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A comparison of VLSM and VBM in a
cohort of patients with post-stroke aphasia
Introduction
ā€¢ Studies attempting to map post-stroke cognitive or motor symptoms to lesion location have been
available in the literature for over 150 years. In the last two decades, two computational techniques
have been developed to identify the lesion sites associated with behavioural impairments. Voxel
Based Morphometry (VBM) has now been used extensively for this purpose in many different patient
populations. More recently, Voxel-based Lesion Symptom Mapping (VLSM) was developed specifically
for the purpose of identifying lesionā€“symptom relationships in stroke patients, and has been used
extensively to study, among others functions, language, motor abilities and attention. However, no
studies have compared the results of these two techniques so far. In this study we compared VLSM
and VBM in a cohort of 20 patients with chronic post-stroke aphasia.
Materials and methods
ā€¢ Participants
ā€¢ Patients were tested cognitive-behavioral tests
ā€¢ Imaging data acquisitionusing a 3 T Siemens Magentom Trio Tim MRI scanne and 1.5 T MRI Siemens
scanner
ā€¢ Data pre-processing for VLSM and VBM
ā€¢ Data analysis
Material and methods
1. Participants
Material and methods
2. Behavioral test
ā€¢ Comprehensive Aphasia Test were analysed:
ā€¢ 1) Auditory sentence comprehension: participants
were read a sentence and were asked to point to
one of four pictures which best fitted the sentence.
The task had 16 trials.
ā€¢ 2) Word repetition: participants were asked to
repeat words read out by the examiner. This task
included 16 short words.
ā€¢ 3) Object naming: participants were asked to name
24 pictures of objects. In all tasks, a correct answer
was given 2 points. A delayed answer or a correct
answer following self-correction was given 1 point.
In the auditory sentence comprehension and the
word repetition tasks, if the participant asked the
examiner to repeat the question, and this was
followed by a correct answer, 1 point was given as
well. Maximum possible scores and the cut-off
score for defining impaired function are presented
in Fig 1
Fig. 1. Behavioural scores for all patients in
the various language tasks. Red lines
represent the cut-off score for deļ¬ning
impaired function in each task.
3. Imaging data acquisition
ā€¢ Imaging was performed using a 3 T Siemens Magentom Trio Tim MRI
scanner. Four patients could not undergo a 3 T MRI scan due to
cardiac stents (n = 2) or PFO devices (n = 2) which were not 3 T
compatible. These four patients were scanned using a 1.5 T MRI
Siemens scanner (Erlangen, Germany) and the effect of using a
different scanner on the results was considered
Data pre-processing for VLSM
1.Lesion Identification
2.Validation:
3.Mask Creation:
4.Spatial Normalization:
VBM
ā€¢ 1. Creation of masks.
ā€¢ 2. Data pre-processing for VBM.
ā€¢ Fig. 2. An overlay of all
patients' lesions. Colours
represent number of patients
with a lesion to a speciļ¬c
voxel. Warmer areas indicate
areas of greater lesion
overlap. Colour range runs
from 1 (the lowest value in the
image) to 14 (the highest
value in the image).
Auditory sentence comprehension
1.Common Findings:
1.Both VBM and VLSM found associations with auditory sentence
comprehension in the superior and middle temporal gyri (STG/MTG).
2.Poor performance correlated with lower gray matter (GM) voxel
intensity in the STG/MTG border and lower white matter (WM) voxel
intensity.
3.Adding age as a covariate did not alter the pattern of results.
2.Differences Between VBM and VLSM:
1.VBM extended more laterally and medially, involving the post-central
gyrus and the supramarginal gyrus (SMG).
2.VLSM extended more posteriorly, including the post-central gyrus,
superior parietal lobule, pre-central gyrus, inferior frontal gyrus (IFG),
and insula.
ā€¢ Fig. 3. Colour maps of signiļ¬cant regions in the VBM (top); VLSM (middle);
and both methods (bottom) in the auditory sentence comprehension task
(p b 0.05, FDR correction). All voxels lesioned in at least 5% of patients are
included. Colours represent Z-scores.
Word Repetition:
ā€¢ Overlap and Differences:Limited overlap between VBM and
VLSM in the supramarginal gyrus (SMG) and superior temporal
gyrus (STG).
ā€¢ VBM highlighted larger clusters, including the insula, inferior
frontal gyrus (IFG), and pre-central gyrus.
ā€¢ VLSM identified small unconnected clusters in frontal and
parietal lobes.
Object Naming:
1.Common Findings:
1.Both methods associated poorer performance in object naming with
the IFG, insula, STG, and SMG.
2.Differences:
1.VBM found additional associations in IFG pars triangularis/BA 45 and
subcortical regions.
2.VLSM found associations with white matter regions.
