Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity.

Sex differences in age- and puberty-related maturation of human brain structure have been observed in typically developing age-matched boys and girls. Because girls mature 1-2 years earlier than boys, the present study aimed at assessing sex differences in brain structure by studying 80 adolescent boys and girls matched on sexual maturity, rather than age. We evaluated pubertal influences on medial temporal lobe (MTL), thalamic, caudate, and cortical gray matter volumes utilizing structural magnetic resonance imaging and 2 measures of pubertal status: physical sexual maturity and circulating testosterone. As predicted, significant interactions between sex and the effect of puberty were observed in regions with high sex steroid hormone receptor densities; sex differences in the right hippocampus, bilateral amygdala, and cortical gray matter were greater in more sexually mature adolescents. Within sex, we found larger volumes in MTL structures in more sexually mature boys, whereas smaller volumes were observed in more sexually mature girls. Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys, which may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.

[1]  L. Galea,et al.  Gonadal hormone modulation of hippocampal neurogenesis in the adult , 2006, Hippocampus.

[2]  P. C. Murphy,et al.  Cerebral Cortex , 2017, Cerebral Cortex.

[3]  Arthur W Toga,et al.  The LONI Pipeline Processing Environment , 2003, NeuroImage.

[4]  Suzanne E. Welcome,et al.  Longitudinal Mapping of Cortical Thickness and Brain Growth in Normal Children , 2022 .

[5]  R. Dahl,et al.  Positive and Negative Affect in Depression: Influence of Sex and Puberty , 2004, Annals of the New York Academy of Sciences.

[6]  W. D. Johnson,et al.  Intraclass Correlation Coefficient , 2006, International Encyclopedia of Statistical Science.

[7]  Richard J Davidson,et al.  Regional brain function, emotion and disorders of emotion , 1999, Current Opinion in Neurobiology.

[8]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[9]  E. Crone,et al.  A Developmental Study of Risky Decisions on the Cake Gambling Task: Age and Gender Analyses of Probability Estimation and Reward Evaluation , 2008, Developmental neuropsychology.

[10]  Suzanne E. Welcome,et al.  Normal developmental changes in inferior frontal gray matter are associated with improvement in phonological processing: a longitudinal MRI analysis. , 2006, Cerebral cortex.

[11]  J. Gray,et al.  Medial septal lesions, hippocampal theta rhythm and the control of vibrissal movement in the freely moving rat. , 1971, Electroencephalography and clinical neurophysiology.

[12]  Dorret I. Boomsma,et al.  Sex steroids and brain structure in pubertal boys and girls , 2009, Psychoneuroendocrinology.

[13]  Gary G. Koch,et al.  Intraclass Correlation Coefficient , 2011, International Encyclopedia of Statistical Science.

[14]  J. Zauszniewski,et al.  Patterns of depressive symptoms in children. , 2007, Journal of child and adolescent psychiatric nursing : official publication of the Association of Child and Adolescent Psychiatric Nurses, Inc.

[15]  B. Cooke Steroid-dependent plasticity in the medial amygdala , 2006, Neuroscience.

[16]  Paul M. Thompson,et al.  Sexual dimorphism of brain developmental trajectories during childhood and adolescence , 2007, NeuroImage.

[17]  A. Banks Puberty* , 1958, Encyclopedia of Evolutionary Psychological Science.

[18]  E. Leibenluft,et al.  The social re-orientation of adolescence: a neuroscience perspective on the process and its relation to psychopathology , 2005, Psychological Medicine.

[19]  A. Arnold,et al.  Sex chromosomes and brain gender , 2004, Nature Reviews Neuroscience.

[20]  Yasumasa Arai,et al.  Sexual dimorphism in synaptic organization in the amygdala and its dependence on neonatal hormone environment , 1981, Brain Research.

[21]  L. Doncarlos,et al.  Classical androgen receptors in non-classical sites in the brain , 2008, Hormones and Behavior.

