| Author: | Krishnamurthy, Karthikeyan |
| Title: | Neural bases for temperamental effortful control deficit and its response to transcranial direct current stimulation in autism spectrum disorder |
| Advisors: | Han, Yvonne (RS) Siu, Andrew (RS) |
| Degree: | Ph.D. |
| Year: | 2023 |
| Subject: | Magnetic brain stimulation Autism spectrum disorder Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Rehabilitation Sciences |
| Pages: | xxii, 194 pages : color illustrations |
| Language: | English |
| Abstract: | Autism spectrum disorder (ASD) is a neurodevelopmental condition that characterizes impairment in communication and social interaction with the presence of repetitive stereotypic behavioral patterns and interests. These clinical features are heightened in autistic individuals as a result of dysfunctional temperamental effortful control (EC), which employs executive attention skills for suppressing a dominant response and/or to initiate a subdominant response for planning and/or recognizing errors. EC encompasses attentional control, inhibitory control, and cognitive flexibility subcomponents that aid in activating, modulating, or withdrawing tendencies pertinent to chosen behavior. Although EC deficits in autism have been arbitrated with parents' or caregivers' perception in Western populations, the exact neural underpinnings and the magnitude of EC impairment in the Chinese-Hong Kong population remain elusive. Additionally, individuals with ASD presented with abnormal structural and functional neural systems, including the prefrontal cortex, which is responsible for supervising attention, inhibitory control, and cognitive flexibility functions. Reversal of such abnormal brain functions requires intervention to modulate underlying neural activities, which can be accomplished using transcranial direct current stimulation (tDCS). Given that this doctoral thesis includes a combination of four interlinked studies, Study one aimed to synthesize available whole-brain fMRI studies on EC components, including attention control, inhibitory control, and cognitive flexibility, separately using SDM-PSI software. The study compared the brain activation pattern between individuals with autism and healthy controls (HCs) while controlling for age and further examines the aging effect on task-induced brain activation during each EC component. The results showed that there was a significant deactivation of brain regions in autism patients compared to HCs in all EC components. Notably, hypoactivation was evident in the left inferior frontal gyrus, left fusiform gyri, left precentral gyrus, right cerebellum crus II, right superior occipital gyrus during attentional control; left anterior cingulate gyrus, right angular gyrus during inhibitory control; and left anterior cingulate gyrus, left inferior frontal gyrus, left precuneus during cognitive flexibility tasks. Meta-regression analysis revealed age-increased deactivation in the right precentral gyrus and left inferior gyrus during attention control; the left anterior cingulate during cognitive flexibility was found in ASD. Study two examined the relationship between EC and prefrontal cortex activation and connectivity in children with high-functioning ASD. Thirty-nine right-handed children (ASD n = 20; HC n = 19) aged 8-12 years were recruited. The EC level was assessed with the Early Adolescent Temperament Questionnaire-Revised (EATQ-R), and PFC functioning, in terms of activation and connectivity during the n-back task, was recorded using functional near infrared spectroscopy (fNIRS). Children with ASD showed a significant deficit in EC, executive, and socioemotional functions compared to HC. The ASD group also showed significantly increased overall PFC activation and reduced right frontal connectivity during the n-back task. Among children with ASD, the EC level correlated significantly with neither PFC activation nor connectivity and correlated with social functioning only. This study demonstrated EC deficits and altered PFC functioning in children with ASD, but the exact neural basis of EC deficits remains to be determined. Study three investigated the relationship between EC and prefrontal cortex activation and connectivity in adolescents and adults with high-functioning ASD. Twenty-seven right-handed individuals (ASD n = 14; HC n = 13) aged 15-22 years were recruited. The EC level was assessed with the Early Adolescent Temperament Questionnaire-Revised (EATQ-R) and Adult Temperament Questionnaire (ATQ), and PFC functioning, in terms of activation and connectivity during the Wisconsin Card Sorting Test (WCST), was assessed using functional near infrared spectroscopy (fNIRS). The ASD group showed a significant deficit in EC, executive, and socioemotional functions compared to the HC group. The ASD group also showed significantly reduced intra- and interfrontal connectivity during the WCST. Among individuals with ASD, the EC level correlated significantly with neither PFC activation nor connectivity and correlated with attentional (reaction time task) and social functions. This study demonstrated EC deficits and altered PFC functioning in adolescents and adults with ASD, but the exact neural underpinnings of EC deficit remain to be clarified. Study four compared the effect of cathodal and sham tDCS on temperamental EC, social behaviour, information processing speed, and PFC functional connectivity in individuals with ASD. Thirty right-handed individuals (tDCS n = 15; sham n = 15) aged 14-21 years were recruited. Early Adolescent Temperament Questionnaire (EATQ), Adult Temperament Questionnaire (ATQ), Social Responsiveness Scale (SRS-2), neuropsychological tests tapping information processing efficiency, and fNIRS PFC connectivity at rest were measured before and after tDCS intervention. Results showed that only the repetitive cathodal tDCS improved activation control of EC, social function, information processing efficiency, and resting state functional connectivity of the right medial prefrontal cortex (PFC). Such cathodal tDCS on functional connectivity enhancement in the right medial PFC was further associated with information processing efficiency and cognitive flexibility skills which might explain a potential neurophysiological mechanism underlying the desirable behavioral modifications. These findings have offered valuable evidence regarding the neural bases for temperamental EC deficits in autism. Findings have further extended that Chinese-Hong Kong individuals with high-functioning ASD have EC deficits, and such deficits have been associated with social, emotional, and attentional skills in ASD. Additionally, findings also provided preliminary evidence that the repetitive cathodal tDCS could be an effective intervention for enhancing activation control of EC, social skills, cognitive flexibility, information processing speed, and resting state functional connectivity of the medial PFC. |
| Rights: | All rights reserved |
| Access: | open access |
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