Download - Autism Genetics
What does the brain look like in autism?
Ed Bullmore
National Autistic Society Meeting: September 2002, London
What do we think the brain looks like?
Gall, c. 1800 Freud, 1898
What does the brain ideally look like?
Of course, really the brain is dynamic and individually variable…
Magnetic resonance imaging
One scanner can safely take pictures of brain structure and function
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
Modules and Networks
The Social BrainBrothers (1990)
Facial perception
Affect recognition
Social judgement
Mentalizing
Gaze detection
Social brain function in autismSimon 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
Abnormal amygdalar response to fearful facesin 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
Mind blindness and the brain Uta Frith (2001) Neuron
Consistent activation by mentalizing tasks of medial frontal (paracingulate), temporo-parietal and peri-amygdaloid cortex
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
Conscious and unconscious social processingHugo Critchley et al (2000) Brain
Automatic and deliberate facial processing activate different brain systems
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Drawing boundaries by hand round “regions of interest” is being superseded by greater use of computers to measure anatomical differences comprehensively
Computational mapping of anatomical abnormalities in autism
Grainne McAlonan et al (2002) Brain
Grey matter White matter
Neurodevelopmental trajectories in brain structure
Eric Courchesne et al (2001) Neurology McAlonan et al (2002) Brain
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
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)
Intervention/compensation
+31mm +37mm +42mm +48mm
Generic Brain Activation Maps
ANCOVA
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
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
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.
http://www.psychiatry.cam.ac.uk/bmu