Analysis of Variations and Covariates:
1.VBM Analysis:
1.No significant correlations at corrected thresholds for auditory
sentence comprehension.
2.Effects of scanner type and number of voxels analyzed did not
significantly affect results.
2.VLSM Analysis:
1.No differences between analyzing 5% or 20% of damaged voxels.
2.Changes in VBM cluster sizes with different percentages of damaged
voxels.
Conclusions
ā€¢ We compared the use of VBM and VLSM in the study of language
impairments in a cohort of chronic stroke patients. Areas where the
two techniques gave overlapping results are those areas previously
shown to be relevant for the cognitive functions tested. This suggests
that using both techniques and looking for overlaps can potentially
increase results reliability when seeking to map cognitive functions in
the brain. However, the two techniques do not produce precisely the
same results and potentially answer somewhat different questions.
Since each method has some clear advantages over the other, we
suggest that in future studies of chronic stroke patients, researchers
consider the differences between the techniques when evaluating
results and their implications.
Differences
ā€¢ VBM extended more laterally and medially, involving the post-
central gyrus and the supramarginal gyrus (SMG).
ā€¢ VLSM extended more posteriorly, including the post-central
gyrus, superior parietal lobule, pre-central gyrus, inferior frontal
gyrus (IFG), and insula.
Specific Voxels:
ā€¢ Voxel [āˆ’ 60, āˆ’ 6, āˆ’ 6] in the anterior MTG was significant in both
analyses.
ā€¢ A posterior voxel [āˆ’ 66, āˆ’ 24, 4] was significant only in VBM.
ā€¢ A frontal lobe voxel [āˆ’ 30, 48, āˆ’ 8] was significant only in VLSM.

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A comparison of VLSM and VBM in a cohort of patients with post-stroke aphasia

  • 1. A comparison of VLSM and VBM in a cohort of patients with post-stroke aphasia
  • 2. Introduction ā€¢ Studies attempting to map post-stroke cognitive or motor symptoms to lesion location have been available in the literature for over 150 years. In the last two decades, two computational techniques have been developed to identify the lesion sites associated with behavioural impairments. Voxel Based Morphometry (VBM) has now been used extensively for this purpose in many different patient populations. More recently, Voxel-based Lesion Symptom Mapping (VLSM) was developed specifically for the purpose of identifying lesionā€“symptom relationships in stroke patients, and has been used extensively to study, among others functions, language, motor abilities and attention. However, no studies have compared the results of these two techniques so far. In this study we compared VLSM and VBM in a cohort of 20 patients with chronic post-stroke aphasia.
  • 3. Materials and methods ā€¢ Participants ā€¢ Patients were tested cognitive-behavioral tests ā€¢ Imaging data acquisitionusing a 3 T Siemens Magentom Trio Tim MRI scanne and 1.5 T MRI Siemens scanner ā€¢ Data pre-processing for VLSM and VBM ā€¢ Data analysis
  • 4. Material and methods 1. Participants
  • 5. Material and methods 2. Behavioral test ā€¢ Comprehensive Aphasia Test were analysed: ā€¢ 1) Auditory sentence comprehension: participants were read a sentence and were asked to point to one of four pictures which best fitted the sentence. The task had 16 trials. ā€¢ 2) Word repetition: participants were asked to repeat words read out by the examiner. This task included 16 short words. ā€¢ 3) Object naming: participants were asked to name 24 pictures of objects. In all tasks, a correct answer was given 2 points. A delayed answer or a correct answer following self-correction was given 1 point. In the auditory sentence comprehension and the word repetition tasks, if the participant asked the examiner to repeat the question, and this was followed by a correct answer, 1 point was given as well. Maximum possible scores and the cut-off score for defining impaired function are presented in Fig 1 Fig. 1. Behavioural scores for all patients in the various language tasks. Red lines represent the cut-off score for deļ¬ning impaired function in each task.
  • 6. 3. Imaging data acquisition ā€¢ Imaging was performed using a 3 T Siemens Magentom Trio Tim MRI scanner. Four patients could not undergo a 3 T MRI scan due to cardiac stents (n = 2) or PFO devices (n = 2) which were not 3 T compatible. These four patients were scanned using a 1.5 T MRI Siemens scanner (Erlangen, Germany) and the effect of using a different scanner on the results was considered
  • 7. Data pre-processing for VLSM 1.Lesion Identification 2.Validation: 3.Mask Creation: 4.Spatial Normalization: VBM ā€¢ 1. Creation of masks. ā€¢ 2. Data pre-processing for VBM.
  • 8. ā€¢ Fig. 2. An overlay of all patients' lesions. Colours represent number of patients with a lesion to a speciļ¬c voxel. Warmer areas indicate areas of greater lesion overlap. Colour range runs from 1 (the lowest value in the image) to 14 (the highest value in the image).
