Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in Frontal Lobes in Autism Spectrum Disorder Toddlers

Overview

Journal Biol Psychiatry

Publisher Elsevier

Specialty Psychiatry

Date 2015 Aug 25

PMID 26300272

Citations 85

Authors

Stephanie Solso

Ronghui Xu

James Proudfoot

Donald J Hagler Jr

Kathleen Campbell

Vijay Venkatraman

Cynthia Carter Barnes

Clelia Ahrens-Barbeau

Karen Pierce

Anders Dale

Lisa Eyler

Eric Courchesne

Affiliations

Soon will be listed here.

Abstract

Background: Theories of brain abnormality in autism spectrum disorder (ASD) have focused on underconnectivity as an explanation for social, language, and behavioral deficits but are based mainly on studies of older autistic children and adults.

Methods: In 94 ASD and typical toddlers ages 1 to 4 years, we examined the microstructure (indexed by fractional anisotropy) and volume of axon pathways using in vivo diffusion tensor imaging of fronto-frontal, fronto-temporal, fronto-striatal, and fronto-amygdala axon pathways, as well as posterior contrast tracts. Differences between ASD and typical toddlers in the nature of the relationship of age to these measures were tested.

Results: Frontal tracts in ASD toddlers displayed abnormal age-related changes with greater fractional anisotropy and volume than normal at younger ages but an overall slower than typical apparent rate of continued development across the span of years. Posterior cortical contrast tracts had few significant abnormalities.

Conclusions: Frontal fiber tracts displayed deviant early development and age-related changes that could underlie impaired brain functioning and impact social and communication behaviors in ASD.

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References

Pierpaoli C, Jezzard P, Basser P, Barnett A, DI CHIRO G . Diffusion tensor MR imaging of the human brain. Radiology. 1996; 201(3):637-48. DOI: 10.1148/radiology.201.3.8939209. View

Eyler L, Pierce K, Courchesne E . A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism. Brain. 2012; 135(Pt 3):949-60. PMC: 3286331. DOI: 10.1093/brain/awr364. View

Xu R . Measuring explained variation in linear mixed effects models. Stat Med. 2003; 22(22):3527-41. DOI: 10.1002/sim.1572. View

Chow M, Pramparo T, Winn M, Barnes C, Li H, Weiss L . Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages. PLoS Genet. 2012; 8(3):e1002592. PMC: 3310790. DOI: 10.1371/journal.pgen.1002592. View

ORoak B, Vives L, Fu W, Egertson J, Stanaway I, Phelps I . Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science. 2012; 338(6114):1619-22. PMC: 3528801. DOI: 10.1126/science.1227764. View

Courchesne E, Mouton P, Calhoun M, Semendeferi K, Ahrens-Barbeau C, Hallet M . Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011; 306(18):2001-10. DOI: 10.1001/jama.2011.1638. View

Carper R, Moses P, Tigue Z, Courchesne E . Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage. 2002; 16(4):1038-51. DOI: 10.1006/nimg.2002.1099. View

Pierce K, Carter C, Weinfeld M, Desmond J, Hazin R, Bjork R . Detecting, studying, and treating autism early: the one-year well-baby check-up approach. J Pediatr. 2011; 159(3):458-465.e1-6. PMC: 3157595. DOI: 10.1016/j.jpeds.2011.02.036. View

Buxhoeveden D, Semendeferi K, Buckwalter J, Schenker N, Switzer R, Courchesne E . Reduced minicolumns in the frontal cortex of patients with autism. Neuropathol Appl Neurobiol. 2006; 32(5):483-91. DOI: 10.1111/j.1365-2990.2006.00745.x. View

10.

Dunbar R, Shultz S . Evolution in the social brain. Science. 2007; 317(5843):1344-7. DOI: 10.1126/science.1145463. View

11.

Casanova M, Trippe J . Radial cytoarchitecture and patterns of cortical connectivity in autism. Philos Trans R Soc Lond B Biol Sci. 2009; 364(1522):1433-6. PMC: 2677589. DOI: 10.1098/rstb.2008.0331. View

12.

Fischl B, Salat D, Busa E, Albert M, Dieterich M, Haselgrove C . Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002; 33(3):341-55. DOI: 10.1016/s0896-6273(02)00569-x. View

13.

Jones E, Gliga T, Bedford R, Charman T, Johnson M . Developmental pathways to autism: a review of prospective studies of infants at risk. Neurosci Biobehav Rev. 2013; 39:1-33. PMC: 3969297. DOI: 10.1016/j.neubiorev.2013.12.001. View

14.

Schumann C, Barnes C, Lord C, Courchesne E . Amygdala enlargement in toddlers with autism related to severity of social and communication impairments. Biol Psychiatry. 2009; 66(10):942-9. PMC: 2795360. DOI: 10.1016/j.biopsych.2009.07.007. View

15.

Holmboe K, Elsabbagh M, Volein A, Tucker L, Baron-Cohen S, Bolton P . Frontal cortex functioning in the infant broader autism phenotype. Infant Behav Dev. 2010; 33(4):482-91. DOI: 10.1016/j.infbeh.2010.05.004. View

16.

Dini L, Vedolin L, Bertholdo D, Grando R, Mazzola A, Dini S . Reproducibility of quantitative fiber tracking measurements in diffusion tensor imaging of frontal lobe tracts: A protocol based on the fiber dissection technique. Surg Neurol Int. 2013; 4:51. PMC: 3640224. DOI: 10.4103/2152-7806.110508. View

17.

Fang W, Chen W, Jiang L, Liu K, Yung W, Fu A . Overproduction of upper-layer neurons in the neocortex leads to autism-like features in mice. Cell Rep. 2014; 9(5):1635-1643. DOI: 10.1016/j.celrep.2014.11.003. View

18.

Damasio A, Maurer R . A neurological model for childhood autism. Arch Neurol. 1978; 35(12):777-86. DOI: 10.1001/archneur.1978.00500360001001. View

19.

Courchesne E, Pierce K . Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr Opin Neurobiol. 2005; 15(2):225-30. DOI: 10.1016/j.conb.2005.03.001. View

20.

Bailey A . Postmortem studies of autism. Autism Res. 2009; 1(5):265. DOI: 10.1002/aur.51. View