title: Establishing a link between sex-related differences in the structural connectome and behaviour.
abstract: Recent years have witnessed an increased attention to studies of sex differences, partly because such differences offer important considerations for personalized medicine. While the presence of sex differences in human behaviour is well documented, our knowledge of their anatomical foundations in the brain is still relatively limited. As a natural gateway to fathom the human mind and behaviour, studies concentrating on the human brain network constitute an important segment of the research effort to investigate sex differences. Using a large sample of healthy young individuals, each assessed with diffusion MRI and a computerized neurocognitive battery, we conducted a comprehensive set of experiments examining sex-related differences in the meso-scale structures of the human connectome and elucidated how these differences may relate to sex differences at the level of behaviour. Our results suggest that behavioural sex differences, which indicate complementarity of males and females, are accompanied by related differences in brain structure across development. When using subnetworks that are defined over functional and behavioural domains, we observed increased structural connectivity related to the motor, sensory and executive function subnetworks in males. In females, subnetworks associated with social motivation, attention and memory tasks had higher connectivity. Males showed higher modularity compared to females, with females having higher inter-modular connectivity. Applying multivariate analysis, we showed an increasing separation between males and females in the course of development, not only in behavioural patterns but also in brain structure. We also showed that these behavioural and structural patterns correlate with each other, establishing a reliable link between brain and behaviour.
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology.
authors.forename: Birkan
authors.initials: B
authors.lastname: Tunç
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology.
authors.forename: Berkan
authors.initials: B
authors.lastname: Solmaz
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology.
authors.forename: Drew
authors.initials: D
authors.lastname: Parker
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Satterthwaite
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Elliott
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kosha
authors.initials: K
authors.lastname: Ruparel
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology, ragini.verma@uphs.upenn.edu.
authors.forename: Ragini
authors.initials: R
authors.lastname: Verma
mesh_terms: D000293:Adolescent; D000818:Animals; D001921:Brain / Q000502:physiology*; D002648:Child; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009415:Nerve Net / Q000502:physiology*; D012737:Sex Factors; D055815:Young Adult
keywords: behaviour; connectome; diffusion imaging; gender; sex; structural connectivity
references.citation: Behav Brain Funct. 2010;6(1):74
references.pmid: 21182785
references.citation: Neuroimage. 2008 Jan 15;39(2):566-77
references.pmid: 17951075
references.citation: World Psychiatry. 2014 Oct;13(3):296-305
references.pmid: 25273303
references.citation: Psychol Bull. 1985 Sep;98(2):260-82
references.pmid: 3901062
references.citation: Cereb Cortex. 2015 Sep;25(9):2383-94
references.pmid: 24646613
references.citation: PLoS One. 2012;7(6):e38272
references.pmid: 22701619
references.citation: Neuroreport. 2003 Dec 19;14(18):2469-73
references.pmid: 14663212
references.citation: Appl Neuropsychol. 1995 May;2(2):79-88
references.pmid: 16318528
references.citation: Hum Brain Mapp. 2008 Jun;29(6):696-710
references.pmid: 17598163
references.citation: J Neurosci. 2011 Nov 2;31(44):15775-86
references.pmid: 22049421
references.citation: Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8643-8
references.pmid: 24912164
references.citation: Brain Res. 2011 Feb 23;1375:41-8
references.pmid: 21172320
references.citation: Trends Cogn Sci. 2012 Apr;16(4):231-9
references.pmid: 22425667
references.citation: Science. 1995 Jul 7;269(5220):41-5
references.pmid: 7604277
references.citation: Neuron. 2011 Nov 17;72(4):665-78
references.pmid: 22099467
references.citation: J Clin Exp Neuropsychol. 2009 Apr;31(3):257-77
references.pmid: 18720177
references.citation: Psychol Sci Public Interest. 2007 Aug;8(1):1-51
references.pmid: 25530726
references.citation: Neuroimage. 2010 Sep;52(3):1059-69
references.pmid: 19819337
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7821-6
references.pmid: 12060727
references.citation: J Neurosci Methods. 2010 Mar 30;187(2):254-62
references.pmid: 19945485
references.citation: Magn Reson Imaging. 2008 Sep;26(7):914-20
references.pmid: 18479871
references.citation: Psychol Bull. 1995 Mar;117(2):250-70
references.pmid: 7724690
references.citation: PLoS Biol. 2008 Jul 1;6(7):e159
references.pmid: 18597554
references.citation: Annu Rev Psychol. 2009;60:693-716
references.pmid: 18771388
references.citation: Med Image Anal. 2014 Dec;18(8):1337-48
references.pmid: 25037933
references.citation: Neuropsychologia. 2013 Sep;51(11):2062-9
references.pmid: 23911778
references.citation: Inf Process Med Imaging. 2015;24:650-61
references.pmid: 26221710
references.citation: Neuropsychology. 2012 Mar;26(2):251-65
references.pmid: 22251308
references.citation: Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):823-8
references.pmid: 24297904
references.citation: Cereb Cortex. 2012 Aug;22(8):1738-47
references.pmid: 21940703
references.citation: Neuroimage. 2012 Feb 15;59(4):3889-900
references.pmid: 22119652
references.citation: Front Psychol. 2012 Aug 27;3:295
references.pmid: 22969735
references.citation: Curr Opin Neurobiol. 2013 Jun;23(3):361-72
references.pmid: 23352202
references.citation: Cereb Cortex. 2012 Sep;22(9):1979-92
references.pmid: 22002939
references.citation: J Neurosci. 1999 May 15;19(10):4065-72
references.pmid: 10234034
references.citation: Proc Natl Acad Sci U S A. 1994 May 24;91(11):5033-7
references.pmid: 8197179
references.citation: Psychiatry Res. 1992 Jun;42(3):231-40
references.pmid: 1496055
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8
references.pmid: 12506194
references.citation: Neuroimage. 2003 Apr;18(4):880-94
references.pmid: 12725764
references.citation: Neuroimage. 2014 Feb 1;86:544-53
references.pmid: 23921101
references.citation: Am J Psychiatry. 1993 Jan;150(1):130-4
references.pmid: 8417555
references.citation: PLoS Comput Biol. 2005 Sep;1(4):e42
references.pmid: 16201007
references.citation: Child Dev. 1985 Dec;56(6):1479-98
references.pmid: 4075870
references.citation: Trends Cogn Sci. 2010 Oct;14(10):448-56
references.pmid: 20724210
references.citation: Biophys J. 1994 Jan;66(1):259-67
references.pmid: 8130344