting Diagnostic Information

from Intrinsic Networks

•Accurate classification requires single-subject accuracy -> very stringent requirement!

•We cannot use knowledge of the diagnosis in the development of the classification algorithm

Overview

• Motivation

• A brief review of group ICA

• A Testing Framework

• Application to large study

• Application to disease groups

• A Simulation Framework & Toolbox (simTB)

• Pushing the limits of Group ICA

• Summary

5 6

Group ICA

R L

V.D. Calhoun, T. Adali, G.D. Pearlson, and J.J. Pekar, "A Method for Making Group Inferences From Functional

MRI Data Using Independent Component Analysis," Hum. Brain Map., vol. 14, pp. 140-151, 2001.

2

Single Subject ICA vs Group ICA

E. Erhardt, E. A. Allen, Y. Wei, T. Eichele, and V. D. Calhoun, "SimTB, a simulation toolbox for fMRI data under a model of spatiotemporal separability," NeuroImage, Under Review. & Poster #657. E. A. Allen, E. Erhardt, Y. Wei, T. Eichele, and V. D. Calhoun, "Capturing inter-subject variability with group independent component analysis of fMRI data: a simulation study," NeuroImage, Under Review. & Poster# 690.

8

Group ICA

:

Subject 1

Subject N

Data

Subject i

Back-reconstruction through inversion1

1

Ai Si

ICA (Forward Estimation)

PCA reduction1

A S_agg

ICA

A1

AN

PCA reduction2

Subject i

Back-reconstruction through Spatial-temporal (dual) regression2,3

Ai

Si

S_agg 1) Regress onto each timepoint of to generate

Subject i Ai 2) Regress onto each image of to generate

Iterate steps 1 & 2 until converged

1. V. D. Calhoun et al Hum.Brain Map., vol. 14, pp. 140-151, 2001. 2. V. D. Calhoun et al Neuropsychopharmacology, vol. 29, pp. 2097-2107, 2004.

3. N. Filippini et al Proc Natl Acad Sci U S A, vol. 106, pp. 7209-7214, Apr 28 2009

Default Mode Group Maps

9

Inversion STR

E. Erhardt, S. Rachakonda, E. Bedrick, T. Adali, and V. D. Calhoun, "Comparison of multi-subject ICA methods for analysis of fMRI data," Hum Brain Mapp, In Press.

Evaluation of Group ICA Methods

10

E. Erhardt, S. Rachakonda, E. Bedrick, T. Adali, and V. D. Calhoun, "Comparison of multi-subject ICA methods for analysis of fMRI data," Hum Brain Mapp, In Press.

11

X

Subject 1

Subject N

Data

A S_agg

ICA

A1

AN

Subject i

Back-reconstruction

1

Ai Si

Comp# R2 Subject Reg1 Reg2

2 0.81

1 1.89 0.02

2 2.28 0.66

10 0.80

1 0.28 2.19

2 0.65 2.03

4 0.017

1 -0.19 -0.40

2 -0.10 0.08

Component Timecourses

Task-modulation

(e.g. Fit timecourses

to GLM model then

test parameter)

Component Images

Voxel-wise stats

(e.g. one-sample t-test,

two-sample t-test,

correlation, etc)

}

}

Component

images

(one per

subject)

T-statistic

}

}

Multiple

regression

fit to ICA

timecourses

Beta-weights

(second

level

model)

} Model

timecourses

Spectra

(e.g. power spectra,

fractal parameters,

etc)

Controls-Patients

-5

-4

-3

-2

-1

0

1

2

3

4

0.03 0.08 0.13 0.19 0.24 0.3

Frequency (Hz)

T-v

alu

e

T-Values

} Component

timecourses

} Power

spectra

group

differences

Tim

e

Components Voxels Voxels

Co

mp

oe

nts

Tim

e

Tim

e

Voxels

Tim

e

Components

Functional Network

Connectivity

(e.g. inter-component

correlation)

Overview

• Motivation

• A brief review of group ICA

• A Testing Framework

• Application to large study

• Application to disease groups

• A Simulation Framework & Toolbox (simTB)

• Pushing the limits of Group ICA

• Summary

12

3

Rest fMRI Networks (N=603)

13

E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011.

Main Effects & MANCOVA Model

14

E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011.

1

1

1

log ,..., log

,...,

atanh ,..., atanh

TT T

c c Mc

TT T

c c Mc

TT T

M

P P P

S S S

K K K

Selecting/Labeling Components

15

E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011.

28 labeled components superset of 75 components

N=603 subjects http://mialab.mrn.org/data/index.html

Various Metrics for component selection Compare with below atlas

Spatial Maps

16

E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011.

Functional Network Connectivity (FNC)

17

E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011.

