Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

High-resolution language mapping of Broca’s region with transcranial magnetic stimulation

Abstract

Broca’s region, corresponding roughly to cytoarchitectonic areas 44 and 45 in the inferior frontal cortex, holds a multifunctional role in language processing, as shown, e.g., by functional imaging data. Neuro-navigated transcranial magnetic stimulation (TMS) enables complementary non-invasive mapping of cortical functions with high spatial resolution. Here, we report on detailed TMS language mapping of Broca’s region in 12 healthy participants. The test protocol with an object naming task was adapted for high-resolution and semi-quantitative mapping of TMS-induced effects on speech and language performance. Hierarchical cluster analysis of normalized ratings of error frequency and severity revealed a clear focus of TMS impact at dorso-posterior target sites, close to the inferior frontal junction. Adjacent clusters of moderate and slightly affected stimulation sites yielded a posterosuperior-to-anteroinferior gradient of TMS susceptibility. Our findings indicate that the part of Broca’s region most susceptible to TMS-induced language inhibition in object naming is located in the dorsal area 44.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Amunts K, von Cramon DY (2006) The anatomical segregation of the frontal cortex: what does it mean for function? Cortex 42(4):525–528

  2. Amunts K, Zilles K (2012) Architecture and organizational principles of Broca’s region. Trends Cogn Sci 16(8):418–426

  3. Amunts K, Schleicher A, Bürgel U, Mohlberg H, Uylings HB, Zilles K (1999) Broca’s region revisited: cytoarchitecture and intersubject variability. J Comp Neurol 412(2):319–341

  4. Amunts K, Lenzen M, Friederici AD, Schleicher A, Morosan P, Palomero-Gallagher N, Zilles K (2010) Broca’s region: novel organizational principles and multiple receptor mapping. PLoS Biol 8(9):e1000489

  5. Baayen RH, Piepenbrock R, Gulikers L (1996) CELEX2. Linguistic Data Consortium, Philadelphia

  6. Belmaker B, Fitzgerald P, George MS, Lisanby HS, Pascual-Leone A, Schlaepfer TE, Wassermann E (2003) Managing the risks of repetitive transcranial stimulation. CNS Spectr 8:489

  7. Bergmann TO, Karabanov A, Hartwigsen G, Thielscher A, Siebner HR (2016) Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: current approaches and future perspectives. Neuroimage 140:4–19

  8. Bestmann S, Baudewig J, Siebner HR, Rothwell JC, Frahm J (2003) Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS. Neuroimage 20(3):1685–1696

  9. Brass M, Derrfuss J, Forstmann B, von Cramon DY (2005) The role of the inferior frontal junction area in cognitive control. Trends Cogn Sci 9(7):314–316

  10. Brodmann K (1909) Vergleichende Lokalisationslehre der Großhirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Barth, Leipzig

  11. Bungert A, Antunes A, Espenhahn S, Thielscher A (2017) Where does TMS stimulate the motor cortex? Combining electrophysiological measurements and realistic field estimates to reveal the affected cortex position. Cereb Cortex 27(11):5083–5094

  12. Clos M, Amunts K, Laird AR, Fox PT, Eickhoff SB (2013) Tackling the multifunctional nature of Broca’s region meta-analytically: co-activation-based parcellation of area 44. Neuroimage 83:174–188

  13. Corina DP, Loudermilk BC, Detwiler L, Martin RF, Brinkley JF, Ojemann G (2010) Analysis of naming errors during cortical stimulation mapping: implication for models of language representation. Brain Lang 115(2):101–112

  14. De Witte E, Mariën P (2013) The neurolinguistic approach to awake surgery reviewed. Clin Neurol Neurosurg 115(2):127–145

  15. Derrfuss J, Brass M, von Cramon DY (2004) Cognitive control in the posterior frontolateral cortex: evidence from common activations in task coordination, interference control, and working memory. Neuroimage 23(2):604–612

  16. Derrfuss J, Brass M, Neumann J, von Cramon DY (2005) Involvement of the inferior frontal junction in cognitive control: meta-analyses of switching and Stroop studies. Hum Brain Mapp 25(1):22–34

  17. Devlin JT, Watkins KE (2007) Stimulating language: insights from TMS. Brain 130(Pt3):610–622

  18. Duffau H (2007) Contribution of cortical and subcortical electrostimulation in brain glioma surgery: methodological and functional considerations. Neurophysiol Clin 37(6):373–382

  19. Duffau H, Capelle L, Denvil D, Gatignol P, Sichez N, Lopes M, Sichez JP, Van Effenterre R (2003) The role of dominant premotor cortex in language: a study using intraoperative functional mapping in awake patients. Neuroimage 20(4):1903–1914

