Using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder
<p>The aim of this thesis was to better understand hyperexcitability and atypical connectivity in Autism Spectrum Disorder (ASD) by using a combination of neuroimaging and histology techniques. Three regions of interest were of particular interest: primary visual cortex, the fusiform gyrus, an...
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| Format: | Thesis |
| Language: | English |
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2015
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| _version_ | 1826310471598211072 |
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| author | Ravishankar, M |
| author2 | Chance, S |
| author_facet | Chance, S Ravishankar, M |
| author_sort | Ravishankar, M |
| collection | OXFORD |
| description | <p>The aim of this thesis was to better understand hyperexcitability and atypical connectivity in Autism Spectrum Disorder (ASD) by using a combination of neuroimaging and histology techniques. Three regions of interest were of particular interest: primary visual cortex, the fusiform gyrus, and dorsolateral prefrontal cortex. These functionally diverse regions have previously been implicated in ASD, and one of the goals was to determine whether the disorder is better characterized by primary sensory deficits or dysfunction in higher-order processing areas.</p> <p>Diffusion Tensor Imaging results across two different datasets suggested that mean diffusivity in the cortex may be sensitive to detect microstructural differences in ASD. Gender and hemisphere were factors that significantly affected diagnostic differences in the first dataset. In the second dataset, ASD individuals (n = 14) compared to Typically Developing (TD) individuals (n = 25) showed reduced mean diffusivity across regions, which may be linked to increased neuropil or neuronal density. Magnetoencephalography findings suggested that both ASD (n = 13) and TD (n = 14) individuals showed no apparent differences in primary visual cortex activity in response to simple visual stimuli, whereas frontal regions of the ASD brain showed more deviations in gamma oscillations, providing some evidence for the executive dysfunction theory of ASD. Magnetic Resonance Spectroscopy results revealed elevated glutamate levels in primary visual cortex and medial prefrontal cortex in ASD (n = 11) compared to TD individuals (n = 13), as well as elevated creatine levels in the medial prefrontal cortex, which may be linked to hyperactivity of glial cells. ASD individuals also showed superior performance on a visual task, which correlated with glutamate levels in medial prefrontal cortex, and both of these measurements correlated with autism severity scores, providing evidence for the specificity of these findings to the disorder.</p> <p>Immunohistochemistry was used to study the distribution of parvalbumin cells – a subset of fastspiking GABAergic cells – in 14 ASD and 15 TD post-mortem cases. No significant group differences were found in any of the three regions of interest. These results taken together with the neuroimaging findings support the idea that hyperexcitability in ASD is a complex interplay between several cell-types.</p> |
| first_indexed | 2024-03-07T07:52:26Z |
| format | Thesis |
| id | oxford-uuid:11b6b56b-118f-49ca-9082-399e98781151 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:52:26Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | oxford-uuid:11b6b56b-118f-49ca-9082-399e987811512023-08-02T11:55:28ZUsing neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorderThesishttp://purl.org/coar/resource_type/c_bdccuuid:11b6b56b-118f-49ca-9082-399e98781151NeuropathologyPsychiatryMedical sciencesAutismNeuroscienceEnglishOxford University Research Archive - Valet2015Ravishankar, MChance, SNewton, C<p>The aim of this thesis was to better understand hyperexcitability and atypical connectivity in Autism Spectrum Disorder (ASD) by using a combination of neuroimaging and histology techniques. Three regions of interest were of particular interest: primary visual cortex, the fusiform gyrus, and dorsolateral prefrontal cortex. These functionally diverse regions have previously been implicated in ASD, and one of the goals was to determine whether the disorder is better characterized by primary sensory deficits or dysfunction in higher-order processing areas.</p> <p>Diffusion Tensor Imaging results across two different datasets suggested that mean diffusivity in the cortex may be sensitive to detect microstructural differences in ASD. Gender and hemisphere were factors that significantly affected diagnostic differences in the first dataset. In the second dataset, ASD individuals (n = 14) compared to Typically Developing (TD) individuals (n = 25) showed reduced mean diffusivity across regions, which may be linked to increased neuropil or neuronal density. Magnetoencephalography findings suggested that both ASD (n = 13) and TD (n = 14) individuals showed no apparent differences in primary visual cortex activity in response to simple visual stimuli, whereas frontal regions of the ASD brain showed more deviations in gamma oscillations, providing some evidence for the executive dysfunction theory of ASD. Magnetic Resonance Spectroscopy results revealed elevated glutamate levels in primary visual cortex and medial prefrontal cortex in ASD (n = 11) compared to TD individuals (n = 13), as well as elevated creatine levels in the medial prefrontal cortex, which may be linked to hyperactivity of glial cells. ASD individuals also showed superior performance on a visual task, which correlated with glutamate levels in medial prefrontal cortex, and both of these measurements correlated with autism severity scores, providing evidence for the specificity of these findings to the disorder.</p> <p>Immunohistochemistry was used to study the distribution of parvalbumin cells – a subset of fastspiking GABAergic cells – in 14 ASD and 15 TD post-mortem cases. No significant group differences were found in any of the three regions of interest. These results taken together with the neuroimaging findings support the idea that hyperexcitability in ASD is a complex interplay between several cell-types.</p> |
| spellingShingle | Neuropathology Psychiatry Medical sciences Autism Neuroscience Ravishankar, M Using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder |
| title | Using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder |
| title_full | Using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder |
| title_fullStr | Using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder |
| title_full_unstemmed | Using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder |
| title_short | Using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder |
| title_sort | using neuroimaging and histology to understand hyperexcitability and atypical connectivity in autism spectrum disorder |
| topic | Neuropathology Psychiatry Medical sciences Autism Neuroscience |
| work_keys_str_mv | AT ravishankarm usingneuroimagingandhistologytounderstandhyperexcitabilityandatypicalconnectivityinautismspectrumdisorder |