Skip to main content
SpringerLink
Log in

The Neuropathology of Autism

  • Chapter
  • First Online:
Imaging the Brain in Autism

Abstract

This chapter studies the processes or behaviors of cells and tissue that may be considered abnormal in the brains of autistic individuals. The chapter will be divided into sections describing gross and microscopic changes. Another section will describe alterations within the modular organization of the cerebral cortex (i.e., minicolumns) that may serve as useful clinicopathological correlates to autism. A commentary by a senior investigator will examine how postmortem research may be complemented by neuroimaging techniques.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Avino TA, Hutsler JJ (2010) Abnormal cell patterning at the cortical gray-white matter boundary in autism spectrum disorders. Brain Res 1360:138–146

    Article  PubMed  CAS  Google Scholar 

  • Aylward EH, Minshew NJ, Field K, Sparks B-F, Singh N (2002) Effects of age on brain volume and head circumference in autism. Neurology 59:175–183

    Article  PubMed  CAS  Google Scholar 

  • Bailey A, Luthert PJ, Dean AF, Harding B, Janota I, Montgomery M, Rutter M, Lantos PL (1998) A clinicopathological study of autism. Brain 121:889–905

    Article  PubMed  Google Scholar 

  • Bauman ML, Kemper TL (1985) Histoanatomic observations of the brain in early infantile autism. Neurology 35:866–874

    Article  PubMed  CAS  Google Scholar 

  • Bauman ML, Kemper TL (1994) Neuroanatomic observations of the brain in autism. In: Bauman ML, Kemper TL (eds) The neurobiology of autism. Johns Hopkins University Press, Baltimore, pp 119–145

    Google Scholar 

  • Blamire AM, Rowe JG, Styles P, McDonald B (1999) Optimising imaging parameters for post mortem MR imaging of the human brain. Acta Radiol 40:593–597

    Article  PubMed  CAS  Google Scholar 

  • Bobinski M, de Leon MJ, Wegiel J, De Santi SM, Convit A, Saint Louis LA, Rusinek H, Wisniewski HM (1999) The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer’s disease. Neuroscience 95:721–725

    Article  Google Scholar 

  • Buxhoeveden DP, Switala AE, Roy E, Casanova MF (2000) Quantitative analysis of cell columns in the cerebral cortex. J Neurosci Methods 97:7–17

    Article  PubMed  CAS  Google Scholar 

  • Casanova MF (2004) White matter volume increase and minicolumns in autism. Ann Neurol 56:453

    Article  PubMed  Google Scholar 

  • Casanova MF (2006) Neuropathological and genetic findings in autism: the significance of a putative minicolumnopathy. Neuroscientist 12:435–441

    Article  PubMed  Google Scholar 

  • Casanova MF (2007) The neuropathology of autism. Brain Pathol 17:422–433

    Article  PubMed  Google Scholar 

  • Casanova MF (2008) The significance of minicolumnar size variability in autism: a perspective from comparative anatomy. In: Zimmerman AW (ed) Autism: current theories and evidence. Humana Press, Totowa, NJ, pp 349–360

    Google Scholar 

  • Casanova MF (2012) The minicolumnopathy of autism. In: Hof PR, Buxbaum J (eds) Neuroscience of autism spectrum disorders. Elsevier, Amsterdam, pp 327–334

    Google Scholar 

  • Casanova MF, Buxhoeveden DP, Switala AE, Roy E (2002a) Asperger’s syndrome and cortical neuropathology. J Child Neurol 17:142–145

    Article  PubMed  Google Scholar 

  • Casanova MF, Buxhoeveden DP, Switala AE, Roy E (2002b) Neuronal density and architecture (Gray Level Index) in the brains of autistic patients. J Child Neurol 17:515–521

    Article  PubMed  Google Scholar 

  • Casanova MF, Buxhoeveden DP, Switala AE, Roy E (2002c) Minicolumnar pathology in autism. Neurology 58:428–432

    Article  PubMed  Google Scholar 

  • Casanova MF, Buxhoeveden DP, Gomez J (2003) Disruption in the inhibitory architecture of the cell minicolumn: implications for autism. Neuroscientist 9:496–507

