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Machine learning for functional connectomes
Gaël Varoquaux
Machine learning for functional connectomes
Gaël Varoquaux
Outline:
1 Intuitions on machine learning
2 Machine learning on rest fMRI
Pointers to code in nilearn & scikit-learn
nilearn.github.io — scikit-learn.org
Use the “API reference” to look up functions
and scroll down for examples of usage
1 Intuitions on machine learning
Adjusting models for prediction
G Varoquaux 2
1 Machine learning in a nutshell: an example
Face recognition
Andrew Bill Charles Dave
G Varoquaux 3
1 Machine learning in a nutshell: an example
Face recognition
Andrew Bill Charles Dave
?G Varoquaux 3
1 Machine learning in a nutshell
A simple method:
1 Store all the known (noisy) images and the names
that go with them.
2 From a new (noisy) images, find the image that is
most similar.
“Nearest neighbor” method
G Varoquaux 4
1 Machine learning in a nutshell
A simple method:
1 Store all the known (noisy) images and the names
that go with them.
2 From a new (noisy) images, find the image that is
most similar.
“Nearest neighbor” method
How many errors on already-known images?
... 0: no errors
Test data = Train data
G Varoquaux 4
1 Machine learning in a nutshell
A simple method:
1 Store all the known (noisy) images and the names
that go with them.
2 From a new (noisy) images, find the image that is
most similar.
“Nearest neighbor” method
How many errors on already-known images?
... 0: no errors
Test data = Train data
G Varoquaux 4
1 Machine learning in a nutshell: intuitions
A single descriptor:
one dimension
x
y
G Varoquaux 5
1 Machine learning in a nutshell: intuitions
A single descriptor:
one dimension
x
y
x
y
Which model to prefer?
G Varoquaux 5
1 Machine learning in a nutshell: intuitions
A single descriptor:
one dimension
x
y
x
y
Problem of “over-fitting”
Minimizing error is not always the best strategy
(learning noise)
Test data = train data
G Varoquaux 5
1 Machine learning in a nutshell: intuitions
A single descriptor:
one dimension
x
y
x
y
Prefer simple models
= concept of “regularization”
Balance the number of parameters to learn
with the amount of data
G Varoquaux 5
1 Machine learning in a nutshell: intuitions
A single descriptor:
one dimension
x
y
Two descriptors:
2 dimensions
X_1
X_2
y
The higher the number of descriptors
the more the trouble
G Varoquaux 5
1 Machine learning in a nutshell: intuitions
A single descriptor:
one dimension
x
y
Two descriptors:
2 dimensions
X_1
X_2
y
The higher the number of descriptors
the more the trouble
The higher the required number of subjects
G Varoquaux 5
1 Testing prediction: generalization and cross-validation
[Varoquaux... 2017]
x
y
x
y
G Varoquaux 6
1 Testing prediction: generalization and cross-validation
[Varoquaux... 2017]
x
y
x
y
⇒ Need test on independent, unseen data
Train set Validation
set
Measures prediction accuracy
sklearn.model_selection.train_test_split
G Varoquaux 6
1 Testing prediction: generalization and cross-validation
[Varoquaux... 2017]
x
y
x
y
⇒ Need test on independent, unseen data
Loop
Test setTrain set
Full data
sklearn.
model_selection.
cross_val_score
G Varoquaux 6
2 Machine learning on rest
fMRI
for population imaging
finding differences between subjects
in functional connectomesG Varoquaux 7
From rest-fMRI to biomarkers
No salient features in rest fMRI
G Varoquaux 8
From rest-fMRI to biomarkers
Define functional regions
G Varoquaux 8
From rest-fMRI to biomarkers
Define functional regions
Learn interactions
G Varoquaux 8
From rest-fMRI to biomarkers
Define functional regions
Learn interactions
Find differences
G Varoquaux 8
From rest-fMRI to biomarkers
Functional
connectivity
matrix
Time series
extraction
Region
definition
Supervised learning
RS-fMRI
Typical pipeline [Varoquaux and Craddock 2013]
1. Define regions
2. Extract times series
3. Build functional-connectivity matrix
4. Apply supervised machine learning
G Varoquaux 9
2 Defining regions from rest-fMRI
Clustering nilearn.regions.Parcellations
k-means
Fast (in nilearn)
No spatial model
⇒ smooth the data
G Varoquaux 10
2 Defining regions from rest-fMRI
Clustering nilearn.regions.Parcellations
k-means
Fast (in nilearn)
No spatial model
⇒ smooth the data
Ward agglomerative clustering
Recursive merges of clusters
Spatial model constraints merges
⇒ fast
... ... ...
