Skip to main content
Log in

Dyslexia—A molecular disorder of neuronal migration

The 2004 Norman Geschwind memorial lecture

  • Published:
Annals of Dyslexia Aims and scope Submit manuscript

Abstract

For 25 years now, there has been a serious attempt to get at the fundamental cause(s) of dyslexia in our laboratory. A great deal of research has been carried out on the psychological and brain underpinnings of the linguistic dysfunctions seen in dyslexia, but attempts to get at its cause have been limited. Initially, observations were made on the brains of persons with dyslexia who had died and their brains donated for research. These observations were modeled in animal models in order to better understand the full extent of anatomical and developmental brain characteristics. More recently, models have begun to employ genetic manipulations in order to close the gap between genes, brain, and behavior. In this article based on a lecture given in memory of Dr. Norman Geschwind to the International Dyslexia Association assembly in Philadelphia in 2004, I outline the history of the research leading up to the most recent findings. These findings consist of experiments using methods that interfere with the function of DNA, using as constructs genes that have been implicated in dyslexia, which cause developmental problems of neuronal migration in rats, secondary brain changes in response to the migration problems, and abnormal processing of sounds.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Best, M., & Demb, J. B. (1999). Normal planum temporale asymmetry in dyslexics with a magnocellular pathway deficit. Neuroreport, 10(3), 607–612.

    Article  Google Scholar 

  • Brambati, S. M., Termine, C., Ruffino, M., Stella, G., Fazio, F., Cappa, S. F., et al. (2004). Regional reductions of gray matter volume in familial dyslexia. Neurology, 63(4), 742–745.

    Google Scholar 

  • Cohen, L., Dehaene, S., Naccache, L., Lehericy, S., Dehaene-Lambertz, G., Henaff, M. A., et al. (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), 291–307.

    Article  Google Scholar 

  • Cope, N., Harold, D., Hill, G., Moskvina, V., Stevenson, J., Holmans, P., et al. (2005). Strong evidence that kiaa0319 on chromosome 6p is a susceptibility gene for developmental dyslexia. American Journal of Human Genetics, 76(4), 581–591.

    Article  Google Scholar 

  • Deffenbacher, K. E., Kenyon, J. B., Hoover, D. M., Olson, R. K., Pennington, B. F., DeFries, J. C., et al. (2004). Refinement of the 6p21.3 quantitative trait locus influencing dyslexia: Linkage and association analyses. Human Genetics, 115(2), 128–138.

    Article  Google Scholar 

  • Dehaene, S., Cohen, L., Sigman, M., & Vinckier, F. (2005). The neural code for written words: A proposal. Trends in Cognitive Sciences, 9(7), 335–341.

    Article  Google Scholar 

  • Eckert, M. A., & Leonard, C. M. (2000). Structural imaging in dyslexia: The planum temporale. Mental Retardation and Developmental Disabilility Research Review, 6(3), 198–206.

    Article  Google Scholar 

  • Fisher, S. E., Marlow, A. J., Lamb, J., Maestrini, E., Williams, D. F., Richardson, A. J., et al. (1999). A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia. American Journal of Human Genetics, 64(1), 146–156.

    Article  Google Scholar 

  • Fitch, R. H., Brown, C. P., Tallal, P., & Rosen, G. D. (1997). Effects of sex and mk-801 on auditory-processing deficits associated with developmental microgyric lesions in rats. Behavioral Neuroscience, 111(2), 404–412.

    Article  Google Scholar 

  • Francks, C., Paracchini, S., Smith, S. D., Richardson, A. J., Scerri, T. S., Cardon, L. R., et al. (2004). A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States. American Journal of Human Genetics, 75(6), 1046–1058.

    Article  Google Scholar 

  • Friedman, J. T., Peiffer, A. M., Clark, M. G., Benasich, A. A., & Fitch, R. H. (2004). Age and experience-related improvements in gap detection in the rat. Brain Research. Developmental Brain Research, 152(2), 83–91.

    Article  Google Scholar 

  • Galaburda, A. M. (1994). Developmental dyslexia and animal studies: At the interface between cognition and neurology. Cognition, 50(1–3), 133–149.

    Article  Google Scholar 

  • Galaburda, A. M., & Kemper, T. L. (1979). Cytoarchitectonic abnormalities in developmental dyslexia: A case study. Annals of Neurology, 6, 94–100.

    Article  Google Scholar 

  • Galaburda, A. M., LeMay, M., Kemper, T. L., & Geschwind, N. (1978). Right-left asymmetries in the brain. Science, 199, 852–856.

    Article  Google Scholar 

  • Galaburda, A. M., Sherman, G. F., Rosen, G. D., Aboitiz, F., & Geschwind, N. (1985). Developmental dyslexia: Four consecutive cases with cortical anomalies. Annals of Neurology, 18, 222–233.

    Article  Google Scholar 

  • Geschwind, N. (1982). Why Orton was right. Annals of Dyslexia, 23, 13–30.

