Brain Structure and Function

, Volume 223, Issue 4, pp 1953–1970 | Cite as

Investigation of brain structure in the 1-month infant

  • Douglas C. DeanIIIEmail author
  • E. M. Planalp
  • W. Wooten
  • C. K. Schmidt
  • S. R. Kecskemeti
  • C. Frye
  • N. L. Schmidt
  • H. H. Goldsmith
  • A. L. Alexander
  • R. J. Davidson
Original Article


The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.


Magnetic resonance imaging Brain volume Sexual dimorphism Brain asymmetry 



We sincerely thank the children and families who participated in this research. We thank Ronald Fisher, Michael Anderle, Scott Mikkelson, Morgan Johnson, and Madeline Peters for assistance with recruitment and data collection. This work was supported by the National Institutes of Mental Health (P50 MH100031 to HHG, ALA, RJD; R01 MH101504 to HHG). DCD is supported by a Postdoctoral fellowship through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32 HD007489) and the National Institute of Mental Health (K99MH110596). EMP is supported by a Postdoctoral fellowship through the National Institutes of Mental Health (T32 MH018931-26). Infrastructure support was also provided by a core grant to the Waisman Center from the National Institute of Child Health and Human Development (U54 HD090256).

Supplementary material

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  1. Allen JS, Damasio H, Grabowski TJ et al (2003) Sexual dimorphism and asymmetries in the gray-white composition of the human cerebrum. Neuroimage 18:880–894CrossRefPubMedGoogle Scholar
  2. Andersen SL (2003) Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 27:3–18CrossRefPubMedGoogle Scholar
  3. Avants BB, Tustison NJ, Song G et al (2011a) A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage 54:2033–2044CrossRefPubMedGoogle Scholar
  4. Avants BB, Tustison NJ, Wu J et al (2011b) An open source multivariate framework for n-tissue segmentation with evaluation on public data. Neuroinformatics 9:381–400CrossRefPubMedPubMedCentralGoogle Scholar
  5. Barkovich AJ, Kjos BO, Jackson DE, Norman D (1988) Normal maturation of the neonatal and infant brain: MR imaging at 1.5 T. Radiology 166:173–180CrossRefPubMedGoogle Scholar
  6. Bartzokis G (2004) Quadratic trajectories of brain myelin content: unifying construct for neuropsychiatric disorders. Neurobiol Aging 25:49–62CrossRefGoogle Scholar
  7. Belmonte MK, Allen G, Beckel-Mitchener A et al (2004) Autism and abnormal development of brain connectivity. J Neurosci 24:9228–9231CrossRefPubMedGoogle Scholar
  8. Brody BA, Kinney HC, Kloman AS, Gilles FH (1987) Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination. J Neuropathol Exp Neurol 46:283–301CrossRefPubMedGoogle Scholar
  9. Cabezas M, Oliver A, Lladó X et al (2011) A review of atlas-based segmentation for magnetic resonance brain images. Comput Meth Prog Bio 104:e158–e177CrossRefGoogle Scholar
  10. Casey BJ, Tottenham N, Liston C, Durston S (2005) Imaging the developing brain: what have we learned about cognitive development? Trends Cogn Sci 9:104–110CrossRefPubMedGoogle Scholar
  11. Caviness VS Jr, Kennedy DN, Richelme C et al (1996) The human brain age 7–11 years: a volumetric analysis based on magnetic resonance images. Cereb Cortex 6:726–736CrossRefPubMedGoogle Scholar
  12. Chang YS, Owen JP, Pojman NJ et al (2015) White matter changes of neurite density and fiber orientation dispersion during human brain maturation. PLoS One 10:e0123656CrossRefPubMedPubMedCentralGoogle Scholar
