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Ga¨ el Varoquaux Manuscript submitted A. Abraham
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Page 1: Inter-site autism biomarkers from resting state fMRI

Inter-site autism biomarkersfrom resting-state fMRI

Gael Varoquaux

Manuscript submitted A. Abraham

Page 2: Inter-site autism biomarkers from resting state fMRI

Predictive biomarkers from restSuitable for diminished patients

Probing intrinsic brain structurePredicting pathologies as a validation proxy

Multi-site large autism dataset: ABIDEAutism Spectrum Disorder [Di Martino... 2014]

⇒ Patient/Control classification

16 sites

∼ 1200 subjects (900 after QC)

G Varoquaux 2

Page 3: Inter-site autism biomarkers from resting state fMRI

Experiments: autism predictionSeen sites: predicting to new subjects

Training set Testing set

Unseen sites: predicting to new sites

Training set Testing set

Training set Test setG Varoquaux 3

Page 4: Inter-site autism biomarkers from resting state fMRI

A connectome classification pipeline

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Prediction accuracy (%)Seen sites 67±3

Unseen sites 67±5

What is important to predict?

G Varoquaux 4

Page 5: Inter-site autism biomarkers from resting state fMRI

A connectome classification pipeline

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Prediction accuracy (%)Seen sites 67±3

Unseen sites 67±5

What is important to predict?

G Varoquaux 4

Page 6: Inter-site autism biomarkers from resting state fMRI

A connectome classification pipeline

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Prediction accuracy (%)Seen sites 67±3

Unseen sites 67±5

What is important to predict?

G Varoquaux 4

Page 7: Inter-site autism biomarkers from resting state fMRI

1 ROI definition

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

G Varoquaux 5

Page 8: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Learning functional regions

Harvard Oxford

Anatomical atlases do not resolve functionalstructures

Where is the default mode network?

G Varoquaux 6

Page 9: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Clustering approaches

K-MeansRelated to [Yeo... 2011]

Normalized cuts[Craddock... 2012]

Ward clustering[Thirion... 2014]

G Varoquaux 7

Page 10: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

G Varoquaux 8

Page 11: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

Language

G Varoquaux 8

Page 12: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

Audio

G Varoquaux 8

Page 13: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

Visual

G Varoquaux 8

Page 14: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

Dorsal Att.

G Varoquaux 8

Page 15: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

Motor

G Varoquaux 8

Page 16: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

Salience

G Varoquaux 8

Page 17: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: Linear decomposition approaches

Model: Observing linear mixtures of networks at rest

Time courses

Observing a mixtureHow to unmix networks?

ICA: minimize mutual information across SSparse decompositions: sparse penalty on maps

G Varoquaux 8

Page 18: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: MSDL linear decomposition

[Varoquaux... 2011, Abraham... 2013]

MSDL: multi-subject dictionary learning

Sparse

Multi-subject

Subject maps + Population-levelatlas

Spatial penalty(total variation)

L R

y=-23 x=0

L R

z=18

L R

y=-78 x=2

L R

z=4

Ventricular system Visual CortexL R

y=-47 x=51

L R

z=11

L R

y=-17 x=-47

L R

z=8

TPJ Auditory Network

G Varoquaux 9

Page 19: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: MSDL linear decomposition

[Varoquaux... 2011, Abraham... 2013]

MSDL: multi-subject dictionary learning

Sparse

Multi-subject

Subject maps + Population-levelatlas

Spatial penalty(total variation)

L R

y=-23 x=0

L R

z=18

L R

y=-78 x=2

L R

z=4

Ventricular system Visual CortexL R

y=-47 x=51

L R

z=11

L R

y=-17 x=-47

L R

z=8

TPJ Auditory Network

G Varoquaux 9

Page 20: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: different optionsAt

lase

s

Craddock2011 Ncuts

Harvard-Oxford

Yeo 2011

Regi

onle

arni

ng

K-Means Ward MSDL ICA

G Varoquaux 10

Page 21: Inter-site autism biomarkers from resting state fMRI

1 ROI definition: impact of choice

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

G Varoquaux 11

Page 22: Inter-site autism biomarkers from resting state fMRI

2 Time-series extraction

Time series

2

RS-fMRI

Functionalconnectivity

43

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Remove motion regressorsCompcorrGlobal mean regression?Empirically: different ways work

