Aphasia Neuroplasticity Review

Hartwigsen et al. (2020)

Reference

Authors	Hartwigsen G, Stockert A, Charpentier L, Wawrzyniak M, Klingbeil J, Wrede K, Obrig H, Saur
Title	Short-term modulation of the lesioned language network
Reference	eLife 2020; 9: e54277
PMID	32181741
DOI	10.7554/elife.54277

Participants

Language	German
Inclusion criteria	Lesion involving left temporo-parietal cortex and sparing left frontal cortex; relatively well-recovered
Number of individuals with aphasia	12 (plus 2 excluded: 1 lost to follow-up; 1 did not show any sound-related neural activation in auditory cortex after sham cTBS)
Number of control participants	0
Were any of the participants included in any previous studies?	No
Is age reported for patients and controls, and matched?	Yes (mean 58.8 years, range 43-72 years)
Is sex reported for patients and controls, and matched?	Yes (males: 8; females: 4)
Is handedness reported for patients and controls, and matched?	Yes (right: 12; left: 0)
Is time post stroke onset reported and appropriate to the study design?	Yes (mean 37.9 ± 34.8 months, range 6-122 months)
To what extent is the nature of aphasia characterized?	Not at all
Language evaluation	AAT
Aphasia severity	7 mild residual aphasia, 5 recovered
Aphasia type	Not stated
First stroke only?	Yes
Stroke type	Ischemic only
To what extent is the lesion distribution characterized?	Lesion overlay
Lesion extent	Range 11.9-176.3 cc
Lesion location	Left temporo-parietal cortex; maximal overlap in SMG
Participants notes	—

Imaging

Modality	fMRI
Is the study cross-sectional or longitudinal?	Longitudinal—chronic treatment
If longitudinal, at what time point(s) were imaging data acquired?	T1/T2/T3: chronic; sessions consisted of cTBS over left anterior IFG, cTBS over left posterior IFG, or sham; sessions at least 7 days apart in randomized order
If longitudinal, was there any intervention between the time points?	CTBS
Is the scanner described?	Yes (Siemens Verio 3 Tesla)
Is the timing of stimulus presentation and image acquisition clearly described and appropriate?	No* (moderate limitation) (stimulus timing not described in detail; stated duration of data acquisition substantially outside possible range of duration of stimuli)
Design type	Block
Total images acquired	740
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?	No (lesion impact not addressed)
Imaging notes	—

Conditions

Are the conditions clearly described?

Yes

Condition	Response type	Repetitions	All groups could do?	All individuals could do?
syllable count decision	Button press	10	Yes	Yes
semantic decision	Button press	10	Yes	Yes
rest	None	20	N/A	N/A

Conditions notes

Extent of recovery supports the assertion that all individuals could do the tasks

Contrasts

Are the contrasts clearly described?

Yes

Contrast 1: syllable count decision vs rest

Language condition	Syllable count decision
Control condition	Rest
Are the conditions matched for visual demands?	Yes
Are the conditions matched for auditory demands?	No
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?	N/A, tasks not comparable
Is reaction time matched between the language and control tasks for all relevant groups?	N/A, tasks not comparable
Behavioral data notes	—
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?	Somewhat
Control activation notes	Control data in Hartwigsen et al. (2017); L-lateralized IFG but bilateral SMG
Contrast notes	—

Contrast 2: semantic decision vs rest

Language condition	Semantic decision
Control condition	Rest
Are the conditions matched for visual demands?	Yes
Are the conditions matched for auditory demands?	No
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?	N/A, tasks not comparable
Is reaction time matched between the language and control tasks for all relevant groups?	N/A, tasks not comparable
Behavioral data notes	—
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	Control data in Hartwigsen et al. (2017); L-lateralized IFG and AG most prominent
Contrast notes	—

Analyses

Are the analyses clearly described?

Yes

Voxelwise analysis 1

First level contrast	Syllable count decision vs rest
Analysis class	Cross-sectional between two groups with aphasia
Group(s)	Aphasia after cTBS to posterior IFG vs sham; same patients, repeated measures
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?	Yes, matched
Is reaction time matched across the second level contrast?	No, different
Behavioral data notes	Significantly slower response times when cTBS was applied over pIFG relative to when sham cTBS was applied
Type of analysis	Voxelwise
Search volume	Voxels spared in all patients
Correction for multiple comparisons	Clusterwise correction with with GRFT and stringent voxelwise p
Software	SPM12
Voxelwise p	.001
Cluster extent	Based on GRFT
Statistical details	—
Findings	↓ L IFG pars opercularis ↓ L SMA/medial prefrontal ↓ R SMA/medial prefrontal ↓ R basal ganglia
Findings notes	Based on Figure 4A and Table 3

