Neuroimaging young children and associations with neurocognitive development in a South African birth cohort study

Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2–3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2–3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ≥0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation.

[1]  M. Styner,et al.  Longitudinal development of cortical and subcortical gray matter from birth to 2 years. , 2012, Cerebral cortex.

[2]  Andrew Simmons,et al.  The effects of intracranial volume adjustment approaches on multiple regional MRI volumes in healthy aging and Alzheimer's disease , 2014, Front. Aging Neurosci..

[3]  Hao Huang,et al.  Delineation of early brain development from fetuses to infants with diffusion MRI and beyond , 2019, NeuroImage.

[4]  G. Berns Functional neuroimaging. , 1999, Life sciences.

[5]  John H. Gilmore,et al.  A review on neuroimaging studies of genetic and environmental influences on early brain development , 2019, NeuroImage.

[6]  M. Bornstein,et al.  A decade of infant neuroimaging research: What have we learned and where are we going? , 2019, Infant behavior & development.

[7]  Alan C. Evans,et al.  The NIH MRI study of normal brain development , 2006, NeuroImage.

[8]  Dan J Stein,et al.  A study of the effects of prenatal alcohol exposure on white matter microstructural integrity at birth , 2015, Acta Neuropsychiatrica.

[9]  Paul C Fletcher,et al.  Childhood Obesity, Cortical Structure, and Executive Function in Healthy Children , 2019, Cerebral cortex.

[10]  Brain Development Cooperative Group,et al.  The NIH MRI study of normal brain development (Objective-2): Newborns, infants, toddlers, and preschoolers , 2007, NeuroImage.

[11]  A. Akobeng,et al.  Melatonin for the management of sleep problems in children with neurodevelopmental disorders: a systematic review and meta-analysis , 2018, Archives of Disease in Childhood.

[12]  K. Blomgren,et al.  Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. , 2013, British journal of anaesthesia.

[13]  John O. Willis,et al.  Bayley Scales of Infant and Toddler Development, Third Edition , 2014 .

[14]  S. Black Early Childhood Exposure to Anesthesia and Risk of Developmental and Behavioral Disorders in a Sibling Birth Cohort , 2012 .

[15]  S. Dehaene,et al.  Functional Neuroimaging of Speech Perception in Infants , 2002, Science.

[16]  Martha J. Holmes,et al.  Altered brain morphometry in 7-year old HIV-infected children on early ART , 2018, Metabolic Brain Disease.

[17]  G. Dehaene-Lambertz,et al.  The early development of brain white matter: A review of imaging studies in fetuses, newborns and infants , 2014, Neuroscience.

[18]  Danielle Posthuma,et al.  Incidental Findings on Brain Imaging in the General Pediatric Population. , 2017, The New England journal of medicine.

[19]  P. Nieminen,et al.  Standardised regression coefficient as an effect size index in summarising findings in epidemiological studies , 2013, Epidemiology, Biostatistics, and Public Health.

[20]  Cedric E. Ginestet,et al.  White matter development and early cognition in babies and toddlers , 2014, Human brain mapping.

[21]  Dan J Stein,et al.  White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates , 2016, Medicine.

[22]  Deborah Dewey,et al.  Brain white matter structure and language ability in preschool-aged children , 2017, Brain and Language.

[23]  Dinggang Shen,et al.  Cortical Structure and Cognition in Infants and Toddlers. , 2019, Cerebral cortex.

[24]  Chunling Lu,et al.  Early childhood development coming of age: science through the life course , 2017, The Lancet.

[25]  Yi Li,et al.  Challenges in pediatric neuroimaging , 2019, NeuroImage.

[26]  T. Chirwa,et al.  Developmental outcome of very low birth weight infants in a developing country , 2012, BMC Pediatrics.

[27]  N. Gaab,et al.  Pediatric neuroimaging in early childhood and infancy: challenges and practical guidelines , 2012, Annals of the New York Academy of Sciences.

[28]  Anders M. Dale,et al.  Sequence-independent segmentation of magnetic resonance images , 2004, NeuroImage.

[29]  T. Nir,et al.  Brain Imaging and Neurodevelopment in HIV-uninfected Thai Children Born to HIV-infected Mothers , 2015, The Pediatric infectious disease journal.

[30]  R. Elliott,et al.  Dissociable functions in the medial and lateral orbitofrontal cortex: evidence from human neuroimaging studies. , 2000, Cerebral cortex.

[31]  Rebecca C. Knickmeyer,et al.  A Structural MRI Study of Human Brain Development from Birth to 2 Years , 2008, The Journal of Neuroscience.

[32]  David R. Williams,et al.  Social determinants of psychological distress in a nationally-representative sample of South African adults. , 2008, Social science & medicine.

[33]  M. Schmidt,et al.  Pediatric magnetic resonance research and the minimal-risk standard. , 2011, IRB.

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

[35]  Torsten Baldeweg,et al.  Maturation of language networks in children: A systematic review of 22years of functional MRI , 2015, NeuroImage.

[36]  H. Bayrampour,et al.  Risk and protective factors in early child development: Results from the All Our Babies (AOB) pregnancy cohort. , 2016, Research in developmental disabilities.

[37]  T. Sejnowski,et al.  Associations between cortical thickness and neurocognitive skills during childhood vary by family socioeconomic factors , 2017, Brain and Cognition.

[38]  Guohua Li,et al.  Early Childhood Exposure to Anesthesia and Risk of Developmental and Behavioral Disorders in a Sibling Birth Cohort , 2011, Anesthesia and analgesia.

[39]  Craig A. Albers,et al.  Test Review: Bayley, N. (2006). Bayley Scales of Infant and Toddler Development– Third Edition. San Antonio, TX: Harcourt Assessment , 2007 .