  13. Courchesne E, Pierce K (2005) Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity. Int J Dev Neurosci 23:153–170CrossRefPubMedGoogle Scholar
  14. Courchesne E, Chisum HJ, Townsend J et al (2000) Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. Radiology:672–682Google Scholar
  15. Croteau-Chonka EC, Dean DC, Remer J et al (2016) Examining the relationships between cortical maturation and white matter myelination throughout early childhood. Neuroimage 125:413–421CrossRefPubMedGoogle Scholar
  16. Davidson RJ (2002) Anxiety and affective style: role of prefrontal cortex and amygdala. Biol Psychiatry 51:68–80CrossRefPubMedGoogle Scholar
  17. Davidson RJ (2008) Cerebral asymmetry and emotion: conceptual and methodological conundrums. Cogn Emot 7:115–138CrossRefGoogle Scholar
  18. Davidson RJ, McEwen BS (2012) Social influences on neuroplasticity: stress and interventions to promote well-being. Nat Neurosci 15:689–695CrossRefPubMedPubMedCentralGoogle Scholar
  19. Davison AN, Dobbing J (1966) Myelination as a vulnerable period in brain development. Br Med Bull 22:40–44CrossRefPubMedGoogle Scholar
  20. Dean DC III, Dirks H, O’Muircheartaigh J et al (2014a) Pediatric neuroimaging using magnetic resonance imaging during non-sedated sleep. Pediatr Radiol 44:64–72CrossRefPubMedGoogle Scholar
  21. Dean DC III, O’Muircheartaigh J, Dirks H et al (2014b) Modeling healthy male white matter and myelin development: 3 through 60 months of age. Neuroimage 84:742–752CrossRefPubMedPubMedCentralGoogle Scholar
  22. Dean DC III, O’Muircheartaigh J, Dirks H et al (2014c) Characterizing longitudinal white matter development during early childhood. Brain Struct Funct:1921–1931Google Scholar
  23. Dean DC III, O’Muircheartaigh J, Dirks H et al (2016) Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging. Neuroimage 132:225–237CrossRefPubMedPubMedCentralGoogle Scholar
  24. Dean DC III, Planalp EM, Wooten W et al (2017) Mapping white matter microstructure in the one month human brain. Sci Rep 7(1):9759CrossRefPubMedPubMedCentralGoogle Scholar
  25. Dehaene-Lambertz G, Hertz-Pannier L, Dubois J (2006) Nature and nurture in language acquisition: anatomical and functional brain-imaging studies in infants. Trends Neurosci 29:367–373CrossRefPubMedGoogle Scholar
  26. Demerens C, Stankoff B, Logak M et al (1996) Induction of myelination in the central nervous system by electrical activity. PNAS 93:9887–9892CrossRefPubMedPubMedCentralGoogle Scholar
  27. Deoni SCL, Mercure E, Blasi A et al (2011) Mapping infant brain myelination with magnetic resonance imaging. J Neurosci 31:784–791. CrossRefPubMedGoogle Scholar
  28. Deoni SCL, Dean DC, O’Muircheartaigh J et al (2012) Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping. Neuroimage 63:1038–1053CrossRefPubMedPubMedCentralGoogle Scholar
  29. Deoni SCL, Dean DC, Remer J et al (2015) Cortical maturation and myelination in healthy toddlers and young children. Neuroimage 115:147–161CrossRefPubMedPubMedCentralGoogle Scholar
  30. DiCicco-Bloom E, Lord C, Zwaigenbaum L et al (2006) The developmental neurobiology of autism spectrum disorder. J Neurosci 26:6897–6906CrossRefPubMedGoogle Scholar
  31. Dobbing J (1990) Vulnerable periods in developing brain. In: Commentary. Springer, London, pp 1–17Google Scholar
  32. Dubois J, Hertz-Pannier L, Dehaene-Lambertz G et al (2006) Assessment of the early organization and maturation of infants’ cerebral white matter fiber bundles: a feasibility study using quantitative diffusion tensor imaging and tractography. Neuroimage 30:1121–1132CrossRefPubMedGoogle Scholar
