Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism
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OBJECTIVE: Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months. METHOD: The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity. RESULTS: The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values. CONCLUSIONS: These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.
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Wolff and colleagues reported altered tract development between 6 and 24 months in infants subsequently diagnosed with autism, suggesting that atypical structural maturation may appear early, preceding overt behavioral diagnosis.
“Wolff and colleagues reported altered tract development between 6 and 24 months in infants subsequently diagnosed with autism, suggesting that atypical structural maturation may appear early, preceding overt behavioral diagnosis (Wolff et al., 2012).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Wolff et al., 2012
The findings are consistent with prior studies suggesting that physiologic changes may be detectable before behavioral changes become manifest in a variety of neurological and neurodevelopmental disorders.
“Our findings are consistent with prior studies suggesting that physiologic changes may be detectable before behavioral changes become manifest in a variety of neurological and neurodevelopmental disorders [36–43].”
From EEG power at 3 months in infants at high familial risk for autism (2017) · cites this paper as [39]
This work aligns with an emerging body of evidence demonstrating changes in brain development prior to the manifestation of overt behavioral changes in infants at high familial risk for ASD and points to the potential of brain-based markers for early identification and prognostication in neurodevelopmental disorders.
“This work aligns with an emerging body of evidence demonstrating changes in brain development prior to the manifestation of overt behavioral changes in infants at high familial risk for ASD [39, 42, 43], and points to the potential of brain-based markers for early identification and prognostication in neurodevelopmental disorders.”
From EEG power at 3 months in infants at high familial risk for autism (2017) · cites this paper as [39]
Developmental trajectories of white matter are most predictive of later ASD diagnosis in studies of high-risk infants.
“It has already been shown in studies of high-risk infants that developmental trajectories of white matter are most predictive of later ASD diagnosis.68”
From Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder (2017) · cites this paper as [68]
The number of children who met later criteria for ASD was comparable with recent studies of infants with later ASD.
“The number of children who met later criteria for ASD was comparable with recent studies of infants with later ASD [18, 21, 86].”
Children at risk of autism have higher FA values at 6 months and a slower increase of FA after 6 months, resulting in lower FA values at 24 months.
“Children who are at risk of autism have higher FA values at 6 months and a slower increase of FA after 6 months, resulting in lower FA values at 24 months188”
From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [188]
There is evidence for alterations in event-related potentials and in microstructural organization of white matter tracts in infants later diagnosed with ASD.
“There is also evidence for alterations in event-related potentials (Elsabbagh et al ., 2012) and in the microstructural organization of white matter tracts (Wolff et al ., 2012) in infants later diagnosed with ASD.”
From Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder (2013) · cites this paper as Wolff et al., 2012
Structural atypicalities have been measured within projection pathways connecting frontal and parietal areas to posterior cortical areas in 6-month-old Sib-A.
“Structural atypicalities have also been measured within projection pathways connecting frontal and parietal areas to posterior cortical areas in 6-month-old Sib-A (Wolff et al., 2012) but have not yet been related to saccadic reaction times.”
From From early markers to neuro-developmental mechanisms of autism (2014) · cites this paper as Wolff et al., 2012
Differences in patterns of head growth and aberrant white matter organization have occurred in some cases during the first year of life, and differences in event-related potential to face processing and in electroencephalographic activity have been detected at as early as 6-10 months of age.
“Differences in patterns of head growth 29 and aberrant white matter organization 30 have been occurred in some cases during the first year of life, and differences in event-related potential to face processing 31 and in electroencephalographic activity 32 have been detected at as early as 6-10 months of age.”
From Progress toward treatments for synaptic defects in autism (2013) · cites this paper as [30]
Similar species-specific aberrant social behaviours in offspring are caused by injecting pregnant mice with human IgG-ASD.
“Similar species-specific aberrant social behaviours in offspring are caused by injecting pregnant mice with human IgG-ASD82.”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [82]
The developmental trajectory of specific measurements is probably more important for defining early risk than deficits at specific time points during development.
“However, since not every individual develops at exactly the same pace 145 , the developmental trajectory of specific measurements is probably more important for defining early risk than deficits at specific time points during development.”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [145]
Recent evidence from the IBIS network demonstrates differences in DTI white matter fiber tract trajectories at 6 months of age.
“Recent evidence, also from the IBIS network, demonstrates differences in DTI white matter fiber tract trajectories at 6 months of age [50].”
From Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life (2015) · cites this paper as [50]
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White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism
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“The present behavioral findings not only complement and extend recent data suggesting early functional and structural brain abnormalities in infants who go on to develop ASD (41, 42), they also have the potential to enhance early identification of individuals with ASD and to inform targeted interventions developed for…”
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Progress toward treatments for synaptic defects in autism
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Speech Disturbs Face Scanning in 6-Month-Old Infants Who Develop Autism Spectrum Disorder
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EEG hyper-connectivity in high-risk infants is associated with later autism
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Brain adaptation and alternative developmental trajectories
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Limited Fine Motor and Grasping Skills in 6-Month-Old Infants at High Risk for Autism
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White matter development and early cognition in babies and toddlers
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“cent studies of infants with later ASD [18, 21, 86].”