[40]  L. Jacklin,et al.  A study to evaluate the performance of black South African urban infants on the Bayley Scales of Infant Development III , 2013 .

[41]  M. Gee,et al.  Strategies to minimize sedation in pediatric body magnetic resonance imaging , 2016, Pediatric Radiology.

[42]  M. Bornstein,et al.  Imbalances in the knowledge about infant mental health in rich and poor countries: too little progress in bridging the gap. , 2014, Infant mental health journal.

[43]  Sean C. L. Deoni,et al.  Quantifying cortical development in typically developing toddlers and young children, 1–6 years of age , 2017, NeuroImage.

[44]  Z. Bhutta,et al.  Early childhood development: the foundation of sustainable development , 2017, The Lancet.

[45]  C. Maxfield,et al.  Pediatric Imaging in Global Health Radiology , 2014 .

[46]  S. Sawilowsky New Effect Size Rules of Thumb , 2009 .

[47]  C. Nelson,et al.  Inequality in early childhood: risk and protective factors for early child development , 2011, The Lancet.

[48]  Alan C. Acock,et al.  A Gentle Introduction to Stata , 2005 .

[49]  Dan J Stein,et al.  Drakenstein Child Health Study (DCHS): investigating determinants of early child development and cognition , 2018, BMJ Paediatrics Open.

[50]  Dinggang Shen,et al.  Developmental topography of cortical thickness during infancy , 2019, Proceedings of the National Academy of Sciences.

[51]  J. Wilmshurst,et al.  The role of melatonin to attain electroencephalograms in children in a sub-Saharan African setting , 2017, Seizure.

[52]  Elizabeth Bates,et al.  Plasticity, localization, and language development. , 2014 .

[53]  Lara M. Wierenga,et al.  A multisample study of longitudinal changes in brain network architecture in 4–13‐year‐old children , 2018, Human brain mapping.

[54]  Anders M. Dale,et al.  Image processing and analysis methods for the Adolescent Brain Cognitive Development Study , 2019, NeuroImage.

[55]  P. Kuhl,et al.  Infant speech perception activates Broca's area: a developmental magnetoencephalography study , 2006, Neuroreport.

[56]  Kelvin O. Lim,et al.  Associations between cortical thickness and verbal fluency in childhood, adolescence, and young adulthood , 2011, NeuroImage.

[57]  Hangyi Jiang,et al.  Pediatric diffusion tensor imaging: Normal database and observation of the white matter maturation in early childhood , 2006, NeuroImage.

[58]  Gary J. Robertson,et al.  Bayley Scales of Infant and Toddler Development , 2017 .

[59]  Jonathan O'Muircheartaigh,et al.  Cortical maturation and myelination in healthy toddlers and young children , 2015, NeuroImage.

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

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

[62]  Dan J Stein,et al.  Investigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study , 2014, Thorax.

[63]  Vaidehi S. Natu,et al.  Apparent thinning of human visual cortex during childhood is associated with myelination , 2019, Proceedings of the National Academy of Sciences.

[64]  S. Selbst,et al.  Adverse Sedation Events in Pediatrics: A Critical Incident Analysis of Contributing Factors , 2000, Pediatrics.

[65]  Carlo Pierpaoli,et al.  The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI) , 2016, NeuroImage.

[66]  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.

[67]  A M Dale,et al.  Measuring the thickness of the human cerebral cortex from magnetic resonance images. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[68]  John H. Gilmore,et al.  Spatial processing: An 'other' kind of place cell , 2018, Nature Reviews Neuroscience.

[69]  C. Rummel,et al.  Cortical morphometry and cognition in very preterm and term-born children at early school age. , 2018, Early human development.

[70]  Minoru Asada,et al.  Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions , 2016, Front. Hum. Neurosci..

[71]  Owen J. Arthurs,et al.  Paediatric MRI under sedation: is it necessary? What is the evidence for the alternatives? , 2011, Pediatric Radiology.

[72]  A. Costello,et al.  What will it take for children and adolescents to thrive? The Global Strategy for Women's, Children's, and Adolescents' Health. , 2019, The Lancet. Child & adolescent health.

[73]  C. Lebel,et al.  Factors Associated With Successful MRI Scanning in Unsedated Young Children , 2018, Front. Pediatr..

[74]  Holly Dirks,et al.  Pediatric neuroimaging using magnetic resonance imaging during non-sedated sleep , 2013, Pediatric Radiology.

[75]  W. Whitehouse,et al.  The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination. , 2002, Clinical radiology.

[76]  Wendy Johnson,et al.  Cognitive ability changes and dynamics of cortical thickness development in healthy children and adolescents , 2014, NeuroImage.

[77]  Dan J Stein,et al.  Investigating the psychosocial determinants of child health in Africa: The Drakenstein Child Health Study , 2015, Journal of Neuroscience Methods.

[78]  S. Heim,et al.  Development of structure and function in the infant brain: Implications for cognition, language and social behaviour , 2006, Neuroscience & Biobehavioral Reviews.

[79]  S. Dehaene,et al.  Language or music, mother or Mozart? Structural and environmental influences on infants’ language networks , 2010, Brain and Language.

[80]  Anders M. Dale,et al.  Image processing and analysis methods for the Adolescent Brain Cognitive Development Study , 2018, NeuroImage.

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

[82]  A. Dale,et al.  Whole Brain Segmentation Automated Labeling of Neuroanatomical Structures in the Human Brain , 2002, Neuron.

[83]  Arthur W Toga,et al.  Relationships between IQ and regional cortical gray matter thickness in healthy adults. , 2007, Cerebral cortex.