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Title: Magnetoencephalography and neuropathological studies of autism spectrum disorders and the comorbidity with epilepsy
Author: Menassa, David Antoine
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2013
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Autism spectrum disorders (ASD) are neurodevelopmental disorders with multiple neurobiological aetiologies, which could be genetic, structural, metabolic or immune-mediated. ASDs are diagnosed with deficits in social communication and restricted and repetitive behaviours, and are associated with sensorial atypicalities. 30% of cases have co-existing epilepsy. A series of in vitro, in vivo and post-mortem investigations were undertaken to examine sensory atypicalities in ASD. In vitro characterisation of hippocampal neuronal cultures using immunofluorescence demonstrated the presence of multiple cell types including neurons, astrocytes and microglia. The distribution of ion channels of the Shaker family and tumour necrosis factor α receptors in astrocytes and neurons were identified but not explored further. Neuroanatomical and neuropathological investigations of primary olfactory cortex, using post-mortem stereology, demonstrated a specific increase in glial cell densities in layer II, which was negatively associated with age in ASD. Increases in glia were also associated with symptom severity and often co-localised with the presence of corpora amylacea in layer I. Qualitative analysis of the olfactory tubercle demonstrated that corpora amylacea did not extend to this neighbouring region of the primary olfactory cortex in ASD. These changes were independent of co-existing epilepsy and not observed in epilepsy without ASD. Preliminary pilot studies of the hippocampus provided a stereological sampling strategy to quantify cell densities in future investigations of this area in ASD. Neurophysiological investigations using collected magnetoencephalography data demonstrated diminished occipital gamma oscillatory synchrony in ASD in a visual time perception task. This did not always predict behavioural outcome but was specific to ASD and could not be explained simply in terms of changes in task performance. Moreover, changes in oscillatory synchrony were associated with symptom severity. These observations in primary sensory domains in post-mortem tissue and in patients suggest possible novel mechanisms in ASD and extend knowledge of the neurobiological bases of these disorders.
Supervisor: Vincent, Angela; Braeutigam, Sven; Chance, Steven Sponsor: Clarendon Fund
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medical Sciences ; Anatomy ; Pathology ; Neuroscience ; Neuropathology ; Neuropsychology ; Psychiatry ; Autism ; Child and adolescent psychiatry ; Experimental psychopathology ; Neurology ; Psychology ; Behavioural Neuroscience ; Clinical Neuropsychology ; Cognitive development ; Developmental psychology ; autism spectrum disorders ; epilepsy ; neurophysiology ; magnetoencephalography ; stereology