Mapping Gray Matter Development: Implications for Typical Development and Vulnerability to Psychopathology

Recent studies with brain magnetic resonance imaging (MRI) have scanned large numbers of children and adolescents repeatedly over time, as their brains develop, tracking volumetric changes in gray and white matter in remarkable detail. Focusing on gray matter changes specifically, here we explain how earlier studies using lobar volumes of specific anatomical regions showed how different lobes of the brain matured at different rates. With the advent of more sophisticated brain mapping methods, it became possible to chart the dynamic trajectory of cortical maturation using detailed 3D and 4D (dynamic) models, showing spreading waves of changes evolving through the cortex. This led to a variety of time-lapse films revealing characteristic deviations from normal development in schizophrenia, bipolar illness, and even in siblings at genetic risk for these disorders. We describe how these methods have helped clarify how cortical development relates to cognitive performance, functional recovery or decline in illness, and ongoing myelination processes. These time-lapse maps have also been used to study effects of genotype and medication on cortical maturation, presenting a powerful framework to study factors that influence the developing brain.

[1]  J. Rapoport,et al.  Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia. , 2003, The American journal of psychiatry.

[2]  Nitin Gogtay,et al.  Cortical Brain Development in Schizophrenia: Insights From Neuroimaging Studies in Childhood-Onset Schizophrenia , 2007, Schizophrenia bulletin.

[3]  J. Rapoport,et al.  Childhood onset schizophrenia: familial neurocognitive measures , 2004, Schizophrenia Research.

[4]  P. Goldman-Rakic,et al.  Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness. , 1994, Progress in brain research.

[5]  Daniel R Weinberger,et al.  Neurotoxicity, neuroplasticity, and magnetic resonance imaging morphometry: what is happening in the schizophrenic brain? , 2002, Archives of general psychiatry.

[6]  Jeffrey A Lieberman,et al.  Is schizophrenia a neurodegenerative disorder? a clinical and neurobiological perspective , 1999, Biological Psychiatry.

[7]  Alain Pitiot,et al.  Genes, maternal smoking, and the offspring brain and body during adolescence: Design of the Saguenay Youth Study , 2007, Human brain mapping.

[8]  Arthur W Toga,et al.  Structural MRI and brain development. , 2005, International review of neurobiology.

[9]  Paul M. Thompson,et al.  Detecting Disease-Specific Patterns of Brain Structure Using Cortical Pattern Matching and a Population-Based Probabilistic Brain Atlas , 2001, IPMI.

[10]  Tyrone D. Cannon,et al.  Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions. , 2003, Schizophrenia bulletin.

[11]  B. Woods.  Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. , 1998, The American journal of psychiatry.

[12]  J. Rapoport,et al.  Lessons from childhood-onset schizophrenia , 2000, Brain Research Reviews.

[13]  P S Goldman-Rakic,et al.  Synaptogenesis in the prefrontal cortex of rhesus monkeys. , 1994, Cerebral cortex.

[14]  E. Gordon,et al.  Brain maturation in adolescence: Concurrent changes in neuroanatomy and neurophysiology , 2007, Human brain mapping.

[15]  P. Huttenlocher.  Synaptic density in human frontal cortex - developmental changes and effects of aging. , 1979, Brain research.

[16]  Agatha D. Lee,et al.  Genetics of Brain Fiber Architecture and Intellectual Performance , 2009, The Journal of Neuroscience.

[17]  Tyrone D. Cannon,et al.  Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J L Rapoport,et al.  Childhood-Onset Schizophrenia: Progressive Ventricular Change During Adolescence , 1997 .

[19]  Rob Nicolson,et al.  Childhood-onset schizophrenia: rare but worth studying , 1999, Biological Psychiatry.

[20]  Arthur W Toga,et al.  Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry , 2008, Proceedings of the National Academy of Sciences.

[21]  Paul M. Thompson,et al.  Lifespan trajectory of myelin integrity and maximum motor speed , 2010, Neurobiology of Aging.

[22]  J. Rapoport,et al.  Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study. , 1999, Archives of general psychiatry.

[23]  R. Woods,et al.  Mapping cortical thickness and gray matter concentration in first episode schizophrenia. , 2005, Cerebral cortex.

[24]  John Suckling,et al.  For personal use. Only reproduce with permission from The Lancet Publishing Group. Effect of sunlight and season on serotonin turnover in the brain , 2002 .

