Stages of Brain Development
- 0-4 weeks: Neurolation
- 4-8 weeks: Neuronal Proliferation
- 12-Birth: Neural Migration
- 16/18 weeks – late childhood: Apotosis
- 18 weeks – Late childhood: Synaptogenesis
- 30 weeks – Adulthood: Myelination
Neuronal Proliferation
Neurons destined for the neocortex are produced in the proliferative zone near the cerebral ventricle (ventricular zone)
(proliferation means cells greatly increase in #)
organizer controls pattern of proliferation via chemical signals in neural tube
Neurolation
Folding & fusion of the ectoderm to create the neural tube
Neural tube becomes the CNS
Happens week 0-4;
Week 5: ecotoderm differentiated into different brain structures
Neural Migration
Neurons migrate along radial glial cells to the relevant layer of the cortex
phase 3 of prenatal development
cells need to migrate from ventricular zone and aggregate in this process
Brain volume growth
Total: Peak = 10 (females) & 14 (Males)
Grey: Peak = 10 (males) & 8 (females)
WM: steep increase in first year; Then less rapid growth up to young adulthood
Grey Matter in adolesence
So despite global changes in GM – we can see that it the thickness that is showing the most marked reduction
Change in grey matter volume refers to a change in:
Thickness
Surface area
Sulcation
Process of brain growth in the 2nd – 3rd trimester
Abnormality = Lissencephaly (smooth brain)
Abnormality of sulcation
Lissencephaly (smooth brain)
Gyrification
development of the surface folds
Sulcation development
13-17 gestational weeks - appearance of the first sulcus
18-19 gestational weeks - development of the periinsular sulci
20-22 gestational weeks - central sulci and opercularization of the insula
24-26 gestational weeks - covering of the posterior insula
27-28 gestational weeks - closure of the lateral sulcus (Sylvian fissure or lateral fissure)
3 types of sulci
Primary
Consistently located
Easily recognisable
Central and Superior Frontal
2) Secondary
Branches of the Primary Sulci
3) Tertiary
Branches of the secondary Sulci
Individual differences
8/9month of pregnancy and into first year of life
Theories of Gyrification
- Skull preventing the brain growing
- Axonal Tension Theory
- Differential Radial Growth – Richman 1975
- Differential Tangential Growth – Ronan 2014
- Constrained cortical expansion - Tallinen 2014, 2016
Axonal Tension Theory
Axons connecting two areas are pulling on cortex and this causes them to fold. BUT: Axonal tension does exist but it quite weak; there are more gyri than sulci
Constrained Cortical Expansion
Grey matter is expanding rapidly
White matter isn’t
Based on this theory:
Polymicrogyria based on Constrained Cortical Expansion Theory
Poly microgryia = thin cortex but large surface area so it folds more
Lissencephaly based on Constrained Cortical Expansion Theory
Lisencephaly = thick cortex but low surface area so it folds less
2 ways neurons migrate along radial glial cells
2 ways cells move:
radial migration: move out in a straight line
tangential migration: cells travel in right angles
Radial Unit Hypothesis process…
1. Ventricular zone = Generate Neurons Intermediate Progenitor (IP) divide to forms pairs of neurons
- Neurons Transverse Intermediate zone and Subplate Zones along RG cells
- Pass through deep layers and settle between Cortical Plate and Marginal Zone
Symmetrical Radial Division
Laterally – side way and therefore affects surface area
Asymmetrical Radial Division
Linear increase in radial coloumns results in an increase in cortical thickness
What determines position of neurons in neuronal migration?
Position of the neurons is determined by information in the VZ + a protomap in the SP and CP & is preserved by transient radial glial scaffolding
What impacts cortical thickness?
