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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

Atypical architecture of prefrontal cortex in young children with autism

Principal Investigator

Principal Investigator

Courchesne, Eric

Description

Description

Autism impairs the early development of social, emotional and communication functions, but the early neural defects that cause this disorder remain a mystery due to the near absence of genetic, molecular and cellular studies of the young autistic brain. Because prefrontal cortex plays an important role in these early developmental functions and displays abnormal growth and function during the first years of life in autism, we performed a detailed analysis of the structural organization of prefrontal cortex in the youngest postmortem autistic cases available. We discovered that young autistic males consistently display abnormal architecture in prefrontal cortex that occurs in discrete patches (roughly 1cm by 1cm), this is undeniably of very early developmental origin, and is likely to be the neural defect that causes autism. Moreover, using whole genome analyses of gene expression of prefrontal cortex in these same young autistic cases we also discovered evidence of dysregulation of early developmental processes, including cell proliferation, cell death, cell cycle regulation and DNA damage repair. This suggests that autism may result from alterations in these early developmental processes that can lead to the formation of patches of abnormally organized cortex. We propose several next steps to further investigate cortical patches in autism and test this theory that local alterations can lead to a cortical patch phenotype. We will (1) determine how common these abnormalities are across ages, gender and level of functioning in autism, (2) determine if they are commonly found in multiple cortical regions, (3) analyze the structural and genetic properties of cells in these abnormal regions, and (4) develop animal models that replicate these changes. Understanding the mechanisms that cause these patches will lead to new methods for determining early risk and prognosis and may lead to new therapies for autism.

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

0

Current Award Period

Current Award Period

2010-2015

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

2O. Not specific to Question 2 objectives

Project Link

Project Link

Atypical architecture of prefrontal cortex in young children with autism (External web link)

Institution

Institution

University of California, San Diego

State/Country

State/Country

California

Project Number

Project Number

176540

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Atypical architecture of prefrontal cortex in young children with autism | 565183 | 2011 | 176540
Atypical architecture of prefrontal cortex in young children with autism | 335103 | 2012 | 176540
Atypical architecture of prefrontal cortex in young children with autism | 149715 | 2013 | 176540
Atypical architecture of prefrontal cortex in young children with autism | 0 | 2014 | 176540

 
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