1. Neuroscience
Download icon

Short-term modulation of the lesioned language network

  1. Gesa Hartwigsen  Is a corresponding author
  2. Anika Stockert
  3. Louise Charpentier
  4. Max Wawrzyniak
  5. Julian Klingbeil
  6. Katrin Wrede
  7. Hellmuth Obrig
  8. Dorothee Saur
  1. Lise Meitner Research Group Cognition and Plasticity, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany
  2. Language and Aphasia Laboratory, Department of Neurology, University of Leipzig Medical Centre, Germany
  3. Clinic for Cognitive Neurology, University of Leipzig Medical Centre & Max Planck Institute for Human Cognitive and Brain Sciences, Germany
Research Article
Cite this article as: eLife 2020;9:e54277 doi: 10.7554/eLife.54277
5 figures, 3 tables, 1 data set and 1 additional file


Overview of the experimental design.

(A) After a short training session, patients received effective or sham continuous theta burst stimulation (cTBS-600) either over the anterior or posterior inferior frontal gyrus (a/pIFG) in different sessions. Thereafter, they performed phonological and semantic word judgement tasks in two fMRI runs. (B) Tasks were divided into 10 miniblocks per task and run, each consisting of 6 German words (e.g. ‘Zebra’ or ‘Computer’) with varying stimulus onset asynchrony. min = minutes; s = seconds.

Behavioral results.

(A) Lesion overlap for all patients. All patients had lesions in their left temporo-parietal cortex with the strongest overlap in the supramarginal gyrus. Note that the frontal cortex was intact in all patients. (B) Continuous theta burst stimulation (cTBS) sites over the left anterior and posterior inferior frontal gyrus (a/pIFG). Mean stimulation sites were taken from a previous study and transferred to the individual patient’s brain. (C) Effects of cTBS on task processing. Left panel: Relative to cTBS over aIFG or sham cTBS, cTBS of pIFG significantly delayed phonological response speed. The opposite pattern was found for semantic processing. Relative to cTBS over pIFG or sham cTBS, cTBS over aIFG significantly delayed semantic response speed. Right panel: Effects of cTBS on error rates were not significant. *p<0.05. (*) does not survive a Bonferroni-Holm correction for multiple comparisons. RTs = reaction times, SEM = standard error of the mean. Coordinates are given in MNI space.

Residual language network after sham continuous theta burst stimulation.

(A) Phonological decisions compared to rest and (B) semantic decisions compared to rest. Voxels with at least one lesion are masked in dark grey and were excluded from the analysis. Results are shown at p<0.001 uncorrected for display reasons. 

Task-specific continuous theta burst stimulation (cTBS) effects on word decisions.

(A) Phonological decisions. Relative to sham cTBS, cTBS of pIFG significantly decreased neural activity at the stimulated area. (B) Semantic decisions. Relative to sham cTBS, cTBS of aIFG significantly decreased neural activity in a larger network, including the bilateral anterior insula and adjacent aIFG. Right panels display the respective parameter estimates (arbitrary units) for the different cTBS conditions that were extracted at the respective mean group peak coordinates from the effect of interest for each task condition against rest. p<0.001 uncorrected for display reasons. a/pIFG = anterior/posterior inferior frontal gyrus. Coordinates are given in MNI space.

Compensatory effects during phonological processing.

(A) Regression analysis. The individual delay in phonological response speed after effective continuous theta burst stimulation (cTBS) over pIFG vs. sham cTBS (pIFG – sham cTBS) was correlated with the upregulation of the contralesional right supramarginal gyrus (SMG; shown at p<0.001 uncorrected for display reasons). (B) Correlation between the individual mean fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF) and the behavioural cTBS effect. Upper panel: 3D rendering generated with FSLview showing the region of interest in the right SLF that was used to extract the mean FA. The SLF ROI was obtained from the Juelich Histological atlas. Lower panel: Regression analysis. The individual FA for the right SLF was negatively correlated with the relative increase in the individual mean reaction times for the phonological task after cTBS of pIFG relative to sham cTBS.