G Varoquaux 12

Page 23: Inter-site autism biomarkers from resting state fMRI

2 Time-series extraction

Time series

2

RS-fMRI

Functionalconnectivity

43

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Remove motion regressorsCompcorrGlobal mean regression?Empirically: different ways work

G Varoquaux 12

Page 24: Inter-site autism biomarkers from resting state fMRI

3 Functional-connectivity matrix

Time series

2

RS-fMRI

41

Diagnosis

ROIs Functionalconnectivity

3

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Correlation matrix?Partial correlation matrix?Tangent-space embedding?

[Varoquaux... 2010]

G Varoquaux 13

Page 25: Inter-site autism biomarkers from resting state fMRI

3 Functional-connectivity matrix

Time series

2

RS-fMRI

41

Diagnosis

ROIs Functionalconnectivity

3

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Correlation matrix?Partial correlation matrix?Tangent-space embedding?

[Varoquaux... 2010]

G Varoquaux 13

Page 26: Inter-site autism biomarkers from resting state fMRI

3 Functional-connectivity matrix: different options

0 5 10 15 20 25

0

5

10

15

20

25 Control0 5 10 15 20 25

0

5

10

15

20

25 Control0 5 10 15 20 25

0

5

10

15

20

25 Control0 5 10 15 20 25

0

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10

15

20

25Large lesion

Correlation matrices

0 5 10 15 20 25

0

5

10

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25 Control0 5 10 15 20 25

0

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25 Control0 5 10 15 20 25

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25 Control0 5 10 15 20 25

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25Large lesion

Partial correlation matrices

0 5 10 15 20 25

0

5

10

15

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25 Control0 5 10 15 20 25

0

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25 Control0 5 10 15 20 25

0

5

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25 Control0 5 10 15 20 25

0

5

10

15

20

25Large lesion

Tangent-space embedding[varoquaux 2010]

G Varoquaux 14

Page 27: Inter-site autism biomarkers from resting state fMRI

3 Functional-connectivity matrix: impact of choice

Time series

2

RS-fMRI

41

Diagnosis

ROIs Functionalconnectivity

3

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

G Varoquaux 15

Page 28: Inter-site autism biomarkers from resting state fMRI

4 Supervised learning method

Functionalconnectivity

Time series

34

Diagnosis

2

RS-fMRI

1 ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Standard supervised learningRidge classifierSVC `2 penalizedSVC `1 penalized

G Varoquaux 16

Page 29: Inter-site autism biomarkers from resting state fMRI

4 Supervised learning method

Functionalconnectivity

Time series

34

Diagnosis

2

RS-fMRI

1 ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Standard supervised learningRidge classifierSVC `2 penalizedSVC `1 penalized

G Varoquaux 16

Page 30: Inter-site autism biomarkers from resting state fMRI

4 Supervised learning method: impact of choice

Functionalconnectivity

Time series

34

Diagnosis

2

RS-fMRI

1 ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

G Varoquaux 17

Page 31: Inter-site autism biomarkers from resting state fMRI

Importance of pipeline steps

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

G Varoquaux 18

Page 32: Inter-site autism biomarkers from resting state fMRI

Importance of pipeline steps

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

G Varoquaux 18

Page 33: Inter-site autism biomarkers from resting state fMRI

How general are these conclusions?Different subsets:

Set Card. Sites Selection criteriaA 871 17 All subjects after QCB 736 11 Remove 6 smallest sitesC 639 14 A without left handed and womenD 420 14 C between 9 and 18 years oldE 226 3 D from 3 biggest sites

