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Drawing boundaries by hand round “regions of interest” is being superseded by greater use of computers to measure anatomical differences comprehensively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