Acta Neuropathologica

, Volume 124, Issue 1, pp 67–79 | Cite as

Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism

  • Sarah Jacot-Descombes
  • Neha Uppal
  • Bridget Wicinski
  • Micaela Santos
  • James Schmeidler
  • Panteleimon Giannakopoulos
  • Helmut Heinsein
  • Christoph Schmitz
  • Patrick R. Hof
Original Paper


Autism is a neurodevelopmental disorder characterized by deficits in social interaction and social communication, as well as by the presence of repetitive and stereotyped behaviors and interests. Brodmann areas 44 and 45 in the inferior frontal cortex, which are involved in language processing, imitation function, and sociality processing networks, have been implicated in this complex disorder. Using a stereologic approach, this study aims to explore the presence of neuropathological differences in areas 44 and 45 in patients with autism compared to age- and hemisphere-matched controls. Based on previous evidence in the fusiform gyrus, we expected to find a decrease in the number and size of pyramidal neurons as well as an increase in volume of layers III, V, and VI in patients with autism. We observed significantly smaller pyramidal neurons in patients with autism compared to controls, although there was no difference in pyramidal neuron numbers or layer volumes. The reduced pyramidal neuron size suggests that a certain degree of dysfunction of areas 44 and 45 plays a role in the pathology of autism. Our results also support previous studies that have shown specific cellular neuropathology in autism with regionally specific reduction in neuron size, and provide further evidence for the possible involvement of the mirror neuron system, as well as impairment of neuronal networks relevant to communication and social behaviors, in this disorder.


Autism Brodmann area 44 Brodmann area 45 Inferior frontal gyrus Neuropathology Stereology 



The authors thank Autism Speaks (the Autism Celloidin Library Project, PRH), the James S. MacDonnell Foundation (PRH), the Seaver Foundation (NU), and the Vachoux Foundation (SJD, MS), Drs J. Wegiel, D. Lightfoot, and J. Pickett, as well as Ms E. Xiu for their generous support. We would also like to acknowledge the Bronx VA Medical Center Brain Bank, Harvard Brain Tissue Resource Center, National Institute of Child Health and Human Development Brain Tissue Bank, New York State Institute for Basic Research in Developmental Disabilities, Oxford Brain Bank, University of Maryland Brain and Tissue Bank, University of Wuerzburg Morphologic Brain Research Unit, and the Autism Tissue Program for providing the materials used in this study. We are especially grateful to the families who donated tissue to make this study possible.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Sarah Jacot-Descombes
    • 1
    • 4
  • Neha Uppal
    • 1
    • 3
  • Bridget Wicinski
    • 1
  • Micaela Santos
    • 1
    • 4
  • James Schmeidler
    • 2
  • Panteleimon Giannakopoulos
    • 4
    • 5
  • Helmut Heinsein
    • 6
  • Christoph Schmitz
    • 7
  • Patrick R. Hof
    • 1
  1. 1.Fishberg Department of NeuroscienceMount Sinai School of MedicineNew YorkUSA
  2. 2.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA
  3. 3.Seaver Autism CenterMount Sinai School of MedicineNew YorkUSA
  4. 4.Department of Mental Health and PsychiatryUniversity Hospitals and School of MedicineGenevaSwitzerland
  5. 5.Department of PsychiatryUniversity of Lausanne School of MedicineLausanneSwitzerland
  6. 6.Morphological Brain Research Unit, Department of Psychiatry, Psychosomatics, and PsychotherapyUniversity of WuerzburgWuerzburgGermany
  7. 7.Department of Neuroanatomy, School of MedicineLudwig-Maximilians UniversityMunichGermany

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