  • 9. Auditory sentence comprehension 1.Common Findings: 1.Both VBM and VLSM found associations with auditory sentence comprehension in the superior and middle temporal gyri (STG/MTG). 2.Poor performance correlated with lower gray matter (GM) voxel intensity in the STG/MTG border and lower white matter (WM) voxel intensity. 3.Adding age as a covariate did not alter the pattern of results. 2.Differences Between VBM and VLSM: 1.VBM extended more laterally and medially, involving the post-central gyrus and the supramarginal gyrus (SMG). 2.VLSM extended more posteriorly, including the post-central gyrus, superior parietal lobule, pre-central gyrus, inferior frontal gyrus (IFG), and insula.
  • 10. ā€¢ Fig. 3. Colour maps of signiļ¬cant regions in the VBM (top); VLSM (middle); and both methods (bottom) in the auditory sentence comprehension task (p b 0.05, FDR correction). All voxels lesioned in at least 5% of patients are included. Colours represent Z-scores.
  • 11. Word Repetition: ā€¢ Overlap and Differences:Limited overlap between VBM and VLSM in the supramarginal gyrus (SMG) and superior temporal gyrus (STG). ā€¢ VBM highlighted larger clusters, including the insula, inferior frontal gyrus (IFG), and pre-central gyrus. ā€¢ VLSM identified small unconnected clusters in frontal and parietal lobes.
  • 12. Object Naming: 1.Common Findings: 1.Both methods associated poorer performance in object naming with the IFG, insula, STG, and SMG. 2.Differences: 1.VBM found additional associations in IFG pars triangularis/BA 45 and subcortical regions. 2.VLSM found associations with white matter regions.
  • 13. Analysis of Variations and Covariates: 1.VBM Analysis: 1.No significant correlations at corrected thresholds for auditory sentence comprehension. 2.Effects of scanner type and number of voxels analyzed did not significantly affect results. 2.VLSM Analysis: 1.No differences between analyzing 5% or 20% of damaged voxels. 2.Changes in VBM cluster sizes with different percentages of damaged voxels.
  • 14. Conclusions ā€¢ We compared the use of VBM and VLSM in the study of language impairments in a cohort of chronic stroke patients. Areas where the two techniques gave overlapping results are those areas previously shown to be relevant for the cognitive functions tested. This suggests that using both techniques and looking for overlaps can potentially increase results reliability when seeking to map cognitive functions in the brain. However, the two techniques do not produce precisely the same results and potentially answer somewhat different questions. Since each method has some clear advantages over the other, we suggest that in future studies of chronic stroke patients, researchers consider the differences between the techniques when evaluating results and their implications.
  • 15. Differences ā€¢ VBM extended more laterally and medially, involving the post- central gyrus and the supramarginal gyrus (SMG). ā€¢ VLSM extended more posteriorly, including the post-central gyrus, superior parietal lobule, pre-central gyrus, inferior frontal gyrus (IFG), and insula.
  • 16. Specific Voxels: ā€¢ Voxel [āˆ’ 60, āˆ’ 6, āˆ’ 6] in the anterior MTG was significant in both analyses. ā€¢ A posterior voxel [āˆ’ 66, āˆ’ 24, 4] was significant only in VBM. ā€¢ A frontal lobe voxel [āˆ’ 30, 48, āˆ’ 8] was significant only in VLSM.

Editor's Notes

  1. Lesion Identification: Lesions were defined using the Regions of Interest (ROI) facility in Analyze 7.5 software. One author manually traced lesions on T2-weighted scans in native space, consulting coregistered sequences (FLAIR, PD, and MPRAGE). Lesion contours were drawn on the outer borders of hyper-intense regions, considering intensity changes in other modalities. Sulci widening was included in lesion definition only if there was clear asymmetry. Periventricular regions were defined as lesioned with clear signal intensity change and cortical extension to the periventricular space. Areas around enlarged ventricles with normal signal intensity or symmetric periventricular white matter changes were not defined as lesioned. Validation: Drawn lesions were validated by a trained neurologist who was blinded to patient diagnoses. A lesion overlap map was generated (Fig. 2) to visualize common areas of lesions. Mask Creation: Binary masks were created from the lesions using MRIcron. MPRAGE images were normalized and segmented into grey matter (GM), white matter (WM), and cerebro-spinal fluid (CSF) probability maps in standard Montreal Neurological Institute (MNI) space. The unified segmentation-normalization algorithm in Statistical Parametric Mapping software (SPM8) was used for this process. Spatial Normalization: Lesion masks were utilized to mask out abnormal tissue during spatial normalization. Spatial parameter files from the normalization routine were applied to the original drawn lesions. This resulted in spatially normalized binary lesion definitions for each patient in standard MNI stereotactic space. These pre-processing steps are crucial for accur