Table 1
Patient characteristics: Test data.
PatientAgeSexEducationLaterality Time since strokeLesion siteLesion size (cm3)% overlap
with AG
% overlap
with SMG
0154.2m120.9 10.1temporo-parietal 66.907640Isolated paraphasias comprehension deficits
0252.9m120.8 17.7parietal 59.281974No aphasia, expressive phon.deficits
0363.9m 8 1 76.1parietal 93.199460Residual aphasia,expressive phon.deficits
0449.6m100.9122.4parietal 76.478579Residual aphasia,expressive phon.deficits
0543.2w10 1 57.8parietal 70.183382Residual aphasia
0665.2m12 1 36.2parietal 18.55 228No aphasia
0772.8w10 1 24.0parietal176.348682Residual aphasia,decreased verbalmemory span
0866.2w 8 1 6.2temporo-parietal 37.99 055Residual aphasia
0961.9m 8 1 6.6temporo-parietal 11.89 3 2No aphasia, decreased verbalmemory span
1046.0m10 1 23.8parietal105.429736Residual aphasia
1163.8w12 1 14.5parietal 37.972012No aphasia, decreased verbalmemory span
1263.8m100.9 24.6temporo-parietal 25.66 236No aphasia,decreased verbal memory span
  1. Laterality = Handedness (Oldfield score), % overlap = lesion overlap with angular gyrus (AG; BA 39) or supramarginal gyrus (SMG, BA 40); Education is given in years, Time since stroke in months. AAT = Aachener Aphasie Test (Aaachen Aphasia Inventory). phon = phonological.

Table 2
Behavioral results.
Task/conditionRTs ± SEM (in ms)ERs ± SEM (in %)
Phonological judgements
sham cTBS1895 ± 132.5411.28 ± 3.42
cTBS of aIFG1888 ± 120.90 9.55 ± 2.69
cTBS of pIFG2411 ± 151.31 9.10 ± 1.97
Semantic judgements
sham cTBS1486 ± 112.98 9.04 ± 4.69
cTBS of aIFG1632 ± 129.7912.95 ± 5.88
cTBS of pIFG1452 ± 84.18 9.36 ± 4.82
  1. RTs = reaction times; ERs = error rates; SEM = standard error of the mean.

Table 3
Task-related changes in neural activity.
RegionSideMNI coordinates (x, y, z)TCluster size
Phonological decisions > rest after sham cTBS
Supplementary motor areaL/R–3 2 568.57619
Supplementary motor areaL–6 11 478.15subcluster
Supplementary motor areaR 9 17 446.90subcluster
anterior insulaL−30 26 28.281527
posterior inferior frontal gyrus (pars opercularis)L−49 9 118.15subcluster
posterior inferior frontal gyrus (pars opercularis)L−54 1416.97subcluster
Frontal operculumR 42 20 56.61532
Posterior inferior frontal gyrus (pars opercularis)R 48 11 176.47subcluster
anterior insulaR 33 23 56.32subcluster
Precentral gyrus (extending to the postcentral gyrus and parietal cortex)R 33−22 535.9095
Semantic decisions > rest
Supplementary motor areaL/R–6 14 477.54708
Supplementary motor areaL–3–1 566.87subcluster
Supplementary motor areaR 9 17 416.69subcluster
anterior insulaL−30 26 26.791054
anterior inferior frontal gyrus (pars orbitalis / triangularis)L−46 42–56.01subcluster
posterior inferior frontal gyrus (pars opercularis)L−50 10 105.91subcluster
Precentral gyrusR 39−19 566.62318
Postcentral gyrus (extending to the parietal cortex)R 48−22 534.91subcluster
Frontal operculumR 39 23 26.05299
Phonological decisions: sham cTBS > cTBS of pIFG
posterior inferior frontal gyurs (pars opercularis)L−54 12 174.9764
Supplementary motor areaR 1 3 544.9060
PutamenR 18 8–74.8035
Phonological decisions: cTBS of aIFG > cTBS of pIFG
posterior inferior frontal gyrus (pars opercularis)L−54 23 184.9260
Semantic decisions: sham cTBS > cTBS of aIFG
Middle frontal gyrusR 45 35325.20347
Inferior frontal gyrus (pars orbitalis) / insulaR 40 3734.90subcluster
Superior frontal gyrusR 9 35414.99158
Inferior frontal gyrus (pars orbitalis) / insulaL−36 31-14.8065
Middle frontal gyrusL−45 35264.7860
Semantic decisions: cTBS of pIFG > cTBS of aIFG
Middle frontal gyrusR 45 30285.00242
Inferior frontal gyrus (pars orbitalis) / insulaR 42 3844.80subcluster
Inferior frontal gyrus (pars orbitalis) / insulaL−38 3114.7860
  1. p<0.05, FWE corrected at the cluster level.

Data availability

Data cannot be shared completely due to the data protection agreement (approved by the local ethics committee) signed by the participants. Some processed datasets can be found at https://osf.io/4bhrt/.

The following data sets were generated
  1. 1

Additional files

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)