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Autism Genetics

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  • 1. What does the brain look like in autism? Ed Bullmore National Autistic Society Meeting: September 2002, London
  • 2. What do we think the brain looks like? Gall, c. 1800 Freud, 1898
  • 3. What does the brain ideally look like? Of course, really the brain is dynamic and individually variable…
  • 4. Magnetic resonance imaging One scanner can safely take pictures of brain structure and function
  • 5. Contrasting experimental stimuli cause changes in local brain blood supply which are measured by rapid, repeated measurements of MR signal, and statistically mapped onto brain anatomy www.fmrib.ox.ac.uk Pierce et al (2001) Brain Psychology Physics Statistics
  • 6. Modules and Networks
  • 7. The Social Brain Brothers (1990) Facial perception Affect recognition Social judgement Mentalizing Gaze detection
  • 8. Social brain function in autism Simon Baron-Cohen et al (1999) European Journal of Neuroscience Assigning mental states to eyes-only facial stimuli activates amygdala, superior temporal, dorsal cingulate and frontal brain regions
  • 9. Abnormal amygdalar response to fearful faces in people with Asperger’s syndrome Chris Ashwin et al (2002) Normal amygdalar activation Attenuated amygdalar activation in autism Experimental stimuli: Faces expressing variable intensities of fear Attenuated orbitofrontal activation in autism Random Neutral 25% Fear 100% Fear
  • 10. Mind blindness and the brain Uta Frith (2001) Neuron Consistent activation by mentalizing tasks of medial frontal (paracingulate), temporo-parietal and peri-amygdaloid cortex
  • 11. Brain mechanisms for preserved or superior function in autism Howard Ring et al (1999) Brain People with autism may be better at local processing and activate ventral occipital coretx more strongly during embedded figures task performance
  • 12. Conscious and unconscious social processing Hugo Critchley et al (2000) Brain Automatic and deliberate facial processing activate different brain systems
  • 13. Measuring brain structure in MR images Drawing boundaries by hand round “regions of interest” is being superseded by greater use of computers to measure anatomical differences comprehensively
  • 14. Computational mapping of anatomical abnormalities in autism Grainne McAlonan et al (2002) Brain Grey matter White matter
  • 15. Neurodevelopmental trajectories in brain structure Eric Courchesne et al (2001) Neurology McAlonan et al (2002) Brain
  • 16. Where next in neuroimaging of autism?
    • Genetics
      • diagnostic reconstruction
    • Intervention/compensation
      • education, training, savant skills
    • “ Autism at large”
      • life-cycle changes, autistic spectrum, preventable risk factors
  • 17. Genetic neuroimaging
    • Genetic effects on brain structure and function can be studied using
    • family or twin designs
    • or knowledge of single gene mutations or polymorphisms
    Wright et al (2002) NeuroImage Ellison et al (2002)
  • 18. Intervention/compensation FMRI can show recovery of brain function following (drug) treatment in schizophrenia… what about recovery of function following educational interventions in autism? Honey et al (1999) PNAS
  • 19. Autism at large Sigmundsson et al (2000) American Journal of Psychiatry
    • Autism is a heterogeneous disorder and different kinds or degrees of autism will likely have different brain correlates
    • autistic traits in general population
    • variability in autistic traits over life-cycle
    • preventable risk factors
  • 20. Conclusions
    • Neuroimaging has identified a social brain network and shown that the social brain does not function normally in people with autism
    • Neuroimaging has also begun to explain why people with autism may have superior skills in some domains and/or how they may consciously compensate for social brain abnormalities
    • It would be timely to consider larger-scale imaging studies in autism focused on genetic and environmental causes, and on clinical autism as an extreme variant of normal brain development trajectories.
  • 21. http://www.psychiatry.cam.ac.uk/bmu