Emotional and behavioral problems change the development of cerebellar gray matter volume, thickness, and surface area from childhood to adolescence: A longitudinal cohort study

AIMS Increasing evidence indicates that major neurodevelopmental disorders have potential links to abnormal cerebellar development. However, the developmental trajectories of cerebellar subregions from childhood to adolescence are lacking, and it is not clear how emotional and behavioral problems affect them. We aim to map the developmental trajectories of gray matter volume (GMV), cortical thickness (CT), and surface area (SA) in cerebellar subregions from childhood to adolescence and examine how emotional and behavioral problems change the cerebellar development trajectory in a longitudinal cohort study. METHOD This population-based longitudinal cohort study used data on a representative sample of 695 children. Emotional and behavioral problems were assessed at baseline and at three annual follow-ups with the Strengths and Difficulties Questionnaire (SDQ). RESULTS Using an innovative automated image segmentation technique, we quantified the GMV, CT, and SA of the whole cerebellum and 24 subdivisions (lobules I-VI, VIIB, VIIIA&B, and IX-X plus crus I-II) with 1319 MRI scans from a large longitudinal sample of 695 subjects aged 6-15 years and mapped their developmental trajectories. We also examined sex differences and found that boys showed more linear growth, while girls showed more nonlinear growth. Boys and girls showed nonlinear growth in the cerebellar subregions; however, girls reached the peak earlier than boys. Further analysis found that emotional and behavioral problems modulated cerebellar development. Specifically, emotional symptoms impede the expansion of the SA of the cerebellar cortex, and no gender differences; conduct problems lead to inadequate cerebellar GMV development only in girls, but not boys; hyperactivity/inattention delays the development of cerebellar GMV and SA, with left cerebellar GMV, right VIIIA GMV and SA in boys and left V GMV and SA in girls; peer problems disrupt CT growth and SA expansion, resulting in delayed GMV development, with bilateral IV, right X CT in boys and right Crus I GMV, left V SA in girls; and prosocial behavior problems impede the expansion of the SA and lead to excessive CT growth, with bilateral IV, V, right VI CT, left cerebellum SA in boys and right Crus I GMV in girls. CONCLUSIONS This study maps the developmental trajectories of GMV, CT, and SA in cerebellar subregions from childhood to adolescence. In addition, we provide the first evidence for how emotional and behavioral problems affect the dynamic development of GMV, CT, and SA in the cerebellum, which provides an important basis and guidance for the prevention and intervention of cognitive and emotional behavioral problems in the future.

[1]  R. Plomin,et al.  Gene–environment interaction using polygenic scores: Do polygenic scores for psychopathology moderate predictions from environmental risk to behavior problems? , 2022, Development and Psychopathology.

[2]  Thomas Pletschko,et al.  Evaluating the diagnostic validity of the cerebellar cognitive affective syndrome (CCAS) in pediatric posterior fossa tumor patients , 2022, Neuro-oncology advances.

[3]  Jessica B. Girault,et al.  Genetic Influences on Longitudinal Trajectories of Cortical Thickness and Surface Area during the First 2 Years of Life. , 2021, Cerebral cortex.

[4]  S. Duan,et al.  Basal forebrain mediates prosocial behavior via disinhibition of midbrain dopamine neurons , 2021, Proceedings of the National Academy of Sciences.

[5]  José E. Romero,et al.  Toward a unified analysis of cerebellum maturation and aging across the entire lifespan: A MRI analysis , 2021, Human brain mapping.

[6]  Lei Hao,et al.  Cerebellar thickness changes associated with heavy cannabis use: A 3‐year longitudinal study , 2020, Addiction biology.

[7]  Lei Hao,et al.  Longitudinal Changes of Cerebellar Thickness in Autism Spectrum Disorder , 2020, Neuroscience Letters.

[8]  Catherine J. Stoodley,et al.  The Theory and Neuroscience of Cerebellar Cognition. , 2019, Annual review of neuroscience.

[9]  D. Heck,et al.  Emerging connections between cerebellar development, behaviour and complex brain disorders , 2019, Nature Reviews Neuroscience.

[10]  R. Plomin,et al.  The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence , 2019, bioRxiv.

[11]  Kamran Khodakhah,et al.  Cerebellar modulation of the reward circuitry and social behavior , 2019, Science.

[12]  Egidio D'Angelo,et al.  The cerebellum gets social , 2019, Science.

[13]  R. Lanius,et al.  The cerebellum after trauma: Resting‐state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype , 2018, Human brain mapping.

[14]  Gabriel A. Devenyi,et al.  A multicohort, longitudinal study of cerebellar development in attention deficit hyperactivity disorder , 2018, Journal of child psychology and psychiatry, and allied disciplines.

[15]  Sabine Peters,et al.  Longitudinal development of hippocampal subregions from childhood to adulthood , 2017, Developmental Cognitive Neuroscience.

[16]  K. Mills,et al.  Structural brain development: A review of methodological approaches and best practices , 2017, Developmental Cognitive Neuroscience.

[17]  G. Fairchild,et al.  Disrupted default mode network connectivity in male adolescents with conduct disorder , 2016, Brain Imaging and Behavior.

[18]  J. Buitelaar,et al.  Neuro-cognitive system dysfunction and symptom sets: A review of fMRI studies in youth with conduct problems , 2016, Neuroscience & Biobehavioral Reviews.

[19]  Murat Yücel,et al.  Brain development during adolescence: A mixed‐longitudinal investigation of cortical thickness, surface area, and volume , 2016, Human brain mapping.

[20]  N. Šestan,et al.  The Cellular and Molecular Landscapes of the Developing Human Central Nervous System , 2016, Neuron.

[21]  Samuel E. Ehrenreich,et al.  Prosocial Behavior: Long-Term Trajectories and Psychosocial Outcomes. , 2015, Social development.

