Brain Development

1. Brain Development Good book: Johnson, M. H. (2011). Developmental Cognitive Neuroscience: An Introduction, Oxford: Blackwell. (3rd edition) In Education library (x1) Arts & Social Sci library (x11)

2. Development – the reduced version: Development is interaction of genes and environment PHENOTYPE = GENOTYPE * ENVIRONMENTAL HISTORY Phenotype (the organism you get, inc. traits, behaviour in any context) BEHAVIOUR = PHENOTYPE * PRESENT CONTEXT In theory, every action taken could be explained in this way……?! i.e. ACTIONS = (Genes * environmental history) * present context

3. Cells multiply and differentiate Inner cells cluster to leave a cavity The outer cells “hatch”/implant into uterine wall Two new types of tissue form (a bilaminar disc ) from inner and outer cells (according to bird/reptile or mammal). By Zephyris (SVG version of .) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

4. Between the top (ectoderm) and bottom layer (endoderm), the mesoderm forms (whose cells create the notocord). On the ectodermlayer, opposite the primitive streak (if symmetric), the neural plate forms.

5. Primitive streak Neural plate forming Ectoderm Notocord (releases proteins that drive neurulation Mesoderm Endoderm Ectoderm will become the outer layer of the embryo and later skin and, via the neural tube, the brain Mesoderm will become muscle, bone connective tissue Endoderm will become internal organs

6. Embryonic folding/neurulation then occurs

7. Neurulation Cells from the neural crest become the Peripheral Nervous System (PNS) The neural tube becomes the Central Nervous System (CNS) By OpenStax College [CC-BY-3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

8. The Central Nervous System develops…. The neural tube generates neuroblasts and glioblasts - cells that produce neurons and glial cells One end becomes a series of repeated units -> spinal cord The other end becomes a series of bulges ….becoming the forebrain, midbrain and hindbrain….and finer structures…

9. Chick embryo I, Nrets [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC-BY-SA-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0-1.0)], via Wikimedia Commons By User Magnus Manske on en.wikipedia [Public domain], via Wikimedia Commons

11. Cells on the move... Precursor cells (neuroblasts and glioblasts) produce: - neurons and - glial cells (poss. structure rather than cognition) The bulges in the tube grow larger as cells: - proliferate (are born) - migrate (travel) - differentiate into types These either: * migrate past older ones, e.g. cortex, from inside to out • displace older ones pushing them further away – passive cell displacement – e.g. thalamus The laminate structure of the cortex forms….

12. Laminate (layered) structure of cortex Can you spot the layers?  Visual cortex (stained pink). Subcortical white matter (blue)  Three drawings by Santiago Ramon y Cajal, taken from the book "Comparative study of the sensory areas of the human cortex", pages 314, 361, and 363. By User:Looie496 created file, Santiago Ramon y Cajal created artwork [Public domain], via Wikimedia Commons By Nephron (Own work) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

13. What are the key changes?Weight, neurons, synapses, myelin Prior to birth: neurons are generated at around 250,000 per minute, most of your life’s stock arrives in the first 3 months after your conception. Postnatal: Additive changes: - 4 x increase in weight - increase in synaptic density – peaks (e.g. in visual cortex) after 10 months, then pruned back. - myelination (insulation) increases NB: Some changes continue into teens: Synaptic pruning in Prefrontal Cortex is post-pubertal. Over-production related to plasticity? PFC myelination also increases in teens. By Ed Uthman, MD (Flickr, Wikipedia) (http://www.flickr.com/photos/euthman/304334264) [Public domain], via Wikimedia Commons By SCA Svenska Cellulosa Aktiebolaget (Flickr: Teens sharing a song) [CC-BY-2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons

14. Q: What sort of interaction is responsible for cortical laminate structure? How do different neurons know where to go?!  Three drawings by Santiago Ramon y Cajal, taken from the book "Comparative study of the sensory areas of the human cortex", pages 314, 361, and 363. By User:Looie496 created file, Santiago Ramon y Cajal created artwork [Public domain], via Wikimedia Commons

15. Q: What sort of interaction is responsible for cortical laminate structure? Neuronal migration appears aided by radial glioblasts - that act as “training stalks” or “guides” - appears regulated by local intrinsic cellular and molecular interactions - i.e., to some extent innate. On a petri dish Molnar & Blakemore (1991) placed visual thalamus with a) visual cortex - thalamus afferents invaded, stopped at layer 4 b) Hippocampal tissue - they grew unconstrained c) Cerebellum - just simply turned away

16. Levels of genetic/biological interaction with environment Johnson and Morton (1991): Interaction LevelTerm 1.Mollecular Internal Environment (e.g. blood oxygenation ) 2. Cellular Internal Environment – innate (e.g. embryonic neurogenesis) 3. Whole Organism a) Species-typical environment – primal -external environment(e.g. light and visual cortext) b) Individual-specific environment - learning (e.g. language)

17. Q: What sort of interaction is responsible for areal structure? Areal structure = areas of the brain can be differentiated by microstructure - Brodmann Areas (BA) - strongly associated with function

18. 2 theories for areal structure * due to a protomap: early differentiation into cortical regions according to intrinsic factors. No activity required. * due to protocortex: later differentiation depending on external factors e.g. input from thalamus and other areas of the cortex

19. 2 theories for areal structure- evidence * protomap (early differentiation due to intrinsic factors. No activity required) - “knockout” rodents without the thalamic connections still have well-defined boundaries due to gene expression * protocortex (later differentiation due to external factors e.g. i/p from thalamus other areas of the cortex - spontaneous pre-natal activity in the brain appears important for differentiation(Shatz, 2002) - Later plasticity and lack of “neat” regionalisation/function relationships - even primary sensory areas can shift according to later experience - known gene expressions (above) can still give rise to “graded maps” through overlay and different combinations