[25]  F. Benes,et al.  Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. , 1994, Archives of general psychiatry.

[26]  Kiralee M. Hayashi,et al.  Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia. , 2006, Archives of general psychiatry.

[27]  J. Rapoport,et al.  Childhood onset schizophrenia: cortical brain abnormalities as young adults. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[28]  Thomas F. Nugent,et al.  Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. , 2004, Archives of general psychiatry.

[29]  Alan C. Evans,et al.  Growth patterns in the developing brain detected by using continuum mechanical tensor maps , 2000, Nature.

[30]  T. Jernigan,et al.  Maturation of human cerebrum observed in vivo during adolescence. , 1991, Brain : a journal of neurology.

[31]  A. Peters,et al.  Oligodendrocytes, their progenitors and other neuroglial cells in the aging primate cerebral cortex. , 2004, Cerebral cortex.

[32]  Alan C. Evans,et al.  Intellectual ability and cortical development in children and adolescents , 2006, Nature.

[33]  I. Feinberg,et al.  The adolescent decline of NREM delta, an indicator of brain maturation, is linked to age and sex but not to pubertal stage. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[34]  Tyrone D. Cannon,et al.  Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. , 2005, Archives of general psychiatry.

[35]  J. Rapoport,et al.  Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Xue Hua,et al.  Detecting brain growth patterns in normal children using tensor‐based morphometry , 2009, Human brain mapping.

[37]  P. Thompson,et al.  Neuroimaging endophenotypes: Strategies for finding genes influencing brain structure and function , 2007, Human brain mapping.

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

[39]  Kiralee M. Hayashi,et al.  Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness. , 2007, Journal of child psychology and psychiatry, and allied disciplines.

[40]  J. Morrison,et al.  Life and death of neurons in the aging brain. , 1997, Science.

[41]  E. Granholm,et al.  Cognitive/neuropsychological studies of children with a schizophrenic disorder. , 1994, Schizophrenia bulletin.

[42]  M. Keshavan,et al.  Obstetric complications correlate with neurobehavioral and brain structural alterations in young relatives at risk for schizophrenia , 2003, Schizophrenia Research.

[43]  J. Rapoport,et al.  Update on childhood-onset schizophrenia , 2000, Current psychiatry reports.

[44]  R. Thatcher,et al.  Human cerebral hemispheres develop at different rates and ages. , 1987, Science.

[45]  N. Andreasen,et al.  Gyrification abnormalities in childhood- and adolescent-onset schizophrenia , 2003, Biological Psychiatry.

[46]  J. Stiles.  Drawing Abilities in Williams Syndrome: A Case Study , 2000, Developmental neuropsychology.

[47]  Paul M. Thompson,et al.  The multivariate A/C/E model and the genetics of fiber architecture , 2009, 2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[48]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[49]  Kristina M. Visscher,et al.  Functional Neuroanatomical Differences Between Adults and School-Age Children in the Processing of Single Words , 2002, Science.

[50]  Mark H. Johnson.  Functional brain development in humans , 2001, Nature Reviews Neuroscience.

[51]  Kiralee M. Hayashi,et al.  Plaque and tangle imaging and cognition in normal aging and Alzheimer's disease , 2010, Neurobiology of Aging.

[52]  K H Nuechterlein,et al.  Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study. , 2001, Archives of general psychiatry.

[53]  J. Rapoport,et al.  Longitudinal brain changes in early-onset psychosis. , 2007, Schizophrenia bulletin.

[54]  T. Paus.  Mapping brain maturation and cognitive development during adolescence , 2005, Trends in Cognitive Sciences.

[55]  Thomas F. Nugent,et al.  Dynamic mapping of human cortical development during childhood through early adulthood. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[56]  M. Yücel,et al.  Neuroimaging and emerging psychotic disorders: The Melbourne ultra-high risk studies , 2007, International review of psychiatry.

[57]  A. Toga,et al.  In vivo evidence for post-adolescent brain maturation in frontal and striatal regions , 1999, Nature Neuroscience.

[58]  Paul M. Thompson,et al.  Mapping heritability and molecular genetic associations with cortical features using probabilistic brain atlases , 2007, Neuroinformatics.