  20. Duffau H, Gatignol P, Mandonnet E, Peruzzi P, Tzourio-Mazoyer N, Capelle L (2005) New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations. Brain 128(Pt 4):797–810

  21. Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, Zilles K (2005) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage 25(4):1325–1335

  22. Eickhoff SB, Paus T, Caspers S, Grosbras MH, Evans A, Zilles K, Amunts K (2007) Assignment of functional activations to probabilistic cytoarchitectonic areas revisited. Neuroimage 36(3):511–521

  23. Epstein CM, Lah JJ, Meador K, Weissman JD, Gaitan LE, Dihenia B (1996) Optimum stimulus parameters for lateralized suppression of speech with magnetic brain stimulation. Neurology 47(6):1590–1593

  24. Epstein CM, Woodard JL, Stringer AY, Bakay RA, Henry TR, Pennell PB, Litt B (2000) Repetitive transcranial magnetic stimulation does not replicate the Wada test. Neurology 55(7):1025–1027

  25. Espadaler JM, Conesa G (2011) Navigated repetitive Transcranial Magnetic Stimulation (TMS) for language mapping: a new tool for surgical planning. In: Duffau H (ed) Brain mapping: from neural basis of cognition to surgical applications. Springer, New York, pp 253–261

  26. Friederici AD (2011) The brain basis of language processing: from structure to function. Physiol Rev 91(4):1357–1392

  27. Gough PM, Nobre AC, Devlin JT (2005) Dissociating linguistic processes in the left inferior frontal cortex with transcranial magnetic stimulation. J Neurosci 25(35):8010–8016

  28. Hagoort P (2005) On Broca, brain, and binding: a new framework. Trends Cogn Sci 9(9):416–423

  29. Hagoort P (2014) Nodes and networks in the neural architecture for language: Broca’s region and beyond. Curr Opin Neurobiol 28:136–141

  30. Hartwigsen G (2015) The neurophysiology of language: insights from non-invasive brain stimulation in the healthy human brain. Brain Lang 148:81–94

  31. Hartwigsen G, Siebner HR (2012) Probing the involvement of the right hemisphere in language processing with online transcranial magnetic stimulation in healthy volunteers. Aphasiology 26(9):1131–1152

  32. Hauck T, Tanigawa N, Probst M, Wohlschlaeger A, Ille S, Sollmann N, Maurer S, Zimmer C, Ringel F, Meyer B, Krieg SM (2015) Task type affects location of language-positive cortical regions by repetitive navigated transcranial magnetic stimulation mapping. PLoS One 10(4):e0125298

  33. Heim S, Eickhoff SB, Amunts K (2008) Specialisation in Broca’s region for semantic, phonological, and syntactic fluency? Neuroimage 40(3):1362–1368

  34. Heim S, Eickhoff SB, Amunts K (2009a) Different roles of cytoarchitectonic BA 44 and BA 45 in phonological and semantic verbal fluency as revealed by dynamic causal modelling. Neuroimage 48(3):616–624

  35. Heim S, Eickhoff SB, Friederici AD, Amunts K (2009b) Left cytoarchitectonic area 44 supports selection in the mental lexicon during language production. Brain Struct Funct 213(4–5):441–456

  36. Heller L, van Hulsteyn DB (1992) Brain stimulation using electromagnetic sources: theoretical aspects. Biophys J 63(1):129–138

  37. Ille S, Sollmann N, Hauck T, Maurer S, Tanigawa N, Obermueller T, Negwer C, Droese D, Boeckh-Behrens T, Meyer B, Ringel F, Krieg SM (2015a) Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study. J Neurosurg 123(2):314–324

  38. Ille S, Sollmann N, Hauck T, Maurer S, Tanigawa N, Obermueller T, Negwer C, Droese D, Zimmer C, Meyer B, Ringel F, Krieg SM (2015b) Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation. J Neurosurg 123(1):212–225

  39. Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174

  40. Lee L, Siebner HR, Rowe JB, Rizzo V, Rothwell JC, Frackowiak RS, Friston KJ (2003) Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J Neurosci 23(12):5308–5318

  41. Lioumis P, Zhdanov A, Mäkelä N, Lehtinen H, Wilenius J, Neuvonen T, Hannula H, Deletis V, Picht T, Mäkelä JP (2012) A novel approach for documenting naming errors induced by navigated transcranial magnetic stimulation. J Neurosci Methods 204(2):349–354

  42. Ojemann G, Ojemann J, Lettich E, Berger M (1989) Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. J Neurosurg 71(3):316–326

  43. Ojemann G, Ojemann J, Lettich E, Berger M (2008) Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. 1989. J Neurosurg 108(2):411–421

  44. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9(1):97–113

  45. Opitz A, Legon W, Rowlands A, Bickel WK, Paulus W, Tyler WJ (2013) Physiological observations validate finite element models for estimating subject-specific electric field distributions induced by transcranial magnetic stimulation of the human motor cortex. Neuroimage 81:253–264

