Lecture 3 Flashcards
the human brain has a mass of ____g and has ____ billion neurons
1500; 90
the cerebral cortex has:
1. ___ billion neurons (___% of all neurons)
2. ____ trillion synapses (9.5 connection/neuron)
3. _____km of white matter axons
16; 20-50%
150
160,000
the cerebellum has ___ billion neurons (___% of all neurons)
69; 50-80%
subcortical structures contain ___ billion neurons (___% of all neurons)
0.7; 0.8%
brain architecture is also known as brain ___
structure
the brain is __% of body mass
the brain consumes ___% of body energy consumption
changes in region specific activity only account for <__% of baseline activity
2; 20; 5
how does brain development relate to synaptic density?
looks like a log function (increases, then slowly decreases)
how does brain development relate to grey-matter density?
normalized at 15 years of age
see peaks in grey matter earlier in life (6yo), with slight decline, showing that the brain is always refining
which founding father of the MRI did experiments on himself?
Peter Mansfield
what are the changes in what we see using a 1) 0.1T, 2) 1.5T and 3) 7T?
1) general form
2) see how parts are connected (great contrast)
3) see sub-ml structure and blood vessels
what is the temporal/spatial resolution of 1)aMRI, 2)fMRI, 3)FDG-PET, 4)EEG/MEG?
1) great spatial res (sub-milimetric), bad temporal res (days/weeks)
2) OK spatial res (millimetres) and pretty good temporal res (ms-s)
3) not great spatial res (ml-cm) and OK temporal res (minutes)
4) worst spatial res (cm), best temporal res (ms)
how does the aMRI work?
- differences in density are all product of how you manipulate water in a magnet
- this works since the brain is mostly made up of water
- manipulate the H atoms in the water (each have proton in nucleus) -> protons can be manipulated by the magnet
what are the nuclear spin systems?
Collection of identical nuclei (regardless of environment)
___% of the human body is water
____% of the human brain is water
H atoms are abundant throughout the human ____
57% of the human body is water
75-78% of the human brain is water
H atoms are abundant throughout the human body
protons in H have ___, ___ and are ____ charged
mass, spin positively
what happens when a proton is left alone?
wants to precess (magnetic moment), so it sits around and rotates, creating current (since its charged)
what is the magnetic moment vector?
in presence of no mag field, each magnetic moment live with no preferred direction
in field, the moments align in the direction of the field
explain: μ = ϒϕ
μ: tendency of a proton to align with magnetic field
ϒ: gyromagnetic ratio
ϕ: angular momentum
what is nuclear magnetism?
Macroscopic alignment of a spin system in the presence of a magnetic field
(once we have the alignment, can add another pulse which pushes the alignment a bit -> ask what properties occur when they try to go back in the right direction)
explain what happens during the application of a RF field
B1 is a radiofrequency field tuned to the Larmor Frequency and applied in the transverse lane (ie: x,y) plane
The bulk magnetization (M) tips away from the z-axis and towards the x,y plane (also at the Larmor Frequency)
B0 causes M to precess
around B0
The Larmor Frequency (ω0) is the frequency of the precession
what is the main source of signal/contrast in the mri?
so they start to rotate down in the x-y plane, measure how long it takes it to do that or come back
basic fundamentals to understanding how we get a signal
why structural mri ? (3)
Acquisition: Detailed, Reliable and Reproducible
Analysis: Flexible and Multi-featured
Underlying biology: Dynamic rather than Static
what is acquisition?
measure brain changes in response to drugs or things happening in short period of time
subtle changes detected in vivo
who invented the mri and how many Nobel prizes were given?
Laterbur, Mansfield
2
why do we use an integrated neuroscience approach?
think about how brain may change in response to diff functions of life
what brain morphology can be detected in vivo?
tissue classification, white-matter density, deformation field, segmentation, cortical thickness, cerebral sulci
what are caveats?
choice of acquisition protocol (FLASH, MPRAGE, MDEFT) -> differences in contrast
why do we use caveats ?
since u manipulate water, lot of free parameters u can use
same person scanned with three diff parameters
same algorithm set to work on mri data can give different answers based on which parameter used to acquire it (keep in mind)
what is the MNI space?
need common coordinate frame -> how homologous anatomy is over time — need way to create this reference system
how was the MNI space derived?
initially derived by aligning 300 brains and saying that this is the normative anatomy of the brain
can then look at mean morphology
what is the common work flow? (5)
- principle is the same — you get volume from scanner and want to align it to a space
- normalize it across scans
- do some linearization/transformation
- use algorithm to classify the grey and white voxels
- smooth out and by voxel/voxel level, run stats (color map — high = lot of difference)
how do you detect changes in cortical thickness?