Spectra

18

E. Allen, et al, "A baseline for the multivariate comparison of resting state networks," Frontiers in Human Neuroscience, vol. 1, p. 12, 2011.

4

Overview

• Motivation

• A brief review of group ICA

• A Testing Framework

• Application to large study

• Application to disease groups

• A Simulation Framework & Toolbox (simTB)

• Pushing the limits of Group ICA

• Summary

19

Relationship to Disease (N=1140)

Healthy (N=590) Substance Use (N=469)

Schizo/BP (N=81)

Within network example: anterior DMN Between network example:

precuneus-cerebellar connectivity

Overview

• Motivation

• A brief review of group ICA

• A Testing Framework

• Application to large study

• Application to disease groups

• A Simulation Framework & Toolbox (simTB)

• Pushing the limits of Group ICA

• Summary

23

• Motivation

• Simulated data facilitate comparative evaluations

• Creating reasonable simulations can be challenging

given the complexities of fMRI data

• SimTB goals

• Flexible, easy and fast generation of simulated fMRI

data under an ICA model

• Ability to answer basic questions regarding the group

ICA model

A simulation toolbox

1

Cnn r

i ic ic ic i i i i i

c

Y g N diag N

r s R g S

5

E. Erhardt, E. A. Allen, Y. Wei, T. Eichele, and V. D. Calhoun, "SimTB, a simulation toolbox for fMRI data under a model of spatiotemporal separability," NeuroImage, Under Review. & Poster #657.

Overview of simTB Spatial Maps

• Roughly 30 SMs can be selected through the graphical

user interface by clicking on components, or by component

number in the batch script

• For each subject, each selected component can be included

or not, be translated and rotated in space, and the spatial

spread of the component can be increased or decreased

• Each SM is normalized to have a peak-to-peak amplitude

range of one

Moments compared with real fMRI data

• Tissue types affect baseline intensity

• Possible to match simulation to real fMRI data

27

Two paradigm examples

28

• x- and y- translation and rotation

• Subject 1 (bold) has half the motion of subject 2

http://mialab.mrn.org/software

Overview

• Motivation

• A brief review of group ICA

• A Testing Framework

• Application to large study

• Application to disease groups

• A Simulation Framework & Toolbox (simTB)

• Pushing the limits of Group ICA

• Summary

29

Group ICA: Pushed to the Limits

• Four Experiments

• Varied component rotation

• Varied component position

• Varied component amplitude

• Varied the temporal correlation among components

30

E. A. Allen, E. Erhardt, Y. Wei, T. Eichele, and V. D. Calhoun, "Capturing inter-subject variability with group independent component analysis of fMRI data: a simulation study," NeuroImage, Under Review. & Poster #690.

http://mialab.mrn.org/software

6

Rotation

31

Position

32

Amplitude

33

Temporal Correlation Among Components (FNC)

34

Constrained ICA

35

1{ ( ) } { ( : ) }

2

T TE G E g y yλ W ρ Wx x μ y W x

Q. Lin, J. Liu, Y. Zheng, H. Liang, and V. D. Calhoun, "Semi-blind Spatial ICA of fMRI Using Spatial Constraints”, Hum. Brain Map., vol. 31, 2010

Overview

• Motivation

• A brief review of group ICA

• A Testing Framework

• Application to large study

• Application to disease groups

• A Simulation Framework & Toolbox (simTB)

• Pushing the limits of Group ICA

• Summary

36

7

Summary

• groupICA provides excellent estimates of single

subject SMs and TC and captures extensive spatial,

temporal, and amplitude variability.

• In general spatial ICA assumes consistency across

space, however estimation is surprisingly robust to

modest violation of this model.

• We introduce a tool for rapidly producing realistic

simulations of fMRI data under an ICA model.

• Enable rapidly answering questions about existing and

new ICA and group ICA approaches.

37

E. Erhardt, E. A. Allen, Y. Wei, T. Eichele, and V. D. Calhoun, "SimTB, a simulation toolbox for fMRI data under a model of spatiotemporal separability," NeuroImage, Under Review. & Poster #657. E. A. Allen, E. Erhardt, Y. Wei, T. Eichele, and V. D. Calhoun, "Capturing inter-subject variability with group independent component analysis of fMRI data: a simulation study," NeuroImage, Under Review. & Poster# 690.

http://mialab.mrn.org/software

Software/Algorithms

Left Hemisphere

Visual Stimuli Onset

Left Hemisphere

Visual Stimuli Onset

http://mialab.mrn.org/software 4100+ unique downloads

Funded by: 1R01EB006841

http://mialab.mrn.org/software

39

http://mialab.mrn.org Posters: #657 (M-T), #690 (W-Th)

40