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Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection
Abstract
Although it has long been thought that frontal lobe abnormality must play an important part in generating the severe impairment in higher-order social, emotional and cognitive functions in autism, only recently have studies identified developmentally early frontal lobe defects. At the microscopic level, neuroinflammatory reactions involving glial activation, migration defects and excess cerebral neurogenesis and/or defective apoptosis might generate frontal neural pathology early in development. It is hypothesized that these abnormal processes cause malformation and thus malfunction of frontal minicolumn microcircuitry. It is suggested that connectivity within frontal lobe is excessive, disorganized and inadequately selective, whereas connectivity between frontal cortex and other systems is poorly synchronized, weakly responsive and information impoverished. Increased local but reduced long-distance cortical-cortical reciprocal activity and coupling would impair the fundamental frontal function of integrating information from widespread and diverse systems and providing complex context-rich feedback, guidance and control to lower-level systems.
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“This general model was subsequently anatomically refined and modified to focus primarily on reduced long-range, and increased short range frontal lobe connectivity [53].”
From Genetics of autism spectrum disorders (2011) · cites this paper as [53]
In the citing paper
“Remarkably, one ASD child-based cellular model finds a 10-fold decrease in spontaneous neural activity and a 6-fold decrease in synchronized bursts of neural network activity, a type of defect theorized long ago [6].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [6]
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Metadata
- Authors
- Courchesne, E., & Pierce, K.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Courchesne, Eric
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 15
- Issue
- 2
- Pages
- 225-230
- ISSN
- 0959-4388 (ISSN-L)
- OpenAlex
- W2131541104
- Cited by
- 968
- References
- 51
- Citations by year
- 2026: 30 · 2025: 32 · 2024: 23 · 2023: 52 · 2022: 31 · 2021: 37 · 2020: 40 · 2019: 44 · 2018: 52 · 2017: 50 · 2016: 73 · 2015: 81 · 2014: 71 · 2013: 68 · 2012: 59
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (K01-MH01814, 2R01 MH 36840, R01MH036840, K01MH001814)
- National Institute of Neurological Disorders and Stroke (2-R01-NS-19855, R01NS019855)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- autism spectrum disorder, frontal cortex, cortical connectivity, neuroinflammation, glial activation, neuronal migration defects, apoptosis, information integration
- MeSH terms
- Autistic Disorder, Frontal Lobe, Humans, Nerve Net
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