surface representation is just points in space
- can go and measure differences btw white and black matter surface
- can then put this in a color map
algorithm creates mesh
- see points that define the surface (edges of triangles)
- ask algorithm to fold the sphere to match the voxel representation of the white matter
- constantly creating more points that allow it to fold more
- big brain morphologies are the ones done earlier on
what was the conclusion of the study on brain morphology and individual history?
one fold increase in terms of brain volume in rats housed in the complex house
explain the study on the V5 and juggling
made people learn to juggle
scan1-2 increase in grey matter (region V5 —> regions is like motor and visual)
sees rapid growth (3% change) in this part of the brain over time
then asks people to stop juggling and three months later → this part of the brain is still enlarged compared to baseline
explain the study on musicianship and the brain
differences in brains of musicians (uni level) vs control
see increased cortical thickness in PFC and regions involved in working memory and involved in sound processing
representation is far more compact (not diffuse)
suggests that years of training have specific imprint on the brain that doesnt exist in non-musicians
what has neuroimaging taught us about the brain’s development?
brain changes a lot in early life
things that change are grey matter, myelin, white matter concentration
brain is continuously refining across lifespan
white matter conc peaks in end middle age
explain the study on adhd and cortical thickness
brain matures later in adhd kids
in PFC there’s almost a 3y delay of reaching cortical thickness as normal developing kids
what are the grey matter deficits in childhood onset schizophrenia (COS)?
- parietal-frontal progression of GM loss during adolescence (from age 12-16)
- GM loss declines and is circumscribed to prefrontal and temporal cortices by age 24
how is GM affected in siblings of COS patients?
healthy COS siblings show cortical GM deficits in early ages that NORMALIZE by age 18
is ASD homogeneous or heterogenous?
heterogenous; many factors contribute
what are the sex differences in ASD prevalence?
prevalence: 1 in 68
The ratio of males to females diagnosed is about 4:1 (more pronounced in higher functioning (6-9:1), but closer in lower functioning (2:1))
what theory might explain the gender differences in ASD?
female protective effect hypothesis
what is the female protective effect hypothesis? (4)
States that females may be protected against neurodevelopmental disorders
May take more autism risk factors (genetic or environmental) to manifest the autistic phenotype
Females have higher threshold for the amount of genetic liability or risk factors needed to cause autism (dotted line), so affected less often than males
Supported by the fact that, presumably due to this higher burden or number of risk factors, when females are affected, tend to be more severe
how does cortical thickness and age affect asd? (3)
Other studies have examined the neuroanatomy of autism into development and adulthood and found significant effects, in particular cortical thickness
But inconsistent: many studies have found greater thickness in individuals with ASD, but others have found thinner cortex or no differences.
age seems to be more important: found greater CT but effects normalize with age
how might IQ and cortical thickness relate to asd?
may have moderating effect: CT positively correlated with IQ in controls, but not in ASD (no or negative relations)
what is the impact of motion on cortical morphometry?
Participant motion is:
Associated with reduced average cortical thickness
Higher in clinical populations
More strongly correlated with CT than volumetric estimates
what is the quality control procedure for motion?
Assign motion score (4 point scale)
Two independent raters of motion
→ QC manual, trained raters, checked reliability after first 100 scans
→ Consensus score
Objective exclusion cut-off
looking for ringing and blurring
what is the vertex-wise meta-analysis technique?
Random effects meta-analysis used to account for inter-site differences and heterogeneity of sample
Multiple linear regression across 80,000 vertices conducted within each site
Cohen’s d effect size calculated per site at each vertex and pooled in meta-analysis
False Discovery Rate (FDR) for multiple comparisons correction
what is advantageous of the vertex-wise analysis? (2)
allows to treat sites as separate studies and analyse that way
to avoid confounds of scanner and variability of demographics between sites
what is the diagnosis main effect in CT and adhd? (3)
First, we looked at the main effect of DX in all subjects, controlling for age and sex, and found widespread increases in CT across in the brain in ASD
These are maps of q-values across the brain, regions where significant diffs between ASD and controls - all increases in ASD
All coming slides are 5 or 10% FDR, and min 1%, all increases in ASD
what sex differences in ASD did they find in the study (using vertex analysis)?
We then broke this down to look at males and females separately, and here is what we found in the males – shown at 10% FDR
Again, increases in CT, primarily in inferior frontal and superior temporal regions.
Finally as cubic, effects even stronger, still strongest at 8, decreasing at 12 and 16, still small areas of significance visible at 20 (drop after 40)