Exploring variabilityFrom most heterogeneousto most homogeneous

G Varoquaux 19

Page 34: Inter-site autism biomarkers from resting state fMRI

Across different sets of subjects

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

MSDL outperform alternatives

Intra-siteInter-site

G Varoquaux 20

Page 35: Inter-site autism biomarkers from resting state fMRI

Across different sets of subjects

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

Tangent space outperform alternatives

Intra-siteInter-site

G Varoquaux 20

Page 36: Inter-site autism biomarkers from resting state fMRI

Across different sets of subjects

RS-fMRI

Functionalconnectivity

Time series

24

3

1

Diagnosis

ROIs

1 ROI definition2 Time-series extraction3 Connectivity matrices4 Supervised learning

`2 classifiers outperform alternatives

Intra-siteInter-site

G Varoquaux 20

Page 37: Inter-site autism biomarkers from resting state fMRI

MSDL atlas

L R

y=-54 x=0

L R

z=3

L RL R

L RL R

L RL R

Page 38: Inter-site autism biomarkers from resting state fMRI

More data is better

Multivariate processing of a 1Tb of heterogeneous datais worth the trouble

Page 39: Inter-site autism biomarkers from resting state fMRI

@GaelVaroquaux

Intersite biomarkers from rest [Abraham submitted]

Prediction of autismCarries out across sites

Recipe for a good pipelineChoice of regions critical (MSDL to learn them)Tangent-space embeddingStandard SVM

Definition of regions MSDLLinear decomposition + sparsity

+ total-variation

ni

Page 40: Inter-site autism biomarkers from resting state fMRI

@GaelVaroquaux

Intersite biomarkers from rest [Abraham submitted]

Prediction of autismCarries out across sites

Recipe for a good pipelineChoice of regions critical (MSDL to learn them)Tangent-space embeddingStandard SVMConnectome structure not central for prediction

Definition of regions MSDLLinear decomposition + sparsity

+ total-variation

ni

Page 41: Inter-site autism biomarkers from resting state fMRI

@GaelVaroquaux

Intersite biomarkers from rest [Abraham submitted]

Prediction of autismCarries out across sites

Recipe for a good pipelineChoice of regions critical (MSDL to learn them)Tangent-space embeddingStandard SVM

Definition of regions MSDLLinear decomposition + sparsity

+ total-variation

ni

Page 42: Inter-site autism biomarkers from resting state fMRI

References I

A. Abraham, E. Dohmatob, B. Thirion, D. Samaras, andG. Varoquaux. Extracting brain regions from rest fMRI withtotal-variation constrained dictionary learning. In MICCAI, page607. 2013.

R. C. Craddock, G. A. James, P. E. Holtzheimer, X. P. Hu, andH. S. Mayberg. A whole brain fMRI atlas generated via spatiallyconstrained spectral clustering. Human brain mapping, 33(8):1914–1928, 2012.

A. Di Martino, C.-G. Yan, Q. Li, E. Denio, F. X. Castellanos,K. Alaerts, J. S. Anderson, M. Assaf, S. Y. Bookheimer,M. Dapretto, ... The autism brain imaging data exchange:towards a large-scale evaluation of the intrinsic brainarchitecture in autism. Molecular psychiatry, 19:659, 2014.

B. Thirion, G. Varoquaux, E. Dohmatob, and J. Poline. WhichfMRI clustering gives good brain parcellations? Name: Frontiersin Neuroscience, 8:167, 2014.

Page 43: Inter-site autism biomarkers from resting state fMRI

References IIG. Varoquaux, F. Baronnet, A. Kleinschmidt, P. Fillard, and

B. Thirion. Detection of brain functional-connectivity differencein post-stroke patients using group-level covariance modeling. InMICCAI, pages 200–208. 2010.

G. Varoquaux, A. Gramfort, F. Pedregosa, V. Michel, andB. Thirion. Multi-subject dictionary learning to segment an atlasof brain spontaneous activity. In Inf Proc Med Imag, pages562–573, 2011.

B. Yeo, F. Krienen, J. Sepulcre, M. Sabuncu, ... The organizationof the human cerebral cortex estimated by intrinsic functionalconnectivity. J Neurophysio, 106:1125, 2011.