... ...
G Varoquaux 10
2 Defining regions from rest-fMRI
Clustering nilearn.regions.Parcellations
k-means
Fast (in nilearn)
No spatial model
⇒ smooth the data
Ward agglomerative clustering
Recursive merges of clusters
Spatial model constraints merges
⇒ fast
Decomposition models
time
voxels
time
voxels
time
voxels
Y +E · S=
25
N
G Varoquaux 10
2 Defining regions from rest-fMRI
Clustering nilearn.regions.Parcellations
k-means
Fast (in nilearn)
No spatial model
⇒ smooth the data
Ward agglomerative clustering
Recursive merges of clusters
Spatial model constraints merges
⇒ fast
Decomposition models
ICA: nilearn.decomposition.CanICA
seek independence of maps
Sparse dictionary learning:
seek sparse maps
nilearn.decomposition.DictLearning
G Varoquaux 10
2 For connectome prediction [Dadi... 2018]
RS-fMRI
Functional
connectivity
Time series
2
4
3
1
Diagnosis
ROIs
Choice of regions for best prediction?
G Varoquaux 11
2 For connectome prediction [Dadi... 2018]
RS-fMRI
Functional
connectivity
Time series
2
4
3
1
Diagnosis
ROIs
Choice of regions for best prediction?
G Varoquaux 11
2 Region definition: resulting parcellations
Dictionary learning Group ICA
Ward clustering K-Means clustering
2 Region definition: resulting parcellations
Dictionary learning Group ICA
Ward clustering K-Means clustering
2 Region definition: resulting parcellations
Dictionary learning Group ICA
Ward clustering K-Means clustering
2 Time-series extraction
Extract ROI-average signal:
Optional low-pass filter
(≈ .1 Hz – .3 Hz)
Regress out confounds (movement parameters, CSF &
white matter signals, Compcorr, Global mean)
Hard parcellations (eg from clustering)
nilearn.input_data.NiftiLabelsMasker
Soft parcellations (eg from ICA)
nilearn.input_data.NiftiMapsMasker
G Varoquaux 13
2 Connectome: building a connectivity matrix
How to capture and represent interactions?
G Varoquaux 14
2 Connectome: differences across subjects
0 5 10 15 20 25
0
5
10
15
20
25
0 5 10 15 20 25
0
5
10
15
20
25
0 5 10 15 20 25
0
5
10
15
20
25
0 5 10 15 20 25
0
5
10
15
20
25
Correlation matrices
0 5 10 15 20 25
0
5
10
15
20
25
0 5 10 15 20 25
0
5
10
15
20
25
0 5 10 15 20 25
0
5
10
15
20
25
0 5 10 15 20 25
0
5
10
15
20
25
Partial correlation matrices
3 controls, 1 severe stroke patient
Which is which?
G Varoquaux 15
2 Connectome: differences across subjects
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25Large lesion
Correlation matrices
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25Large lesion
Partial correlation matrices
Spread-out variability in correlation matrices
Noise in partial-correlations
Strong dependence between coefficients
[Varoquaux... 2010]
G Varoquaux 15
2 Information geometry: uniform-error parametrization
Subject-specific noise in covariance form manifold
Tangent space removes coupling in coefficients
Controls
Patient
dΣ
M
anifold
Tangent
Tangent embedding[Varoquaux... 2010]