  46. Opitz A, Zafar N, Bockermann V, Rohde V, Paulus W (2014) Validating computationally predicted TMS stimulation areas using direct electrical stimulation in patients with brain tumors near precentral regions. Neuroimage Clin 4:500–507

  47. Papoutsi M, de Zwart JA, Jansma JM, Pickering MJ, Bednar JA, Horwitz B (2009) From phonemes to articulatory codes: an fMRI study of the role of Broca’s area in speech production. Cereb Cortex 19(9):2156–2165

  48. Pascual-Leone A, Gates JR, Dhuna A (1991) Induction of speech arrest and counting errors with rapid-rate transcranial magnetic stimulation. Neurology 41(5):697–702

  49. Pascual-Leone A, Valls-Solé J, Wassermann EM, Hallett M (1994) Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117(Pt 4):847–858

  50. Pascual-Leone A, Bartres-Faz D, Keenan JP (1999) Transcranial magnetic stimulation: studying the brain-behaviour relationship by induction of ‘virtual lesions’. Philos Trans R Soc Lond B Biol Sci 354(1387):1229–1238

  51. Picht T, Krieg SM, Sollmann N, Rösler J, Niraula B, Neuvonen T, Savolainen P, Lioumis P, Mäkelä JP, Deletis V, Meyer B, Vajkoczy P, Ringel F (2013) A comparison of language mapping by preoperative navigated transcranial magnetic stimulation and direct cortical stimulation during awake surgery. Neurosurgery 72(5):808–819

  52. Poldrack RA, Wagner AD, Prull MW, Desmond JE, Glover GH, Gabrieli JD (1999) Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex. Neuroimage 10(1):15–35

  53. Price CJ (2010) The anatomy of language: a review of 100 fMRI studies published in 2009. Ann N Y Acad Sci 1191:62–88

  54. Price CJ (2012) A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language and reading. Neuroimage 62(2):816–847

  55. Rogić M, Deletis V, Fernández-Conejero I (2014) Inducing transient language disruptions by mapping of Broca’s area with modified patterned repetitive transcranial magnetic stimulation protocol. J Neurosurg 120(5):1033–1041

  56. Rösler J, Niraula B, Strack V, Zdunczyk A, Schilt S, Savolainen P, Lioumis P, Mäkelä J, Vajkoczy P, Frey D, Picht T (2014) Language mapping in healthy volunteers and brain tumor patients with a novel navigated TMS system: evidence of tumor-induced plasticity. Clin Neurophysiol 125(3):526–536

  57. Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijević MR, Hallett M, Katayama Y, Lücking CH, Maertens de Noordhout AL, Marsden CD, Murray NMF, Rothwell CJ, Swash M, Tomberg C (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 91(2):79–92

  58. Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U (2015) Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol 126:1071–1107

  59. Ruff CC, Driver J, Bestmann S (2009) Combining TMS and fMRI: from ‘virtual lesions’ to functional-network accounts of cognition. Cortex 45(9):1043–1049

  60. Sack AT (2006) Transcranial magnetic stimulation, causal structure-function mapping and networks of functional relevance. Curr Opin Neurobiol 16(5):593–599

  61. Sakreida K, Schubotz RI, Wolfensteller U, von Cramon DY (2005) Motion class dependency in observers’ motor areas revealed by functional magnetic resonance imaging. J Neurosci 25(6):1335–1342

  62. Sandrini M, Umiltà C, Rusconi E (2011) The use of transcranial magnetic stimulation in cognitive neuroscience: a new synthesis of methodological issues. Neurosci Biobehav Rev 35(3):516–536

  63. Schäffler L, Lüders HO, Dinner DS, Lesser RP, Chelune GJ (1993) Comprehension deficits elicited by electrical stimulation of Broca’s area. Brain 116(Pt3):695–715

  64. Schubotz RI (2007) Prediction of external events with our motor system: towards a new framework. Trends Cogn Sci 11(5):211–218

  65. Schubotz RI, von Cramon DY (2001) Functional organization of the lateral premotor cortex: fMRI reveals different regions activated by anticipation of object properties, location and speed. Brain Res Cogn Brain Res 11(1):97–112

  66. Schubotz RI, von Cramon DY (2003) Functional-anatomical concepts of human premotor cortex: evidence from fMRI and PET studies. Neuroimage 20(Suppl 1):S120–S131

  67. Schuhmann T, Schiller NO, Goebel R, Sack AT (2012) Speaking of which: dissecting the neurocognitive network of language production in picture naming. Cereb Cortex 22(3):701–709

