lecture 15- brain development part 2

Question 1

Gray and white matter

Answer 1

• Gray matter: neuron soma (cell body) and dendrites

- White matter: glial cells and the myelinated axons of the neurons

Question 2

Principles

Answer 2

Childhood and adolescence are periods of significant change
Behaviour, emotion, hormones, cognition
Brain function is inherently linked with brain structure
Different parts of the brain develop at different rates
Maturation of the commissures and projection fibres occur earliest in development
Association fibres continue to mature at later ages
Fronto-temporal connections have the most prolonged development
Longitudinal studies provide data of age-related changes within an individual
Many psychiatric disorders emerge during late adolescence, which may be related to abnormal brain development (and genetics, epigenetics, environmental factors)

Question 3

Commissures

Answer 3

• A point or line of union between two anatomical parts
  Anterior commissure; posterior commissure; corpus callosum; habenular commissure (near pineal gland); hippocampal commissure

Question 4

Projection fibres

Answer 4

– nerve fibres that connect the cerebral cortex with lower sensory or motor centres

Question 5

Association fibre

Answer 5

nerve fibres that connect different parts of the brain, especially within each hemisphere

Question 6

Fronto-temporal connections

Answer 6

– connections between the frontal and temporal lobes

Question 7

structure

Answer 7

First longitudinal tractography study of brain development from childhood to adulthood
Diffusion Tensor Imaging (DTI) tractography method used with data
from 103 healthy subjects
221 scans from childhood to young adulthood (5-32 years)
92 people with 2 scans; 7 with 3 scans; 4 with 4 scans
Mean age between first and second scan was 4.0 years
Commissural, projection and association white matter tracts
Brain volume – total brain, gray and white matter volumes
Tract volume – functional anisotropy (FA) reflects axon packing and myelination; mean diffusivity (MD) reflects water content and density of white matter

Question 8

brain volume

Answer 8

White matter volume increased significantly across the age range.

Gray matter volume decreased across the age range.

White matter increases were offset by gray matter decreases, so there was no overall change in total brain volume with age.

Question 9

Conclusions from this study

Answer 9

-Development occurs for most children across all 10 major white matter tracts studied
-This development continues during the twenties in several association tracts
Inferior and superior longitudinal and fronto-occipital fasciculi
-These tracts support complex cognitive processing – inhibition, executive functioning, attention
-White matter increases and gray matter decreases in most subjects across age
-Increase in white matter presumably reflects myelination…whilst the decrease in gray matter presumably reflects synaptic pruning and myelination

Question 10

what about function

Answer 10

-In line with structural development, functional MRI studies show progressive increases with age between childhood and adulthood in activation and functional inter-regional connectivity of task-relevant brain areas
-Also, there is a progressively stronger deactivation of the resting state network with age; suggestive of more mature brain activation
-Children have more short-range connections between areas
…these are progressively replaced by longer-range connections in adulthood

Question 11

Response inhibition

Answer 11

Orange areas show progressive increase in activation with age; Blue areas show progressive decreases in activation with age.

Frontal regions show increased activation with age, whilst posterior and limbic regions show a decrease in activation with age
Orange areas show progressive increase in activation with age; Blue areas show progressive decreases in activation with age.

Progressively more right dorsal and inferior lateral prefrontal regions are recruited with increasing age.

Diminishing recruitment of medial frontal activation with age (may reflect enhanced deactivation of default mode network)

Question 12

What about networks?

Answer 12

Changes in synaptic connectivity and axonal myelination are among the very important microscopic changes occurring in development
Changes in cortical thickness and white matter volume are well-replicated measures of macroscopic development
It is reasonable to assume that connections between cells at both the micro and macro scale occur also, during development
Cognitive processes rely on large-scale networks of brain areas. These networks may not necessarily by directly connected to each other
It is reasonable to assume that the behavioural changes we see in childhood and adolescence are accompanied by major changes in anatomical and functional brain networks

Question 13

graph theory

Answer 13

Graph theoretical models have been used to analyse the development of brain networks
Collection of nodes interconnected by edges
On the microscale, nodes could be neurons and the edges could be synapses
On the macroscale, nodes could be brain regional volumes and edges could be measures of structural or functional connectivity between regions
These brain graphs could be used to estimate network properties – distance between connected nodes, resilience to attack
Can incorporate data from electrical recordings, fMRI, EEG etc

Question 14

Network properties

Answer 14

Same mathematical language can be used to assess networks at different scales
Can identify scale invariant aspects of networks and shared organisational properties
E.g. small-world phenomenon: networks are simultaneously highly clustered and highly efficient
Nodes connected to each other are likely to have many neighbours in common
Average path length between a pair of nodes is short

Question 15

nodes

Answer 15

The degree of a node is the number of links or connections it has with the rest of the network.

Most nodes in the brain only have a few connections, but a few nodes are extensively connected.

These high-degree nodes are referred to as “rich” nodes.

These nodes have a tendency to preferentially connect to one another, forming an elite group of nodes called a “rich club”.

Question 16

node paths

Answer 16

The minimum path length between two nodes is the minimum number of edges that need to be traversed from one node to another.

Real-world networks tend to have low average path length, facilitating the flow of information between distant parts of the network.

Networks that have a small average path length from one node to another have high global efficiency.
Local efficiency is found through triangular connections around nodes
Many complex networks have a modular community structure.
Subsets of highly interconnected nodes called modules.
They may represent biological functional units.

Question 17

Schizophrenia example

Answer 17

Brain dysfunction may result from abnormal wiring of the brain’s network
Wernicke and Bleuler both suggested that SCZ may be associated with disrupted brain pathways
DTI and fMRI studies suggest widespread disconnectivity, especially between frontal and temporal white matter connections
Hyp: disturbed wiring of central “rich club” may contribute to pathophysiology of SCZ

Question 18

Method

Answer 18

48 patients and 45 controls
Replication with an additional 41 patients and 51 controls
Created structural and functional (resting state fMRI) connectivity networks per person
Graph analysis of structural network
Degree of strength, clustering coefficient, shortest path length, efficiency, modularity
Rich club – when highly connected hubs of a network are more densely connected among themselves than predicted
Looked at coupling between structural and functional connectivity

Question 19

Summary of Rich Club study

Answer 19

Patients with SCZ showed a reduced level of rich club interconnectivity…supporting the notion that SCZ is associated with a disturbance in structural connectivity in the brain
Rich club areas play a central role in integrating information from different sources in the brain
Problem with global brain communication
No clear association between clinical metrics of patients and rich club organisation, however, suggesting a complex relationship between connectome abnormalities and clinical symptoms

Question 20

Summary

Answer 20

• Networks seem to be topologically complex at birth. -Their organisation changes over childhood and adolescence from a local architecture (dominated by sensory and sensorimotor areas) to a more diffuse topology
• These changes are underpinned by two processes:
• Synaptic pruning (leads to decreases in local connectivity and gray matter volume)
• Progressive myelination of long-range connectivity (contributes to anatomical connectivity and increased white matter volume, and increases in functional correlations between regions in the brain)