G Varoquaux 16
2 Connectome: which parametrization maps differences?
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25Large lesion
Correlation matrices
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25Large lesion
Partial correlation matrices
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25 Control
0 5 10 15 20 25
0
5
10
15
20
25Large lesion
Tangent-space embedding
[varoquaux 2010]
G Varoquaux 17
2 For connectome prediction [Dadi... 2018]
Time series
2
RS-fMRI
41
Diagnosis
ROIs Functional
connectivity
3
Connectivity matrix
Correlation nilearn.connectome.ConnectivityMeasure
Partial correlations
Tangent space
G Varoquaux 18
2 For connectome prediction [Dadi... 2018]
Time series
2
RS-fMRI
41
Diagnosis
ROIs Functional
connectivity
3
Connectivity matrix
Correlation nilearn.connectome.ConnectivityMeasure
Partial correlations
Tangent space
G Varoquaux 18
2 Supervised learning step [Dadi... 2018]
Functional
connectivity
Time series
3
4
Diagnosis
2
RS-fMRI
1 ROIs
Supervised learning
Stick with Linear models
sklearn.linear_model.LogisticRegression
G Varoquaux 19
2 Supervised learning step [Dadi... 2018]
Functional
connectivity
Time series
3
4
Diagnosis
2
RS-fMRI
1 ROIs
Supervised learning
Stick with Linear models
sklearn.linear_model.LogisticRegression
G Varoquaux 19
Predicting from brain activity at rest
RS-fMRI
Functional
connectivity
Time series
2
4
3
1
Diagnosis
ROIs
1. Functional regions (eg clustering, decomposition, or BASC atlas)
2. Filtering and or confound removal
3. Tangent-space parametrization
4. Supervised linear models (eg SVMs)
G Varoquaux 20
3 References I
A. Abraham, E. Dohmatob, B. Thirion, D. Samaras, and
G. Varoquaux. Extracting brain regions from rest fMRI with
total-variation constrained dictionary learning. In MICCAI, page
607. 2013.
K. Dadi, M. Rahim, A. Abraham, D. Chyzhyk, M. Milham,
B. Thirion, and G. Varoquaux. Benchmarking functional
connectome-based predictive models for resting-state fmri. 2018.
G. Varoquaux and R. C. Craddock. Learning and comparing
functional connectomes across subjects. NeuroImage, 80:405,
2013.
G. Varoquaux and B. Thirion. How machine learning is shaping
cognitive neuroimaging. GigaScience, 3:28, 2014.
G. Varoquaux, F. Baronnet, A. Kleinschmidt, P. Fillard, and
B. Thirion. Detection of brain functional-connectivity difference
in post-stroke patients using group-level covariance modeling. In
MICCAI. 2010.G Varoquaux 21
3 References II
G. Varoquaux, P. R. Raamana, D. A. Engemann, A. Hoyos-Idrobo,
Y. Schwartz, and B. Thirion. Assessing and tuning brain
decoders: cross-validation, caveats, and guidelines. NeuroImage,
145:166–179, 2017.
G Varoquaux 22

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Machine learning for functional connectomes

  • 1. Machine learning for functional connectomes Gaël Varoquaux
  • 2. Machine learning for functional connectomes Gaël Varoquaux Outline: 1 Intuitions on machine learning 2 Machine learning on rest fMRI Pointers to code in nilearn & scikit-learn nilearn.github.io — scikit-learn.org Use the “API reference” to look up functions and scroll down for examples of usage
  • 3. 1 Intuitions on machine learning Adjusting models for prediction G Varoquaux 2
  • 4. 1 Machine learning in a nutshell: an example Face recognition Andrew Bill Charles Dave G Varoquaux 3
  • 5. 1 Machine learning in a nutshell: an example Face recognition Andrew Bill Charles Dave ?G Varoquaux 3
  • 6. 1 Machine learning in a nutshell A simple method: 1 Store all the known (noisy) images and the names that go with them. 2 From a new (noisy) images, find the image that is most similar. “Nearest neighbor” method G Varoquaux 4
  • 7. 1 Machine learning in a nutshell A simple method: 1 Store all the known (noisy) images and the names that go with them. 2 From a new (noisy) images, find the image that is most similar. “Nearest neighbor” method How many errors on already-known images? ... 0: no errors Test data = Train data G Varoquaux 4
  • 8. 1 Machine learning in a nutshell A simple method: 1 Store all the known (noisy) images and the names that go with them. 2 From a new (noisy) images, find the image that is most similar. “Nearest neighbor” method How many errors on already-known images? ... 0: no errors Test data = Train data G Varoquaux 4
