Frontal networks in adults with autism spectrum disorder

Marco Catani; Flavio Dell'Acqua; Sanja Budisavljevic; Henrietta Howells; Michel Thiebaut De Schotten; Seán Froudist-Walsh; Lucio D'Anna; Abigail Thompson; Stefano Sandrone; Edward T. Bullmore; John Suckling; Simon Baron-Cohen; Michael V. Lombardo; Sally J. Wheelwright; Bhismadev Chakrabarti; Meng Chuan Lai; Amber N.V. Ruigrok; Alexander Leemans; Christine Ecker; Michael C. Craig; Declan G.M. Murphy; Anthony J. Bailey; Patrick F. Bolton; Sarah Carrington; Eileen M. Daly; Sean C. Deoni; Francesca Happé; Julian Henty; Peter Jezzard; Patrick Johnston; Derek K. Jones; Anya Madden; Diane Mullins; Clodagh M. Murphy; Declan G.M. Murphy; Greg Pasco; Susan A. Sadek; Debbie Spain; Rose Stewart; Steven C. Williams

doi:10.1093/brain/awv351

Frontal networks in adults with autism spectrum disorder

Marco Catani^*, Flavio Dell'Acqua, Sanja Budisavljevic, Henrietta Howells, Michel Thiebaut De Schotten, Seán Froudist-Walsh, Lucio D'Anna, Abigail Thompson, Stefano Sandrone, Edward T. Bullmore, John Suckling, Simon Baron-Cohen, Michael V. Lombardo, Sally J. Wheelwright, Bhismadev Chakrabarti, Meng Chuan Lai, Amber N.V. Ruigrok, Alexander Leemans, Christine Ecker, Michael C. CraigDeclan G.M. Murphy, Anthony J. Bailey, Patrick F. Bolton, Sarah Carrington, Eileen M. Daly, Sean C. Deoni, Francesca Happé, Julian Henty, Peter Jezzard, Patrick Johnston, Derek K. Jones, Anya Madden, Diane Mullins, Clodagh M. Murphy, Declan G.M. Murphy, Greg Pasco, Susan A. Sadek, Debbie Spain, Rose Stewart, Steven C. Williams

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate - predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

Original language	English
Pages (from-to)	616-630
Number of pages	15
Journal	Brain
Volume	139
Issue number	2
Early online date	29 Jan 2016
DOIs	https://doi.org/10.1093/brain/awv351
Publication status	Published - 1 Feb 2016

Keywords

arcuate fasciculus
autism spectrum disorder
diffusion tractography
frontal networks
language

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Frontal networks in adults_CATANI_Firstonline29January2016_GOLD VoR (CC-BY)Final published version, 1.03 MBLicence: CC BY

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Catani, M., Dell'Acqua, F., Budisavljevic, S., Howells, H., Thiebaut De Schotten, M., Froudist-Walsh, S., D'Anna, L., Thompson, A., Sandrone, S., Bullmore, E. T., Suckling, J., Baron-Cohen, S., Lombardo, M. V., Wheelwright, S. J., Chakrabarti, B., Lai, M. C., Ruigrok, A. N. V., Leemans, A., Ecker, C., ... Williams, S. C. (2016). Frontal networks in adults with autism spectrum disorder. Brain, 139(2), 616-630. https://doi.org/10.1093/brain/awv351

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title = "Frontal networks in adults with autism spectrum disorder",

abstract = "It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate - predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.",

keywords = "arcuate fasciculus, autism spectrum disorder, diffusion tractography, frontal networks, language",

