Brain Structure and Function

, Volume 220, Issue 1, pp 205–219 | Cite as

Receptor architecture of visual areas in the face and word-form recognition region of the posterior fusiform gyrus

  • Julian Caspers
  • Nicola Palomero-Gallagher
  • Svenja Caspers
  • Axel Schleicher
  • Katrin Amunts
  • Karl ZillesEmail author
Original Article


Recently, two extrastriate visual areas on the posterior fusiform gyrus, areas FG1 and FG2, were identified based on cytoarchitectonical criteria (Caspers et al. in Brain Struct Funct 218:511–526, 2013a). They are located within the object-related ventral visual stream at the transition between early and higher-order (category-specific) visual areas. FG2 has a topographical position which is best comparable to the face or visual word-form recognition area. However, the precise function of FG2 is presently unknown. Since transmitter receptors are key molecules of neurotransmission, we analysed the regional and laminar distribution of 15 different receptor binding sites by means of quantitative in vitro receptor autoradiography. Significant differences between receptor densities of both areas were found for NMDA, GABAB, M3, nicotinic α42 and 5-HT1A receptors as well as for GABAA associated benzodiazepine binding sites. These results support the cytoarchitectonic segregation of FG1 and FG2 into two distinct cortical areas. In addition, principal component and hierarchical cluster analyses of the multireceptor data of both fusiform areas and 24 visual, auditory, somatosensory and multimodal association areas not only revealed the typical receptor architectonic characteristics of visual areas for FG1 and FG2, but also suggest their putative function as object recognition regions due to the similarity of their receptor fingerprints with those of areas of the ventral visual stream. Furthermore, FG1 and FG2 build a cluster with the multimodal association areas of the inferior parietal lobule. This underlines their hierarchically high position in the visual system of the human cerebral cortex.


Neuroanatomy In vitro receptor autoradiography Transmitter receptors Extrastriate visual cortex Ventral stream 



This work was supported by the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (Human Brain Model to K.Z.), the DFG (IRTG 1328 to K.A.), the Human Brain Project (WP2.1: multi-level organisation of the human brain, T2.1.1: distribution of receptors in the human cerebral cortex to K.Z. and K.A.), and the Helmholtz Alliance for Mental Health in an Aging Society (HelMA to K.Z. and K.A.).


  1. Amunts K, Malikovic A, Mohlberg H, Schormann T, Zilles K (2000) Brodmann’s areas 17 and 18 brought into stereotaxic space-where and how variable? Neuroimage 11:66–84PubMedCrossRefGoogle Scholar
  2. 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). doi: 10.1371/journal.pbio.1000489
  3. Andersen RA, Asanuma C, Essick G, Siegel RM (1990) Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule. J Comp Neurol 296:65–113PubMedCrossRefGoogle Scholar
  4. Arcaro MJ, McMains SA, Singer BD, Kastner S (2009) Retinotopic organization of human ventral visual cortex. J Neurosci 29:10638–10652PubMedCentralPubMedCrossRefGoogle Scholar
  5. Bernardi N, Pizzorusso T, Ratto GM, Maffei L (2003) Molecular basis of plasticity in the visual cortex. Trends Neurosci 26:369–378CrossRefGoogle Scholar
  6. Brewer AA, Liu J, Wade AR, Wandell BA (2005) Visual field maps and stimulus selectivity in human ventral occipital cortex. Nat Neurosci 8:1102–1109PubMedCrossRefGoogle Scholar
  7. Caspers S, Geyer S, Schleicher A, Mohlberg H, Amunts K, Zilles K (2006) The human inferior parietal cortex: cytoarchitectonic parcellation and interindividual variability. Neuroimage 33:430–448PubMedCrossRefGoogle Scholar
  8. Caspers S, Eickhoff SB, Geyer S, Scheperjans F, Mohlberg H, Zilles K, Amunts K (2008) The human inferior parietal lobule in stereotaxic space. Brain Struct Funct 212:481–495PubMedCrossRefGoogle Scholar
