Sex Differences in Functional Connectivity of the Salience, Default Mode, and Central Executive Networks in Youth with ASD

Katherine E Lawrence; Leanna M Hernandez; Hilary C Bowman; Namita T Padgaonkar; Emily Fuster; Allison Jack; Elizabeth Aylward; Nadine Gaab; John D Van Horn; Raphael A Bernier; Daniel H Geschwind; James C McPartland; Charles A Nelson; Sara J Webb; Kevin A Pelphrey; Shulamite A Green; Susan Y Bookheimer; Mirella Dapretto; GENDAAR Consortium

doi:10.1093/cercor/bhaa105

Sex Differences in Functional Connectivity of the Salience, Default Mode, and Central Executive Networks in Youth with ASD

Cereb Cortex. 2020 Jul 30;30(9):5107-5120. doi: 10.1093/cercor/bhaa105.

Authors

Katherine E Lawrence¹, Leanna M Hernandez¹, Hilary C Bowman¹, Namita T Padgaonkar¹, Emily Fuster¹, Allison Jack^{2

3}, Elizabeth Aylward⁴, Nadine Gaab^{5

6

7}, John D Van Horn⁸, Raphael A Bernier⁹, Daniel H Geschwind¹⁰, James C McPartland^{11

12}, Charles A Nelson^{5

6}, Sara J Webb^{9

13}, Kevin A Pelphrey¹⁴, Shulamite A Green¹, Susan Y Bookheimer¹, Mirella Dapretto¹; GENDAAR Consortium

Affiliations

¹ Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
² Autism & Neurodevelopmental Disorders Institute, The George Washington University, Washington, DC 20052, USA.
³ Dept. of Pharmacology & Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA.
⁴ Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98195, USA.
⁵ Division of Developmental Medicine, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
⁶ Department of Pediatrics, Harvard Medical School, Cambridge, MA 02138, USA.
⁷ Harvard Graduate School of Education, Cambridge, MA 02138, USA.
⁸ Department of Psychology, University of Virginia, Charlottesville, VA 22904, USA.
⁹ Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195, USA.
¹⁰ Department of Neurology and Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
¹¹ Department of Pediatrics, Yale School of Medicine, New Haven, CT 06520, USA.
¹² Child Study Center, Yale School of Medicine, New Haven, CT 06520, USA.
¹³ Center on Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, Washington 98195, USA.
¹⁴ Department of Neurology, University of Virginia, Charlottesville, VA 22904, USA.

Abstract

Autism spectrum disorder (ASD) is associated with the altered functional connectivity of 3 neurocognitive networks that are hypothesized to be central to the symptomatology of ASD: the salience network (SN), default mode network (DMN), and central executive network (CEN). Due to the considerably higher prevalence of ASD in males, however, previous studies examining these networks in ASD have used primarily male samples. It is thus unknown how these networks may be differentially impacted among females with ASD compared to males with ASD, and how such differences may compare to those observed in neurotypical individuals. Here, we investigated the functional connectivity of the SN, DMN, and CEN in a large, well-matched sample of girls and boys with and without ASD (169 youth, ages 8-17). Girls with ASD displayed greater functional connectivity between the DMN and CEN than boys with ASD, whereas typically developing girls and boys differed in SN functional connectivity only. Together, these results demonstrate that youth with ASD exhibit altered sex differences in these networks relative to what is observed in typical development, and highlight the importance of considering sex-related biological factors and participant sex when characterizing the neural mechanisms underlying ASD.

Keywords: autism spectrum disorder; functional connectivity; resting-state functional magnetic resonance imaging; sex differences; sexual differentiation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Autism Spectrum Disorder / physiopathology*
Brain / physiopathology*
Brain Mapping / methods
Child
Female
Humans
Magnetic Resonance Imaging
Male
Neural Pathways / physiopathology*
Sex Characteristics*

Abstract

Publication types

MeSH terms

Grants and funding