author = "Marco Catani and Flavio Dell'Acqua and Sanja Budisavljevic and Henrietta Howells and {Thiebaut De Schotten}, Michel and Se{\'a}n Froudist-Walsh and Lucio D'Anna and Abigail Thompson and Stefano Sandrone and Bullmore, {Edward T.} and John Suckling and Simon Baron-Cohen and Lombardo, {Michael V.} and Wheelwright, {Sally J.} and Bhismadev Chakrabarti and Lai, {Meng Chuan} and Ruigrok, {Amber N.V.} and Alexander Leemans and Christine Ecker and Craig, {Michael C.} and Murphy, {Declan G.M.} and Bailey, {Anthony J.} and Bolton, {Patrick F.} and Sarah Carrington and Daly, {Eileen M.} and Deoni, {Sean C.} and Francesca Happ{\'e} and Julian Henty and Peter Jezzard and Patrick Johnston and Jones, {Derek K.} and Anya Madden and Diane Mullins and Murphy, {Clodagh M.} and Murphy, {Declan G.M.} and Greg Pasco and Sadek, {Susan A.} and Debbie Spain and Rose Stewart and Williams, {Steven C.}",

year = "2016",

month = feb,

day = "1",

doi = "10.1093/brain/awv351",

language = "English",

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journal = "Brain",

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Catani, M, Dell'Acqua, F , Budisavljevic, S , Howells, H , Thiebaut De Schotten, M , Froudist-Walsh, S , D'Anna, L , Thompson, A , Sandrone, S, Bullmore, ET, Suckling, J, Baron-Cohen, S, Lombardo, MV, Wheelwright, SJ, Chakrabarti, B, Lai, MC, Ruigrok, ANV, Leemans, A, Ecker, C , Craig, MC , Murphy, DGM, Bailey, AJ, Bolton, PF, Carrington, S, Daly, EM , Deoni, SC , Happé, F, Henty, J, Jezzard, P, Johnston, P, Jones, DK , Madden, A , Mullins, D , Murphy, CM , Murphy, DGM , Pasco, G, Sadek, SA, Spain, D, Stewart, R & Williams, SC 2016, 'Frontal networks in adults with autism spectrum disorder', Brain, vol. 139, no. 2, pp. 616-630. https://doi.org/10.1093/brain/awv351

TY - JOUR

T1 - Frontal networks in adults with autism spectrum disorder

AU - Catani, Marco

AU - Dell'Acqua, Flavio

AU - Budisavljevic, Sanja

AU - Howells, Henrietta

AU - Thiebaut De Schotten, Michel

AU - Froudist-Walsh, Seán

AU - D'Anna, Lucio

AU - Thompson, Abigail

AU - Sandrone, Stefano

AU - Bullmore, Edward T.

AU - Suckling, John

AU - Baron-Cohen, Simon

AU - Lombardo, Michael V.

AU - Wheelwright, Sally J.

AU - Chakrabarti, Bhismadev

AU - Lai, Meng Chuan

AU - Ruigrok, Amber N.V.

AU - Leemans, Alexander

AU - Ecker, Christine

AU - Craig, Michael C.

AU - Murphy, Declan G.M.

AU - Bailey, Anthony J.

AU - Bolton, Patrick F.

AU - Carrington, Sarah

AU - Daly, Eileen M.

AU - Deoni, Sean C.

AU - Happé, Francesca

AU - Henty, Julian

AU - Jezzard, Peter

AU - Johnston, Patrick

AU - Jones, Derek K.

AU - Madden, Anya

AU - Mullins, Diane

AU - Murphy, Clodagh M.

AU - Murphy, Declan G.M.

AU - Pasco, Greg

AU - Sadek, Susan A.

AU - Spain, Debbie

AU - Stewart, Rose

AU - Williams, Steven C.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate - predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

AB - It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate - predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

KW - arcuate fasciculus

KW - autism spectrum disorder

KW - diffusion tractography

KW - frontal networks

KW - language

UR - http://www.scopus.com/inward/record.url?scp=84959872442&partnerID=8YFLogxK

U2 - 10.1093/brain/awv351

DO - 10.1093/brain/awv351

M3 - Article

C2 - 26912520

AN - SCOPUS:84977074291

SN - 0006-8950

VL - 139

SP - 616

EP - 630

JO - Brain

JF - Brain

IS - 2

ER -

Frontal networks in adults with autism spectrum disorder

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Keywords

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