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Longitudinal changes in cortical thickness in autism and typical development
Open accessAbstract
The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood.
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“Here, we used microelectrode arrays that were implanted in the animal’s mPFC (Extended Data Fig. 1b), an area suggested to be involved in social behavior 1,7,12,26,34 and disorders such as ASD 14,21,35,36.”
From Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time (2021) · cites this paper as [35]
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“various neurophysiological features such as cortical volume 35,47 and connectivity 27 are also altered in ASD.”
From Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time (2021) · cites this paper as [35]
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Metadata
- Authors
- Zielinski, B. A., Prigge, M. B. D., Nielsen, J. A., Froehlich, A. L., Abildskov, T. J., Anderson, J. S., Fletcher, P. T., Zygmunt, K. M., Travers, B. G., Lange, N., Alexander, A. L., Bigler, E. D., & Lainhart, J. E.
- Affiliations
- Primary Children's Hospital (US)
- University of Utah (US)
- Brigham Young University (US)
- University of Wisconsin–Madison (US)
- Harvard University (US)
- University of Wisconsin System (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-04-22
- Volume
- 137
- Issue
- 6
- Pages
- 1799-1812
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC4032101
- OpenAlex
- W2115716215
- Cited by
- 378
- References
- 63
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 27 · 2023: 20 · 2022: 37 · 2021: 35 · 2020: 32 · 2019: 36 · 2018: 45 · 2017: 24 · 2016: 37 · 2015: 35 · 2014: 7
- FWCI
- 19.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (K08MH100609, R01MH097464, K08MH092697, R01MH084795)
- National Institute of Neurological Disorders and Stroke (T32NS076067)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD001410, T32 HD 07489, P30HD003352, T32HD007489)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- autism spectrum disorder, cortical thickness, cortical development, brain growth, typically developing controls, inferior frontal gyrus, frontal pole, frontal lobe, parietal cortex, occipital cortex, IQ
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Brain Mapping, Cerebral Cortex, Child, Child, Preschool, Humans, Intelligence Tests, Functional Laterality, Longitudinal Studies, Magnetic Resonance Imaging, Male, Young Adult
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