  • 9. 1 Machine learning in a nutshell: intuitions A single descriptor: one dimension x y G Varoquaux 5
  • 10. 1 Machine learning in a nutshell: intuitions A single descriptor: one dimension x y x y Which model to prefer? G Varoquaux 5
  • 11. 1 Machine learning in a nutshell: intuitions A single descriptor: one dimension x y x y Problem of “over-fitting” Minimizing error is not always the best strategy (learning noise) Test data = train data G Varoquaux 5
  • 12. 1 Machine learning in a nutshell: intuitions A single descriptor: one dimension x y x y Prefer simple models = concept of “regularization” Balance the number of parameters to learn with the amount of data G Varoquaux 5
  • 13. 1 Machine learning in a nutshell: intuitions A single descriptor: one dimension x y Two descriptors: 2 dimensions X_1 X_2 y The higher the number of descriptors the more the trouble G Varoquaux 5
  • 14. 1 Machine learning in a nutshell: intuitions A single descriptor: one dimension x y Two descriptors: 2 dimensions X_1 X_2 y The higher the number of descriptors the more the trouble The higher the required number of subjects G Varoquaux 5
  • 15. 1 Testing prediction: generalization and cross-validation [Varoquaux... 2017] x y x y G Varoquaux 6
  • 16. 1 Testing prediction: generalization and cross-validation [Varoquaux... 2017] x y x y ⇒ Need test on independent, unseen data Train set Validation set Measures prediction accuracy sklearn.model_selection.train_test_split G Varoquaux 6
  • 17. 1 Testing prediction: generalization and cross-validation [Varoquaux... 2017] x y x y ⇒ Need test on independent, unseen data Loop Test setTrain set Full data sklearn. model_selection. cross_val_score G Varoquaux 6
  • 18. 2 Machine learning on rest fMRI for population imaging finding differences between subjects in functional connectomesG Varoquaux 7
  • 19. From rest-fMRI to biomarkers No salient features in rest fMRI G Varoquaux 8
  • 20. From rest-fMRI to biomarkers Define functional regions G Varoquaux 8
  • 21. From rest-fMRI to biomarkers Define functional regions Learn interactions G Varoquaux 8
  • 22. From rest-fMRI to biomarkers Define functional regions Learn interactions Find differences G Varoquaux 8
  • 23. From rest-fMRI to biomarkers Functional connectivity matrix Time series extraction Region definition Supervised learning RS-fMRI Typical pipeline [Varoquaux and Craddock 2013] 1. Define regions 2. Extract times series 3. Build functional-connectivity matrix 4. Apply supervised machine learning G Varoquaux 9
  • 24. 2 Defining regions from rest-fMRI Clustering nilearn.regions.Parcellations k-means Fast (in nilearn) No spatial model ⇒ smooth the data G Varoquaux 10
  • 25. 2 Defining regions from rest-fMRI Clustering nilearn.regions.Parcellations k-means Fast (in nilearn) No spatial model ⇒ smooth the data Ward agglomerative clustering Recursive merges of clusters Spatial model constraints merges ⇒ fast ... ... ... ... ... G Varoquaux 10
  • 26. 2 Defining regions from rest-fMRI Clustering nilearn.regions.Parcellations k-means Fast (in nilearn) No spatial model ⇒ smooth the data Ward agglomerative clustering Recursive merges of clusters Spatial model constraints merges ⇒ fast Decomposition models time voxels time voxels time voxels Y +E · S= 25 N G Varoquaux 10
  • 27. 2 Defining regions from rest-fMRI Clustering nilearn.regions.Parcellations k-means Fast (in nilearn) No spatial model ⇒ smooth the data Ward agglomerative clustering Recursive merges of clusters Spatial model constraints merges ⇒ fast Decomposition models ICA: nilearn.decomposition.CanICA seek independence of maps Sparse dictionary learning: seek sparse maps nilearn.decomposition.DictLearning G Varoquaux 10
  • 28. 2 For connectome prediction [Dadi... 2018] RS-fMRI Functional connectivity Time series 2 4 3 1 Diagnosis ROIs Choice of regions for best prediction? G Varoquaux 11
  • 29. 2 For connectome prediction [Dadi... 2018] RS-fMRI Functional connectivity Time series 2 4 3 1 Diagnosis ROIs Choice of regions for best prediction? G Varoquaux 11
  • 30. 2 Region definition: resulting parcellations Dictionary learning Group ICA Ward clustering K-Means clustering