    Article  PubMed  Google Scholar 

  • Casanova MF, Van Kooten IAJ, Switala AE, Van Engeland H, Heinsen H, Steinbusch HWM, Hof PR, Schmitz C (2006a) Abnormalities of cortical minicolumnar organization in the prefrontal lobes of autistic patients. Clin Neurosci Res 6:127–133

    Article  Google Scholar 

  • Casanova MF, Van Kooten IAJ, Switala AE, Van Engeland H, Heinsen H, Steinbusch HWM, Hof PR, Trippe J, Stone J, Schmitz C (2006b) Minicolumnar abnormalities in autism. Acta Neuropathol 112:287–303

    Article  PubMed  Google Scholar 

  • Casanova MF, Trippe J, Tillquist C, Switala AE (2009a) Morphometric variability of minicolumns in the striate cortex of Homo sapiens, Macaca mulatta, and Pan troglodytes. J Anat 214:226–234

    Article  PubMed  Google Scholar 

  • Casanova MF, El-Baz AS, Mott M, Mannheim GB, Hassan H, Fahmi R, Giedd J, Rumsey JM, Switala AE, Farag AA (2009b) Reduced gyral window and corpus callosum size in autism: possible macroscopic correlates of a minicolumnopathy. J Autism Dev Disord 39:751–764

    Article  PubMed  Google Scholar 

  • Casanova MF, El-Baz AS, Vanbogaert E, Narahari P, Switala A (2010) A topographic study of minicolumnar core width by lamina comparison between autistic subjects and controls: possible minicolumnar disruption due to an anatomical element in-common to multiple laminae. Brain Pathol 20:451–458

    Article  PubMed  Google Scholar 

  • Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL (1988) Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med 318:1349–1354

    Article  PubMed  CAS  Google Scholar 

  • Courchesne E, Saitoh O, Yeung-Courchesne R, Press GA, Lincoln AJ, Haas RH, Schreibman LE (1994) Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging. Am J Radiol 162:123–130

    CAS  Google Scholar 

  • Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, Chisum HJ, Moses P, Pierce K, Lord C, Lincoln AJ, Pizzo S, Schreibman LE, Haas RH, Akshoomoff NA, Courchesne RY (2001) Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 57:245–254

    Article  PubMed  CAS  Google Scholar 

  • Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Carter Barnes C, Pierce K (2011) Neuron number and size in prefrontal cortex of children with autism. JAMA 306:2001–2010

    Article  PubMed  CAS  Google Scholar 

  • DeFelipe J (2005) Reflections on the structure of the cortical minicolumn. In: Casanova MF (ed) Neocortical modularity and the cell minicolumn. Nova Biomedical, New York, pp 57–92

    Google Scholar 

  • Deisseroth K (2012) Optogenetics and psychiatry: applications, challenges, and opportunities. Biol Psychiatry 71:1030–1032

    Article  PubMed  Google Scholar 

  • El-Baz AS, Casanova MF, Gimel’farb GL, Mott M, Switala AE (2007) Autism diagnostics by 3D texture analysis of cerebral white matter gyrifications. In: Ayache N, Ourselin S, Maeder AJ (eds) Medical image computing and computer-assisted intervention—MICCAI 2007, part II. Springer, New York, pp 882–890

    Chapter  Google Scholar 

  • Fahmi R, El-Baz AS, Abd El Munim HE, Farag AA, Casanova MF (2007) Classification techniques for autistic vs. typically developing brain using MRI data. In: Casanova MF (ed) Biomedical imaging: from nano to macro. IEEE, Piscataway, NJ, pp 1348–1351

    Google Scholar 

  • Fidler DJ, Bailey JN, Smalley SL (2000) Macrocephaly in autism and other pervasive developmental disorders. Dev Med Child Neurol 42:737–740

    Article  PubMed  CAS  Google Scholar 

  • Fombonne E, Rogé B, Claverie J, Courty S, Frémolle J (1999) Microcephaly and macrocephaly in autism. J Autism Dev Disord 29:113–119

    Article  PubMed  CAS  Google Scholar 

  • Goldberg J, Szatmari P, Nahmias C (1999) Imaging of autism: lessons from the past to guide studies in the future. Can J Psychiatry 44:793–801

