Abnormal Functional Brain Networks In Autism Spectrum Disorder And Network Guided Stimulation

Autism spectrum disorder(ASD)is a neurodevelopmental condition with atypical brain connectivity.It is characterized by substantial impairments in communication,social interaction,and restricted and repetitive behaviors.The etiology of ASD remains unclear,and its prevalence is steadily increasing,posing significant economic and psychological burdens on affected individuals and their families.Early diagnosis and intervention for ASD have become urgent scientific challenges.With the advancements in magnetic resonance imaging(MRI)technology and the development of network neuroscience,researchers can investigate the pathological mechanisms of ASD from a brain connectivity perspective.Additionally,the development of neuromodulation techniques,such as transcranial magnetic stimulation(TMS),offers novel strategies for clinical intervention in children with ASD.This dissertation proposed novel method to explore atypical functional brain networks of ASD from both static and dynamic persepectives,as well as the associations between the functional brain networks and social deficits of ASD.Furthermore,based on resting-state functional connectivity,this dissertation proposed network-guided stimulation strategies that effectively alleviate core symptoms of ASD,offering new hope for early intervention in children with ASD.The main research contents consist of the following four parts:1.To explore the the relationship between functional brain network and social deficits in ASD,this dissertation proposed a method of whole-brain network-based regression(NBR)to offers a representation of the communication and social interaction deficits in ASD that encompasses multiple functional brain networks widely distributed across primary sensory perceptual and high-level cognitive networks.The functional networks associated with communication and social interaction can predict the merged symptom dimension.Our findings reveal how specific brain functional subnetwork architectures may underlie social deficits and provide neuroimaging evidence describing how these symptom dimensions coalesce with each other in ASD.2.To explore the spatial and temporal organization of brain dynamics in ASD.this dissertation present a dynamic decomposition model to explore the spatial-temporal structure of brain dynamics.Following this framework,whole brain dynamic functional connectivity was decomposed as the linear combination of dynamic modules and corresponding time-varying weights.This dissertation characterized the temporal variation of the dynamic modules between different brain states,which suggests that the temporal variation of dynamic modules may contribute to brain state transitions.Moreover,this dissertation conceptualized temporal variability as the flexibility of the corresponding dynamic modules and found that different dynamic modules exhibit different flexibility,and the module flexibility can predict social deficits in ASD.This study revealed the spatio-temporal organization of functional network and the representation of the social deficits of ASD in brain dynamics.3.This dissertation proposed a personalized social brain network(amygdalaoptimized functional connectivity)-guided continuous theta-burst stimulation(cTBS)as a novel,non-invasive treatment for young children with ASD,leveraging a rigorous double-blind randomized controlled trial.Our findings demonstrate that cTBS reduces social-communication deficits in minimally verbal ASD.Analysis of pre-and posttreatment multimodal brain imaging data revealed changes in morphology,spontaneous neural activity,and functional connectivity of the amygdala following treatment.Retrospective analysis of the control group indicated that the clinical response to treatment was better when the stimulated target was closer in proximity to a personalized stimulation target.Our study demonstrates that personalized social brain network-guided cTBS is a promising treatment for young children with ASD.4.To explore how brain stimulation affects the functional brain network in ASD,this dissertation conducted static and dynamic functional network analysis based on data collected in Chapter Four.Results indicated that cTBS stimulation significantly reduced the functional connectivity strength and module flexibility,while enhanced the global efficiency in ASD.This process may mitigate the ‘Hyper-connectivity’ in ASD.Furthermore,the changes in functional network were associated with core symptoms in ASD and the sptial pattern of neurotransmitter receptor.Our study provided evidence of the relationship between cTBS-induced changes in functional network,core symptoms in ASD,and neurotransmitter receptor patterns.In summary,this dissertation focused on ‘representation and intervention of social deficits of ASD through brain network’.By utilizing functional magnetic resonance imaging(f MRI)technology and TMS techniques,this dissertation investigated the characterization of abnormal functional brain networks in ASD from both static and dynamic perspectives and their associations with core dimensions of ASD.Furthermore,this dissertation proposed a novel functional connectivity-guided cTBS stimulation strategy,which effectively alleviates core symptoms of ASD,offering new hope for early intervention in children with ASD.