[22]  J. Gilmore,et al.  Dynamic Development of Regional Cortical Thickness and Surface Area in Early Childhood. , 2015, Cerebral cortex.

[23]  Alan C. Evans,et al.  Changes in thickness and surface area of the human cortex and their relationship with intelligence. , 2015, Cerebral cortex.

[24]  A. Moustafa,et al.  The Cerebellum and Psychiatric Disorders , 2015, Front. Public Health.

[25]  Lara M. Wierenga,et al.  Typical development of basal ganglia, hippocampus, amygdala and cerebellum from age 7 to 24 , 2014, NeuroImage.

[26]  Jay N. Giedd,et al.  The influence of puberty on subcortical brain development , 2014, NeuroImage.

[27]  Lara M. Wierenga,et al.  Unique developmental trajectories of cortical thickness and surface area , 2014, NeuroImage.

[28]  R. Berman,et al.  Longitudinal four-dimensional mapping of subcortical anatomy in human development , 2014, Proceedings of the National Academy of Sciences.

[29]  Deanna Greenstein,et al.  Trajectories of Cerebral Cortical Development in Childhood and Adolescence and Adult Attention-Deficit/Hyperactivity Disorder , 2013, Biological Psychiatry.

[30]  Abraham Z. Snyder,et al.  Human Connectome Project informatics: Quality control, database services, and data visualization , 2013, NeuroImage.

[31]  D. Louis Collins,et al.  Volumetric analysis of medial temporal lobe structures in brain development from childhood to adolescence , 2013, NeuroImage.

[32]  Vijay K. Venkatraman,et al.  Multimodal imaging of the self-regulating developing brain , 2012, Proceedings of the National Academy of Sciences.

[33]  Luca Passamonti,et al.  Brain structure abnormalities in adolescent girls with conduct disorder , 2012, Journal of child psychology and psychiatry, and allied disciplines.

[34]  J. Giedd,et al.  Review: magnetic resonance imaging of male/female differences in human adolescent brain anatomy , 2012, Biology of Sex Differences.

[35]  A. Evans,et al.  Development of Cortical Surface Area and Gyrification in Attention-Deficit/Hyperactivity Disorder , 2012, Biological Psychiatry.

[36]  Jacqueline N. Crawley,et al.  Autistic-like behavior and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice , 2012, Nature.

[37]  A. Jackowski,et al.  Is cerebellar volume related to bipolar disorder? , 2011, Journal of affective disorders.

[38]  Russell H. Tobe,et al.  Cerebellar morphology in Tourette syndrome and obsessive‐compulsive disorder , 2010, Annals of neurology.

[39]  Henning Tiemeier,et al.  Cerebellum development during childhood and adolescence: A longitudinal morphometric MRI study , 2010, NeuroImage.

[40]  A. Dale,et al.  Distinct genetic influences on cortical surface area and cortical thickness. , 2009, Cerebral cortex.

[41]  S. Baron-Cohen,et al.  Talent in autism: hyper-systemizing, hyper-attention to detail and sensory hypersensitivity , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[42]  A. Mechelli,et al.  Size matters: increased grey matter in boys with conduct problems and callous-unemotional traits. , 2009, Brain : a journal of neurology.

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

[44]  T. Beauchaine,et al.  Sex differences in autonomic correlates of conduct problems and aggression. , 2008, Journal of the American Academy of Child and Adolescent Psychiatry.

[45]  M. Keshavan,et al.  MRI study of the cerebellum in young bipolar patients , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[46]  Alan C. Evans,et al.  Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation , 2007, Proceedings of the National Academy of Sciences.

[47]  Patrick E Shrout,et al.  ADHD and gender: are risks and sequela of ADHD the same for boys and girls? , 2007, Journal of Child Psychology and Psychiatry and Allied Disciplines.

[48]  S. Perren,et al.  Pathways of behavioural and emotional symptoms in kindergarten children: What is the role of pro-social behaviour? , 2007, European Child & Adolescent Psychiatry.

[49]  P. Shrout,et al.  ADHD Correlates, Comorbidity, and Impairment in Community and Treated Samples of Children and Adolescents , 2007, Journal of abnormal child psychology.

[50]  Philip Shaw,et al.  Cerebellar development and clinical outcome in attention deficit hyperactivity disorder. , 2007, The American journal of psychiatry.

[51]  Ganesan Venkatasubramanian,et al.  IMAGING STUDY: Gray matter volume abnormalities and externalizing symptoms in subjects at high risk for alcohol dependence , 2007, Addiction biology.

[52]  Dinggang Shen,et al.  Puberty-related influences on brain development , 2006, Molecular and Cellular Endocrinology.

[53]  Adrian F. Ashman,et al.  The Development of Adolescents' Emotional Stability and General Self-Concept: The interplay of parents, peers, and gender , 2003 .

[54]  Huda Y. Zoghbi,et al.  Genetic regulation of cerebellar development , 2001, Nature Reviews Neuroscience.

[55]  H. G. Dunn,et al.  Rett Syndrome: Review of Biological Abnormalities , 2001, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[56]  T. Perneger What's wrong with Bonferroni adjustments , 1998, BMJ.

[57]  R. Goodman The Strengths and Difficulties Questionnaire: a research note. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[58]  E. Courchesne,et al.  Attentional Activation of the Cerebellum Independent of Motor Involvement , 1997, Science.

[59]  D. Cox,et al.  An Analysis of Transformations , 1964 .

[60]  J. Andrews-Hanna,et al.  Default mode network activity in male adolescents with conduct and substance use disorder. , 2014, Drug and alcohol dependence.

[61]  Christopher L. Asplund,et al.  The organization of the human cerebellum estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.