Altered white matter connectivity as a neural substrate for social impairment in Autism spectrum disorder
Abstract
Background Autism Spectrum Disorder (ASD) symptoms have been hypothesized to result from altered brain connectivity. The 'disconnectivity' hypothesis has been used to explain characteristic impairments in socio-emotional function, observed clinically in ASD. Here, we review the evidence for impaired white matter connectivity as a neural substrate for socio-emotional dysfunction in ASD. A review of diffusion tensor imaging (DTI) studies, and focused discussion of relevant post-mortem, structural, and functional neuroimaging studies, is provided. Methods Studies were identified using a sensitive search strategy in MEDLINE, Embase and PsycINFO article databases using the OvidSP database interface. Search terms included database subject headings for the concepts of pervasive developmental disorders, and DTI. Seventy-two published DTI studies examining white matter microstructure in ASD were reviewed. A comprehensive discussion of DTI studies that examined white matter tracts linking socio-emotional structures is presented. Results Several DTI studies reported microstructural differences indicative of developmental alterations in white matter organization, and potentially myelination, in ASD. Altered structure within long-range white matter tracts linking socio-emotional processing regions was implicated. While alterations of the uncinate fasciculus and frontal and temporal thalamic projections have been associated with social symptoms in ASD, few studies examined association of t…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In ASD, there is a recurrent pattern of reduced FA and increased diffusivity, consistent with altered development.
“Overall, there is a recurrent pattern of reduced FA and increased diffusivity, consistent with altered development (Ameis and Catani, 2015; Rane et al., 2015; Travers et al., 2012).”
From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as Ameis and Catani, 2015
Cites
<i>The Brain's Default Network</i>: <i>Anatomy, Function, and Relevance to Disease</i>
Buckner, R. L., Andrews‐Hanna, J. R., & Schacter, D. L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1440.011 · Cited by 9,761 · see citing works
Does the autistic child have a “theory of mind” ?
Baron-Cohen, S., Leslie, A. M., & Frith, U. (1985) · Cognition · doi:10.1016/0010-0277(85)90022-8 · Cited by 8,599 · see citing works
The basis of anisotropic water diffusion in the nervous system—A technical review.
Beaulieu, C. (2002) · NMR in Biomedicine · doi:10.1002/nbm.782 · Cited by 4,653 · see citing works
Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water
Song, S.-K., Sun, S.-W., Ramsbottom, M. J., Chang, C., Russell, J., & Cross, A. H. (2002) · NeuroImage · doi:10.1006/nimg.2002.1267 · Cited by 2,582 · see citing works
Neuroglial activation and neuroinflammation in the brain of patients with autism
Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005) · Annals of Neurology · doi:10.1002/ana.20315 · Cited by 2,149 · see citing works
Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
Voineagu, I., Wang, X., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., Mill, J., Cantor, R. M., Blencowe, B. J., & Geschwind, D. H. (2011) · Nature · doi:10.1038/nature10110 · Cited by 1,874 · see citing works
The Social Brain: Neural Basis of Social Knowledge
Adolphs, R. (2009) · Annual Review of Psychology · doi:10.1146/annurev.psych.60.110707.163514 · Cited by 1,827 · see citing works
Adult outcome for children with autism
Howlin, P., Goode, S., Hutton, J., & Rutter, M. (2004) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2004.00215.x · Cited by 1,813 · see citing works
Cognitive neuroscience of human social behaviour
Adolphs, R. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1056 · Cited by 1,657 · see citing works
Gaze fixation and the neural circuitry of face processing in autism
Dalton, K. M., Nacewicz, B. M., Johnstone, T., Schaefer, H. S., Gernsbacher, M. A., Goldsmith, H. H., Alexander, A. L., & Davidson, R. J. (2005) · Nature Neuroscience · doi:10.1038/nn1421 · Cited by 1,543 · see citing works
Microstructural maturation of the human brain from childhood to adulthood
Lebel, C., Walker, L., Leemans, A., Phillips, L., & Beaulieu, C. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.12.053 · Cited by 1,398 · see citing works
About “axial” and “radial” diffusivities
