Uncovering the inferior fronto-occipital fascicle and its topological organization in non-human primates: the missing connection for language evolution

  • Silvio SarubboEmail author
  • Laurent Petit
  • Alessandro De Benedictis
  • Franco Chioffi
  • Maurice Ptito
  • Tim B. Dyrby
Original Article


Whether brain networks underlying the multimodal processing of language in humans are present in non-human primates is an unresolved question in primate evolution. Conceptual awareness in humans, which is the backbone of verbal and non-verbal semantic elaboration, involves intracerebral connectivity via the inferior fronto-occipital fascicle (IFOF). While non-human primates can communicate through visual information channels, there has been no formal demonstration that they possess a functional homologue of the human IFOF. Therefore, we undertook a post-mortem diffusion MRI tractography study in conjunction with Klingler micro-dissection to search for IFOF fiber tracts in brain of Old-World (vervet) monkeys. We found clear and concordant evidence from both techniques for the existence of bilateral fiber tracts connecting the frontal and occipital lobes. These tracts closely resembled the human IFOF with respect to trajectory, topological organization, and cortical terminal fields. Moreover, these fibers are clearly distinct from other bundles previously described in this region of monkey brain, i.e., the inferior longitudinal and uncinate fascicles, and the external and extreme capsules. This demonstration of an IFOF in brain of a species that diverged from the human lineage some 22 millions years ago enhances our comprehension about the evolution of language and social behavior.


White matter Klingler dissection Inferior fronto-occipital fascicle Brain connectivity Tractography Monkey anatomy 



We are very grateful to the valuable work of proofreading of the present manuscript provided by Inglewood Biomedical Editing (

Compliance with ethical standards

Conflict of interest

Authors have no conflict of interests and did not receive funding for this work.

Ethical approval

The brain specimens were collected from animals enrolled in a terminal project reviewed and approved by the Institutional Review Board of the Behavioural Science Foundation (BSF; St-Kitts, West Indies) and were donated by Prof. Roberta Palmour of McGill University, in a collaboration with the BSF. The human brain dissection presented in the paper was performed in the context of the Structural and Functional Connectivity Lab Project, approved by the Research Ethics Committee of the Azienda Provinciale dei Servizi Sanitari (APSS) of Trento (Italy).

Supplementary material

429_2019_1856_MOESM1_ESM.docx (841 kb)
Supplementary material 1 (DOCX 840 KB)


