Regulating Anterior Insula Function And Associated Behavior Using Oxytocin And Neurofeedback Training

Anterior insula is a core hub of the emotional processing network and the salience network and plays an important role in human social cognition and emotional processing.The dysfunction of anterior insula is highly associated with mental disorders especially emotional disorders.Given that triaditional research approcach is lack of noninvasive way to regulate brain function actively,the main goal of the present project is to investigate the anterior insula regulation and its behavioral effects using intranasal administration of oxytocin and real-time fMRI-based neurofeedback training.The present project consisted of two studies.Study 1 employed a double-blind,between-subject,placebo-controlled design to investigate the effect of intranasal administration of oxytocin on regulating anterior insula activity and the associated interoceptive accuracy changes.In experiment 1,we studied the modulatory effect of oxytocin on basic interoceptive processing.Results showed that,for the first time,oxytocin could enhance the activity of the interoceptive core network especially the anterior insula.However,no significant effect was observed on interoceptive acuuracy.In experiment 2,we investigated whether the modulatory effect of oxytocin vaired as a function of different emotions.Results showed disassociated effects of oxytocin on neural responses and behavioral changes.While oxytocin increased the neural responses in the interoceptive core network it decreased the interoceptive accuracy in the heartbeat detection task.Oxytocin had a general negative effect on interovetive accuracy to all emotions but increased the anterior insula activity,which might reflect less dependence of interoceptive processing on feedback from peripheral nervous system but increased integration to external socially arousing stimuli and thus guide behavior.For specific emotions,oxytocin could enhance activity of the interoceptive nework to scrambled,neutral and disgust faces,indicating a different role of different emotions in modulating oxytocin effects on interoception.In study 2,a real-time fMRI-based neurofeedback training paradigm was used to investigate the impact of self-regulation of anterior insula on empathic responses,whether the self-regulation ability could maintain after neurofeedback training,and its effects on the intrinsic functional connectivity.Results revealed that voluntary increase of anterior insula could enhance subjects' empathic ratings and that subjects could maintain their ability in regulating anterior insula activity after 2 days even when there was no neurofeedback information provided.These findings demonstrated for the first time that self-regulation of anterior insula could increase empathic responses and that subjects could maintain the regulation ability for a relative long time.Furthermore,neurofeedback training could also alter functional connectivity of anterior insula with other relevant brain networks including prefrontal regions involved in emotion regulation.For resting-state functional connectivity changes between pre-and post-neurofeedback traning,increased intrinsic functional connectivity between amterior insula and empathic networks was found in post-relative to pre resting state scan.This connectivity changes could also maintain until the follow-up meansuement on day 3,suggesting the theraputic application potential of real-time fMRI-based neurofeedback training in clinical populations.In conclusion,the present project used two different noninvasive intervention approachs to investigate active anterior insula regulation and the associated behavioral effects.Results showed that these two approaches both could regulate anterior insula activity effectively and induce coprresponding behavioral changes.Given the wide modulatory effects of oxytocin in social cognition and affective processing,it is possible to combine the two approaches when using regulation strategies related to social cognition and affective processing.Oxytocin might facilate the nerofeedback tranining efficiency by enhancing the validity of regulation startegies.Given the close associations between anterior insula function and emotional disorders,these findings were of important therapeutic application significance.