Brain Donation and the BRAIN BANK for AUTISM & Related Developmental Research Dr Jenny Longmore PhD Director of Research and Programmes, Europe Autism Speaks NAS Research Into Practice Conference 20 th September Freephone

Agenda Introductions Why the need for brain research Latest research findings About the Brain Bank for Autism & Related Developmental Disorders About brain donation

Unravelling autism The brain is a useful place to start Research is needed: to understand the causes and biological basis of autism through that understanding develop new interventions help those affected by autism spectrum disorders This it cannot be achieved without using human tissue Finding the causes of a wide variety of disorders and conditions and better interventions is a concern for us all.

Some emotional and behavioural problems associated with autism Epilepsy / seizures Mood – aggression, irritability, tantrums, self injury, anxiety, depression ADHD OCD / impulsiveness Sensory issues - light, sound, pain, taste, smell, balance Cognition, intellectual disability, memory, attention Sleep Eating Gastrointestinal Most involve the brain

The Brain is the Control Room

Based on meta-analysis of 15 studies published by Redcay and Courchesne 2005 Course of brain development is altered in autism Head (brain) size autism v ‘normal ’ mmmmmmmmmmm

Based on meta-analysis of 15 studies published by Redcay and Courchesne 2005 Course of brain development is altered in autism Head (brain) size autism v ‘normal ’ mmmmmmmmmmm Latest findings suggest (Amaral et al 2008): 5-10% enlarged brain volume for children aged 18months to 4 years (but needs confirmation in a properly designed study)

Methodologies to examine the brain Structural imaging eg MRI magnetic resonance imaging - safe, non-invasive - gross neuroanatomy - ‘older’, higher functioning individuals with autism Functional imaging eg MEG magnetoencephalography - safe, non-invasive - function Post mortem / microscopic examination - high resolution - understand underlying neurobiology - number of neurons, synapses, connections, chemistry

Autism and the cerebellum: an example of the power of combined research methodologies Autism: 16y maleNeurotypical: 16y male The cerebellum is smaller (hypoplasia) in autism Adapted from Palmen et al 2004 Structural (MRI) Brain Imaging

Microscopic examination of the cerebellum

Reduced number of cerebellar Purkinje neurones in autism Microscopic structure of the cerebellum What does it mean? – movement, planning fine movement, sensory processing, higher functions? AutismNeurotypical From Bailey et al 1998

Central role of the amygdala in emotion / fear processing

Autism and the amygdala Highly relevant brain area: Production and recognition of emotions (e.g. fear) MRI imaging shows amygdala is enlarged in children with autism From Schumann et al 2004 Post mortem: Amygdala reaches ‘adult size’ by age 8 Fewer neurones in amygdala but only in lateral sub division

‘No consistent post-mortem brain tissue findings in autism’ Reasoning behind this opinion? The disorder is heterogenous: Multiple causes and courses Range of severity of symptoms and impact Associated problems The science: Different brain areas Different methodologies Low sample size Lack of knowledge to interpret the data

Cerebellum pathology most consistent neuropathological finding relevance - sensory processing, movement, learning? how? why? when? Course of brain development is altered in autism some brain areas involved Emerging consensus of neuropathology but many unanswered questions The scarcity of human brain tissue hinders critical research