  1. Avants BB, Tustison NJ, Wu J, Cook PA, Gee JC (2011) An open source multivariate framework for n-tissue segmentation with evaluation on public data. Neuroinformatics 9(4):381–400. PubMedPubMedCentralGoogle Scholar
  2. Burdach KF (1822) Vom Baue und Leben des Gehirns. Dyk, LeipzigGoogle Scholar
  3. Calabrese E, Badea A, Coe CL, Lubach GR, Shi Y, Styner MA, Johnson GA (2015) A diffusion tensor MRI atlas of the postmortem rhesus macaque brain. NeuroImage 117:408–416. PubMedPubMedCentralGoogle Scholar
  4. Caverzasi E, Papinutto N, Amirbekian B, Berger MS, Henry RG (2014) Q-Ball of inferior fronto-occipital fasciculus and beyond. PLoS One 9(6):e100274. PubMedPubMedCentralGoogle Scholar
  5. Côté M-A, Garyfallidis E, Larochelle H, Descoteaux M (2015) Cleaning up the mess: tractography outlier removal using hierarchical QuickBundles clustering. In: 23rd ISMRM annual meeting, Toronto, Canada, vol 2844Google Scholar
  6. Curran EJ (1909) A new association fiber tract in the cerebrum with remarks on the fiber tract dissection method of studying the brain. J Comp Neurol Psychol 19(6):645–656. Google Scholar
  7. Daducci A, Dal Palu A, Descoteaux M, Thiran JP (2016) Microstructure informed tractography: pitfalls and open challenges. Front Neurosci 10(247):247. PubMedPubMedCentralGoogle Scholar
  8. De Benedictis A, Duffau H, Paradiso B, Grandi E, Balbi S, Granieri E, Colarusso E, Chioffi F, Marras CE, Sarubbo S (2014) Anatomo-functional study of the temporo-parieto-occipital region: dissection, tractographic and brain mapping evidence from a neurosurgical perspective. J Anat 225(2):132–151. PubMedPubMedCentralGoogle Scholar
  9. De Benedictis A, Petit L, Descoteaux M, Marras CE, Barbareschi M, Corsini F, Dallabona M, Chioffi F, Sarubbo S (2016) New insights in the homotopic and heterotopic connectivity of the frontal part of the human corpus callosum revealed by microdissection and diffusion tractography. Hum Brain Mapp 37(12):4718–4735PubMedGoogle Scholar
  10. De Benedictis A, Nocerino E, Menna F, Remondino F, Barbareschi M, Rozzanigo U, Corsini F, Olivetti E, Marras CE, Chioffi F, Avesani P, Sarubbo S (2018) Photogrammetry of the human brain: a novel method for three-dimensional quantitative exploration of the structural connectivity in neurosurgery and neurosciences. World Neurosurg 115:e279–e291. PubMedGoogle Scholar
  11. Decramer T, Swinnen S, van Loon J, Janssen P, Theys T (2018) White matter tract anatomy in the rhesus monkey: a fiber dissection study. Brain Struct Funct. PubMedGoogle Scholar
  12. Descoteaux M, Deriche R, Knosche TR, Anwander A (2009) Deterministic and probabilistic tractography based on complex fibre orientation distributions. IEEE Trans Med Imaging 28(2):269–286. PubMedGoogle Scholar
  13. Duffau H (2015) Stimulation mapping of white matter tracts to study brain functional connectivity. Nat Rev Neurol 11(5):255–265. PubMedGoogle Scholar
  14. Duffau H, Capelle L, Denvil D, Gatignol P, Sichez N, Lopes M, Sichez J-P, 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. PubMedGoogle Scholar
  15. Dyrby TB, Baaré WFC, Alexander DC, Jelsing J, Garde E, Søgaard LV (2011) An ex vivo imaging pipeline for producing high-quality and high-resolution diffusion-weighted imaging datasets. Hum Brain Mapp 32(4):544–563. PubMedGoogle Scholar
  16. Dyrby TB, Innocenti GM, Bech M, Lundell H (2018) Validation strategies for the interpretation of microstructure imaging using diffusion MRI. NeuroImage 182:62–79. PubMedGoogle Scholar