  68. Sollmann N, Ille S, Obermueller T, Negwer C, Ringel F, Meyer B, Krieg SM (2015) The impact of repetitive navigated transcranial magnetic stimulation coil positioning and stimulation parameters on human language function. Eur J Med Res 20:47

  69. Tarapore PE, Findlay AM, Honma SM, Mizuiri D, Houde JF, Berger MS, Nagarajan SS (2013) Language mapping with navigated repetitive TMS: proof of technique and validation. Neuroimage 82:260–272

  70. Tate MC, Herbet G, Moritz-Gasser S, Tate JE, Duffau H (2014) Probabilistic map of critical functional regions of the human cerebral cortex: Broca’s area revisited. Brain 137(Pt 10):2773–2782

  71. Tettamanti M, Weniger D (2006) Broca’s area: a supramodal hierarchical processor? Cortex 42(4):491–494

  72. Thielscher A, Kammer T (2002) Linking physics with physiology in TMS: a sphere field model to determine the cortical stimulation site in TMS. Neuroimage 17(3):1117–1130

  73. Thielscher A, Kammer T (2004) Electric field properties of two commercial figure-8 coils in TMS: calculation of focality and efficiency. Clin Neurophysiol 115(7):1697–1708

  74. Thielscher A, Wichmann FA (2009) Determining the cortical target of transcranial magnetic stimulation. Neuroimage 47(4):1319–1330

  75. Thielscher A, Opitz A, Windhoff M (2011) Impact of the gyral geometry on the electric field induced by transcranial magnetic stimulation. Neuroimage 54(1):234–243

  76. Vigneau M, Beaucousin V, Hervé PY, Duffau H, Crivello F, Houdé O, Mazoyer B, Tzourio-Mazoyer N (2006) Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. Neuroimage 30(4):1414–1432

  77. Wassermann EM (1998) Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996. Electroencephalogr Clin Neurophysiol 108(1):1–16

  78. Wellmer J, Weber C, Mende M, von der Groeben F, Urbach H, Clusmann H, Elger CE, Helmstaedter C (2009) Multitask electrical stimulation for cortical language mapping: hints for necessity and economic mode of application. Epilepsia 50(10):2267–2275

  79. Xiang HD, Fonteijn HM, Norris DG, Hagoort P (2010) Topographical functional connectivity pattern in the perisylvian language networks. Cereb Cortex 20(3):549–560

  80. Zhang Y, Fan L, Caspers S, Heim S, Song M, Liu C, Mo Y, Eickhoff SB, Amunts K, Jiang T (2017) Cross-cultural consistency and diversity in intrinsic functional organization of Broca’s Region. Neuroimage 150:177–190

  81. Ziemann U, Siebner HR (2015) Inter-subject and inter-session variability of plasticity induction by non-invasive brain stimulation: boon or bane? Brain Stimul 8(3):662–663

  82. Zilles K, Bacha-Trams M, Palomero-Gallagher N, Amunts K, Friederici AD (2015) Common molecular basis of the sentence comprehension network revealed by neurotransmitter receptor fingerprints. Cortex 63:79–89

Download references

Acknowledgements

We would like to thank Julia Amunts for valuable help in stimulus selection, material preparation, and data analysis assistance as well as Johanna Blume-Schnitzler for support with data acquisition and analysis. For excellent technical advice and support, we thank Uli Heuter of the Audio-Visual-Media-Centre of the Faculty of Medicine, RWTH Aachen University. For their endurance through the process of exporting the stimulation markers, we thank Johanna Blume-Schnitzler and Jonas Ort. Hong Chen and Simon Koppers programmed valuable MATLAB scripts, and Ryssa Moffat (Ottawa, Canada) proofread the manuscript. Finally, we send cordial thanks to our volunteers for their participation.

Author information

Correspondence to Katrin Sakreida.

Ethics declarations

Funding

This research project was supported by a grant from the START Programme [25/14] of the Faculty of Medicine, RWTH Aachen University. The funding source had no involvement in study design, in collection, analysis and interpretation of data, in writing of the report, and in the decision to submit the article for publication.

Ethical standards

Our experimental standards and all procedures performed in this study involving human participants were in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards and were approved by the local ethics committee [EK 054/13]. Prior to investigation, we obtained written informed consent from all of our volunteers. This article does not contain any studies with animals performed by any of the authors.

Conflict of interest

The authors declare that they have no personal financial or institutional interest in any of the materials or devices described in this paper.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 272 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sakreida, K., Lange, I., Willmes, K. et al. High-resolution language mapping of Broca’s region with transcranial magnetic stimulation. Brain Struct Funct 223, 1297–1312 (2018). https://doi.org/10.1007/s00429-017-1550-8

Download citation

Keywords

  • Cytoarchitectonic mapping
  • Transcranial magnetic stimulation
  • Language mapping
  • Broca’s region
  • Hierarchical cluster analysis