[22]  L. Steinberg Cognitive and affective development in adolescence , 2005, Trends in Cognitive Sciences.

[23]  J. D. McGaugh,et al.  Microinfusions of Flumazenil into the Basolateral but Not the Central Nucleus of the Amygdala Enhance Memory Consolidation in Rats , 1999, Neurobiology of Learning and Memory.

[24]  Stefano M. Iacus,et al.  cem: Software for Coarsened Exact Matching , 2009, Journal of Statistical Software.

[25]  J. D. McGaugh The amygdala modulates the consolidation of memories of emotionally arousing experiences. , 2004, Annual review of neuroscience.

[26]  R. Dahl Adolescent Brain Development: A Period of Vulnerabilities and Opportunities. Keynote Address , 2004, Annals of the New York Academy of Sciences.

[27]  Michael G. Hardin,et al.  Triadic model of the neurobiology of motivated behavior in adolescence , 2005, Psychological Medicine.

[28]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[29]  B. Everitt An R and S-Plus® Companion to Multivariate Analysis , 2007 .

[30]  Annie Chu,et al.  SOCR Analyses: Implementation and Demonstration of a New Graphical Statistics Educational Toolkit. , 2009, Journal of statistical software.

[31]  Ulric J Lund,et al.  An R and S-Plus® Companion to Multivariate Analysis , 2006 .

[32]  J. Rapoport,et al.  Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: Ages 4–18 years , 1995, The Journal of comparative neurology.

[33]  S. Horvath,et al.  Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. , 2003, Brain research. Molecular brain research.

[34]  J. Archer,et al.  Rodent sex differences in emotional and related behavior. , 1975, Behavioral biology.

[35]  S. Blakemore,et al.  Development of the adolescent brain: implications for executive function and social cognition. , 2006 .

[36]  W. A. Marshall,et al.  Growth and physiological development during adolescence. , 1968, Annual review of medicine.

[37]  S. Mizukami,et al.  Sexual difference in nuclear volume and its ontogeny in the rat amygdala , 1983, Experimental Neurology.

[38]  A. Toga,et al.  Mapping Changes in the Human Cortex throughout the Span of Life , 2004, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[39]  J. Hellmann,et al.  BIAS, PRECISION, AND ACCURACY OF FOUR MEASURES OF SPECIES RICHNESS , 1999 .

[40]  Suzanne E. Welcome,et al.  Mapping cortical change across the human life span , 2003, Nature Neuroscience.

[41]  J. Ormel,et al.  The developmental course of anxiety symptoms during adolescence: the TRAILS study. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[42]  Steven J. Stanton,et al.  Endogenous testosterone levels are associated with amygdala and ventromedial prefrontal cortex responses to anger faces in men but not women , 2009, Biological Psychology.

[43]  Deborah A Yurgelun-Todd,et al.  Cognitive Correlates of Medial Temporal Lobe Development across Adolescence: A Magnetic Resonance Imaging Study , 2003, Perceptual and motor skills.

[44]  C. Sisk,et al.  Pubertal and seasonal plasticity in the amygdala , 2001, Brain Research.

[45]  Gereon R Fink,et al.  Sex differences and the impact of steroid hormones on the developing human brain. , 2009, Cerebral cortex.

[46]  M. McCarthy,et al.  Impact of sex and hormones on new cells in the developing rat hippocampus: a novel source of sex dimorphism? , 2008, The European journal of neuroscience.

[47]  Deborah Yurgelun-Todd,et al.  Emotional and cognitive changes during adolescence , 2007, Current Opinion in Neurobiology.

[48]  Stephen Maren,et al.  Estrogen modulates sexually dimorphic contextual fear conditioning and hippocampal long-term potentiation (LTP) in rats 1 1 Published on the World Wide Web on 1 December 2000. , 2001, Brain Research.

[49]  Anders M. Dale,et al.  Cortical Surface-Based Analysis I. Segmentation and Surface Reconstruction , 1999, NeuroImage.

