title: Mapping the stability of human brain asymmetry across five sex-chromosome aneuploidies.
abstract: The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Amy
authors.initials: A
authors.lastname: Lin
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Liv
authors.initials: L
authors.lastname: Clasen
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Nancy Raitano
authors.initials: NR
authors.lastname: Lee
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and Department of Speech and Hearing Sciences, George Washington University, Washington, DC 20052.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Wallace
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Francois
authors.identifier: http://orcid.org/0000-0002-4945-0032
authors.initials: F
authors.lastname: Lalonde
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Blumenthal
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Jay N
authors.initials: JN
authors.lastname: Giedd
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health-National Institutes of Health, Bethesda, Maryland 20892 and raznahana@mail.nih.gov.
authors.forename: Armin
authors.identifier: http://orcid.org/0000-0002-5622-1190
authors.initials: A
authors.lastname: Raznahan
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D001921:Brain / Q000002:abnormalities* / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012730:Sex Chromosomes / Q000235:genetics*; D055815:Young Adult
keywords: asymmetry; brain; neurodevelopment; sex chromosome