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Structural lesion analysis: applications
Dagmar Timmann
Department of Neurology
University of Duisburg-Essen, Germany
Human cerebellar lesion conditions
1. Focal cerebellar lesions
a. Stroke
Pro‘s: - acute testing possible
Con‘s: - mean age 50 years;
- chronic: recovery; - acute: disconnection
b. Tumors
Pro‘s: - young age
Con‘s: - acute: lesion-symptom mapping not possible;
- increased intracranial pressure; - brain development
2. Cerebellar (cortical) degeneration
Pro‘s: - good access; - significant cerebellar signs
Con‘s: - mean age 50 years; - no 100% pure conditions
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Titel
Timmann et al. Neuroscience 2009
Structural MRI sequences
Chronic focal lesions (stroke or tumor)
3D T1-weighted: e.g. MPRAGE 1 mm3
sagittal
coronal
axial
Acute focal lesions (stroke)
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< 48 hours: diffusion weighted MRI, perfusion MRI
> 48 hours: FLAIR
Titel
Lesion delineation
Gold standard: manual tracing
Wilke et al. Neuroimage 2011
ROI
Region („lesion“) of interest
www.cabiatl.com/mricro/mricron
Rorden and Karnath Nat Rev Neurosci 2004
Folie 4
Titel
Normalization
Lesions are masked during normalization of cerebellum
Brett et al. Neuroimage 2001
SUIT (spatially unbiased atlas template of the cerebellum
and brainstem) toolbox in SPM
Diedrichsen Neuroimage 2006
SUIT-normalized
cerebellum
SUIT-normalized
ROI
ROI overlay on
probabilitistic MR atlas
Diedrichsen et al. 2009
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Titel
Lesion symptom maps
1. Superimposition of lesions in patients showing
the same disorder
2. Comparing lesion site in two groups of patients
- Pooling across predefined anatomical regions
- Pooling across behavioural cut-offs
- Subtraction analysis
3. Voxel-wise statistical mapping
- Binary data
- Continuous data
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www.cabiatl.com/mricro/mricron
(including NPM; by Chris Rorden)
Titel
Superimposition of lesions
in patients showing cerebellar dysarthria
n = 31
(surgery)
Lechtenberg and Gilman
Ann Neurol 1978
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n=7
(stroke)
Urban et al. Neurology 2001
No control group, biased by anatomy of lesions
Titel
Comparing lesion site in two groups
Pooling brain images across predefined anatomical regions
Eyeblink conditioning
CR
CS
1
US
Gerwig
et al. Brain
2003
Titel
Folie 8
10
Posterior inferior
1
12
Superior cerebellar artery
Biased by anatomy of lesions
Comparing lesion site in two groups
Pooling brain images based on behavioural cut-offs
Working memory (n-back)
3-back 2 6 4 1 6 7 9 8 7 ..
- Control task: 3-back + sitting
- Dual-task: 3-back + tandem gait
Ilg et al. in
Titelpreparation
Folie 9
Comparing lesion site in two groups
based on behavioural cut-offs: 90% percentile
3-back + sitting
impaired: 5/17
unimpaired: 12/17
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3-back + tandem gait
impaired: 9/17
unimpaired: 8/17
Titel
http://www.icn.ucl.ac.uk/motorcontrol/imaging/propatlas.htm
Voxel-wise subtraction analysis
Is a given voxel involved in a certain behaviour?
Behaviour
not impaired
Voxel
impaired
with lesion
consistent
inconsistent
no lesion
inconsistent
consistent
(%) consistent voxels – (%) inconsistent voxels
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Titel
Voxel-wise subtraction analysis
3-back + sitting
Ventral dentate
3-back + tandem gait
Dorsal dentate, interposed
Cut-off not defined, no inferential statistics done
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No graduation of abnormality
Titel
Inferential statistical mapping
- Binary data (no graduation of abnormality)
binomial tests:
MRICro: chi-square test (Fisher‘s exact test)
NPM in MRICroN: Liebermeister test
- Continuous (graduation of abnormality)
parametric: t test
nonparametric (NPM): Brunner and Munzel test*
*Medina et al. Neuropsychologia 2009: at least 10 lesioned and unlesioned
- Multiple comparisons:
larger groups: permutation
smaller groups: FDR
T test FDR corrected
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Titel
T test: p < 0.01, FDR corrected
3-back + sitting: ventral dentate
3-back + tandem gait: dorsal dentate, interposed
y=-67
Folie 14
Ilg et Titel
al. in preparation
y=-63
y=-59
Problems and future directions
Improve lesion delineation
Combine data of different MR sequences
(e.g. MPRAGE and FLAIR)
White matter changes
Implement DTI
Secondary changes in chronic lesion
How to treat secondary atrophy?
ROI based normalization of the dentate nuclei
acquire 3T or 7T MR images
ANOVA: compare two conditions, find possible interactions
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Titel
Cerebellar degeneration
Healthy
SCA6
Spinocerebellar ataxia type 6
Jung et al. Cerebellum 2011: Region specific atrophy patterns
Folie 16
Titel
Cerebellar degeneration
1. Conventional volumetry
- No normalization required
- Predefined anatomical regions
2. Voxel-based morphometry (VBM)
- Normalization required (e.g. SUIT)
- No predefined anatomical regions
- Better spatial resolution
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Titel
Conventional volumetry
Reach adaptation
Visuomotor
Force
field
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Rabe et al. J Neurophysiol 2009
Titel
Conventional volumetry
Reach adaptation
Visuomotor adaptation and
Force field posterior intermediate zone:
- L. VI anterior arm area?
Rotation
- Crus I, II parietal reach area?
- L. VIII posterior arm area?
www.eccet.de
Andreas Beck,
Volker Aurich University of Düsseldorf
Titel
Folie 19
VBM: better spatial resolution
Reach adaptation
Visuomotor
L. VI
Force field
L. V
y=-76
y=-62
y=-55
Correlation analysis [t values]
Donchin, Diedrichsen
et al. J Neurophysiol 2011
Titel
Folie 20
Reach adaptation
Intermediate
Anterior arm area:
Subdivision in functional moduls;
Force field adaptation – L. V
Visuomotor adaptation – L. VI
I-V
VI
Glickstein et al. 1995, 2009
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Titel
Problems and future directions
Conventional volumetry
Do on a lobule wise basis
Include volumetry of the nuclei using e.g. SWI
T1 mapping instead of VBM
White matter changes
Implement DTI
ANOVA: compare two conditions, find possible interactions
Folie 22
Titel
Essen
Neurology
Marcus Gerwig
Michael Küper
Markus Thürling
Neurosurgery
Beate Schoch
Neuroradiology
Elke R. Gizewski
Collaborators
UCL, London
Jörn Diedrichsen
Ben Gurion University, Israel
Opher Donchin
Hertie Institute, Uni Tübingen
Winfried Ilg
University of Düsseldorf
Andreas Beck, Volker Aurich
German Research Foundation DFG TI 239/9-1;10-1
Marie Curie Initial Training Grant (EU)