20. Cortical Plasticity: role of thalamic (sensory) inputs * Reducing thalamic input to a cortical region reduces its size * rewiring of thalamic inputs causes new target region to take on properties of the normal target tissue, and transplanted cortex takes on characteristics of new location So: Neural activity (external environment) appears a critical factor in areal development - not just innate. The answer maybe protomap AND protocortex

21. Development is about Interaction of Nature + Nurture Biological structures emerge from a complex interaction between genes and the environment - Piaget (amongst others) PHENOTYPE = GENOTYPE * ENVIRONMENTAL HISTORY Phenotype (the organism you get, inc. traits, + behaviour in specific context) GENOTYPE = genes – heritable part but….also see epigenetics

22. Our genetic background is very important for our educational outcomes For example, amongst UK 9 year-olds , most of the variance in UK English , Science and Maths achievement is genetic (Plomin et al. 2007) We can assume (?) the rest is the environment But life is probabilistic. Biology is not destiny, but there may be a progressive restriction of fate……

23. The probabilistic developmental landscape Large perturbations influence selection of predefined routes, or smaller perturbations if close to a decision…. (Waddington, 1975 - influenced Piaget)

24. Beyond “simple” genetics… DNA→RNA→protein (->structures, e.g. brain structure) Waddington referred to this as an “epigenetic” landscape – meaning all environmental influences on development epi- (Greek: επί- over, outside of, around) -genetics. These days, “epigentics” refers to heritable changes not caused by DNA changes

25. Epigenetics epi- (Greek: επί- over, outside of, around) -genetics. Generally = Heritable changes not caused by DNA changes But be aware that some use this term to mean all environmental influences on development DNA→RNA→protein (->structures, e.g. brain structure) Epigenetic factors influencing DNA expression may be inherited

26. Epigenetics Example“Methylation” Areas where many methyl groups attach to DNA become less “transcriptionally” active This can be heritable – although the mechanisms are not well understood May help tune an anticipated environment over 1-3 generations  May produce negative looping patterns  if anticipated environment mismatches the experienced. E.g. deficient licking and grooming of rat pups by mother -> altered pattern of methylation in pups -> heightened stress response in a normal environment.

27. Views on the role of genetics 1 The instructions encoded in DNA have acquired “a unique causal status in developmental outcomes due to their unidirectional influence” (Plomin et al., 2007) - specialist genes, e.g. linked to reading disability (Paracchini et al., 2007) - ‘generalist genes’ largely responsible for genetic influence across domains of academic achievement and cognitive ability (Plomin et al., 2007) - possibility of tailoring education to genetic profile

28. Views on the role of genetics 2 • Genetics provides probable not certain outcomes-Why? • Microbiologists often assume (their central dogma) DNA→RNA→protein (->structures, e.g. brain) • Neuroconstructivists reject a maturational unfolding of pre-existing information in the genes (Johnson, 2004) • Epigenetic and protein synthesis processes that are bidirectional (proteins can act on RNA and DNA processes and, in exceptional cases, RNA can even transform DNA in a process called reverse transcription (Gottlieb, 2004)). • These processes influenced by (normal) environments BIOLOGY IS NOT DESTINY

29. Neuroconstructivism Cognitive and neural outcomes emerge from a complex bi-directional interaction between inputs - including genetic, environmental, both sensory and cortical activity from other regions “Evolution is argued to have selected for adaptive outcomes and a strong capacity to learn, rather than prior knowledge. Within such a perspective, it is more plausible to think in terms of what we might call domain-relevant mechanisms that might gradually become domain specific [during our development] as a result of processing of different kinds of input” Annette Karmiloff-Smith

30. Neuroconstructivism: consequences Neuroconstructivist approaches: * probabilistic Waddington landscape and epigenetics * considers external environmental effects and emphasises importance of common stimuli (e.g. faces) * if neural pathway construction influenced by neural inputs from other areas, then “atypicality” in one area will produce “atypicality” elsewhere. * damage to brain systems more devasting in development terms than damage to cortical areas * different types of initial atypicality can result in same outcomes - if the same one brain system affected.

31. The Developing Brain(Morton and Frith, 1995)

32. The Learning Brain(Howard-Jones, 2010) ENVIRONMENT ENVIRONMENT (see HJ(2010) Intro NeuroEd Res And …. not forgetting experiential/insider perspectives!!

33. In summary – you can assume it’s as below – but know it’s not that simple: Development is interaction of genes and environment PHENOTYPE = GENOTYPE * ENVIRONMENTAL HISTORY Phenotype (the organism you get, inc. traits, behaviour in any context) BEHAVIOUR = PHENOTYPE * PRESENT CONTEXT In theory, every action taken could be explained in this way……?! i.e. ACTIONS = (Genes * environmental history) * present context

34. Next Time - Language and Development What would a Neuroconstructivist say? • Areal structure, e.g. Wernicke’s and Brocke’s – protomap/protocortex - left lateralisation but this effected by environmental factors – e.g. position in womb • Critical/sensitive periods for very early language, e.g. effects of hearing sounds before 12 months – early language specificity – highly social activity. Probabilistic landscape: Progressive restriction of fate? But later environmental effects on plastic brain: 2nd language effects on basic cognition • Language itself not innate but brain is not a blank slate either: built in start-up mechanisms for highly complex task of communication