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Brain Dev n Cog.pptx
- 1. Dr. Hari Wahyu Nugroho, SpA(K), MKes Spesialis Anak Konsultan Tumbuh Kembang • S1 FK Univ. Sebelas Maret Surakarta 2005 • S2 FK Univ. Sebelas Maret Surakarta 2008 • Spesialis Anak (Sp1) FK Univ. Sebelas Maret Surakarta 2010 • Fellowship RSUP. Hasan Sadikin Bandung 2012 • Fellowship RSUP. Dr. Sardjito Jogjakarta 2013 • Spesialis Anak Konsultan (Sp2) FK. Univ. Gajah Mada Jogjakarta 2016 • Fellowship Univ. Medisch Centrum Groningen, Netherlands 2017 • Dosen Ilmu Kesehatan Anak FK Univ. Sebelas Maret/RSUD. Dr. Moewardi • Kepala Bagian IKA FK. Univ. Sebelas Maret/RSUD. Dr. Moewardi • Wakil Ketua IDAI Cabang. Jawa Tengah • Ketua IDAI Perwakilan Surakarta
- 2. How Does Brain Development Affect’s Child’s Growth and Development
- 3. Sejarah Neuron dan konektivitas antar neuron Ramon y Cajal (1852-1934) (1888) (1899)
- 5. Brain Growth Since fetal, the brain growth in size and in complexity: Billions of neurons get connected for fast & efficient information processing Adapted from Silbereis et al., Neuron, 2016
- 6. Brain Structure • 90 billion neurons (90,000,000,000) • 100 billion non-neuron cells (100,000,000,000) • 1000 Trillion synapses (1,000,000,000,000,000) • 100 km nerves • 600 km blood vessels • Adult brain = 2% of body weight, consumes 20% of energy Synapse Neuron Oligodendrocyte Myelin Astrocyte Blood vessel Microglia
- 8. Myelination is a hallmark of neurodevelopment Myelination Wrapping of nerve fibers (axons) with a lipid-rich sheath
- 9. Protects the axon Matures alongside cognitive and behavioral development Myelination Ensures fast, efficient & synchronized communication between cells and networks • Velocity of unmeylinated axon: 5 m/sec • Velocity of myelinated axon: 100 m/sec
- 10. Deoni SCL, Schneider N, Dean III DC, D’Sa V (2019). White Matter Maturation Underlying Changes in Cognitive Development In Early Childhood. HBM Objective • To examine the longitudinal relationship of maturing brain myelination to variability in cognitive skills. Population • N = 187 children with repeated MRI (Myelin Water Fraction) and cognitive assessments (MSEL) between 2 mo and 6 yrs of age Results • Marked age-related variability in repeated cognitive measures that was variably related to on-going changes in myelination. Myelination & Cognition
- 11. • general cognitive ability1 • language2 & reading3 • working memory4 • processing speed5 • sensory reactivity6 1Schmithorst et al., 2005; Deoni et al., 2014; 2Büchel et al., 2004; Catani et al., 2007; O'Muircheartaigh et al., 2013; 3Nagy et al., 2004; Beaulieu et al., 2005; 4Nagy et al., 2004; Short et al., 2013; 5Turken et al., 2008; Bartzokis et al., 2010; Lu et al., 2013; 6Weinstein et al., 2014 Human clinical studies show the link between myelination and cognition, including: Myelination & Cognition