    Google Scholar 

  • Geschwind, N., & Galaburda, A. M. (1985a). Cerebral lateralization. Biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. Archives of Neurology, 42, 428–462.

    Google Scholar 

  • Geschwind, N., & Galaburda, A. M. (1985b). Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and a program for research. Archives of Neurology, 42, 521–556.

    Google Scholar 

  • Geschwind, N., & Galaburda, A. M. (1985c). Cerebral lateralization. Biological mechanisms, associations, and pathology: III. A hypothesis and a program for research. Archives of Neurology, 42, 634–654.

    Google Scholar 

  • Geschwind, N., & Levitsky, W. (1968). Human brain: Left-right asymmetries in temporal speech region. Science, 161, 186–187.

    Article  Google Scholar 

  • Grigorenko, E. L. (2001). Developmental dyslexia: An update on genes, brains, and environments. Journal of Child Psychology and Psychiatry, 42(1), 91–125.

    Article  Google Scholar 

  • Grigorenko, E. L., Wood, F. B., Golovyan, L., Meyer, M., Romano, C., & Pauls, D. (2003). Continuing the search for dyslexia genes on 6p. American Journal of Medical Genetics. Part B, Neuropsychiatrics Genetics, 118(1), 89–98.

    Article  Google Scholar 

  • Grigorenko, E. L., Wood, F. B., Meyer, M. S., & Pauls, D. L. (2000). Chromosome 6p influences on different dyslexia-related cognitive processes: Further confirmation. American Journal of Human Genetics, 66(2), 715–723.

    Article  Google Scholar 

  • Hatten, M. E. (2002). New directions in neuronal migration. Science, 297(5587), 1660–1663.

    Article  Google Scholar 

  • Herman, A. E., Galaburda, A. M., Fitch, R. H., Carter, A. R., & Rosen, G. D. (1997). Cerebral microgyria, thalamic cell size and auditory temporal processing in male and female rats. Cerebral Cortex, 7(5), 453–464.

    Article  Google Scholar 

  • Kaufmann, W. E., & Galaburda, A. M. (1989). Cerebrocortical microdysgenesis in neurologically normal subjects: A histopathologic study. Neurology, 39(2), 238–244.

    Google Scholar 

  • Londin, E. R., Meng, H., & Gruen, J. R. (2003). A transcription map of the 6p22.3 reading disability locus identifying candidate genes. BMC Genomics, 4(1), 25.

    Article  Google Scholar 

  • Lubs, H. A., Smith, S., Kimberling, W., Pennington, B., Gross-Glenn, K., & Duara, R. (1988). Dyslexia sybtypes: Genetics, behavior, and brain imaging. In F. Plum (Ed.), Language, communication and the brain (pp. 139–147). New York: Raven Press.

    Google Scholar 

  • Marino, C., Giorda, R., Vanzin, L., Molteni, M., Lorusso, M. L., Nobile, M., et al. (2003). No evidence for association and linkage disequilibrium between dyslexia and markers of four dopamine-related genes. European Journal of Child and Adolescent Psychiatry: Acta Paedopsychiatrica, 12(4), 198–202.

    Article  Google Scholar 

  • McClure, M. M., Peiffer, A. M., Rosen, G. D., & Fitch, R. H. (2005). Auditory processing deficits in rats with neonatal hypoxic-ischemic injury. International Journal of Developmental Neuroscience, 23(4), 351–362.

    Article  Google Scholar 

  • McManus, M. F., & Golden, J. A. (2005). Neuronal migration in developmental disorders. Journal of Child Neurology, 20(4), 280–286.

    Article  Google Scholar 

  • Orton, S. T. (1925). “Word-blindness” in school children. Archives of Neurology and Psychiatry, 14, 581–615.

    Google Scholar 

  • Peiffer, A. M., Dunleavy, C. K., Frenkel, M., Gabel, L. A., LoTurco, J. J., Rosen, G. D., et al. (2001). Impaired detection of variable duration embedded tones in ectopic nzb/binj mice. Neuroreport, 12(13), 2875–2879.

    Article  Google Scholar 

  • Peiffer, A. M., Friedman, J. T., Rosen, G. D., & Fitch, R. H. (2004a). Impaired gap detection in juvenile microgyric rats. Brain Research. Developmental Brain Research, 152(2), 93–98.

    Article  Google Scholar 

  • Peiffer, A. M., McClure, M. M., Threlkeld, S. W., Rosen, G. D., & Fitch, R. H. (2004b). Severity of focal microgyria and associated rapid auditory processing deficits. Neuroreport, 15(12), 1923–1926.

    Article  Google Scholar 

  • Peiffer, A. M., Rosen, G. D., & Fitch, R. H. (2002a). Rapid auditory processing and mgn morphology in microgyric rats reared in varied acoustic environments. Brain Research. Developmental Brain Research, 138(2), 187–193.

