Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder
Open accessAbstract
Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly.
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ASD subjects have increased volume of white matter hypointensities around ventricles and in deep subcortical areas compared with controls, and these changes remain static with age, suggesting a developmental origin.
“Subjects with ASD have increased volume of white matter hypointensities around ventricles and in deep subcortical areas as compared to controls, the changes remaining static with age suggesting a developmental origin [34].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [34]
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Tian, P., Yang, X., Zhu, X., Liu, Z., Bian, B., Jia, F., Dou, L., Lv, X., Zhao, T., & Li, D. (2025) · European Journal of Pediatrics · doi:10.1007/s00431-025-06246-x · Cited by 15 · see citing works
den Hof, M. V., Jellema, P. E. J., ter Haar, A. M., Scherpbier, H. J., Schrantee, A., Kaiser, A., Caan, M. W. A., Majoie, C. B. L. M., Reiss, P., Wit, F. W. N. M., et al. (2021) · AIDS · doi:10.1097/qad.0000000000002873 · Cited by 12 · see citing works
Dysfunction of the Auditory Brainstem as a Neurophysiology Subtype of Autism Spectrum Disorder
Chen, J., Wei, Z., Liang, C., Liu, B., Guo, J., Kong, X., Huang, M., Peng, Z., & Wan, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.637079 · Cited by 12 · see citing works
Chen, L., Li, J., Liu, X., Zhao, Z., Jin, Y., Fu, Y., Zhou, A., Wang, C., & Yan, Z. (2023) · Behavioural Neurology · doi:10.1155/2023/6991826 · Cited by 11 · see citing works
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Wu, C., Zhang, B., Trenor, C. C., Rivkin, M. J., Danehy, A. R., & Lehman, L. L. (2023) · Journal of Child Neurology · doi:10.1177/08830738231188395 · Cited by 5 · see citing works
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Pretzsch, C. M., & Ecker, C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-816393-1.00013-0 · Cited by 4 · see citing works
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Ruíz, M. G. H., Arranz, M. J., Pérez, V., & Amaia Hervas, G. (2025) · Actas Españolas de Psiquiatría · doi:10.62641/aep.v53i4.1917 · Cited by 3 · see citing works
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Chapter 11 Imaging the striatum in autism spectrum disorder
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- Authors
- Blackmon, K., Ben-Avi, E., Wang, X., Pardoe, H. R., Di Martino, A., Halgren, E., Devinsky, O., Thesen, T., & Kuzniecky, R.
- Affiliations
- New York University (US)
- University of California San Diego (US)
- Corresponding author
- Blackmon, Karen
- ORCID
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2016
- Volume
- 10
- Pages
- 36-45
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC4660377
- OpenAlex
- W2201030664
- Cited by
- 27
- References
- 72
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 1
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Funders
- FACES
- Epilepsy Foundation (286054)
- 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 › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- autism spectrum disorder, periventricular white matter abnormalities, restricted and repetitive behaviors, restricted interests, malformations of cortical development, heterotopic gray matter, white matter volume, T1-weighted imaging, ABIDE
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Adult, Brain, Cerebral Ventricles, Child, Female, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Severity of Illness Index, Young Adult, White Matter, Gray Matter
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