    PubMed  CAS  Google Scholar 

  • Hardan AY, Minshew NJ, Mallikarjuhn M, Keshavan MS (2001) Brain volume in autism. J Child Neurol 16:421–424

    PubMed  CAS  Google Scholar 

  • Hardan AY, Jou RJ, Keshavan MS, Varma R, Minshew NJ (2004) Increased frontal cortical folding in autism: a preliminary MRI study. Psychiatry Res Neuroimag 131:263–268

    Article  Google Scholar 

  • Harding B, Copp AJ (1997) Malformations. In: Graham DI, Lantos PL (eds) Greenfield’s neuropathology. Arnold, London, pp 397–533

    Google Scholar 

  • Herbert MR, Ziegler DA, Deutsch CK, O’Brien LM, Lange N, Bakardjiev AI, Hodgson J, Adrien KT, Steele S, Makris N, Kennedy DN, Harris GJ, Caviness VS Jr (2003) Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 126:1182–1192

    Article  PubMed  CAS  Google Scholar 

  • Herbert MR, Ziegler DA, Makris N, Filipek PA, Kemper TL, Normandin JJ, Sanders HA, Kennedy DN, Caviness VS Jr (2004) Localization of white matter volume increase in autism and developmental language disorder. Ann Neurol 55:530–540

    Article  PubMed  Google Scholar 

  • Hutsler JJ, Love T, Zhang H (2007) Histological and magnetic resonance imaging assessment of cortical layering and thickness in autism spectrum disorders. Biol Psychiatry 61:449–457

    Article  PubMed  Google Scholar 

  • Kanner L (1943) Autistic disturbances of affective contact. Nerv Child 2:217–250

    Google Scholar 

  • Kemper TL (1988) Neuroanatomic studies of dyslexia and autism. In: Swann JW, Messer A (eds) Disorders of the developing nervous system: changing views on their origins, diagnoses, and treatments. Alan R. Liss, New York, pp 125–154

    Google Scholar 

  • Lainhart JE, Piven J, Wzorek M, Landa R, Santangelo SL, Coon H, Folstein SE (1997) Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry 36:282–290

    Article  PubMed  CAS  Google Scholar 

  • Miller KL, Stagg CJ, Douaud G, Jbabdi S, Smith SM, Behrens TEJ, Jenkinson M, Chance SA, Esiri MM, Voets NL, Jenkinson N, Aziz TZ, Turner MR, Johansen-Berg H, McNab JA (2011) Diffusion imaging of whole, post-mortem human brains on a clinical MRI scanner. Neuroimage 57:167–181

    Article  PubMed  Google Scholar 

  • Miller KL, McNab JA, Jbabdi S, Douaud G (2012) Diffusion tractography of post-mortem human brains: optimization and comparison of spin echo and steady-state free precession techniques. Neuroimage 59:2284–2297

    Article  PubMed  Google Scholar 

  • Nowell MA, Hackney DB, Muralo AS, Coleman M (1990) Varied MR appearance of autism: fifty-three pediatric patients having the full autistic syndrome. Magn Reson Imaging 8:811–816

    Article  PubMed  CAS  Google Scholar 

  • Pardo CA, Vargas DL, Zimmerman AW (2005) Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry 17:485–495

    Article  PubMed  Google Scholar 

  • Piven J, Nehme E, Simon J, Barta P, Pearlson G, Folstein SE (1992) Magnetic resonance imaging in autism: measurement of the cerebellum, pons, and fourth ventricle. Biol Psychiatry 31:491–504

    Article  PubMed  CAS  Google Scholar 

  • Piven J, Arndt S, Bailey J, Havercamp S, Andreasen NC, Palmer P (1995) An MRI study of brain size in autism. Am J Psychiatry 152:1145–1149

    PubMed  CAS  Google Scholar 

  • Raymond GV, Bauman ML, Kemper TL (1995) Hippocampus in autism: a Golgi analysis. Acta Neuropathol 91:117–119

    Article  Google Scholar 

  • Roberts ISD, Benamore RE, Benbow EW, Lee SH, Harris JN, Jackson A, Mallett S, Patankar T, Peebles C, Roobottom C, Traill ZC (2012) Post-mortem imaging as an alternative to autopsy in the diagnosis of adult deaths: a validation study. Lancet 379:136–142

