Cerebellum development during childhood and adolescence: A longitudinal morphometric MRI study

In addition to its well-established role in balance, coordination, and other motor skills, the cerebellum is increasingly recognized as a prominent contributor to a wide array of cognitive and emotional functions. Many of these capacities undergo dramatic changes during childhood and adolescence. However, accurate characterization of co-occurring anatomical changes has been hindered by lack of longitudinal data and methodologic challenges in quantifying subdivisions of the cerebellum. In this study we apply an innovative image analysis technique to quantify total cerebellar volume and 11 subdivisions (i.e. anterior, superior posterior, and inferior posterior lobes, corpus medullare, and three vermal regions) from anatomic brain MRI scans from 25 healthy females and 25 healthy males aged 5-24 years, each of whom was scanned at least three times at approximately 2-year intervals. Total cerebellum volume followed an inverted U shaped developmental trajectory peaking at age 11.8 years in females and 15.6 years in males. Cerebellar volume was 10% to 13% larger in males depending on the age of comparison and the sexual dimorphism remained significant after covarying for total brain volume. Subdivisions of the cerebellum had distinctive developmental trajectories with more phylogenetically recent regions maturing particularly late. The cerebellum's unique protracted developmental trajectories, sexual dimorphism, preferential vulnerability to environmental influences, and frequent implication in childhood onset disorders such as autism and ADHD make it a prime target for pediatric neuroimaging investigations.

[1]  Jack L Lancaster,et al.  MR imaging volumetry of subcortical structures and cerebellar hemispheres in normal persons. , 2003, AJNR. American journal of neuroradiology.

[2]  N Ramnani,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[3]  J. Schmahmann Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. , 2004, The Journal of neuropsychiatry and clinical neurosciences.

[4]  Marc E. R. Hallonet,et al.  Tracing Neuroepithelial Cells of the Mesencephalic and Metencephalic Alar Plates During Cerebellar Ontogeny in Quail – chick Chimaeras , 1993, The European journal of neuroscience.

[5]  Jagath C. Rajapakse,et al.  Quantitative Magnetic Resonance Imaging of Human Brain Development: Ages 4–18 , 1996 .

[6]  J. Voogd The human cerebellum , 2003, Journal of Chemical Neuroanatomy.

[7]  N. Ramnani The primate cortico-cerebellar system: anatomy and function , 2006, Nature Reviews Neuroscience.

[8]  S. Lawrie,et al.  Towards a neuroanatomy of autism: A systematic review and meta-analysis of structural magnetic resonance imaging studies , 2008, European Psychiatry.

[9]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[10]  Ciesielski Kt,et al.  Cerebellar abnormality in autism: a nonspecific effect of early brain damage , 1994 .

[11]  A. Diamond Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex. , 2000, Child development.

[12]  Alan C. Evans,et al.  MRI Atlas of the Human Cerebellum , 2000 .

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

[14]  A. B. Hollingshead,et al.  Four factor index of social status , 1975 .

[15]  Greg Harris,et al.  Structural MR image processing using the BRAINS2 toolbox. , 2002, Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society.

[16]  Im Joo Rhyu,et al.  Magnetic resonance image-based cerebellar volumetry in healthy Korean adults , 1999, Neuroscience Letters.

[17]  J. Allman,et al.  The Scaling of White Matter to Gray Matter in Cerebellum and Neocortex , 2003, Brain, Behavior and Evolution.

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

[19]  E. Courchesne,et al.  Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging. , 1994, AJR. American journal of roentgenology.

[20]  P. Strick,et al.  Cerebellar Projections to the Prefrontal Cortex of the Primate , 2001, The Journal of Neuroscience.

[21]  P. Strick,et al.  Cerebellar output channels. , 1997, International review of neurobiology.

[22]  Alan C. Evans,et al.  Automatic "pipeline" analysis of 3-D MRI data for clinical trials: application to multiple sclerosis , 2002, IEEE Transactions on Medical Imaging.

[23]  P. Strick,et al.  The cerebellum: an overview , 1998, Trends in Neurosciences.