  17. Gannon PJ, Holloway RL, Broadfield DC, Braun AR (1998) Asymmetry of chimpanzee planum temporale: Humanlike pattern of Wernicke’s brain language area homolog. Science 279:220–222PubMedGoogle Scholar
  18. Garyfallidis E, Brett M, Amirbekian B, Rokem A, van der Walt S, Descoteaux M, Nimmo-Smith I, Dipy C (2014) Dipy, a library for the analysis of diffusion MRI data. Front Neuroinform 8:8. PubMedPubMedCentralGoogle Scholar
  19. Gerbella M, Belmalih A, Borra E, Rozzi S, Luppino G (2010) Cortical connections of the macaque caudal ventrolateral prefrontal areas 45A and 45B. Cereb Cortex 20(1):141–168. PubMedGoogle Scholar
  20. Girard G, Whittingstall K, Deriche R, Descoteaux M (2014) Towards quantitative connectivity analysis: reducing tractography biaises. NeuroImage 98:266–278PubMedGoogle Scholar
  21. Glazko GV, Nei M (2003) Estimation of divergence times for major lineages of primate species. Mol Biol Evol 20(3):424–434. PubMedGoogle Scholar
  22. Harrison KH, Hof PR, Wang SS-H (2002) Scaling laws in the mammalian neocortex: does form provide clues to function? J Neurocytol 31(3):289–298. PubMedGoogle Scholar
  23. Hau J, Sarubbo S, Perchey G, Crivello F, Zago L, Mellet E, Jobard G, Joliot M, Mazoyer B, Tzourio-Mazoyer N, Petit L (2016) Cortical terminations of the inferior fronto-occipital and uncinate fasciculi: stem-based anatomical virtual dissection. Front Neuroanat 10:58PubMedPubMedCentralGoogle Scholar
  24. Herbet G, Moritz-Gasser S, Duffau H (2017) Direct evidence for the contributive role of the right inferior fronto-occipital fasciculus in non-verbal semantic cognition. Brain Struct Funct 222(4):1597–1610. PubMedGoogle Scholar
  25. Hofman MA (2012) Chap. 18—Design principles of the human brain: an evolutionary perspective. In: Michel AH, Dean F (eds) Progress in brain research, vol 195. Elsevier, Churchill, pp 373–390. Google Scholar
  26. Hurford JR (2003) The language mosaic and its evolution. In: Christiaens M, Kirby S (eds) Language evolution. Oxford University Press, Oxford, pp 38–57Google Scholar
  27. Innocenti GM, Dyrby TB, Girard G, St-Onge E, Thiran JP, Daducci A, Descoteaux M (2019) Topological principles and developmental algorithms might refine diffusion tractography. Brain Struct Funct 224(1):1–8. PubMedGoogle Scholar
  28. Karbowski J (2003) How does connectivity between cortical areas depend on brain size? Implications for efficient computation. J Comput Neurosci 15(3):347–356. PubMedGoogle Scholar
  29. Kohler E, Keysers C, Umilta MA, Fogassi L, Gallese V, Rizzolatti G (2002) Hearing sounds, understanding actions: action representation in mirror neurons. Science 297(5582):846–848PubMedGoogle Scholar
  30. Maier-Hein KH, Neher PF, Houde JC, Cote MA, Garyfallidis E, Zhong J, Chamberland M, Yeh FC, Lin YC, Ji Q, Reddick WE, Glass JO, Chen DQ, Feng Y, Gao C, Wu Y, Ma J, Renjie H, Li Q, Westin CF, Deslauriers-Gauthier S, Gonzalez JOO, Paquette M, St-Jean S, Girard G, Rheault F, Sidhu J, Tax CMW, Guo F, Mesri HY, David S, Froeling M, Heemskerk AM, Leemans A, Bore A, Pinsard B, Bedetti C, Desrosiers M, Brambati S, Doyon J, Sarica A, Vasta R, Cerasa A, Quattrone A, Yeatman J, Khan AR, Hodges W, Alexander S, Romascano D, Barakovic M, Auria A, Esteban O, Lemkaddem A, Thiran JP, Cetingul HE, Odry BL, Mailhe B, Nadar MS, Pizzagalli F, Prasad G, Villalon-Reina JE, Galvis J, Thompson PM, Requejo FS, Laguna PL, Lacerda LM, Barrett R, Dell’Acqua F, Catani M, Petit L, Caruyer E, Daducci A, Dyrby TB, Holland-Letz T, Hilgetag CC, Stieltjes B, Descoteaux M (2017) The challenge of mapping the human connectome based on diffusion tractography. Nat Commun 8(1):1349. PubMedPubMedCentralGoogle Scholar