  33. Dubois J, Hertz-Pannier L, Cachia A et al (2009) Structural asymmetries in the infant language and sensor–motor networks. Cereb Cortex 19:414–423CrossRefPubMedGoogle Scholar
  34. Dubois J, Dehaene-Lambertz G, Kulikova S et al (2014) The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants. Neuroscience 276:48–71CrossRefPubMedGoogle Scholar
  35. Durston S, Hulshoff Pol HE, Casey BJ et al (2001) Anatomical MRI of the developing human brain: what have we learned? J Am Acad Child Adolesc Psychiatry 40:1012–1020CrossRefPubMedGoogle Scholar
  36. Elston GN, Fujita I (2014) Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology. Front Neuroanat 8:13644Google Scholar
  37. Evans AC, Brain Development Cooperative Group (2006) The NIH MRI study of normal brain development. Neuroimage 30:184–202CrossRefPubMedGoogle Scholar
  38. Fields RD (2005) Myelination: an overlooked mechanism of synaptic plasticity? Neuroscientist 11:528–531CrossRefPubMedPubMedCentralGoogle Scholar
  39. Fields RD (2008a) White matter matters. Sci Am 298:54–61CrossRefGoogle Scholar
  40. Fields RD (2008b) White matter in learning, cognition and psychiatric disorders. Trends Neurosci 31:361–370CrossRefPubMedPubMedCentralGoogle Scholar
  41. Fields RD (2015) A new mechanism of nervous system plasticity: activity-dependent myelination. Nat Rev Neurosci 16:756–767CrossRefPubMedGoogle Scholar
  42. Giedd JN, Rapoport JL (2010) Structural MRI of pediatric brain development: what have we learned and where are we going? Neuron 67:728–734CrossRefPubMedPubMedCentralGoogle Scholar
  43. Giedd JN, Snell JW, Lange N et al (1996) Quantitative magnetic resonance imaging of human brain development: ages 4–18. Cereb Cortex 6:551–559CrossRefPubMedGoogle Scholar
  44. Giedd JN, Blumenthal J, Jeffries NO et al (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2:861–863CrossRefPubMedGoogle Scholar
  45. Gilmore JH, Lin W, Prastawa MW et al (2007) Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain. J Neurosci 27:1255–1260CrossRefPubMedPubMedCentralGoogle Scholar
  46. Gilmore JH, Shi F, Woolson SL et al (2012) Longitudinal development of cortical and subcortical gray matter from birth to 2 years. Cereb Cortex 22:2478–2485CrossRefPubMedGoogle Scholar
  47. Glasser MF, Van Essen DC (2011) Mapping Human cortical areas in vivo based on myelin content as revealed by T1- and T2-weighted MRI. J Neurosci 31:11597–11616CrossRefPubMedPubMedCentralGoogle Scholar
  48. Gogtay N, Thompson PM (2010) Mapping gray matter development: implications for typical development and vulnerability to psychopathology. Brain Cogn 72:6–15CrossRefPubMedGoogle Scholar
  49. Gogtay N, Giedd JN, Lusk L et al (2004) Dynamic mapping of human cortical development during childhood through early adulthood. PNAS 101:8174–8179CrossRefPubMedPubMedCentralGoogle Scholar
  50. Goldstein JM, Seidman LJ, Horton NJ et al (2001) Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb Cortex 11:490–497CrossRefPubMedGoogle Scholar
  51. Hill J, Dierker D, Neil J et al (2010) A surface-based analysis of hemispheric asymmetries and folding of cerebral cortex in term-born human infants. J Neurosci 30:2268–2276CrossRefPubMedPubMedCentralGoogle Scholar
  52. Holland D, Chang L, Ernst TM et al (2014) Structural growth trajectories and rates of change in the first 3 months of infant brain development. JAMA Neurol 71:1266–1274CrossRefPubMedPubMedCentralGoogle Scholar
  53. Huang H, Zhang J, Wakana S et al (2006) White and gray matter development in human fetal, newborn and pediatric brains. Neuroimage 33:27–38CrossRefPubMedGoogle Scholar
