Aphasia Neuroplasticity Review

Saur et al. (2006)

Reference

Authors	Saur D, Lange R, Baumgaertner A, Schraknepper V, Willmes K, Rijntjes M, Weiller C
Title	Dynamics of language reorganization after stroke
Reference	Brain 2006; 129: 1371-1384
PMID	16638796
DOI	10.1093/brain/awl090

Participants

Language	German
Inclusion criteria	MCA; age < 70 years; able to distinguish forward vs backward speech outside the scanner; no pronounced small vessel disease
Number of individuals with aphasia	14 (plus 4 excluded: 1 health problems; 1 scanner noise; 2 did not tolerate fMRI)
Number of control participants	14
Were any of the participants included in any previous studies?	No
Is age reported for patients and controls, and matched?	Yes (mean 51.9 ± 14.2 years, range 16-68 years)
Is sex reported for patients and controls, and matched?	Yes (males: 11; females: 3)
Is handedness reported for patients and controls, and matched?	Yes (right: 12; left: 1; other: 1)
Is time post stroke onset reported and appropriate to the study design?	Yes (T1 acute: mean 1.8 days, range 0-4 days; T2 subacute: mean 12.1 days, range 3-16 days; T3 chronic: mean 321 days, range 102-513 days)
To what extent is the nature of aphasia characterized?	Comprehensive battery
Language evaluation	AABT, AAT including TT, analysis of spontaneous speech, CETI, Language Recovery Score (LRS) derived from all these measures plus in-scanner task performance
Aphasia severity	T1: LRS mean 0.44, range 0.11-0.81; 1 mild, 1 mild-moderate, 7 moderate, 3 moderate-severe, 2 severe per AAT; T2: LRS mean 0.71, range 0.33-0.92; 2 recovered, 2 recovered-mild, 2 mild, 3 mild-moderate, 3 moderate, 2 severe per AAT; T3: LRS mean 0.91, range 0.66-1.00; 8 recovered, 2 recovered-mild, 3 mild, 1 moderate per AAT
Aphasia type	T1: 9 non-fluent, 5 fluent; T2: not stated; T3: 6 recovered, 4 minimal language impairment, 3 anomic, 1 global
First stroke only?	Yes
Stroke type	Ischemic only
To what extent is the lesion distribution characterized?	Individual lesions
Lesion extent	Not stated
Lesion location	L MCA; 4 frontal (2 extending to temporoparietal); 5 temporoparietal (2 extending to subcortical); 4 striatocapsular (2 extending to cortical); 1 frontoparietal
Participants notes	198 patients with aphasia were screened

Imaging

Modality	fMRI
Is the study cross-sectional or longitudinal?	Longitudinal—recovery
If longitudinal, at what time point(s) were imaging data acquired?	T1 acute: mean 1.8 days, range 0-4 days; T2 subacute: mean 12.1 days, range 3-16 days; T3 chronic: mean 321 days, range 102-513 days
If longitudinal, was there any intervention between the time points?	Standard SLT throughout the observation period including at least 3 weeks inpatient
Is the scanner described?	Yes (Siemens Trio 3 Tesla)
Is the timing of stimulus presentation and image acquisition clearly described and appropriate?	Yes
Design type	Event-related
Total images acquired	660
Are the imaging acquisition parameters, including coverage, adequately described and appropriate?	Yes (whole brain)
Is preprocessing and intrasubject coregistration adequately described and appropriate?	Yes
Is first level model fitting adequately described and appropriate?	Yes
Is intersubject normalization adequately described and appropriate?	Yes
Imaging notes	—

Conditions

Are the conditions clearly described?

Yes

Condition	Response type	Repetitions	All groups could do?	All individuals could do?
listening to sentences and making a plausibility judgment	Button press	92	Unknown	No
listening to reversed speech	Button press	92	Yes	Unknown
rest	None	implicit baseline	N/A	N/A

Conditions notes

In the auditory sentence comprehension condition, participants had to press a button to semantically anomalous sentences; in the reversed speech condition, they had to always press the button; the behavioral scores provided are not explained in the paper, but per a personal communication cited by Geranmayeh et al. (2014), 10% of the score reflects discrimination between intelligible and reversed speech, while 90% reflects semantic anomaly judgment; our coding of behavior is based on this limited information

Contrasts

Are the contrasts clearly described?