  9. Caspers S, Eickhoff SB, Rick T, von Kapri A, Kuhlen T, Huang R, Shah NJ, Zilles K (2011) Probabilistic fibre tract analysis of cytoarchitectonically defined human inferior parietal lobule areas reveals similarities to macaques. Neuroimage 58:362–380PubMedCrossRefGoogle Scholar
  10. Caspers J, Zilles K, Eickhoff SB, Schleicher A, Mohlberg H, Amunts K (2013a) Cytoarchitectonical analysis and probabilistic mapping of two extrastriate areas of the human posterior fusiform gyrus. Brain Struct Funct 218:511–526PubMedCentralPubMedCrossRefGoogle Scholar
  11. Caspers J, Zilles K, Amunts K, Laird AR, Fox PT, Eickhoff SB (2013b) Functional characterization and differential coactivation patterns of two cytoarchitectonic visual areas on the human posterior fusiform gyrus. Hum Brain Map. doi: 10.1002/hbm.22364 Google Scholar
  12. Caspers S, Schleicher A, Bacha-Trams M, Palomero-Gallagher N, Amunts K, Zilles K (2013c) Organization of the human inferior parietal lobule based on receptor architectonics. Cereb Cortex 23:615–628PubMedCentralPubMedCrossRefGoogle Scholar
  13. Catani M, Howard RJ, Pajevic S, Jones DK (2002) Virtual in vivo interactive dissection of white matter fasciculi in the human brain. Neuroimage 17:77–94PubMedCrossRefGoogle Scholar
  14. Catani M, Jones DK, Donato R, Ffytche DH (2003) Occipito-temporal connections in the human brain. Brain 126:2093–2107PubMedCrossRefGoogle Scholar
  15. Cavada C, Goldman-Rakic PS (1989a) Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe. J Comp Neurol 287:422–445PubMedCrossRefGoogle Scholar
  16. Cavada C, Goldman-Rakic PS (1989b) Posterior parietal cortex in rhesus monkey: I. Parcellation of areas based on distinctive limbic and sensory corticocortical connections. J Comp Neurol 287:393–421PubMedCrossRefGoogle Scholar
  17. Cohen L, Dehaene S, Naccache L, Lehericy S, Dehaene-Lambertz G, Henaff MA, Michel F (2000) The visual word form area: spatial and temporal characterization of an initial stage of reading in normal subjects and posterior split-brain patients. Brain 123(Pt 2):291–307PubMedCrossRefGoogle Scholar
  18. Cohen L, Lehericy S, Chochon F, Lemer C, Rivaud S, Dehaene S (2002) Language-specific tuning of visual cortex? Functional properties of the visual word form area. Brain 125:1054–1069PubMedCrossRefGoogle Scholar
  19. Collingridge GL, Volianskis A, Bannister N, France G, Hanna L, Mercier M, Tidball P, Fang G, Irvine MW, Costa BM, Monaghan DT, Bortolotto ZA, Molnar E, Lodge D, Jane DE (2013) The NMDA receptor as a target for cognitive enhancement. Neuropharmacology 64:13–26PubMedCrossRefGoogle Scholar
  20. Dehaene S, Le Clec HG, Poline JB, Le Bihan D, Cohen L (2002) The visual word form area: a prelexical representation of visual words in the fusiform gyrus. Neuroreport 13:321–325PubMedCrossRefGoogle Scholar
  21. Dehaene S, Cohen L, Sigman M, Vinckier F (2005) The neural code for written words: a proposal. Trends Cogn Sci 9:335–341PubMedCrossRefGoogle Scholar
  22. DeYoe EA, Carman GJ, Bandettini P, Glickman S, Wieser J, Cox R, Miller D, Neitz J (1996) Mapping striate and extrastriate visual areas in human cerebral cortex. Proc Natl Acad Sci USA 93:2382–2386PubMedCentralPubMedCrossRefGoogle Scholar
  23. Eggermann E, Feldmeyer D (2009) Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4. Proc Natl Acad Sci USA 106:11753–11758PubMedCentralPubMedCrossRefGoogle Scholar
  24. Eickhoff SB, Rottschy C, Zilles K (2007) Laminar distribution and co-distribution of neurotransmitter receptors in early human visual cortex. Brain Struct Funct 212:255–267PubMedCrossRefGoogle Scholar
  25. Eickhoff SB, Rottschy C, Kujovic M, Palomero-Gallagher N, Zilles K (2008) Organizational principles of human visual cortex revealed by receptor mapping. Cereb Cortex 18:2637–2645PubMedCentralPubMedCrossRefGoogle Scholar
  26. Epstein R, Kanwisher N (1998) A cortical representation of the local visual environment. Nature 392:598–601PubMedCrossRefGoogle Scholar