  31. Maldjian JA, Daunais JB, Friedman DP, Whitlow CT (2014) Vervet MRI atlas and label map for fully automated morphometric analyses. Neuroinformatics 12(4):543–550. PubMedPubMedCentralGoogle Scholar
  32. Markov NT, Ercsey-Ravasz MM, Ribeiro Gomes AR, Lamy C, Magrou L, Vezoli J, Misery P, Falchier A, Quilodran R, Gariel MA, Sallet J, Gamanut R, Huissoud C, Clavagnier S, Giroud P, Sappey-Marinier D, Barone P, Dehay C, Toroczkai Z, Knoblauch K, Van Essen DC, Kennedy H (2014) A weighted and directed interareal connectivity matrix for macaque cerebral cortex. Cereb Cortex 24(1):17–36. PubMedGoogle Scholar
  33. Mars RB, Foxley S, Verhagen L, Jbabdi S, Sallet J, Noonan MP, Neubert FX, Andersson JL, Croxson PL, Dunbar RI, Khrapitchev AA, Sibson NR, Miller KL, Rushworth MF (2016) The extreme capsule fiber complex in humans and macaque monkeys: a comparative diffusion MRI tractography study. Brain Struct Funct 221(8):4059–4071. PubMedGoogle Scholar
  34. Martin RF, Bowden DM (2000) Primate brain maps: structure of the macaque brain. Elsevier Science, University of Washington, Washington, DCGoogle Scholar
  35. Martino J, Brogna C, Robles SG, Vergani F, Duffau H (2010) Anatomic dissection of the inferior fronto-occipital fasciculus revisited in the lights of brain stimulation data. Cortex 46(5):691–699. PubMedGoogle Scholar
  36. 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. PubMedGoogle Scholar
  37. Panesar SS, Yeh F-C, Deibert CP, Fernandes-Cabral D, Rowthu V, Celtikci P, Celtikci E, Hula WD, Pathak S, Fernández-Miranda JC (2017) A diffusion spectrum imaging-based tractographic study into the anatomical subdivision and cortical connectivity of the ventral external capsule: uncinate and inferior fronto-occipital fascicles. Neuroradiology 59(10):971–987. PubMedGoogle Scholar
  38. Petkov CI, Wilson B (2012) On the pursuit of the brain network for proto-syntactic learning in non-human primates: conceptual issues and neurobiological hypotheses. Philos Trans R Soc Lond B Biol Sci 367(1598):2077–2088. PubMedPubMedCentralGoogle Scholar
  39. Petkov CI, Kayser C, Steudel T, Whittingstall K, Augath M, Logothetis NK (2008) A voice region in the monkey brain. Nat Neurosci 11(3):367–374PubMedGoogle Scholar
  40. Petrides M (2002) The mid-ventrolateral prefrontal cortex and active mnemonic retrieval. Neurobiol Learn Mem 78(3):528–538. PubMedGoogle Scholar
  41. Petrides M, Cadoret G, Mackey S (2005) Orofacial somatomotor responses in the macaque monkey homologue of Broca’s area. Nature 435(7046):1235–1238. doi
  42. Price T, Wadewitz P, Cheney D, Seyfarth R, Hammerschmidt K, Fischer J (2015) Vervets revisited: a quantitative analysis of alarm call structure and context specificity. Sci Rep 5:13220.
  43. Rheault F, St-Onge E, Tzourio-Mazoyer N, Sidhu J, Petit L, Descoteaux M (2019) Bundle-specific tractography: enhancing fiber tracking with additional anatomical and orientational priors. NeuroImage 186:382–398PubMedGoogle Scholar
  44. Sarubbo S, De Benedictis A, Maldonado IL, Basso G, Duffau H (2013) Frontal terminations for the inferior fronto-occipital fascicle: anatomical dissection, DTI study and functional considerations on a multi-component bundle. Brain Struct Funct 218:21–37. PubMedGoogle Scholar
  45. Sarubbo S, De Benedictis A, Merler S, Mandonnet E, Balbi S, Granieri E, Duffau H (2015a) Towards a functional atlas of human white matter. Hum Brain Mapp 36(8):3117–3136. PubMedGoogle Scholar