  54. Hugdahl K, Davidson RJ (2004) The asymmetrical brain. MIT Press, LondonGoogle Scholar
  55. Hüppi PS, Maier SE, Peled S et al (1998a) Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Pediatr Res 44:584–590CrossRefPubMedGoogle Scholar
  56. Hüppi PS, Warfield S, Kikinis R et al (1998b) Quantitative magnetic resonance imaging of brain development in premature and mature newborns. Ann Neurol 43:224–235CrossRefPubMedGoogle Scholar
  57. Huttenlocher PR, Dabholkar AS (1997) Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 387:167–178CrossRefPubMedGoogle Scholar
  58. Knickmeyer RC, Gouttard S, Kang C et al (2008) A structural MRI study of human brain development from birth to 2 years. J Neurosci 28:12176–12182CrossRefPubMedPubMedCentralGoogle Scholar
  59. Kolb B, Gibb R (2011) Brain plasticity and behaviour in the developing brain. J Can Acad Child Adolesc Psychiatry 20:265–276PubMedPubMedCentralGoogle Scholar
  60. Koolschijn PCMP., Crone EA (2013) Sex differences and structural brain maturation from childhood to early adulthood. Dev Cogn Neurosci 5:106–118CrossRefPubMedGoogle Scholar
  61. Kulikova S, Hertz-Pannier L, Dehaene-Lambertz G et al (2014) Multi-parametric evaluation of the white matter maturation. Brain Struct Funct 1–16Google Scholar
  62. Kunz N, Zhang H, Vasung L et al (2014) Assessing white matter microstructure of the newborn with multi-shell diffusion MRI and biophysical compartment models. Neuroimage 96:288–299CrossRefPubMedGoogle Scholar
  63. Lapate RC, Rokers B, Tromp DPM et al (2016) Awareness of emotional stimuli determines the behavioral consequences of amygdala activation and amygdala-prefrontal connectivity. Sci Rep 6:25826CrossRefPubMedPubMedCentralGoogle Scholar
  64. Lebel C, Beaulieu C (2011) Longitudinal development of human brain wiring continues from childhood into adulthood. J Neurosci 31:10937–10947CrossRefPubMedGoogle Scholar
  65. Lebel C, Walker L, Leemans A et al (2008) Microstructural maturation of the human brain from childhood to adulthood. Neuroimage 40:1044–1055CrossRefPubMedGoogle Scholar
  66. Lebel C, Gee M, Camicioli R et al (2012) Diffusion tensor imaging of white matter tract evolution over the lifespan. Neuroimage 60:340–352CrossRefPubMedGoogle Scholar
  67. Lenroot RK, Giedd JN (2010) Sex differences in the adolescent brain. Brain Cogn 72:46–55CrossRefPubMedGoogle Scholar
  68. Lenroot RK, Gogtay N, Greenstein DK et al (2007) Sexual dimorphism of brain developmental trajectories during childhood and adolescence. Neuroimage 36:1065–1073CrossRefPubMedPubMedCentralGoogle Scholar
  69. Lupien SJ, Parent S, Evans AC et al (2011) Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proc Natl Acad Sci USA 108:14324–14329CrossRefPubMedPubMedCentralGoogle Scholar
  70. Makki MI, Hagmann C (2017) Regional differences in interhemispheric structural fibers in healthy, term infants. J Neurosci Res 95:876–884CrossRefPubMedGoogle Scholar
  71. Makropoulos A, Gousias IS, Ledig C et al (2014) Automatic whole brain MRI segmentation of the developing neonatal brain. IEEE Trans Med Imaging 33:1818–1831CrossRefPubMedGoogle Scholar
  72. Makropoulos A, Aljabar P, Wright R et al (2016) Regional growth and atlasing of the developing human brain. Neuroimage 125:456–478CrossRefPubMedPubMedCentralGoogle Scholar
  73. Morris JS, Öhman A, Dolan RJ (1998) Conscious and unconscious emotional learning in the human amygdala. Nature 393:467–470CrossRefPubMedGoogle Scholar