BackgroundSelf-citationJoint attention and brain functional connectivity in infants and toddlers
Eggebrecht, A. T., Elison, J. T., Feczko, E., Todorov, A., Wolff, J. J., Kandala, S., Adams, C. M., Snyder, A. Z., Lewis, J. D., Estes, A. M., et al. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhw403 · Cited by 156 · see citing works
Self-citationFrom early markers to neuro-developmental mechanisms of autism
Gliga, T., Jones, E. J. H., Bedford, R., Charman, T., & Johnson, M. H. (2014) · Developmental Review · doi:10.1016/j.dr.2014.05.003 · Cited by 150 · see citing works
Common Variants in Psychiatric Risk Genes Predict Brain Structure at Birth
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Self-citationThe IBIS Network, Wolff, J. J., Swanson, M. R., Elison, J. T., Gerig, G., Pruett, J. R., Styner, M. A., Vachet, C., Botteron, K. N., Dager, S. R., et al. (2017) · Molecular Autism · doi:10.1186/s13229-017-0126-z · Cited by 142 · see citing works
Self-citationThe Impact of Neuroimmune Alterations in Autism Spectrum Disorder
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Pediatric neuroimaging using magnetic resonance imaging during non-sedated sleep
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Verhoeff, M. E., Blanken, L. M. E., Kocevska, D., Mileva-Seitz, V. R., Jaddoe, V. W. V., White, T., Verhulst, F., Luijk, M. P. C. M., & Tiemeier, H. (2018) · Molecular Autism · doi:10.1186/s13229-018-0194-8 · Cited by 126 · see citing works
Network inefficiencies in autism spectrum disorder at 24 months.
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Self-citationRepetitive Behavior in 12-Month-Olds Later Classified With Autism Spectrum Disorder
Elison, J. T., Wolff, J. J., Reznick, J. S., Botteron, K. N., Estes, A. M., Gu, H., Hazlett, H. C., Meadows, A. J., Paterson, S. J., Zwaigenbaum, L., et al. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.08.004 · Cited by 113 · see citing works
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EEG power at 3 months in infants at high familial risk for autism
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Aberrant white matter microstructure in children with 16p11.2 deletions
Owen, J. P., Chang, Y. S., Pojman, N. J., Bukshpun, P., Wakahiro, M. L. J., Marco, E. J., Berman, J. I., Spiro, J. E., Chung, W. K., Buckner, R. L., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4495-13.2014 · Cited by 113 · see citing works
Brain Volume Findings in 6-Month-Old Infants at High Familial Risk for Autism
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“More specifically, our findings of reduced functional connectivity associated with risk for ASD are consistent with recent studies of infants and toddlers that have used fNIRS [39], DTI [40], and fMRI [23].”
ResultAssociations between white matter microstructure and infants' working memory
Short, S. J., Elison, J. T., Goldman, B. D., Styner, M., Gu, H., Connelly, M., Maltbie, E., Woolson, S., Lin, W., Gerig, G., et al. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2012.09.021 · Cited by 105 · see citing works
Self-citationDisruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism
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Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene
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Hypersensitive pupillary light reflex in infants at risk for autism
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Self-citationReduced long-range functional connectivity in young children with autism spectrum disorder
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Diagnosing autism in neurobiological research studies
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“It appears that white matter tracts have different growth trajectories from 6 to 24 months of age in infants who later develop ASD compared to those children who do not [36].”
BackgroundInfluentialAnalysis of cortical shape in children with simplex autism
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Genome-wide association analysis identifies common variants influencing infant brain volumes
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40 Years of diffusion MRI in the brain: From history to emerging frontiers
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“Wolff and colleagues reported altered tract development between 6 and 24 months in infants subsequently diagnosed with autism, suggesting that atypical structural maturation may appear early, preceding overt behavioral diagnosis ( Wolff et al., 2012).”
- Authors
- Wolff, J. J., Gu, H., Gerig, G., Elison, J. T., Styner, M., Gouttard, S., Botteron, K. N., Dager, S. R., Dawson, G., Estes, A. M., Evans, A. C., Hazlett, H. C., Kostopoulos, P., McKinstry, R. C., Paterson, S. J., Schultz, R. T., Zwaigenbaum, L., Piven, J., & the IBIS Network
- Affiliations
- Autism Speaks (US)
- From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New...
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2012-06
- Volume
- 169
- Issue
- 6
- Pages
- 589-600
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3377782
- OpenAlex
- W2090153386
- Cited by
- 671
- References
- 63
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 34 · 2023: 36 · 2022: 33 · 2021: 42 · 2020: 48 · 2019: 44 · 2018: 40 · 2017: 53 · 2016: 49 · 2015: 79 · 2014: 60 · 2013: 66 · 2012: 34
- FWCI
- 39.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (EB-005149, U54EB005149)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (#HD03110, HD055741-S1, P30HD003110, HD-055741, HD-40127, T32HD007376, T32HD040127, R01HD055741)
- 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 development, fiber tracts, fractional anisotropy, diffusion tensor imaging, high-risk infants, infant siblings, brain development, radial diffusivity, axial diffusivity
- MeSH terms
- Autistic Disorder, Brain, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Case-Control Studies, Anisotropy, Diffusion Tensor Imaging, Neuroimaging
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