Yes

Contrast 1: listening to sentences and making a plausibility judgment vs listening to reversed speech

Language condition	Listening to sentences and making a plausibility judgment
Control condition	Listening to reversed speech
Are the conditions matched for visual demands?	Yes
Are the conditions matched for auditory demands?	Yes
Are the conditions matched for motor demands?	No
Are the conditions matched for cognitive/executive demands?	No
Is accuracy matched between the language and control tasks for all relevant groups?	Unknown, not reported
Is reaction time matched between the language and control tasks for all relevant groups?	Unknown, not reported
Behavioral data notes	Reported accuracy combines the two conditions in a way that is not explained
Are control data reported in this paper or another that is referenced?	Yes
Does the contrast selectively activate plausible relevant language regions in the control group?	Yes
Are activations lateralized in the control data?	Yes
Control activation notes	L temporal and L > R frontal
Contrast notes	—

Analyses

Are the analyses clearly described?

Yes

Voxelwise analysis 1

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal change in aphasia
Group(s)	Aphasia T2 vs T1
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	↑ L insula ↑ R IFG pars orbitalis ↑ R insula ↑ R SMA/medial prefrontal
Findings notes	R IFG/insula activation noted to survive FWE correction at p < .05

Voxelwise analysis 2

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal change in aphasia
Group(s)	Aphasia T3 vs T2
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.005
Cluster extent	None
Statistical details	Threshold was lowered to reveal the R frontal change in activation
Findings	↓ R IFG pars orbitalis ↓ R occipital
Findings notes	—

Voxelwise analysis 3

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal change in aphasia
Group(s)	Aphasia T3 vs T1
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	↑ L IFG pars orbitalis ↑ L SMA/medial prefrontal ↑ L posterior inferior temporal gyrus/fusiform gyrus ↑ R IFG pars orbitalis ↑ R insula
Findings notes	—

Voxelwise analysis 4

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional aphasia vs control
Group(s)	Aphasia T1 vs control
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	↓ L IFG pars triangularis ↓ L IFG pars orbitalis ↓ L insula ↓ L posterior MTG ↓ L posterior inferior temporal gyrus/fusiform gyrus ↓ R IFG pars orbitalis ↓ R insula
Findings notes	L STG in table is actually MTG based on coordinates

Voxelwise analysis 5

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional aphasia vs control
Group(s)	Aphasia T2 vs control
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.005
Cluster extent	None
Statistical details	Threshold was lowered to reveal L IFG
Findings	↑ L IFG pars orbitalis ↑ L insula ↑ L SMA/medial prefrontal ↑ R IFG
Findings notes	—

Voxelwise analysis 6

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional aphasia vs control
Group(s)	Aphasia T3 vs control
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear similar
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	None
Findings notes	—

Voxelwise analysis 7

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional correlation with language or other measure
Group(s)	Aphasia T1
Covariate	Language recovery score T1
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	↑ L IFG ↑ L SMA/medial prefrontal ↑ R IFG pars triangularis
Findings notes	—

Voxelwise analysis 8

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional correlation with language or other measure
Group(s)	Aphasia T2
Covariate	Language recovery score T2
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Unknown, no test
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	None
Findings notes	—

Voxelwise analysis 9

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional correlation with language or other measure
Group(s)	Aphasia T3
Covariate	Language recovery score T3
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Unknown, no test
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	None
Findings notes	—

Voxelwise analysis 10

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal correlation with language or other measure
Group(s)	Aphasia T2 vs T1
Covariate	% change in language recovery score
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Unknown, no test
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	↑ L SMA/medial prefrontal ↑ R insula ↑ R SMA/medial prefrontal
Findings notes	—

Voxelwise analysis 11

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal correlation with language or other measure
Group(s)	Aphasia T3 vs T2
Covariate	% change in language recovery score
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Unknown, no test
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	None
Findings notes	—

Voxelwise analysis 12

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal correlation with language or other measure
Group(s)	Aphasia T3 vs T1
Covariate	% change in language recovery score
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Unknown, no test
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Voxelwise
Search volume	Whole brain
Correction for multiple comparisons	No correction
Software	SPM2
Voxelwise p	.001
Cluster extent	None
Statistical details	—
Findings	None
Findings notes	—

