Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Deviations in cortex sulcation associated with visual hallucinations in schizophrenia

Subjects

Abstract

Hallucinations, and auditory hallucinations (AH) in particular, constitute the most typical and disabling schizophrenia symptoms. Although visual hallucinations (VH) have been largely neglected in psychiatric disorders, a recent review reported a 27% mean prevalence of VH in schizophrenia patients. The pathophysiology underlying VH in schizophrenia remains elusive. Several schizophrenia studies reported a significant effect of age on VH; therefore, we tested the hypothesis that the neurodevelopmental model of schizophrenia may explain VH occurrence. We analyzed cortex sulcation, a marker of brain development, in healthy controls (HCs) and two subgroups of carefully selected schizophrenia patients suffering from hallucinations: patients with only AH (that is, patients who never reported VH) and patients with audio–visual hallucinations (A+VH). Different cortical sulcation and left–right sulcal asymmetry were found between A+VH and AH patients, with decreased sulcation in both A+VH and AH patients in comparison with the HCs. Although a specific association between VH and neurodegenerative mechanisms, for example, in Body-Lewy Dementia or Parkinson’s Disease, has previously been reported in the literature, the current study provides the first neuroimaging evidence of an association between VH and neurodevelopmental mechanisms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Jardri R, Cachia A, Thomas P, Pins D . The Neuroscience of Hallucinations. Springer: New-York, USA, 2013.

    Book  Google Scholar 

  2. Andreasen NC, Flaum M . Schizophrenia: the characteristic symptoms. Schizophr Bull 1991; 17: 27–49.

    Article  CAS  PubMed  Google Scholar 

  3. Waters F, Collerton D, Ffytche DH, Jardri R, Pins D, Dudley R et al. Visual hallucinations in the psychosis-spectrum, and comparative information from neurodegenerative disorders and eye disease. Schizophr Bull 2014; 40: S233–S245.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cummings JL, Miller BL . Visual hallucinations. Clinical occurrence and use in differential diagnosis. West J Med 1987; 146: 46–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Bracha HS, Wolkowitz OM, Lohr JB, Karson CN, Bigelow LB . High prevalence of visual hallucinations in research subjects with chronic schizophrenia. Am J Psychiatry 1989; 146: 526–528.

    Article  CAS  PubMed  Google Scholar 

  6. Goodwin DW, Alderson P, Rosenthal R . Clinical significance of hallucinations in psychiatric disorders. A study of 116 hallucinatory patients. Arch Gen Psychiatry 1971; 24: 76–80.

    Article  CAS  PubMed  Google Scholar 

  7. Mueser KT, Bellack AS, Brady EU . Hallucinations in schizophrenia. Acta Psychiatr Scand 1990; 82: 26–29.

    Article  CAS  PubMed  Google Scholar 

  8. Frieske DA, Wilson WP . Formal qualities of hallucinations: a comparative study of the visual hallucinations in patients with schizophrenic, organic, and affective psychoses. Proc Annu Meeting Am Psychopathol Assoc 1966; 54: 49–62.

    CAS  Google Scholar 

  9. Allen P, Modinos G, Hubl D, Shields G, Cachia A, Jardri R et al. Neuroimaging auditory hallucinations in schizophrenia: from neuroanatomy to neurochemistry and beyond. Schizophr Bull 2012; 38: 695–703.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Amad A, Cachia A, Gorwood P, Pins D, Delmaire C, Rolland B et al. The multimodal connectivity of the hippocampal complex in auditory and visual hallucinations. Mol Psychiatry 2014; 19: 184–191.

    Article  CAS  PubMed  Google Scholar 

  11. Rapoport JL, Giedd JN, Gogtay N . Neurodevelopmental model of schizophrenia: update 2012. Mol Psychiatry 2012; 17: 1228–1238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mangin JF, Jouvent E, Cachia A . In-vivo measurement of cortical morphology: means and meanings. Curr Opin Neurol 2010; 23: 359–367.

    PubMed  Google Scholar 

  13. Cachia A, Paillere-Martinot ML, Galinowski A, Januel D, de Beaurepaire R, Bellivier F et al. Cortical folding abnormalities in schizophrenia patients with resistant auditory hallucinations. Neuroimage 2008; 39: 927–935.