Voxelwise analysis 2

First level contrast	Syllable count decision vs rest
Analysis class	Cross-sectional between two groups with aphasia
Group(s)	Aphasia after cTBS to posterior IFG vs after cTBS to anterior IFG; same patients, repeated measures
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?	Yes, matched
Is reaction time matched across the second level contrast?	No, different
Behavioral data notes	Significantly slower response times when cTBS was applied over pIFG relative to when cTBS was applied over aIFG
Type of analysis	Voxelwise
Search volume	Voxels spared in all patients
Correction for multiple comparisons	Clusterwise correction with with GRFT and stringent voxelwise p
Software	SPM12
Voxelwise p	.001
Cluster extent	Based on GRFT
Statistical details	—
Findings	↓ L IFG pars opercularis
Findings notes	Based on Table 3

Voxelwise analysis 3

First level contrast	Semantic decision vs rest
Analysis class	Cross-sectional between two groups with aphasia
Group(s)	Aphasia after cTBS to anterior IFG vs sham; same patients, repeated measures
Covariate	—
Is the second level contrast valid in terms of the group(s), time point(s), and measures involved?	Somewhat (no behavioral difference)
Is accuracy matched across the second level contrast?	Yes, matched
Is reaction time matched across the second level contrast?	Yes, matched
Behavioral data notes	Difference in reaction time did not survive correction
Type of analysis	Voxelwise
Search volume	Voxels spared in all patients
Correction for multiple comparisons	Clusterwise correction with with GRFT and stringent voxelwise p
Software	SPM12
Voxelwise p	.001
Cluster extent	Based on GRFT
Statistical details	—
Findings	↓ L insula ↓ L dorsolateral prefrontal cortex ↓ R insula ↓ R dorsolateral prefrontal cortex ↓ R SMA/medial prefrontal
Findings notes	Based on Figure 4B and Table 3

Voxelwise analysis 4

First level contrast	Semantic decision vs rest
Analysis class	Cross-sectional between two groups with aphasia
Group(s)	Aphasia after cTBS to anterior IFG vs after cTBS to posterior IFG ; same patients, repeated measures
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?	Yes, matched
Is reaction time matched across the second level contrast?	No, different
Behavioral data notes	Significantly slower response times when cTBS was applied over aIFG relative to when cTBS was applied over pIFG
Type of analysis	Voxelwise
Search volume	Voxels spared in all patients
Correction for multiple comparisons	Clusterwise correction with with GRFT and stringent voxelwise p
Software	SPM12
Voxelwise p	.001
Cluster extent	Based on GRFT
Statistical details	—
Findings	↓ L insula ↓ R insula ↓ R dorsolateral prefrontal cortex
Findings notes	Based on Table 3

Complex analysis 1

First level contrast	Syllable count decision vs rest
Analysis class	Cross-sectional correlation with language or other measure
Group(s)	Aphasia after cTBS to posterior IFG vs sham; same patients, repeated measures
Covariate	Δ RT for syllable decision (cTBS to posterior IFG timepoint vs sham timepoint)
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, not reported
Is reaction time matched across the second level contrast?	RT is covariate
Behavioral data notes	—
Type of analysis	Complex
Statistical details	Whole brain correlations were computed between the difference in functional activity after cTBS to posterior IFG versus sham stimulation, and the difference in reaction times on the syllable counting task under these two conditions. The resulting SPM was thresholded at voxelwise p < .001 (CDT) followed by correction for multiple comparisons based on cluster extent and GRFT using SPM12.
Findings	Other
Findings notes	Upregulation of the R supramarginal gyrus after cTBS was significantly associated with slowing of RT after cTBS. This finding remained significant after including lesion volume as covariate.

Complex analysis 2

First level contrast	Semantic decision vs rest
Analysis class	Cross-sectional correlation with language or other measure
Group(s)	Aphasia after cTBS to anterior IFG vs sham; same patients, repeated measures
Covariate	Δ RT for semantic decision (cTBS to posterior IFG timepoint vs sham timepoint)
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, not reported
Is reaction time matched across the second level contrast?	RT is covariate
Behavioral data notes	—
Type of analysis	Complex
Statistical details	Whole brain correlations were computed between the difference in functional activity after cTBS to anterior IFG versus sham stimulation, and the difference in reaction times on the semantic decision task under these two conditions. The resulting SPM was thresholded at voxelwise p < .001 (CDT) followed by correction for multiple comparisons based on cluster extent and GRFT using SPM12.
Findings	None
Findings notes	—

Notes

Excluded analyses

—