Wheeler‐Kingshott, C. A. M., & Cercignani, M. (2009) · Magnetic Resonance in Medicine · doi:10.1002/mrm.21965 · Cited by 885 · see citing works
Frith, C. D., & Frith, U. (2007) · Current Biology · doi:10.1016/j.cub.2007.05.068 · Cited by 759 · see citing works
Genetics of autism spectrum disorders
Geschwind, D. H. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.07.003 · Cited by 696 · see citing works
Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients
Assaf, M., Jagannathan, K., Calhoun, V. D., Miller, L., Stevens, M. C., Sahl, R., O'Boyle, J. G., Schultz, R. T., & Pearlson, G. D. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.05.067 · Cited by 680 · see citing works
Imitation performance in toddlers with autism and those with other developmental disorders
Rogers, S. J., Hepburn, S. L., Stackhouse, T., & Wehner, E. (2003) · Journal of Child Psychology and Psychiatry · doi:10.1111/1469-7610.00162 · Cited by 648 · see citing works
Determinants of conduction velocity in myelinated nerve fibers
Waxman, S. G. (1980) · Muscle & Nerve · doi:10.1002/mus.880030207 · Cited by 629 · see citing works
Schumann, C. M., Bloss, C. S., Barnes, C. C., Wideman, G. M., Carper, R. A., Akshoomoff, N., Pierce, K., Hagler, D., Schork, N., Lord, C., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5714-09.2010 · Cited by 554 · see citing works
Atlas of Human Brain Connections
Catani, M., & Thiebaut de Schotten, M. (2012) · doi:10.1093/med/9780199541164.001.0001 · Cited by 467 · see citing works
Self-citationFractionation of social brain circuits in autism spectrum disorders
Gotts, S. J., Simmons, W. K., Milbury, L. A., Wallace, G. L., Cox, R. W., & Martin, A. (2012) · Brain · doi:10.1093/brain/aws160 · Cited by 369 · see citing works
Schumann, C. M., Barnes, C. C., Lord, C., & Courchesne, E. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.07.007 · Cited by 340 · see citing works
White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism
Elison, J. T., Paterson, S. J., Wolff, J. J., Reznick, J. S., Sasson, N. J., Gu, H., Botteron, K. N., Dager, S. R., Estes, A. M., Evans, A. C., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12091150 · Cited by 277 · see citing works
Scott-Van Zeeland, A. A., Abrahams, B. S., Alvarez-Retuerto, A. I., Sonnenblick, L. I., Rudie, J. D., Ghahremani, D., Mumford, J. A., Poldrack, R. A., Dapretto, M., Geschwind, D. H., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001344 · Cited by 252 · see citing works
Altered cerebellar feedback projections in Asperger syndrome
Catani, M., Jones, D. K., Daly, E., Embiricos, N., Deeley, Q., Pugliese, L., Curran, S., Robertson, D., & Murphy, D. G. M. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.03.041 · Cited by 244 · see citing works
Self-citationDamage to Association Fiber Tracts Impairs Recognition of the Facial Expression of Emotion
Philippi, C. L., Mehta, S., Grabowski, T., Adolphs, R., & Rudrauf, D. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0796-09.2009 · Cited by 238 · see citing works
White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism
Cheung, C., Chua, S. E., Cheung, V., Khong, P. L., Tai, K. S., Wong, T. K. W., Ho, T. P., & McAlonan, G. M. (2009) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2009.02086.x · Cited by 178 · see citing works
Atypical diffusion tensor hemispheric asymmetry in autism
Lange, N., DuBray, M. B., Lee, J. E., Froimowitz, M. P., Froehlich, A., Adluru, N., Wright, B., Ravichandran, C., Fletcher, P. T., Bigler, E. D., et al. (2010) · Autism Research · doi:10.1002/aur.162 · Cited by 142 · see citing works
Fronto-temporal disconnectivity and symptom severity in children with autism spectrum disorder
Poustka, L., Jennen-Steinmetz, C., Henze, R., Vomstein, K., Haffner, J., & Sieltjes, B. (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.591824 · Cited by 98 · see citing works
Abnormal cingulum bundle development in autism: a probabilistic tractography study
Ikuta, T., Shafritz, K. M., Bregman, J., Peters, B. D., Gruner, P., Malhotra, A. K., & Szeszko, P. R. (2014) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2013.08.002 · Cited by 69 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The cingulum bundle: Anatomy, function, and dysfunction
Bubb, E. J., Metzler-Baddeley, C., & Aggleton, J. P. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.05.008 · Cited by 740 · see citing works
“, 2015), as well as a review of 72 papers on white matter in this disorder (Ameis and Catani, 2015).”