  46. Sarubbo S, De Benedictis A, Milani P, Paradiso B, Barbareschi M, Rozzanigo U, Colarusso E, Tugnoli V, Farneti M, Granieri E, Duffau H, Chioffi F (2015b) The course and the anatomo-functional relationships of the optic radiation: a combined study with ‘post mortem’ dissections and ‘in vivo’ direct electrical mapping. J Anat 226(1):47–59. PubMedGoogle Scholar
  47. Sarubbo S, De Benedictis A, Merler S, Mandonnet E, Barbareschi M, Dallabona M, Chioffi F, Duffau H (2016) Structural and functional integration between dorsal and ventral language streams as revealed by blunt dissection and direct electrical stimulation. Hum Brain Mapp 37(11):3858–3872. PubMedGoogle Scholar
  48. Saur D, Kreher BW, Schnell S, Kummerer D, Kellmeyer P, Vry MS, Umarova R, Musso M, Glauche V, Abel S, Huber W, Rijntjes M, Hennig J, Weiller C (2008) Ventral and dorsal pathways for language. Proc Natl Acad Sci USA 105(46):18035–18040. PubMedGoogle Scholar
  49. Schmahmann JD, Pandya DN (2006) Fiber pathways of the brain. Oxford University Press, New YorkGoogle Scholar
  50. Schmahmann JD, Pandya DN, Wang R, Dai G, D’Arceuil HE, de Crespigny AJ, Wedeen VJ (2007) Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 130(3):630–653. PubMedGoogle Scholar
  51. Schoenemann PT (2012) Chap. 22—Evolution of brain and language. In: Michel AH, Dean F (eds) Progress in brain research, vol 195. Elsevier, Churchill, pp 443–459. Google Scholar
  52. Seyfarth R, Cheney D, Marler P (1980) Monkey responses to three different alarm calls: evidence of predator classification and semantic communication. Science 210(4471):801–803. PubMedGoogle Scholar
  53. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23(Supplement 1):S208–S219. PubMedGoogle Scholar
  54. Tournier JD, Calamante F, Connelly A (2007) Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. NeuroImage 35(4):1459–1472. PubMedGoogle Scholar
  55. Trolard P (1906) Le faisceau longitudinal inférieur du cerveau. Revue Neurologique 14:440–446Google Scholar
  56. Ungerleider LG, Courtney SM, Haxby JV (1998) A neural system for human visual working memory. Proc Natl Acad Sci USA 95:883–890PubMedGoogle Scholar
  57. Wilson FAW, Scalaidhe SPO, Goldman-Rakic PS (1993) Dissociation of object and spatial processing domains in primate prefrontal cortex. Science 260:1955–1958PubMedGoogle Scholar
  58. Wu Y, Sun D, Wang Y, Wang Y (2016) Subcomponents and connectivity of the inferior fronto-occipital fasciculus revealed by diffusion spectrum imaging fiber tracking. Front Neuroanat 10:88. PubMedPubMedCentralGoogle Scholar
  59. Zemmoura I, Serres B, Andersson F, Barantin L, Tauber C, Filipiak I, Cottier JP, Venturini G, Destrieux C (2014) FIBRASCAN: a novel method for 3D white matter tract reconstruction in MR space from cadaveric dissection. Neuroimage 103:106–118. PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Neurosurgery, Structural and Functional Connectivity Lab Project“S. Chiara” Hospital, Azienda Provinciale per i Servizi Sanitari (APSS)TrentoItaly
  2. 2.Groupe d’Imagerie NeurofonctionnelleInstitut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA University of BordeauxBordeauxFrance
  3. 3.Neurosurgery Unit, Department of Neuroscience and NeurorehabilitationBambino Gesù Children’s Hospital, IRCCSRomeItaly
  4. 4.École d’optométrieUniversité de MontréalMontrealCanada
  5. 5.Danish Research Centre for Magnetic Resonance, Center for Functional and Diagnostic Imaging and ResearchCopenhagen University Hospital HvidovreHvidovreDenmark
  6. 6.Department of Applied Mathematics and Computer ScienceTechnical University of DenmarkKongens LyngbyDenmark

Personalised recommendations