- 12. 12 Objective Assess key inter-relations among nutrition, gut microbiota, and early brain development in the first 3 yrs of life BCP-Enriched: Research Framework and Scope To learn more, visit: https://www.med.unc.edu/neurology/news/unc-launches-new-study-to-uncover-nutritional-impacts-on-early-brain-development https://wyethnutritionsc.org/en/nutrition-topics/brain-development/unc-launches-new-study-to-uncover-nutritional-impacts-on-early-brain-development Jian Yan & Manjiang Yao Approach • Healthy children (03 yrs) • Accelerated longitudinal design • Study breast milk levels of key nutrients (i.e., SM, PLs, HMOs, DHA, pro-myelin blend) on o brain functional connectivity (e.g., visual, language, memory, motor networks) o brain efficiency & flexibility o cognition (i.e., Mullen scores) o microbiome development
- 13. General1 • Gene expression (nature) • Environmental factors (nurture) Molecular cues guide development & are dependent upon the experiences of the developing child Environmental factors1 • Socioeconomic status (SES) • Social interactions • Urbanization • Pollution • Social mobility • Stress • Nutrition & food . 1Kolb B, Gibb R. J Can Acad Adolesc Psychiatry. 2011;20: 265-76; 2Hanson JL, et al. Plos One 2013;8:e80954 Influencing Factors Total Gray Matter (SES Status)2
- 14. General1 • Gene expression (nature) • Environmental factors (nurture) Molecular cues guide development & are dependent upon the experiences of the developing child Environmental factors1 • Socioeconomic status (SES) • Social interactions • Urbanization • Pollution • Social mobility • Stress • Nutrition & food 1Kolb B, Gibb R. J Can Acad Adolesc Psychiatry. 2011;20: 265-76; 2WDR team 2018, using data from Nelson and others (2017). Source: http://bit.do/WDR2018-Fig_S2-1 Total white and gray matter (stunting status)2 Not malnourished n=18 (age 73 ± 8 days) Malnourished n=9 (age 82 ± 11 days) Influencing Factors
- 17. Brain structure adv. Child vs Norm Child vs Delayed Child
- 18. B KANDUNGAN ADULT 1 2 12 400 gr 850 gr 1100 gr 1.400 gr 25% 60% 80% Brain volume 100% HC 32-37 cm HC 46-52 cm HC 50-57 cm Growing fast in the first 2 years of life Need optimal nutrition and other factors
- 19. 2011 Deoni et al. (2011) Journal of Neuroscience 2013 Deoni et al. (2013) NeuroImage 2018 Deoni et al. (2018) NeuroImage Myelin Water Fraction
- 20. Malnutrition and stunting • Malnutrition • Inadequate intake of protein, carbohydrates, micronutrients and frequent infections • Structural and functional pathology of the brain. • Tissue damage, growth retardation, disorderly differentiation, reduction in synapses and synaptic neurotransmitters, delayed myelination and reduced overall development of dendritic arborization. • Disturb the formation of neuronal circuits • Chronic PEM stunting & wasting • Delay in the development of cognitive processes or in permanent cognitive impairment Udani PM: Brain and various facets of child development. Indian J Pediatr 1992, 59:165-186.
- 21. Cognitive development in children with chronic protein energy malnutrition Behavioral and Brain Functions 2008, 4:31 AN = 20 MN= 20
- 22. Cognitive development in children with chronic protein energy malnutrition Behavioral and Brain Functions 2008, 4:31 Stunting affects : • Development of higher cognitive rather than generalized cognitive impairment. • Slowing in the age related improvement in certain higher order cognitive processes • Long lasting cognitive impairments.
