A Study Of The Characteristics Of The Social Cognitive Impairment And Its Mechanism Of Targeted RTMS Intervention For Autism Spectrum Disorder

BackgroundAutism spectrum disorder(ASD)is a neurodevelopmental disorder in children charaterized by social-communication challenges,repetitive behaviors,restricted interests and activities.Among all of these,social-communication challenges are the core impairment.According to a new report on the status survey of ASD,the prevalence rate of ASD is about 1 in 36(around 2.7%),and its prevalence is increasing year by year.Due to the lack of a clear pathogenesis of ASD,there is no effective drug intervention until now.Current treatments for ASD mainly focus on improving basic living abilities and correcting behavioral problems.Given this,it is urgent to carry out the alternative therapy and mechanism research on the core symptoms of ASD,so as to provide important evidences for the treatment.Eye-tracking technology,which is used to record the fixation characteristics and trajectory of human eyes,is gradually applied to the classification,quantification and description of mental illness.Human largely depend on the non-verbal means to communicate,and convey their thoughts,feelings,and intentions through actions,expressions,and postures.The non-specific performance to socially-related stimuli in ASD patients may be the fundamental reason of their social dysfunction.The development and application of eye-tracking technology have greatly enhanced the acquisition of objective indicators of social cognition in ASD.Repetitive Transcranial Magnetic Stimulation(r TMS)is a neuromodulation technique that can change cortical excitability.At present,? explosive magnetic stimulation(i TBS),a new mode developed by r TMS,is suitable for rehabilitation therapy of ASD patients due to its short duration of action and the same effect as traditional r TMS.However,the specific stimulation mode,stimulation target,therapeutic effect and potential neural mechanism of i TBS treatment for ASD are still unclear.Neuroimaging technology provides a way to investigate the neural mechanism of i TBS intervention in ASD.The Voxel-based morphometry(VBM)and the analysis of Functional Connectivity Strength(FCS)of resting state functional Magnetic Resonance Imaging(rs-f MRI)data are helpful to further understand the changes of brain structure and function in ASD patients,and explore the potential mechanism of iTBS intervention.ObjectiveThis study intends to find the key targets of social cognitive impairment by exploring the characteristics of social cognitive impairment in ASD.We use optimized sequence and accurate navigation and positioning technology of i TBS to conduct pre-experiments on autistic individuals,then observe the applicability of the target and sequence,and further explore the intervention of social cognitive impairment in ASD.(1)Using eye-tracking technology,we compare the fixation characteristics of emotional face recognition and selective social attention task between the ASD group and the normal developing children group.And combined with the impairment characteristics of social cognitive ability of ASD,the intervention targets and sequence of transcranial magnetic stimulation can be determined.(2)In order to explore and verify feasibility of the preliminarily determined targets and therapeutic sequences,we use eye-tracking technology to examine the improvements in social cognition of autistic individuals after intervention and magnetic resonance imaging(MRI)to study the potential neural mechanism.(3)On the basis of study 2,We use more optimized stimulation mode and target,and accurate navigation and positioning technology.We provide patients with i TBS intervention,and then observe the changes in clinical symptoms and eye movement indexes of patients after i TBS intervention,explore the potential neural mechanism by using MRI.Methods(1)Use emotional face recognition task and selective social attention eye task.(2)Based on navigation guidance system,use MRI and selected stimulation mode and target to intervene the right posterior superior temporal sulcus of autistic individuals.(3)Based on Study 2,we use optimized stimulation mode to intervene the right posterior superior temporal sulcus of autistic individuals.The experiment is divided into three parts: 1.To observe the changes in clinical symptoms of the real stimulation group and blank control group after i TBS intervention.2.Use open-label study to observe the changes of facial processing and fixation bias in ASD after i TBS stimulation,and to explore the intervention characteristics of i TBS in the treatment of social cognition.3.Use open-label study to explore the potential neural mechanism of i TBS treatment in ASD.Results(1)Children with ASD had processing difficulties in observing emotional faces,and there were atypical observation disorder for positive,neutral and negative expressions(joy,neutral and anger).In particular,there was a significant interaction between group and emotion when looking at the face,nose and mouth areas.In the selective social attention(SSA)task,among the four interest categories(eyes,mouth,body,and toys),the time spent by ASD patients looking at eyes and mouth showed significant interaction between group and emotion.The time spent by ASD patients looking at eyes and nose was significantly lower than that of normal children.(2)The emotional recognition ability of autistic individuals was improved after the intervention of excitatory i TBS,the rp STS and the rs FC between the left cerebellum also largely decreased.This pre-experiment confirmed the effectiveness of the stimulus plan for autistic individuals,and provided a basis for that i TBS can be used to treat ASD in the future.(3)The clinical symptoms of ASD patients were improved after the intervention of excitatory i TBS.Besides,the fixation time spent on the emotional faces and interactive conversations in social situations were increased.This improvement may be related to the significant increase in RSFC in the left hippocampus.Conclusion(1)Emotional face recognition task and selective social attention task show great sensitivity,which provided a good measurement index for the intervention of social cognition in ASD patients.(2)Stimulating the right posterior superior temporal sulcus by i TBS can effectively improve the emotion recognition ability of autistic individuals.The potential neural mechanism may be related to the functional connectivity of the left cerebellum.(3)Stimulating the right posterior superior temporal sulcus by i TBS can significantly improved clinical symptoms in ASD,especially social cognition.This improvement may be related to the enhancement of functional connectivity in the left hippocampus.