    Article  PubMed  Google Scholar 

  14. Hubl D, Dougoud-Chauvin V, Zeller M, Federspiel A, Boesch C, Strik W et al. Structural analysis of Heschl's gyrus in schizophrenia patients with auditory hallucinations. Neuropsychobiology 2010; 61: 1–9.

    Article  PubMed  Google Scholar 

  15. Plaze M, Paillere-Martinot ML, Penttila J, Januel D, de Beaurepaire R, Bellivier F et al. ‘Where do auditory hallucinations come from?’ A brain morphometry study of schizophrenia patients with inner or outer space hallucinations. Schizophr Bull 2011; 37: 212–221.

    Article  PubMed  Google Scholar 

  16. Lowe GR . The phenomenology of hallucinations as an aid to differential diagnosis. Br J Psychiatry 1973; 123: 621–633.

    Article  CAS  PubMed  Google Scholar 

  17. Bauer SM, Schanda H, Karakula H, Olajossy-Hilkesberger L, Rudaleviciene P, Okribelashvili N et al. Culture and the prevalence of hallucinations in schizophrenia. Compr Psychiatry 2011; 52: 319–325.

    Article  PubMed  Google Scholar 

  18. David CN, Greenstein D, Clasen L, Gochman P, Miller R, Tossell JW et al. Childhood onset schizophrenia: high rate of visual hallucinations. J Am Acad Child Adolesc Psychiatry 2011; 50: 681–686, e683.

    Article  PubMed  PubMed Central  Google Scholar 

  19. David C, Rapoport J . A neurodevelopmental perspective on hallucinations. In: Jardri R, Cachia A, Thomas P, Pins D (eds) The Neuroscience of hallucinations. Springer: New-York, USA, pp 203–230 2013.

    Chapter  Google Scholar 

  20. Kay SR, Fiszbein A, Opler LA . The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–276.

    Article  CAS  PubMed  Google Scholar 

  21. Andreasen NC . Methods for assessing positive and negative symptoms. Mod Probl Pharmacopsychiatry 1990; 24: 73–88.

    Article  CAS  PubMed  Google Scholar 

  22. Duchesnay E, Cachia A, Roche A, Riviere D, Cointepas Y, Papadopoulos-Orfanos D et al. Classification based on cortical folding patterns. IEEE Trans Med Imaging 2007; 26: 553–565.

    Article  PubMed  Google Scholar 

  23. Gardner DM, Murphy AL, O'Donnell H, Centorrino F, Baldessarini RJ . International consensus study of antipsychotic dosing. Am J Psychiatry 2010; 167: 686–693.

    Article  PubMed  Google Scholar 

  24. Penttila J, Paillere-Martinot ML, Martinot JL, Mangin JF, Burke L, Corrigall R et al. Global and temporal cortical folding in patients with early-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 2008; 47: 1125–1132.

    Article  PubMed  Google Scholar 

  25. Gay O, Plaze M, Oppenheim C, Mouchet-Mages S, Gaillard R, Olie JP et al. Cortex morphology in first-episode psychosis patients with neurological soft signs. Schizophr Bull 2013; 39: 820–829.

    Article  PubMed  Google Scholar 

  26. Penttila J, Cachia A, Martinot JL, Ringuenet D, Wessa M, Houenou J et al. Cortical folding difference between patients with early-onset and patients with intermediate-onset bipolar disorder. Bipolar Disord 2009; 11: 361–370.

    Article  PubMed  Google Scholar 

  27. Penttila J, Paillere-Martinot ML, Martinot JL, Ringuenet D, Wessa M, Houenou J et al. Cortical folding in patients with bipolar disorder or unipolar depression. J Psychiatry Neurosci 2009; 34: 127–135.

    PubMed  PubMed Central  Google Scholar 

  28. Mangin JF, Riviere D, Cachia A, Duchesnay E, Cointepas Y, Papadopoulos-Orfanos D et al. A framework to study the cortical folding patterns. Neuroimage 2004; 23: S129–S138.

    Article  PubMed  Google Scholar 

  29. Zilles K, Armstrong E, Schleicher A, Kretschmann HJ . The human pattern of gyrification in the cerebral cortex. Anat Embryol (Berl) 1988; 179: 173–179.