    Article  PubMed  Google Scholar 

  • Schaefer GB, Thompson JN Jr, Bodensteiner JB, McConnell JM, Kimberling WJ, Gay CT, Dutton WD, Hutchings DC, Gray SB (1996) Hypoplasia of the cerebellar vermis in neurogenetic syndromes. Ann Neurol 39:382–385

    Article  PubMed  CAS  Google Scholar 

  • Schlaug G, Schleicher A, Zilles K (1995) Quantitative analysis of the columnar arrangement of neurons in the human cingulate cortex. J Comp Neurol 351:441–452

    Article  PubMed  CAS  Google Scholar 

  • Schumann CM, Amaral DG (2005) Stereological estimation of the number of neurons in the human amygdaloid complex. J Comp Neurol 491:320–329

    Article  PubMed  Google Scholar 

  • Schumann CM, Amaral DG (2006) Stereological analysis of amygdala neuron number in autism. J Neurosci 26:7674–7679

    Article  PubMed  CAS  Google Scholar 

  • Schumann CM, Nordahl CW (2011) Bridging the gap between MRI and postmortem research in autism. Brain Res 1380:175–186

    Article  PubMed  CAS  Google Scholar 

  • Schumann CM, Buonocore MH, Amaral DG (2001) Magnetic resonance imaging of the post-mortem autistic brain. J Autism Dev Disord 31:561–568

    Article  PubMed  CAS  Google Scholar 

  • Sparks B-F, Friedman SD, Shaw DW, Aylward EH, Echelard D, Artru AA, Maravilla KR, Giedd JN, Munson J, Dawson G, Dager SR (2002) Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59:158–159

    Article  Google Scholar 

  • Stevenson RE, Schroer RJ, Skinner C, Fender D, Simensen RJ (1997) Autism and macrocephaly. Lancet 349:1744–1745

    Article  PubMed  CAS  Google Scholar 

  • Szentágothai J, Arbib MA (1975) Conceptual models of neural organization. MIT Press, Cambridge, MA

    Google Scholar 

  • Vargas DL, Nascimbene C, Krishan C, Zimmerman AW, Pardo CA (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67–81

    Article  PubMed  CAS  Google Scholar 

  • Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, Ma SY, Chauhan A, Chauhan V, Wierzba Bobrowicz T, De Leon M, Saint Louis LA, Cohen IL, London E, Brown WT, Wisniewski T (2010) The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol 119:755–770

    Article  PubMed  Google Scholar 

  • Williams EL, Casanova MF (2012) Hyperlexia and dyslexia in autism: hitting a moving target. J Spec Educ Rehabil 13(3):39–54

    Google Scholar 

  • Woodhouse W, Bailey A, Rutter M, Bolton PF, Baird G, Le Couteur A (1996) Head circumference in autism and other pervasive developmental disorders. J Child Psychol Psychiatry 37:655–671

    Article  Google Scholar 

  • Zimmerman AW, Jyonouchi H, Comi AM, Connors SL, Milstien S, Varsou A, Heyes MP (2005) Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol 33:195–201 Biblography

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, University of Louisville, Building 55A, Suite 217, 500 South Preston St Bldg 55A Rm 217, Louisville, KY, 40202, USA

    Manuel F. Casanova M.D.

  2. Autism Tissue Program, Autism Speaks, 5119 Alejo St, San Diego, CA, 92124, USA

    Jane Pickett Ph.D.

Authors
  1. Manuel F. Casanova M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jane Pickett Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manuel F. Casanova M.D. .

Editor information

Editors and Affiliations

  1. , Department of Psychiatry, University of Louisville, S. Preston Street 500, Louisville, 40292, Kentucky, USA

    Manuel F. Casanova

  2. , Department of Bioengineering, University of Louisville, Louisville, 40208, USA

    Ayman S. El-Baz

  3. Global Biomedical Technologies, Otter Glen Ct. 208, Roseville, 95661, California, USA

    Jasjit S. Suri

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer New York

About this chapter

Cite this chapter

Casanova, M.F., Pickett, J. (2013). The Neuropathology of Autism. In: Casanova, M., El-Baz, A., Suri, J. (eds) Imaging the Brain in Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6843-1_2

Download citation

Publish with us

Policies and ethics

Search

Navigation