Evidence map›Paper›PMID 31838998›Full record

ArticleJournal of neurodevelopmental disorders2019

Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder.

Anna K Prohl, Benoit Scherrer, Xavier Tomas-Fernandez, Peter E Davis, Rajna Filip-Dhima, Sanjay P Prabhu, Jurriaan M Peters, E Martina Bebin, Darcy A Krueger, Hope Northrup and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurodevelopmental disorders, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 2 pooled it
8.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?Annals of clinical and translational neurology · 2020
    Trial
  4. Article
  5. Article
  6. Tuberous sclerosis complex.Nature reviews. Disease primers · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Neuroanatomy of autism: what is the role of the cerebellum?Cerebral cortex (New York, N.Y. : 1991) · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Anna K ProhlComputational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Benoit ScherrerComputational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Xavier Tomas-FernandezComputational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Peter E DavisDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Rajna Filip-DhimaDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Sanjay P PrabhuComputational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Jurriaan M PetersComputational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
E Martina BebinDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Darcy A KruegerDepartment of Neurology and Rehabilitation Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Hope NorthrupDepartment of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Joyce Y WuDivision of Pediatric Neurology, University of California at Los Angeles Mattel Children's Hospital, David Geffen School of Medicine, University of California, California, Los Angeles, USA.
Mustafa SahinDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Simon K WarfieldComputational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts, USA. simon.warfield@childrens.harvard.edu.ORCID 0000-0002-7659-3880
TACERN Study Group
Boston Children's Hospital · USCincinnati Children's Hospital Medical Center · USUniversity of California, Los Angeles · US

Funding

Early Biomarkers of Autism Spectrum Disorders in infants with Tuberous SclerosisU01NS082320 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI KRUEGER, DARCY, SAHIN, MUSTAFA · 2012 to 2018
$13.3M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI POMEROY, SCOTT LOREN · 2016 to 2020
$5.2M
Improved Motion Robust MRI of ChildrenR01EB019483 · NIBIB · BOSTON CHILDREN'S HOSPITAL · PI WARFIELD, SIMON K · 2015 to 2024
$3.9M
MRI Biomarkers of Patients with Tuberous Sclerosis Complex and AutismR01NS079788 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI WARFIELD, SIMON K · 2013 to 2017
$3.6M
Prospective/Retrospective Motion Correction System for Motion Robust Pediatric MRIR44MH086984 · NIMH · ROBIN MEDICAL, INC. · PI NEVO, EREZ, WARFIELD, SIMON K · 2016 to 2018
$2.4M
Eunice Kennedy Shriver National Institute of Child Health and Human Development U01NS082320Intellectual and Developmental Disabilities Research Center (US) U54HD090255National Institute of Neurological Disorders and Stroke (US) U01NS082320NIBIB NIH HHS R01 EB019483NICHD NIH HHS U54 HD090255NIH HHS R01 EB019483NIH HHS R01 NS079788NIH HHS R44 MH086984NIMH NIH HHS R44 MH086984NINDS NIH HHS R01 NS079788NINDS NIH HHS U01 NS082320NINDS NIH HHS U01NS082320
6 · The paper itself

Abstract

backgroundAutism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants.

methodsTSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD.

resultsSubjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups.

conclusionsUnderconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.

Indexed as

Autism Spectrum DisorderBrainChild, PreschoolDiffusion Tensor ImagingFemaleHumansInfantLongitudinal StudiesMaleProspective StudiesTuberous SclerosisWhite MatterAutism spectrum disorderDiffusion tensor imagingInfant brain developmentTuberous sclerosis complexWhite matter

Identifiers

PMID31838998
PMCPMC6912944
OpenAlexW2995465272

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.