    Article  CAS  Google Scholar 

  30. Perrot M, Riviere D, Mangin JF . Cortical sulci recognition and spatial normalization. Med Image Anal 2011; 15: 529–550.

    Article  PubMed  Google Scholar 

  31. Dubois J, Benders M, Borradori-Tolsa C, Cachia A, Lazeyras F, Ha-Vinh Leuchter R et al. Primary cortical folding in the human newborn: an early marker of later functional development. Brain 2008; 131: 2028–2041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hilgetag CC, Barbas H . Role of mechanical factors in the morphology of the primate cerebral cortex. PLoS Comput Biol 2006; 2: e22.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Van Essen DC . A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 1997; 385: 313–318.

    Article  CAS  PubMed  Google Scholar 

  34. Klyachko VA, Stevens CF . Connectivity optimization and the positioning of cortical areas. Proc Natl Acad Sci USA 2003; 100: 7937–7941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rakic P . Specification of cerebral cortical areas. Science 1988; 241: 170–176.

    Article  CAS  PubMed  Google Scholar 

  36. Dehay C, Giroud P, Berland M, Killackey H, Kennedy H . Contribution of thalamic input to the specification of cytoarchitectonic cortical fields in the primate: effects of bilateral enucleation in the fetal monkey on the boundaries, dimensions, and gyrification of striate and extrastriate cortex. J Comp Neurol 1996; 367: 70–89.

    Article  CAS  PubMed  Google Scholar 

  37. Ford JM, Palzes VA, Roach BJ, Potkin SG, van Erp TG, Turner JA et al. Visual hallucinations are associated with hyperconnectivity between the amygdala and visual cortex in people with a diagnosis of schizophrenia. Schizophr Bull, advance online publication, 11 March 2014; doi:10.1093/schbul/sbu031 (e-pub ahead of print).

  38. Geoffroy P, Houenou J, Duhamel A, Amad A, de Weijer A, Curcic-Blake B et al. The Arcuate fasciculus in auditory-verbal hallucinations: a meta-analysis of diffusion-tensor-imaging studies. Schizophrenia Res 2014; 159: 234–237.

    Article  Google Scholar 

  39. Witelson SF . The brain connection: the corpus callosum is larger in left-handers. Science 1985; 229: 665–668.

    Article  CAS  PubMed  Google Scholar 

  40. Putnam MC, Wig GS, Grafton ST, Kelley WM, Gazzaniga MS . Structural organization of the corpus callosum predicts the extent and impact of cortical activity in the nondominant hemisphere. J Neurosci 2008; 28: 2912–2918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Deary IJ, Penke L, Johnson W . The neuroscience of human intelligence differences. Nat Rev Neurosci 2010; 11: 201–211.

    Article  CAS  PubMed  Google Scholar 

  42. Toga AW, Thompson PM . Mapping brain asymmetry. Nat Rev Neurosci 2003; 4: 37–48.

    Article  CAS  PubMed  Google Scholar 

  43. Crow TJ, Ball J, Bloom SR, Brown R, Bruton CJ, Colter N et al. Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. Arch Gen Psychiatry 1989; 46: 1145–1150.

    Article  CAS  PubMed  Google Scholar 

  44. Crow TJ . Is schizophrenia the price that Homo sapiens pays for language?. Schizophr Res 1997; 28: 127–141.

    Article  CAS  PubMed  Google Scholar 

  45. Dubois J, Hertz-Pannier L, Cachia A, Mangin JF, Le Bihan D, Dehaene-Lambertz G . Structural asymmetries in the infant language and sensori-motor networks. Cereb Cortex 2008; 19: 414–423.

    Article  PubMed  Google Scholar 

  46. Leroy F, Glasel H, Dubois J, Hertz-Pannier L, Thirion B, Mangin JF et al. Early maturation of the linguistic dorsal pathway in human infants. J Neurosci 2011; 31: 1500–1506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Corballis PM . Visuospatial processing and the right-hemisphere interpreter. Brain Cogn 2003; 53: 171–176.

    Article  PubMed  Google Scholar 

  48. Jonas J, Frismand S, Vignal JP, Colnat-Coulbois S, Koessler L, Vespignani H et al. Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex. Hum Brain Mapp 2014; 35: 3360–3371.