  27. Felleman DJ, Van Essen DC (1991) Distributed hierarchical processing in the primate cerebral cortex. Cereb Cortex 1:1–47PubMedCrossRefGoogle Scholar
  28. Geyer S, Ledberg A, Schleicher A, Kinomura S, Schormann T, Bürgel U, Klingberg T, Larsson J, Zilles K, Roland PE (1996) Two different areas within the primary motor cortex of man. Nature 382:805–807PubMedCrossRefGoogle Scholar
  29. Geyer S, Schleicher A, Zilles K (1997) The somatosensory cortex of human: cytoarchitecture and regional distributions of receptor-binding sites. Neuroimage 6:27–45PubMedCrossRefGoogle Scholar
  30. Geyer S, Schleicher A, Zilles K (1999) Areas 3a, 3b, and 1 of human primary somatosensory cortex. Neuroimage 10:63–83PubMedCrossRefGoogle Scholar
  31. Gil Z, Connors BW, Amitai Y (1997) Differential regulation of neocortical synapses by neuromodulators and activity. Neuron 19:679–686PubMedCrossRefGoogle Scholar
  32. Grill-Spector K, Kourtzi Z, Kanwisher N (2001) The lateral occipital complex and its role in object recognition. Vision Res 41:1409–1422PubMedCrossRefGoogle Scholar
  33. Hsieh CY, Cruishank SJ, Metherate R (2000) Differential modulation of auditory thalamocortical and intracortical synaptic transmission by cholinergic agonist. Brain Res 880:51–64PubMedCrossRefGoogle Scholar
  34. Kanwisher N, McDermott J, Chun MM (1997) The fusiform face area: a module in human extrastriate cortex specialized for face perception. J Neurosci 17:4302–4311PubMedGoogle Scholar
  35. Klinkenberg I, Sambeth A, Blokland A (2011) Acetylcholine and attention. Behav Brain Res 221:430–442PubMedCrossRefGoogle Scholar
  36. Kravitz DJ, Saleem KS, Baker CI, Mishkin M (2011) A new neural framework for visuospatial processing. Nat Rev Neurosci 12:217–230PubMedCentralPubMedCrossRefGoogle Scholar
  37. Kujovic M, Zilles K, Malikovic A, Schleicher A, Mohlberg H, Rottschy C, Eickhoff SB, Amunts K (2013) Cytoarchitectonic mapping of the human dorsal extrastriate cortex. Brain Struct Funct 218:157–172PubMedCentralPubMedCrossRefGoogle Scholar
  38. Lawrence NS, Ross TJ, Stein EA (2002) Cognitive mechanisms of nicotine on visual attention. Neuron 36:539–548PubMedCrossRefGoogle Scholar
  39. Malach R, Reppas JB, Benson RR, Kwong KK, Jiang H, Kennedy WA, Ledden PJ, Brady TJ, Rosen BR, Tootell RB (1995) Object-related activity revealed by functional magnetic resonance imaging in human occipital cortex. Proc Natl Acad Sci USA 92:8135–8139PubMedCentralPubMedCrossRefGoogle Scholar
  40. Malach R, Levy I, Hasson U (2002) The topography of high-order human object areas. Trends Cogn Sci 6:176–184PubMedCrossRefGoogle Scholar
  41. Martino J, De Witt Hamer PC, Vergani F, Brogna C, de Lucas EM, Vazquez-Barquero A, Garcia-Porrero JA, Duffau H (2011) Cortex-sparing fiber dissection: an improved method for the study of white matter anatomy in the human brain. J Anat 219:531–541PubMedCentralPubMedCrossRefGoogle Scholar
  42. McCoy PA, Huang HS, Philpot BD (2009) Advances in understanding visual cortex plasticity. Curr Opin Neurobiol 19:298–304PubMedCentralPubMedCrossRefGoogle Scholar
  43. Merker B (1983) Silver staining of cell bodies by means of physical development. J Neurosci Methods 9:235–241PubMedCrossRefGoogle Scholar
  44. Mishkin M, Ungerleider LG, Macko KA (1983) Object vision and spatial vision: two cortical pathways. Trends Neurosci 6:414–417CrossRefGoogle Scholar
  45. Morosan P, Rademacher J, Schleicher A, Amunts K, Schormann T, Zilles K (2001) Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system. Neuroimage 13:684–701PubMedCrossRefGoogle Scholar
  46. Morosan P, Schleicher A, Amunts K, Zilles K (2005) Multimodal architectonic mapping of human superior temporal gyrus. Anat Embryol (Berl) 210:401–406CrossRefGoogle Scholar
  47. Morris RG, Anderson E, Lynch GS, Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist, AP5. Nature 319:774–776PubMedCrossRefGoogle Scholar
