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Introduction to autism research Ilan Dinstein
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What is the cause of autism?
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Dendrites Cell body Axon
חומר אפור ולבן, תאים וקישורים בין תאים - מיילין. Axon
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Neural activity
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Modularity
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Developmental disorder
Brain development movie
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Nature versus nurture Genes or Environment?
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Genetics Control > ASD
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DNA sequencing Control > ASD
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Identify meaningful mutation
Substitution Control > ASD Deletion Insertion
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Determine the function of the gene
What is the function of the protein that the gene encodes? Is it involved in neural transmission? Neural development? Synaptic development? Bourgeron 2009
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Create a genetically modified animal model
Compare animals with extremely similar genetics except for a specific modification. Control > ASD
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Perform behavioral experiments
Control > ASD Testing social behavior in mice
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In vitro electrophysiology
Control > ASD
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In vivo electrophysiology
Control > ASD
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Electrical properties of cells & networks
Control > ASD
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Electrode location Control > ASD
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Cellular morphology and connectivity
Control > ASD
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What about humans? Human genetics – SFARI, Autism Speaks
Neuroimaging – MRI, fMRI, DTI Electrophysiology – EEG Post mortem
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Human genetics
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Magnetic resonance imaging (MRI)
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Anatomy - Separating tissues
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Anatomy – Cortical thickness
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Anatomy – Cortical folding
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Anatomy – white matter Tractography Fiber volume Fiber length
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Electroencephalogram - EEG
Control > ASD
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Signal = Potential Difference
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Source of EEG signals What causes potential changes between the electrodes? Synchronized cortical neural activity over large areas (>1cm) – Sources and Sinks. Muscle contractions anywhere in the head. Heart beat (ECG). Electromagnetic noise – AC, Cell phones, etc…
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Source of EEG signals The larger the synchronicity, the stronger the signal (potential difference). Topography of the brain – Sulci and Gyri. Changing conductance in the brain – CSF, dura, skull (strong resistor). Inverse problem – almost infinite combinations of dipoles can create the same potentials on the scalp.
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Event Related Potentials
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Event Related Potentials
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EEG Frequencies
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EEG and epilepsy Control > ASD Epileptiform activity
Epileptic seizure Spence, Pediatrics Res 2009
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Post mortem studies Brain slices: Control > ASD
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Post mortem studies Cellular morphology Control > ASD
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Post mortem studies Neural numbers and organization Control > ASD
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