ROI analysis 1

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal change in aphasia
Group(s)	Aphasia T2 vs T1
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Regions of interest (ROI)
ROI type	Functional
How many ROIs are there?	6
What are the ROI(s)?	(1) L IFG pars orbitalis; (2) L IFG pars triangularis; (3) L MTG; (4) R insula; (5) R IFG pars triangularis; (6) R SMA
How are the ROI(s) defined?	Peak voxels of overall activation map based on all three time points in patients
Correction for multiple comparisons	Familywise error (FWE)
Statistical details	—
Findings	↑ R insula ↑ R SMA/medial prefrontal
Findings notes	Some other ROIs also significant prior to correction for multiple comparisons; n.b. performance confound

ROI analysis 2

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal change in aphasia
Group(s)	Aphasia T3 vs T2
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Regions of interest (ROI)
ROI type	Functional
How many ROIs are there?	6
What are the ROI(s)?	(1) L IFG pars orbitalis; (2) L IFG pars triangularis; (3) L MTG; (4) R insula; (5) R IFG pars triangularis; (6) R SMA
How are the ROI(s) defined?	Peak voxels of overall activation map based on all three time points in patients
Correction for multiple comparisons	Familywise error (FWE)
Statistical details	—
Findings	None
Findings notes	Some other ROIs also significant prior to correction for multiple comparisons; n.b. performance confound

ROI analysis 3

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Longitudinal change in aphasia
Group(s)	Aphasia T3 vs T1
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Regions of interest (ROI)
ROI type	Functional
How many ROIs are there?	6
What are the ROI(s)?	(1) L IFG pars orbitalis; (2) L IFG pars triangularis; (3) L MTG; (4) R insula; (5) R IFG pars triangularis; (6) R SMA
How are the ROI(s) defined?	Peak voxels of overall activation map based on all three time points in patients
Correction for multiple comparisons	Familywise error (FWE)
Statistical details	—
Findings	↑ L posterior MTG
Findings notes	Some other ROIs also significant prior to correction for multiple comparisons; n.b. performance confound

ROI analysis 4

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional aphasia vs control
Group(s)	Aphasia T1 vs control
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Regions of interest (ROI)
ROI type	Functional
How many ROIs are there?	6
What are the ROI(s)?	(1) L IFG pars orbitalis; (2) L IFG pars triangularis; (3) L MTG; (4) R insula; (5) R IFG pars triangularis; (6) R SMA
How are the ROI(s) defined?	Peak voxels of overall activation map based on all three time points in patients
Correction for multiple comparisons	No correction
Statistical details	Circular because ROIs defined in one group
Findings	↓ L posterior MTG ↓ R IFG pars triangularis
Findings notes	R IFG difference described in text but not table

ROI analysis 5

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional aphasia vs control
Group(s)	Aphasia T2 vs control
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear mismatched
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Regions of interest (ROI)
ROI type	Functional
How many ROIs are there?	6
What are the ROI(s)?	(1) L IFG pars orbitalis; (2) L IFG pars triangularis; (3) L MTG; (4) R insula; (5) R IFG pars triangularis; (6) R SMA
How are the ROI(s) defined?	Peak voxels of overall activation map based on all three time points in patients
Correction for multiple comparisons	No correction
Statistical details	Circular because ROIs defined in one group
Findings	None
Findings notes	—

ROI analysis 6

First level contrast	Listening to sentences and making a plausibility judgment vs listening to reversed speech
Analysis class	Cross-sectional aphasia vs control
Group(s)	Aphasia T3 vs control
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Yes
Is accuracy matched across the second level contrast?	Appear similar
Is reaction time matched across the second level contrast?	Unknown, not reported
Behavioral data notes	Accuracy combines language and control conditions
Type of analysis	Regions of interest (ROI)
ROI type	Functional
How many ROIs are there?	6
What are the ROI(s)?	(1) L IFG pars orbitalis; (2) L IFG pars triangularis; (3) L MTG; (4) R insula; (5) R IFG pars triangularis; (6) R SMA
How are the ROI(s) defined?	Peak voxels of overall activation map based on all three time points in patients
Correction for multiple comparisons	No correction
Statistical details	Circular because ROIs defined in one group
Findings	None
Findings notes	—

Notes

Excluded analyses

Additional analyses using absolute improvements in LRS instead of proportional improvements