  48. Oldford E, Castro-Alamancos MA (2003) Input-specific effects of acetylcholine on sensory and intracortical evoked responses in the “barrel cortex” in vivo. Neuroscience 117:769–778PubMedCrossRefGoogle Scholar
  49. Orban GA, Van Essen D, Vanduffel W (2004) Comparative mapping of higher visual areas in monkeys and humans. Trends Cogn Sci 8:315–324PubMedCrossRefGoogle Scholar
  50. Palomero-Gallagher N, Mohlberg H, Zilles K, Vogt B (2008) Cytology and receptor architecture of human anterior cingulate cortex. J Comp Neurol 508:906–926PubMedCentralPubMedCrossRefGoogle Scholar
  51. Palomero-Gallagher N, Vogt BA, Schleicher A, Mayberg HS, Zilles K (2009) Receptor architecture of human cingulate cortex: evaluation of the four-region neurobiological model. Hum Brain Mapp 30:2336–2355PubMedCrossRefGoogle Scholar
  52. Palomero-Gallagher N, Zilles K, Schleicher A, Vogt BA (2013) Cyto- and receptor architecture of area 32 in human and macaque brains. J Comp Neurol 521:3272–3286PubMedCrossRefGoogle Scholar
  53. Paterson D, Nordberg A (2000) Neuronal nicotinic receptors in the human brain. Prog Neurobiol 61:75–111PubMedCrossRefGoogle Scholar
  54. Pinsk MA, Arcaro M, Weiner KS, Kalkus JF, Inati SJ, Gross CG, Kastner S (2009) Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study. J Neurophysiol 101:2581–2600PubMedCentralPubMedCrossRefGoogle Scholar
  55. Pisella L, Binkofski F, Lasek K, Toni I, Rossetti Y (2006) No double-dissociation between optic ataxia and visual agnosia: multiple sub-streams for multiple visuo-manual integrations. Neuropsychologia 44:2734–2748PubMedCrossRefGoogle Scholar
  56. Rakic P, Goldman-Rakic PS, Gallager D (1988) Quantitative autoradiography of major neurotransmitter receptors in the monkey striate and extrastriate cortex. J Neurosci 8:3670–3690PubMedGoogle Scholar
  57. Rottschy C, Eickhoff SB, Schleicher A, Mohlberg H, Kujovic M, Zilles K, Amunts K (2007) Ventral visual cortex in humans: cytoarchitectonic mapping of two extrastriate areas. Hum Brain Mapp 28:1045–1059PubMedCrossRefGoogle Scholar
  58. Rozzi S, Calzavara R, Belmalih A, Borra E, Gregoriou GG, Matelli M, Luppino G (2006) Cortical connections of the inferior parietal cortical convexity of the macaque monkey. Cereb Cortex 16:1389–1417PubMedCrossRefGoogle Scholar
  59. Scheperjans F, Grefkes C, Palomero-Gallagher N, Schleicher A, Zilles K (2005a) Subdivisions of human parietal area 5 revealed by quantitative receptor autoradiography: a parietal region between motor, somatosensory, and cingulate cortical areas. Neuroimage 25:975–992PubMedCrossRefGoogle Scholar
  60. Scheperjans F, Palomero-Gallagher N, Grefkes C, Schleicher A, Zilles K (2005b) Transmitter receptors reveal segregation of cortical areas in the human superior parietal cortex: relations to visual and somatosensory regions. Neuroimage 28:362–379PubMedCrossRefGoogle Scholar
  61. Schleicher A, Amunts K, Geyer S, Kowalski T, Schormann T, Palomero-Gallagher N, Zilles K (2000) A stereological approach to human cortical architecture: identification and delineation of cortical areas. J Chem Neuroanat 20:31–47PubMedCrossRefGoogle Scholar
  62. Sereno MI, Dale AM, Reppas JB, Kwong KK, Belliveau JW, Brady TJ, Rosen BR, Tootell RBH (1995) Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging. Science 268:889–893PubMedCrossRefGoogle Scholar
  63. Szwed M, Dehaene S, Kleinschmidt A, Eger E, Valabregue R, Amadon A, Cohen L (2011) Specialization for written words over objects in the visual cortex. Neuroimage 56:330–344PubMedCrossRefGoogle Scholar
  64. Tigges J, Tigges M, Anschel S, Cross NA, Letbetter WD, McBride RL (1981) Areal and laminar distribution of neurons interconnecting the central visual cortical areas 17, 18, 19, and MT in squirrel monkey (Saimiri). J Comp Neurol 202:539–560PubMedCrossRefGoogle Scholar
  65. Ungerleider LG, Haxby JV (1994) ‘What’ and ‘where’ in the human brain. Curr Opin Neurobiol 4:157–165PubMedCrossRefGoogle Scholar
