| Author: | Chan, Mei Yan Melody |
| Title: | Predicting treatment response of transcranial direct current stimulation in autism spectrum disorder |
| Degree: | Ph.D. |
| Year: | 2022 |
| Subject: | Autism -- Treatment Brain stimulation -- Therapeutic use Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Rehabilitation Sciences |
| Pages: | 219 pages : color illustrations |
| Language: | English |
| Abstract: | Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder that currently affects 1 in 100 children across the globe. These individuals are found to exhibit abnormal brain development that impedes neural information processing, which results in characteristic behaviors that contribute to lifelong social and occupational dysfunctions, including social communication deficits and the manifestation of restricted, repetitive behaviors. Currently available treatments show limited effects on reducing the core symptoms in ASD. As a result, developing safe and efficacious treatments to alleviate these symptoms is urgently needed to improve the functional outcomes of these individuals. Specifically, treatments that promote neural information processing in both healthy individuals and people with neuropsychiatric disorders, such as transcranial direct current stimulation (tDCS; Study 1), may be a potentially effective treatment modality for alleviating core symptoms in ASD. Converging evidence shows that abnormal neural information processing in ASD is mediated by the balance between excitatory and inhibitory synaptic inputs corresponding to neuronal events supporting different cognitive functions. Neural information processing is the most efficient when a balanced excitation-inhibition ratio (E:I) is achieved. When E:I is imbalanced, brain signaling is impeded, hence affecting information processing efficiency. Evidence from rodent models of ASD shows that disrupted E:I is associated with reduced social behaviors in mice, yet the associations between E:I, information processing and social functioning in humans remain elusive. Study 2 in this thesis provides empirical evidence to support the hypothesis that disordered E:I is evident in ASD compared to typically developing individuals, which is associated with abnormal information processing observed in these individuals that hinder their abilities to modulate flexible and goal-directed behaviors in daily situations. Given that tDCS has been shown to promote neural information processing in both healthy and clinical populations and that E:I imbalance has been shown to be associated with the behavioral manifestations of ASD, it is hypothesized that tDCS can reduce ASD core symptoms by promoting information processing efficiency and modulating the E:I ratio. Study 3, a double-blind, randomized, sham-controlled trial, was conducted to test this hypothesis. The results show that multisession prefrontal tDCS with a cathode placed over the left dorsolateral prefrontal cortex and an anode placed over the right supraorbital region is effective in reducing ASD core symptoms, improving information processing efficiency and reducing the E:I of the cortical midline structures. Study 4 further shows that the enhancement of the resting-state functional connectivity in the right medial prefrontal cortex induced by this tDCS protocol is associated with the observed improvement in information processing efficiency. Although tDCS has demonstrated promising therapeutic outcomes in ASD at the group level, the author observed from the individual data that the treatment effects varied greatly among participants. For this reason, it is important to predict tDCS treatment response in ASD, such that a more personalized and targeted application of tDCS can be achieved. Study 5 in this thesis shows that the effects of multisession prefrontal tDCS can be predicted from baseline ASD symptom severity level and cortical midline E:I ratio. The findings from these studies aid a more cost-effective and precise tDCS treatment delivery in ASD. |
| Rights: | All rights reserved |
| Access: | open access |
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