  74. Mukherjee P, Miller JH, Shimony JS et al (2001) Normal brain maturation during childhood: developmental trends characterized with diffusion-tensor MR imaging. Radiology 221:349–358CrossRefPubMedGoogle Scholar
  75. Mukherjee P, Miller JH, Shimony JS et al (2002) Diffusion-tensor MR imaging of gray and white matter development during normal human brain maturation. AJNR Am J Neuroradiol 23:1445–1456PubMedGoogle Scholar
  76. O’Muircheartaigh J, Dean DC III, Dirks H et al (2013) Interactions between white matter asymmetry and language during neurodevelopment. J Neurosci 33:16170–16177CrossRefPubMedPubMedCentralGoogle Scholar
  77. Oishi K, Mori S, Donohue PK et al (2011) Multi-contrast human neonatal brain atlas: application to normal neonate development analysis. Neuroimage 56:8–20CrossRefPubMedPubMedCentralGoogle Scholar
  78. Paus T, Toro R (2009) Could sex differences in white matter be explained by g ratio? Front Neuroanat 3:14CrossRefPubMedPubMedCentralGoogle Scholar
  79. Paus T, Collins DL, Evans AC et al (2001) Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Res Bull 54:255–266CrossRefPubMedGoogle Scholar
  80. Perrin JS, Leonard G, Perron M et al (2009) Sex differences in the growth of white matter during adolescence. Neuroimage 45:1055–1066CrossRefPubMedGoogle Scholar
  81. Pfefferbaum A, Mathalon DH, Sullivan EV et al (1994) A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 51:874–887CrossRefPubMedGoogle Scholar
  82. R Development Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  83. Reiss AL, Abrams MT, Singer HS et al (1996) Brain development, gender and IQ in children. A volumetric imaging study. Brain 119(Pt 5):1763–1774CrossRefPubMedGoogle Scholar
  84. Shi F, Yap P-T, Wu G et al (2011) Infant brain atlases from neonates to 1- and 2-year-olds. 6:e18746–e18711Google Scholar
  85. Simmonds DJ, Hallquist MN, Asato M, Luna B (2014) Developmental stages and sex differences of white matter and behavioral development through adolescence: a longitudinal diffusion tensor imaging (DTI) study. Neuroimage 92:356–368CrossRefPubMedGoogle Scholar
  86. Stiles J, Jernigan TL (2010) The basics of brain development. Neuropsychol Rev 20:327–348CrossRefPubMedPubMedCentralGoogle Scholar
  87. Toga AW, Thompson PM (2003) Mapping brain asymmetry. Nat Rev Neurosci 4:37–48CrossRefPubMedGoogle Scholar
  88. Wilke M, Krägeloh-Mann I, Holland SK (2007) Global and local development of gray and white matter volume in normal children and adolescents. Exp Brain Res 178:296–307CrossRefPubMedGoogle Scholar
  89. Yakovlev P, Lecours IR (1967) Regional development of the brain in early life. Minkowski AGoogle Scholar
  90. Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. Med Imaging IEEE Trans 20:45–57CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Douglas C. DeanIII
    • 1
    • 2
    Email author
  • E. M. Planalp
    • 1
    • 3
  • W. Wooten
    • 2
  • C. K. Schmidt
    • 1
    • 2
  • S. R. Kecskemeti
    • 1
  • C. Frye
    • 2
  • N. L. Schmidt
    • 1
    • 2
  • H. H. Goldsmith
    • 1
    • 3
  • A. L. Alexander
    • 1
    • 4
    • 5
  • R. J. Davidson
    • 1
    • 2
    • 3
    • 4
  1. 1.Waisman CenterUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Center for Healthy MindsUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Department of PsychologyUniversity of Wisconsin-MadisonMadisonUSA
  4. 4.Department of PsychiatryUniversity of Wisconsin-Madison School of Medicine and Public HealthMadisonUSA
  5. 5.Department of Medical PhysicsUniversity of Wisconsin-Madison School of Medicine and Public HealthMadisonUSA

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