Date on Master's Thesis/Doctoral Dissertation

12-2010

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Committee Chair

Casanova, Manuel F.

Author's Keywords

Autism; TMS; EEG; ERP; Attention; Gamma

Subject

Autism--Physiological aspects

Abstract

Evidence suggests that cortical minicolumns are reduced in size and increased in number in individuals with autism spectrum disorder (ASD), especially in the dorsolateral prefrontal cortex (DLPFC). More specifically minicolumns in individuals with ASD are narrower and contain less peripheral, neuropil space; this may cause an increase in the ratio of cortical excitation to inhibition and adversely affect the functional distinctiveness of minicolumnar activation. A lack of cortical inhibition may cause signal/sensory amplification which can impair functioning, raise physiological stress, and adversely affect social interaction in patients with ASD. Additionally, the DLPFC forms a circuit interconnected with many areas of cortex (e.g., anterior cingulate, orbitofrontal) and is involved in selecting a possible range of responses while suppressing inappropriate ones. Low-frequency (:'SlHz) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. The baseline hypothesis was that individuals with ASD would show electroencephalopgrahic (EEG) and event-related potential (ERP) evidence of amplified cortical activity at early and late stages of visual processing as well as impaired indices of selective attention. The second hypothesis was that low-frequency rTMS would reduce augmented cortical responses at early stage and late stages of visual processing and improve selective attention and behavior in ASD. The baseline findings indicate both ERP and evoked gamma activity are amplified and indiscriminative in ASD at early stages of visual processing which may reflect decreased 'signal to noise' due to decreased cortical inhibitory processing. Additionally, individuals with ASD showed evidence of compromised selective attention, and had a significantly higher rate of motor response errors. After low-frequency rTMS individuals with ASD showed significant reductions in augmented ERP responses at very early stages of visual processing and showed significant improvement in discriminatory EEG gamma activity. There was also evidence of improved ERP indices of selective attention and significant reductions in irritability and repetitive behavior. TMS has the potential to become an important therapeutic tool in ASD treatment and has shown significant benefits in treating core symptoms of ASD with few, if any side effects.

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