[50]  Arthur W. Toga,et al.  Effi cient , distributed and interactive neuroimaging data analysis using the LONI Pipeline , 2009 .

[51]  A. Dale,et al.  Cortical Surface-Based Analysis II: Inflation, Flattening, and a Surface-Based Coordinate System , 1999, NeuroImage.

[52]  Neal D Ryan,et al.  Neural Systems of Threat Processing in Adolescents: Role of Pubertal Maturation and Relation to Measures of Negative Affect , 2011, Developmental neuropsychology.

[53]  K. McGraw,et al.  Forming inferences about some intraclass correlation coefficients. , 1996 .

[54]  A. Toga,et al.  Mapping Continued Brain Growth and Gray Matter Density Reduction in Dorsal Frontal Cortex: Inverse Relationships during Postadolescent Brain Maturation , 2001, The Journal of Neuroscience.

[55]  Ivo D Dinov,et al.  SOCR: Statistics Online Computational Resource. , 2006, Journal of statistical software.

[56]  Arthur W. Toga,et al.  A meta-algorithm for brain extraction in MRI , 2004, NeuroImage.

[57]  C. Woolley,et al.  Gonadal hormone modulation of dendrites in the mammalian CNS. , 2005, Journal of neurobiology.

[58]  Francesco Fera,et al.  The Amygdala Response to Emotional Stimuli: A Comparison of Faces and Scenes , 2002, NeuroImage.

[59]  R. Dahl,et al.  Heightened stress responsiveness and emotional reactivity during pubertal maturation: Implications for psychopathology , 2009, Development and Psychopathology.

[60]  L. Doncarlos,et al.  Pubertal hormones modulate the addition of new cells to sexually dimorphic brain regions , 2008, Nature Neuroscience.

[61]  Y. Arai,et al.  Synapse formation in response to estrogen in the medial amygdala developing in the eye. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[62]  R. Wasserman,et al.  Assessing Inter-Rater Reliability (IRR) of Tanner Staging and Orchidometer Use with Boys: A Study from PROS , 2009, Journal of pediatric endocrinology & metabolism : JPEM.

[63]  R. O’Brien,et al.  A Caution Regarding Rules of Thumb for Variance Inflation Factors , 2007 .

[64]  M. Phillips,et al.  Reward-related brain function and sleep in pre/early pubertal and mid/late pubertal adolescents. , 2009, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[65]  R. Dahl Adolescent Development and the Regulation of Behavior and Emotion: Introduction to Part VIII , 2004, Annals of the New York Academy of Sciences.

[66]  L. Steinberg,et al.  Patterns of Competence and Adjustment Among Adolescents from Authoritative, Authoritarian, Indulgent, and Neglectful Homes: A Replication in a Sample of Serious Juvenile Offenders. , 2006, Journal of research on adolescence : the official journal of the Society for Research on Adolescence.

[67]  A. Aleman,et al.  Sex Differences in Neural Activation to Facial Expressions Denoting Contempt and Disgust , 2008, PloS one.

[68]  C. Worthman,et al.  Hormone measures in finger-prick blood spot samples: new field methods for reproductive endocrinology. , 1997, American journal of physical anthropology.

[69]  E J Costello,et al.  Pubertal changes in hormone levels and depression in girls , 1999, Psychological Medicine.

[70]  E. Paykel,et al.  Psychological Medicine goes monthly , 2005, Psychological Medicine.

[71]  Alan C. Evans,et al.  Brain development during childhood and adolescence: a longitudinal MRI study , 1999, Nature Neuroscience.

[72]  R. Davidson,et al.  The functional neuroanatomy of emotion and affective style , 1999, Trends in Cognitive Sciences.

[73]  Y. Arai,et al.  Organizational action of estrogen on synaptic pattern in the amygdala: implications for sexual differentiation of the brain , 1981, Brain Research.

[74]  Terry L. Jernigan,et al.  Further MRI evidence of late brain maturation : Limbic volume increases and changing asymmetries during childhood and adolescence , 1998 .