SHANK3 controls maturation of social reward circuits in the VTA
Bariselli, S., Tzanoulinou, S., Glangetas, C., Prévost-Solié, C., Pucci, L., Viguié, J., Bezzi, P., O'Connor, E. C., Georges, F., Lüscher, C., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4319 · Cited by 168 · see citing works
Ameis, S. H., Lerch, J. P., Taylor, M. J., Lee, W., Viviano, J. D., Pipitone, J., Nazeri, A., Croarkin, P. E., Voineskos, A. N., Lai, M.-C., et al. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.15111435 · Cited by 155 · see citing works
Self-citationTwo Classes of Secreted Synaptic Organizers in the Central Nervous System
Yuzaki, M. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121322 · Cited by 125 · see citing works
White matter maturation is associated with the emergence of Theory of Mind in early childhood
Grosse Wiesmann, C., Schreiber, J., Singer, T., Steinbeis, N., & Friederici, A. D. (2017) · Nature Communications · doi:10.1038/ncomms14692 · Cited by 114 · see citing works
Vasa, R. A., Mostofsky, S. H., & Ewen, J. B. (2016) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2016.02.003 · Cited by 97 · see citing works
White matter tract signatures of impaired social cognition in frontotemporal lobar degeneration
Downey, L. E., Mahoney, C. J., Buckley, A. H., Golden, H. L., Henley, S. M., Schmitz, N., Schott, J. M., Simpson, I. J., Ourselin, S., Fox, N. C., et al. (2015) · NeuroImage: Clinical · doi:10.1016/j.nicl.2015.06.005 · Cited by 94 · see citing works
Climbing Brain Levels of Organisation from Genes to Consciousness
Changeux, J.-P. (2017) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2017.01.004 · Cited by 61 · see citing works
Allard, M., Bergeron, J. D., Baharnoori, M., Srivastava, L. K., Fortier, L., Poyart, C., & Sébire, G. (2017) · Autism Research · doi:10.1002/aur.1647 · Cited by 48 · see citing works
Opposite development of short- and long-range anterior cingulate pathways in autism
Zikopoulos, B., Liu, X., Tepe, J., Trutzer, I., John, Y. J., & Barbas, H. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1904-1 · Cited by 38 · see citing works
Maternal depressive symptoms, neonatal white matter, and toddler social-emotional development
Lautarescu, A., Bonthrone, A. F., Pietsch, M., Batalle, D., Cordero-Grande, L., Tournier, J.-D., Christiaens, D., Hajnal, J. V., Chew, A., Falconer, S., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02073-y · Cited by 29 · see citing works
Ni, H.-C., Lin, H.-Y., Tseng, W.-Y. I., & Gau, S. S.-F. (2020) · Scientific Reports · doi:10.1038/s41598-020-70836-y · Cited by 13 · see citing works
Structural and functional whole brain changes in autism spectrum disorder at different age stages
Wang, Z., Zheng, L., Yang, L., Yin, S., Yu, S., Chen, K., ZHANG, T., Wang, H., Zhang, T., & Zhang, Y. (2025) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-024-02585-6 · Cited by 13 · see citing works
- Authors
- Ameis, S. H., & Catani, M.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- King's College London (GB)
- Corresponding author
- Ameis, Stephanie H.
- Venue
- Cortex
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 62
- Pages
- 158-181
- ISSN
- 0010-9452 (ISSN-L)
- OpenAlex
- W2034963983
- Cited by
- 301
- References
- 29
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 25 · 2023: 17 · 2022: 20 · 2021: 22 · 2020: 37 · 2019: 32 · 2018: 22 · 2017: 35 · 2016: 32 · 2015: 19
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cortex (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Ontario Mental Health Foundation
- CAMH Foundation
- Guy's and St Thomas' Charity
- Wellcome Trust
- Medical Research Council
- National Division of the South London
- Maudsley NHS Foundation Trust
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, white matter connectivity, social dysfunction, uncinate fasciculus, thalamic projections, myelination, white matter microstructure, diffusion tensor imaging
- MeSH terms
- Brain, Child Development Disorders, Pervasive, Humans, Limbic System, Magnetic Resonance Imaging, Neural Pathways, Diffusion Tensor Imaging, Functional Neuroimaging, Social Skills, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