[24]  P. Huttenlocher,et al.  Synaptic density in human frontal cortex — Developmental changes and effects of aging , 1979, Brain Research.

[25]  B M Dawant,et al.  Brain segmentation and white matter lesion detection in MR images. , 1994, Critical reviews in biomedical engineering.

[26]  J. Desmond,et al.  Dissociation of Frontal and Cerebellar Activity in a Cognitive Task: Evidence for a Distinction between Selection and Search , 1998, NeuroImage.

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

[28]  Jeremy D. Schmahmann,et al.  MRI-based surface-assisted parcellation of human cerebellar cortex: an anatomically specified method with estimate of reliability , 2005, NeuroImage.

[29]  C. Edelbrock,et al.  Child Behavior Checklist (CBCL) , 1983 .

[30]  Jeremy D. Schmahmann,et al.  Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies , 2009, NeuroImage.

[31]  Paul G. Lesnik,et al.  Evidence for cerebellar-frontal subsystem changes in children treated with intrathecal chemotherapy for leukemia: enhanced data analysis using an effect size model. , 1998, Archives of neurology.

[32]  M E Hallonet,et al.  A new approach to the development of the cerebellum provided by the quail-chick marker system. , 1990, Development.

[33]  A. Gandjour The Comparative Anatomy and Histology of the Cerebellum , 1967 .

[34]  Richard Hawkes,et al.  From clusters to stripes: The developmental origins of adult cerebellar compartmentation , 2008, The Cerebellum.

[35]  Daniel S. O'Leary,et al.  Manual and Semiautomated Measurement of Cerebellar Subregions on MR Images , 2002, NeuroImage.

[36]  K. Herrup,et al.  The compartmentalization of the cerebellum. , 1997, Annual review of neuroscience.

[37]  Dorothy V. M. Bishop,et al.  Cerebellar Abnormalities in Developmental Dyslexia: Cause, Correlate or Consequence? , 2002, Cortex.

[38]  N. Makris,et al.  Structural Brain Imaging of Attention-Deficit/Hyperactivity Disorder , 2005, Biological Psychiatry.

[39]  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.

[40]  Karl Zilles,et al.  Expansion of the neocerebellum in Hominoidea. , 2003, Journal of human evolution.

[41]  R. Myers,et al.  Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes , 2004, Neuropsychopharmacology.

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

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

[44]  O. Larsell,et al.  The comparative anatomy and histology of the cerebellum , 1967 .

[45]  K. Tsutsui,et al.  Biosynthesis, mode of action and functional significance of neurosteroids in the developing Purkinje cell , 2006, The Journal of Steroid Biochemistry and Molecular Biology.

[46]  Akiko Nagai,et al.  Differential expression of the estrogen receptors alpha and beta during postnatal development of the rat cerebellum , 2006, Brain Research.

[47]  Isaac Meilijson,et al.  Neuronal Regulation: A Mechanism for Synaptic Pruning During Brain Maturation , 1999, Neural Computation.

[48]  S. Faraone,et al.  Meta-Analysis of Structural Imaging Findings in Attention-Deficit/Hyperactivity Disorder , 2007, Biological Psychiatry.

[49]  D. Kennedy,et al.  The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images. , 1996, Cerebral cortex.

[50]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[51]  M. Ito A new physiological concept on cerebellum. , 1990, Revue neurologique.

[52]  J. Fuster Frontal lobe and cognitive development , 2002, Journal of neurocytology.

[53]  E. Mufson,et al.  Distribution of estrogen receptor alpha and beta immunoreactive profiles in the postnatal rat brain. , 2003, Brain research. Developmental brain research.

[54]  D. Riva,et al.  The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours. , 2000, Brain : a journal of neurology.

[55]  Joseph M. Petrosko,et al.  Wechsler Intelligence Scale for Children—Revised, 1974. David Wechsler , 1975 .

[56]  P. Rakić,et al.  Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[57]  Faith M. Gunning-Dixon,et al.  Age and sex differences in the cerebellum and the ventral pons: a prospective MR study of healthy adults. , 2001, AJNR. American journal of neuroradiology.