The number of IP and RG cells = cortical thickness
Human Vs. Rodent Brain
Outer sub-ventricular zone = larger
the division of the RG cells fromm sub-ventricular RG cells - which allows for ‘extra coloumns’ and a much larger cortex
oRG
oRG = non-epithelial radial-glial like cells – able to self renew and produce neurons similar to classic RG cells
oRG and classic RG divide asymmetrically to produce IP cells
IP cells divide once or twice to produce immature neurons
oRG cells and IP cells are known as ‘transit amplifying neurons’ as they amplify the number on neurons being migrated
THEREFORE contribute to the larger cortex in humans
Founder cells
during cortical development radial founder cells go through stages of symetrical cortical division to generate founder cells. Once the set number of founder cells is reached (different between species) the cells begin to divide assymetrically: forming one ventricular zone RG (vzRG) cell and one immature neuron – the immature neuron migrates up the RG fibre.
Cortical layer formoation
After ascending the RG fibres the immature neurons form somewhere between the CP and Marginal Zone to form a cortical layer
IMP not only is the layer position important but also the coloumnar position
Despite being in different layers research found that neurons in the same COLOUMN respond to the same orientation of a bar of light
Congenital Anopthalmia & Cortical development
Removing monkey’s eyes at 60 days old = reduced LG nucleus (1/2) + folds of occipital lobe are completely different
WHY? Hypotheses:
Thalamic input impact the surface area of V1: no eyes, reduced thalamic input, reduced V1 size
The neurons of this area (Area 17) formed a Hybrid Cortex
They have characteristics of area 17 but received input from Area 18
Class 1 Brain Malformations
Class 1 – number of radial units reduced
Happens in first 6 weeks
Reduced surface area as there are reduced number of radial colomnar units for neurons to migrate along
e.g. Microcephaly
Class 2 Brain Malformations
Class 2 – Number of neurons in each radial unit is reduced
After 6 weeks
Occurs due to interference with cell proliferation or migration
Reduced thickness as reduced neurons to migrate
Class 3 Brain Malformations
Class 3 – Malformations of cortical organisation within the 6 layers
Microcephaly
Class 1
Reduced surface area – reduction in number of radial unit coloumns
Non-genetic Causes
Genetic Causes
Zika Virus – potential link; however not solely microcephaly
Nongenetic causes of Microcephaly
Causes:
Nongenetic
- congenital infection with toxoplasma, CMV
- Zika??
- maternal alcohol consumption during pregnancy Genetic
- Autosomal Recessive Primary Microcephaly
Rubenstein Taybi syndrome
Lissencephaly
Smooth Brain
Class 2 BUT
Recent Research: affects a number of stages of Cortical Development
Therefore may also be contributed to by Class 1 malformations: an early occuring event that affects the number of coloumns - they don’t even get to the point of not being able to migrate
2 Types:
Isolated Lissencephaly Sequence (ILS)
Miller-Dieker Syndrome
Isolated Lissencephaly Sequence (ILS)
Type of Lissencephaly
- Severe intellectual disability
- Microcephaly
- Developmental delay
- Recurrent seizures
- Genes: PAFAH1B1, DCX, or TUBA1A
Miller-Dieker Syndrome
Type of Lissencephaly
- Severe intellectual disability
- Developmental delay
- Seizures
- Spasticity
- Hypotonia
- Feeding difficulties
- Distinctive facial features
Polymicrogyria
Signs and symptoms depends on how many brain regions are affected
Its a disruption of the organisation rather than production or migration of the neurons
3 types:
Unilateral Focal Polymicrogyria
Bilateral Polymicrogyria
Bilateral Generalised Polymicrogyria
Late maturation of Sylvian fissure
late maturation of Sylvian fissure is an indication of atypical brain development
Schizophrenia
Disorder of neuronal development
Regions where there are functional differences show a different growth trajectory
Abnormal non-linear growth processes in prefrontal and temporal areas that have previously been implicated in schizophrenia, distinguishing fbetween cortical areas with age-constant deficits in cortical thickness and areas whose maturational trajectories are altered in schizophrenia