    Article  PubMed  Google Scholar 

  49. Bombin I, Arango C, Buchanan RW . Significance and meaning of neurological signs in schizophrenia: two decades later. Schizophr Bull 2005; 31: 962–977.

    Article  PubMed  Google Scholar 

  50. Peralta V, de Jalon EG, Campos MS, Basterra V, Sanchez-Torres A, Cuesta MJ . Risk factors, pre-morbid functioning and episode correlates of neurological soft signs in drug-naive patients with schizophrenia-spectrum disorders. Psychol Med 2010; 41: 1279–1289.

    Article  PubMed  Google Scholar 

  51. Biswas P, Malhotra S, Malhotra A, Gupta N . Comparative study of neurological soft signs in schizophrenia with onset in childhood, adolescence and adulthood. Acta Psychiatr Scand 2007; 115: 295–303.

    Article  CAS  PubMed  Google Scholar 

  52. Vourdas A, Pipe R, Corrigall R, Frangou S . Increased developmental deviance and premorbid dysfunction in early onset schizophrenia. Schizophr Res 2003; 62: 13–22.

    Article  PubMed  Google Scholar 

  53. Whitfield-Gabrieli S, Thermenos HW, Milanovic S, Tsuang MT, Faraone SV, McCarley RW et al. Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proc Natl Acad Sci USA 2009; 106: 1279–1284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Clos M, Diederen KM, Meijering AL, Sommer IE, Eickhoff SB . Aberrant connectivity of areas for decoding degraded speech in patients with auditory verbal hallucinations. Brain Struct Funct 2014; 219: 581–594.

    Article  PubMed  Google Scholar 

  55. Sommer IE, Clos M, Meijering AL, Diederen KM, Eickhoff SB . Resting state functional connectivity in patients with chronic hallucinations. PLoS ONE 2012; 7: e43516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wolf ND, Sambataro F, Vasic N, Frasch K, Schmid M, Schonfeldt-Lecuona C et al. Dysconnectivity of multiple resting-state networks in patients with schizophrenia who have persistent auditory verbal hallucinations. J Psychiatry Neurosci 2011; 36: 366–374.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Jardri R, Thomas P, Delmaire C, Delion P, Pins D . The neurodynamic organization of modality-dependent hallucinations. Cereb Cortex 2013; 23: 1108–1117.

    Article  PubMed  Google Scholar 

  58. Shine JM, Halliday GM, Naismith SL, Lewis SJ . Visual misperceptions and hallucinations in Parkinson's disease: dysfunction of attentional control networks?. Mov Disord 2011; 26: 2154–2159.

    Article  PubMed  Google Scholar 

  59. Ono M, Kubik S, Abarnathey CD . Atlas of the Cerebral Sulci. Georg Thieme: New York, 1990.

    Google Scholar 

  60. Cachia A, Mangin JF, Riviere D, Papadopoulos-Orfanos D, Kherif F, Bloch I et al. A generic framework for the parcellation of the cortical surface into gyri using geodesic Voronoi diagrams. Med Image Anal 2003; 7: 403–416.

    Article  CAS  PubMed  Google Scholar 

  61. Giedd JN, Rapoport JL . Structural MRI of pediatric brain development: what have we learned and where are we going?. Neuron 2010; 67: 728–734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ramanan VK, Shen L, Moore JH, Saykin AJ . Pathway analysis of genomic data: concepts, methods, and prospects for future development. Trends Genet 2012; 28: 323–332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the GDR CNRS—3557 ‘Institut de Recherche en Psychiatrie’ as well as by grants from the ERANET-NEURON program (AUSZ_EUCan), the Programme Hospitalier de Recherche Clinique (PHRC Multimodhal), the Pierre Houriez foundation (hosted by the Fondation de France), the Pierre Deniker foundation and the NRJ foundation.

Author Contributions

All the authors designed the study; AA, PT, JB, RJ recruited the participants; JB & RJ acquired the MRI data; AC, AA, RJ performed the analyses; All the authors contributed to the manuscript writing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A Cachia.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cachia, A., Amad, A., Brunelin, J. et al. Deviations in cortex sulcation associated with visual hallucinations in schizophrenia. Mol Psychiatry 20, 1101–1107 (2015). https://doi.org/10.1038/mp.2014.140

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2014.140

This article is cited by

Search

Quick links