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Download Cortical activity disruptions during sleep and language development
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Introduction to autism research Ilan Dinstein What is the cause of autism? Dendrites Cell body Axon Neural activity Modularity Developmental disorder Brain development movie Nature versus nurture Genes or Environment? Genetics Control > ASD DNA sequencing Control > ASD Identify meaningful mutation Substitution Control > ASD Deletion Insertion 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 Create a genetically modified animal model Compare animals with extremely similar genetics except for a specific modification. Control > ASD Perform behavioral experiments Control > ASD Testing social behavior in mice In vitro electrophysiology Control > ASD In vivo electrophysiology Control > ASD Electrical properties of cells & networks Control > ASD Electrode location Control > ASD Cellular morphology and connectivity Control > ASD What about humans? Human genetics – SFARI, Autism Speaks Neuroimaging – MRI, fMRI, DTI Electrophysiology – EEG Post mortem Human genetics Magnetic resonance imaging (MRI) Anatomy - Separating tissues T1 T2 Anatomy – Cortical thickness Anatomy – Cortical folding Anatomy – white matter Tractography Fiber volume Fiber length Electroencephalogram - EEG Control > ASD Signal = Potential Difference Source of EEG signals What causes potential changes between the electrodes? 1. Synchronized cortical neural activity over large areas (>1cm) – Sources and Sinks. 2. Muscle contractions anywhere in the head. 3. Heart beat (ECG). 4. Electromagnetic noise – AC, Cell phones, etc… Source of EEG signals 1. The larger the synchronicity, the stronger the signal (potential difference). 2. Topography of the brain – Sulci and Gyri. 3. Changing conductance in the brain – CSF, dura, skull (strong resistor). 4. Inverse problem – almost infinite combinations of dipoles can create the same potentials on the scalp. Event Related Potentials Event Related Potentials EEG Frequencies EEG and epilepsy Control > ASD Epileptiform activity Epileptic seizure Spence, Pediatrics Res 2009 Post mortem studies Brain slices: Control > ASD Post mortem studies Cellular morphology Control > ASD Post mortem studies Neural numbers and organization Control > ASD