  66. Vigneau M, Jobard G, Mazoyer B, Tzourio-Mazoyer N (2005) Word and non-word reading: what role for the visual word form area? Neuroimage 27:694–705PubMedCrossRefGoogle Scholar
  67. Wandell BA, Brewer AA, Dougherty RF (2005) Visual field map clusters in human cortex. Philos Trans R Soc Lond B Biol Sci 360:693–707PubMedCentralPubMedCrossRefGoogle Scholar
  68. Weiner KS, Grill-Spector K (2010) Sparsely-distributed organization of face and limb activations in human ventral temporal cortex. Neuroimage 52:1559–1573PubMedCentralPubMedCrossRefGoogle Scholar
  69. Weiner KS, Grill-Spector K (2012) The improbable simplicity of the fusiform face area. Trends Cogn Sci 16:251–254PubMedCrossRefGoogle Scholar
  70. Weiner KS, Grill-Spector K (2013) Neural representations of faces and limbs neighbor in human high-level visual cortex: evidence for a new organization principle. Psychol Res 77:74–97PubMedCentralPubMedCrossRefGoogle Scholar
  71. Weiner K, Golarai G, Caspers J, Mohlberg H, Zilles K, Amunts K, Grill-Spector K (2013) The mid-fusiform sulcus: A landmark identifying both cytoarchitectonic and functional divisions of the human fusiform gyrus. Neuroimage. doi: 10.1016/j.neuroimage.2013.08.068 Google Scholar
  72. Wilms M, Eickhoff SB, Hömke L, Rottschy C, Kujovic M, Amunts K, Fink GR (2010) Comparison of functional and cytoarchitectonic maps of human visual areas V1, V2, V3d, V3v, and V4(v). Neuroimage 49:1171–1179PubMedCrossRefGoogle Scholar
  73. Wu SS, Chang TT, Majid A, Caspers S, Eickhoff SB, Menon V (2009) Functional heterogeneity of inferior parietal cortex during mathematical cognition assessed with cytoarchitectonic probability maps. Cereb Cortex 19:2930–2945PubMedCentralPubMedCrossRefGoogle Scholar
  74. Zilles K (2005) Human brain evolution and comparative cyto- and receptor architecture. In: Dehaene S, Duhamel J-R, Hauser MD, Rizzolatti G (eds) From monkey brain to human brain. MIT Press, Cambridge, pp 41–56Google Scholar
  75. Zilles K, Amunts K (2009) Receptor mapping: architecture of the human cerebral cortex. Curr Opin Neurol 22:331–339PubMedCrossRefGoogle Scholar
  76. Zilles K, Amunts K (2010) Centenary of Brodmann’s map conception and fate. Nat Rev Neurosci 11:139–145PubMedCrossRefGoogle Scholar
  77. Zilles K, Palomero-Gallagher N (2001) Cyto-, myelo-, and receptor architectonics of the human parietal cortex. Neuroimage 14:S8–S20PubMedCrossRefGoogle Scholar
  78. Zilles K, Palomero-Gallagher N, Grefkes C, Scheperjans F, Boy C, Amunts K, Schleicher A (2002a) Architectonics of the human cerebral cortex and transmitter receptor fingerprints: reconciling functional neuroanatomy and neurochemistry. Eur Neuropsychopharmacol 12:587–599PubMedCrossRefGoogle Scholar
  79. Zilles K, Schleicher A, Palomero-Gallagher N, Amunts K (2002b) Quantitative analysis of cyto- and receptor architecture of the human brain. In: Mazziotta JC, Toga A (eds) Brain mapping: the methods, 2nd edn. Elsevier, Amsterdam, pp 573–602CrossRefGoogle Scholar
  80. Zilles K, Palomero-Gallagher N, Schleicher A (2004) Transmitter receptors and functional anatomy of the cerebral cortex. J Anat 205:417–432PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Julian Caspers
    • 1
    • 2
    • 3
  • Nicola Palomero-Gallagher
    • 1
  • Svenja Caspers
    • 1
    • 3
  • Axel Schleicher
    • 1
  • Katrin Amunts
    • 1
    • 3
  • Karl Zilles
    • 1
    • 4
    • 5
    Email author
  1. 1.Institute of Neuroscience and Medicine (INM-1)Research Centre JülichJülichGermany
  2. 2.Department of Diagnostic and Interventional Radiology, Medical FacultyUniversity DüsseldorfDüsseldorfGermany
  3. 3.C. and O. Vogt Institute for Brain ResearchHeinrich-Heine-University DüsseldorfDüsseldorfGermany
  4. 4.JARA-BRAIN, Jülich-Aachen Research AllianceJülichGermany
  5. 5.Department of Psychiatry, Psychotherapy and PsychosomaticsRWTH Aachen UniversityAachenGermany

Personalised recommendations