- 23. Sanou et al. Child Adolesc Psychiatry Ment Health (2018) 12:30 n = 532, age 6-8 years
- 24. Cipto Mangunkusumo Hospital, 2017 Stunting with malnutrition = 26 Malnutrition with normal height = 25 Constitutional short stature = 7 Pusponegoro HD, Handryastuti S, 2017
- 25. Key Messages 1. The first 1000 days of life are a particularly rapid & dynamic period of brain development 2. One of those dynamic processes is myelination, the coating of axons with lipid-rich myelin sheaths 3. Myelination facilitates signal transduction between cells and thus supports fast, efficient and synchronized brain communication 4. Many factors influence brain growth and myelination; early life nutrition is an important and modifiable factor that can shape myelination and, consequently, cognitive outcomes
Editor's Notes
- To start, I would like to us to cast our minds back before we go forward with the talk. Santiago Ramon Y Cajal – a Spanish neuroscientist and pathologist - known as the father of modern neuroscience It was known at the time and for some decades before that the brain was composed of neurons - from his investigations into the microscopic structure of the brain – worth noting that his pictures and others like it were hand drawn depictions of the strcuture of the brain are still fascinating to this day Ramon was awarded the Nobel prize in physiology or Medicine in 1906 for his Neuron Doctrine where he proposed that information passed from neuron to neuron across gaps – known as synapses His work was the foundation for the idea of brain connectivity
- Prenatal Neuron production begins on embryonic day 42 and is largely complete by mid-gestation Neurons migrate to different brain areas where they begin to make connections establishing rudimentary neural networks By the end of the prenatal period major fiber pathways are complete Postnatal Brain size increases by 4-fold during preschool period, reaching approximately 90% of adult volume by age 6 Structural changes parallel changes in functional organization that are reflected in behavior These early experience dependent processes underlie the well-documented plasticity & capacity for adaptation that is the hallmark of early brain development
- Neuron: information transmission and processing Astrocyte: brain energy provider information transmission modulator Microglia: guardian of the brain Oligodendrocyte: information transmission facilitator Endothelial cell / pericyte: (blood vessels) filter/supplier
- Myelin = insulator by increasing axonal resistance and decreasing capacitance Myelin sheath thickness, affect the conduction velocity of action potentials Velocity: unmeylinated axon: 5m/sec meylinated axon: 100 m/sec Myelination is a key neurodevelopmental process that involves the formation of a lipid (myelin) sheath around nerve fibres in the brain. Myelination starts in utero, continues throughout childhood and into adulthood. The myelin sheath insulates and protects nerve fibres and enables fast and efficient communication between cells and networks in the brain. Role of myelin – not only protects the neuron but is integral to signalling, not only speed but effecient and co-ordinated
- https://www.ncbi.nlm.nih.gov/books/NBK10799/ Myelin = insulator by increasing axonal resistance and decreasing capacitance Myelin sheath thickness, affect the conduction velocity of action potentials Velocity: unmeylinated axon: 5m/sec meylinated axon: 100 m/sec Myelination is a key neurodevelopmental process that involves the formation of a lipid (myelin) sheath around nerve fibres in the brain. Myelination starts in utero, continues throughout childhood and into adulthood. The myelin sheath insulates and protects nerve fibres and enables fast and efficient communication between cells and networks in the brain. Role of myelin – not only protects the neuron but is integral to signalling, not only speed but effecient and co-ordinated most of the axons are only partially myelinated, and the axons can myelinate as a plastic response to requirement
- Our own data in conjunction with Brown University and their longitudinal observational cohort – Brown Assessment of Myelination and Behaviour Across Maturation (BAMBAM) Earlier relationships seem to reflect motor development – motor area– cerbellum, brain stem, visual cortex, Thalamus, CC After 15 months – more verbal and language development These fit with developmental milestones At 22-32 months we see a resurgence in the relationship between cognitive outcomes and myelination – significance is spread diffusely throughout brain, relationship between cog function and different brain areas – prefrontal, internal capsule and CC Reflects the importance of changing levels of myelin to evolving cognitive ability Main message - strongest relationship between myelin and cognition observed near onset of myelination and at transition between rapid to slower myelination (2-3 yrs of age) (association - stress its obersational)
- Using MR imaging the strcuture of myelin, specifically the myelin water fraction, in the developing brain can be visualised. Host of general studies showing the link between these cog functions and myelination These individual components also form parts of executive function
- For BCP, 75% of planned sample size has been enrolled; imaging data have been transferred to NIH data storage facilities on the rolling basis. For BCP-Enriched, the results will be published on a rolling basis as well (preliminary microbiota data and Mullen data have been presented at the Nutrition and Growth meeting in March this year).
- Why nutrition – at earlier points of life – easily modifiable
- Link to this slide: asking the question – given the link between myelination and cognition, what can infleunce myelination? Data obtained from infants 2–3 months old in Dhaka, Bangladesh, using magnetic resonance imaging (MRI). Graph depicts two groups of infants: 18 not stunted (not malnourished) and 9 stunted (malnourished).