[59]  Jagath C. Rajapakse,et al.  Development of the human corpus callosum during childhood and adolescence: A longitudinal MRI study , 1999, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[60]  Dennis Velakoulis,et al.  Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing a psychotic illness. , 2003, The British journal of psychiatry : the journal of mental science.

[61]  M. Shenton,et al.  Prefrontal cortical thickness in first-episode psychosis: a magnetic resonance imaging study , 2004, Biological Psychiatry.

[62]  M. Fitzgerald.  Multidimensionally impaired disorder. , 1998, Journal of the American Academy of Child and Adolescent Psychiatry.

[63]  I. Feinberg,et al.  Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? , 1982, Journal of psychiatric research.

[64]  Paul M. Thompson,et al.  Mapping cortical gray matter in the young adult brain: Effects of gender , 2005, NeuroImage.

[65]  T. Sejnowski,et al.  Brain and cognition , 1989 .

[66]  P. Huttenlocher,et al.  Regional differences in synaptogenesis in human cerebral cortex , 1997, The Journal of comparative neurology.

[67]  Alan C. Evans,et al.  Cortical thickness analysis examined through power analysis and a population simulation , 2005, NeuroImage.

[68]  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.

[69]  Jim Mintz,et al.  Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study , 2003, Biological Psychiatry.

[70]  Arno Klein,et al.  Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration , 2009, NeuroImage.

[71]  Marianna D. Eddy,et al.  Regionally localized thinning of the cerebral cortex in schizophrenia , 2003, Schizophrenia Research.

[72]  T. Paus,et al.  Why do many psychiatric disorders emerge during adolescence? , 2008, Nature Reviews Neuroscience.

[73]  T. Jernigan,et al.  LATE CHILDHOOD CHANGES IN BRAIN MORPHOLOGY OBSERVABLE WITH MRI , 1990, Developmental medicine and child neurology.

[74]  A. Addington,et al.  The neurodevelopmental model of schizophrenia: update 2005 , 2005, Molecular Psychiatry.

[75]  G. Dawson,et al.  Human behavior and the developing brain , 1994 .

[76]  J. Lieberman,et al.  Antipsychotic drug effects on brain morphology in first-episode psychosis. , 2005, Archives of general psychiatry.

[77]  F. Benes,et al.  The Relationship Between Structural Brain Imaging and Histopathologic Findings in Schizophrenia Research , 1993, Harvard review of psychiatry.

[78]  J. Asarnow,et al.  Childhood-Onset Schizophrenia , 1994 .

[79]  B. Reisberg,et al.  Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer’s and other dementing processes , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[80]  J. Lieberman,et al.  Time-lapse mapping of cortical changes in schizophrenia with different treatments. , 2009, Cerebral cortex.

[81]  J. Bourgeois,et al.  Synaptogenesis, heterochrony and epigenesis in the mammalian neocortex , 1997, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[82]  Alan C. Evans,et al.  Maturation of white matter in the human brain: a review of magnetic resonance studies , 2001, Brain Research Bulletin.

[83]  P. Rakić,et al.  Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life. , 1989, Brain research. Developmental brain research.

[84]  S. Kumra.  MULTIDIMENSIONALLY IMPAIRED DISORDER , 1998 .

[85]  Luis Puelles,et al.  Forebrain gene expression domains and the evolving prosomeric model , 2003, Trends in Neurosciences.

[86]  C. Müller,et al.  Critical Period‐dependent Reduction of the Permissiveness of Cat Visual Cortex Tissue for Neuronal Adhesion and Neurite Growth , 1997, The European journal of neuroscience.

[87]  Nick C Fox,et al.  Computer-assisted imaging to assess brain structure in healthy and diseased brains , 2003, The Lancet Neurology.

[88]  Nitin Gogtay,et al.  Brain Neuroplasticity in Healthy, Hyperactive and Psychotic Children: Insights from Neuroimaging , 2008, Neuropsychopharmacology.

[89]  P. Huttenlocher.  Synaptogenesis in human cerebral cortex. , 1994 .

[90]  R Fog,et al.  Schizophrenia Research , 2015 .

[91]  Robert W. Thatcher,et al.  Cyclic cortical reorganization during early childhood , 1992, Brain and Cognition.

[92]  Kiralee M. Hayashi,et al.  Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia , 2004, NeuroImage.

[93]  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.

[94]  A. Mack,et al.  Cortical Brain Development in Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia , 2009 .

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