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Frontoemporal white-matter
microstructural abnormalities
in adolescents with conduct
disorder.
Sarkar et al. (2013)
MRI
• To create a MRI image, magnetic gradients are used to take advantage
of the specific qualities of hydrogen atoms.
• Can use different gradients to create certain weighted images.
It’s all about Diffusion Tensor Imaging (DTI)
• Diffusion = movement of fluid or gas.
• Water normally diffuses randomly- isotrpic.
• But in the brain water movement is constrained by the structure of
cells axons, like water being pushed through a straw.
• So we can exploit the non-random (anisotropic) nature of water
movement to map out these fibres.
• Yes we can.
But how…
• DTI uses MRI (as it’s structural) but the MR signal is now dependent
on diffusion rather than grey or white brain matter.
• Allows researches to look at the connections, wiring, between brain
regions.
http://www.patient.co.uk/doctor/magnetic-resonance-imaging
Diffusion tensor MR imaging of the brain and white matter
tractograhpy, melhem et al. (2002).
The research
• Children with Conduct disorder are at increased risk of developing
antisocial personality disorders.
• And there’s a strong correlation with substance abuse.
• fMRI studies have reported reduced volumes in the prefrontal cortex
(linked to reduce self-control).
• Yet, the brain is a system and crucial to understand the connections
between the brain.
The Uncinate Fasciulus (UF)
• This is a white matter tract (a straw) that connects the amygdala and
the orbitofrontal cortex.
• Past studies have shown that in children with Anti Social Personaility
Disorder the UF is damaged, with reduced diffusion through the tract.
The big question
• UF damage seems to be linked to antisocial behaviour. Would this be
the case for children with conduct disorder when compared against
peers?
• And if so, there should be reduced diffusion through the UF.
Method
• Participants (27 conduct disorder and 16 controls, aged 12-19).
• As a structural experiment participants just sat in the scanner.
• Used a eight-channel head coil to speed up imaging.
• And luckily the scan only took 15min.
• Also completed a battery of tests measuring anti-social behaviour.
Data pre-processing
• Each image was inspected visually for motion artefacts etc.
• Datasets showing significant movement (> 1 cm) were removed.
• Performed further pre-processing to correct and tease out diffusion
tensor.
DTI
• To define the area of the UF a region of interest approach was used.
With trained operators dissecting the images by hand.
• Operators were blind to the clinical groupings.
• Had a defined area by placing the first and second ROI in a specific
space.
• Long tracts that extended outside frontal and temporal lobes were
excluded as were short tracts that didn’t enter the fixed ROI’s.
Results
• Data analysed using SPSS.
• Repeated-measures analysis was used to test for differences in
diffusion between the clinical and control groups.
• Used the Bonferroni method to correct for multiple comparisons.
Results
• The Conduct Disorder group had significantly greater diffusion in the
left UF than controls.
• Also had greater diffusion in the right UF, but this did not withstand
the correction.
• There was also a significant correlation between the left UF
abnormality and high anti-social scores.
• But no significant differences in a control tract.
Results
Discussion
• So, children with conduct disorder have significantly different
connectivity than controls.
• No differences in control tract suggest no global connection
impairment.
• So result support hypothesis that antisocial behaviour is associated
with abnormal connectivity in limbic connections, rather than global
changes.
• Indicates a biological mechanism for conduct disorder traits.
Discussion
• However, change was in the opposite direction to the hypothesis,
increased diffusion.
• Post-hoc explanation argued that alternated connectivity of the OFC
and the amygdala secondary to the observed changes in the UF might
lead to behavioural disinhibition seen in the clinical group.
• Chicken and the egg question as with the experimental design it is
impossible to say how these abnormalities arise, or if they predict
outcome.
Take home message
• Research used DTI to map the UF tract in children with conduct
disorder and controls.
• The authors found that there was a significant difference, with the
clinical group having greater diffusion (counter to the hypothesis)
through the UF.
• Unclear why or what effect this has on conduct disorder. But there is
an effect.