  • 31. 2 Region definition: resulting parcellations Dictionary learning Group ICA Ward clustering K-Means clustering
  • 32. 2 Region definition: resulting parcellations Dictionary learning Group ICA Ward clustering K-Means clustering
  • 33. 2 Time-series extraction Extract ROI-average signal: Optional low-pass filter (≈ .1 Hz – .3 Hz) Regress out confounds (movement parameters, CSF & white matter signals, Compcorr, Global mean) Hard parcellations (eg from clustering) nilearn.input_data.NiftiLabelsMasker Soft parcellations (eg from ICA) nilearn.input_data.NiftiMapsMasker G Varoquaux 13
  • 34. 2 Connectome: building a connectivity matrix How to capture and represent interactions? G Varoquaux 14
  • 35. 2 Connectome: differences across subjects 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 Correlation matrices 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 Partial correlation matrices 3 controls, 1 severe stroke patient Which is which? G Varoquaux 15
  • 36. 2 Connectome: differences across subjects 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25Large lesion Correlation matrices 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25Large lesion Partial correlation matrices Spread-out variability in correlation matrices Noise in partial-correlations Strong dependence between coefficients [Varoquaux... 2010] G Varoquaux 15
  • 37. 2 Information geometry: uniform-error parametrization Subject-specific noise in covariance form manifold Tangent space removes coupling in coefficients Controls Patient dΣ M anifold Tangent Tangent embedding[Varoquaux... 2010] G Varoquaux 16
  • 38. 2 Connectome: which parametrization maps differences? 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25Large lesion Correlation matrices 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25Large lesion Partial correlation matrices 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25 Control 0 5 10 15 20 25 0 5 10 15 20 25Large lesion Tangent-space embedding [varoquaux 2010] G Varoquaux 17
  • 39. 2 For connectome prediction [Dadi... 2018] Time series 2 RS-fMRI 41 Diagnosis ROIs Functional connectivity 3 Connectivity matrix Correlation nilearn.connectome.ConnectivityMeasure Partial correlations Tangent space G Varoquaux 18
  • 40. 2 For connectome prediction [Dadi... 2018] Time series 2 RS-fMRI 41 Diagnosis ROIs Functional connectivity 3 Connectivity matrix Correlation nilearn.connectome.ConnectivityMeasure Partial correlations Tangent space G Varoquaux 18
  • 41. 2 Supervised learning step [Dadi... 2018] Functional connectivity Time series 3 4 Diagnosis 2 RS-fMRI 1 ROIs Supervised learning Stick with Linear models sklearn.linear_model.LogisticRegression G Varoquaux 19
  • 42. 2 Supervised learning step [Dadi... 2018] Functional connectivity Time series 3 4 Diagnosis 2 RS-fMRI 1 ROIs Supervised learning Stick with Linear models sklearn.linear_model.LogisticRegression G Varoquaux 19
  • 43. Predicting from brain activity at rest RS-fMRI Functional connectivity Time series 2 4 3 1 Diagnosis ROIs 1. Functional regions (eg clustering, decomposition, or BASC atlas) 2. Filtering and or confound removal 3. Tangent-space parametrization 4. Supervised linear models (eg SVMs) G Varoquaux 20
  • 44. 3 References I A. Abraham, E. Dohmatob, B. Thirion, D. Samaras, and G. Varoquaux. Extracting brain regions from rest fMRI with total-variation constrained dictionary learning. In MICCAI, page 607. 2013. K. Dadi, M. Rahim, A. Abraham, D. Chyzhyk, M. Milham, B. Thirion, and G. Varoquaux. Benchmarking functional connectome-based predictive models for resting-state fmri. 2018. G. Varoquaux and R. C. Craddock. Learning and comparing functional connectomes across subjects. NeuroImage, 80:405, 2013. G. Varoquaux and B. Thirion. How machine learning is shaping cognitive neuroimaging. GigaScience, 3:28, 2014. G. Varoquaux, F. Baronnet, A. Kleinschmidt, P. Fillard, and B. Thirion. Detection of brain functional-connectivity difference in post-stroke patients using group-level covariance modeling. In MICCAI. 2010.G Varoquaux 21
  • 45. 3 References II G. Varoquaux, P. R. Raamana, D. A. Engemann, A. Hoyos-Idrobo, Y. Schwartz, and B. Thirion. Assessing and tuning brain decoders: cross-validation, caveats, and guidelines. NeuroImage, 145:166–179, 2017. G Varoquaux 22