    Article  Google Scholar 

  • Peiffer, A. M., Rosen, G. D., & Fitch, R. H. (2002b). Sex differences in rapid auditory processing deficits in ectopic bxsb/mpj mice. Neuroreport, 13(17), 2277–2280.

    Article  Google Scholar 

  • Peiffer, A. M., Rosen, G. D., & Fitch, R. H. (2004c). Sex differences in rapid auditory processing deficits in microgyric rats. Brain Research. Developmental Brain Research, 148(1), 53–57.

    Article  Google Scholar 

  • Posner, M. I., DiGirolamo, G. J., & Fernandez-Duque, D. (1997). Brain mechanisms of cognitive skills. Conscious Cognition, 6(2/3), 267–290.

    Article  Google Scholar 

  • Ramus, F. (2004). Neurobiology of dyslexia: A reinterpretation of the data. Trends in Neurosciences, 27(12), 720–726.

    Article  Google Scholar 

  • Rosen, G. D., Galaburda, A. M., & Sherman, G. F. (1989). Cerebrocortical microdysgenesis with anomalous callosal connections: A case study in the rat. International Journal of Neuroscence, 47, 237–247.

    Google Scholar 

  • Rosen, G. D., Herman, B. A., & Galaburda, A. M. (1999). Sex differences in the effects of early neocortical injury on neuronal size distribution of the medial geniculate nucleus in the rat are mediated by perinatal gonadal steroids. Cerebral Cortex, 9(1), 27–34.

    Article  Google Scholar 

  • Rosen, G. D., Press, D. M., Sherman, G. F., & Galaburda, A. M. (1992). The development of induced cerebrocortical microgyria in the rat. Journal of Neuropathology and Experimental Neurology, 51(6), 601–611.

    Google Scholar 

  • Rosen, G. D., Sherman, G. F., & Galaburda, A. M. (1989). Interhemispheric connections differ between symmetrical and asymmetrical brain regions. Neuroscience, 33, 525–533.

    Article  Google Scholar 

  • Scerri, T. S., Fisher, S. E., Francks, C., MacPhie, I. L., Paracchini, S., Richardson, A. J., et al. (2004). Putative functional alleles of dyx1c1 are not associated with dyslexia susceptibility in a large sample of sibling pairs from the UK. Journal of Medical Genetics, 41(11), 853–857.

    Article  Google Scholar 

  • Sheen, V. L., & Walsh, C. A. (2003). Developmental genetic malformations of the cerebral cortex. Current Neurology and Neuroscience Reports, 3(5), 433–441.

    Article  Google Scholar 

  • Sherman, G. F., Morrison, L., Rosen, G. D., Behan, P. O., & Galaburda, A. M. (1990). Brain abnormalities in immune defective mice. Brain Research, 532, 25–33.

    Article  Google Scholar 

  • Sherman, G. F., Stone, J. S., Press, D. M., Rosen, G. D., & Galaburda, A. M. (1990). Abnormal architecture and connections disclosed by neurofilament staining in the cerebral cortex of autoimmune mice. Brain Research, 529, 202–207.

    Article  Google Scholar 

  • Sherman, G. F., Stone, L. V., Galaburda, A. M., & Beier, D. R. (1997). Linkage analysis of neurocortical ectopias in nxsm-d mice. Society for Neuroscience Abstracts, 27, 1133.

    Google Scholar 

  • Smith, S. D., Kimberling, W. J., Pennington, B. F., & Lubs, H. A. (1983). Specific reading disability: Identification of an inherited form through linkage analysis. Science, 219, 1345–1347.

    Article  Google Scholar 

  • Taipale, M., Kaminen, N., Nopola-Hemmi, J., Haltia, T., Myllyluoma, B., Lyytinen, H., et al. (2003). A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain. Proceedings of the National Academy of Sciences of the United States of America, 100(20), 11553–11558.

    Article  Google Scholar 

  • Tallal, P., & Piercy, M. (1973). Defects of non-verbal auditory perception in children with developmental aphasia. Nature, 241, 468–469.

    Article  Google Scholar 

  • Wigg, K. G., Couto, J. M., Feng, Y., Anderson, B., Cate-Carter, T. D., Macciardi, F., et al. (2004). Support for ekn1 as the susceptibility locus for dyslexia on 15q21. Molecular Psychiatry, 9(12), 1111–1121.

    Article  Google Scholar 

  • Ylisaukko-Oja, T., Peyrard-Janvid, M., Lindgren, C. M., Rehnstrom, K., Vanhala, R., Peltonen, L., et al. (2005). Family-based association study of dyx1c1 variants in autism. European Journal of Human Genetics, 13(1), 127–130.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Albert M. Galaburda M.D..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galaburda, A.M. Dyslexia—A molecular disorder of neuronal migration. Ann. of Dyslexia 55, 151–165 (2005). https://doi.org/10.1007/s11881-005-0009-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11881-005-0009-4

Key Words

Navigation