Date on Master's Thesis/Doctoral Dissertation
Anatomical Sciences and Neurobiology
Casanova, Manuel F.
Autism; ASD; Cortical width; Cortical thickness
Corpus callosum; Diagnostic imaging; Autism--Diagnosis; Autism--Physiological aspects
Autism Spectrum Disorders (ASD) are a group of conditions characterized by a broad spectrum of deficiencies related to social communication, both verbal and non-verbal, as well as repetitive behaviors such as rocking back and forth, or arm flapping. This devastating group of disorders affects millions of people regardless of their socioeconomic, ethnic and racial backgrounds. Among other issues such as migraines, sensory deficits and intense aggression, epilepsy is a major neurological disorder very highly associated with ASD; roughly one third of all ASD patients are diagnosed with epilepsy, and a much higher proportion suffer from at least one seizure in their lifetime. Past neuropathological studies have suggested various deformities in the brains of ASD patients, ranging from abnormal brain volume, and head circumference, to the presence of atrophy and cortical dysplasias, such as heterotopias. Other more cellular abnormalities have also been speculated, including neurotransmitter imbalances, as well as neuron proliferation and organization disturbances. Though many intricate techniques have been attempted in order to investigate the etiology and potential treatments of ASD pathology, the results have been inconclusive and highly arguable. This especially applies to magnetic resonance imaging (MRI) studies of cortical thickness, which have produced highly questionable and inconsistent information; researchers have attributed this to the potential instability of the mode of research. Due to the limitations on the resolution of MRI, it is difficult to directly compute the location of the pial surface, which creates difficulty in delineating the cortical gray matter from the subcortical white matter. The goal of our study was to indentify cortical dysplasias, and then to analyze the neuromorphology of the same areas. In order to accomplish this, we retrieved post-mortem tissue from the Autism Tissue Program, and measured the cortical thickness by solving the Laplace equation, followed by the application of the Boolean model and granulometry to determine the potential abnormalities of ASD neuronal morphometry. We found multiple dysplasias in various brain regions, predominantly within the pre-frontal cortex, which correlated nicely with the symptomology of ASD. The anterior commissure (AC) served as the landmark to delineate the prefrontal cortex; when compared with neurotypical tissue, the ASD tissue was thinner surrounding the AC. Upon further analysis of the dysplastic processes, our findings confirmed the presence of smaller, but more numerous pyramidal neurons in the ASD brain when compared with neurotypicals. These findings are also substantial in terms of explaining two of the more prominent issues associated with ASD: aggressive behavior and frequent seizures. Overall, the findings of the current study do support several previous reports and provides further evidence of problematic cortical development and ASD symptom manifestation.
Kamat, Shweta Sunil, "Post-mortem analysis of cortical thickness and neuronal morphometry in autism." (2013). Electronic Theses and Dissertations. Paper 722.