Modulatory Effects Of Transcutaneous Auricular Vagus Nerve Stimulation On Brain,behavioral,and Endocrine Responses

Vagus nerve,as an important part of parasympathetic nervous system,plays a key role in the information conduction between our brain and body,and plays a modulation role in fundamental psychophysiological functions to maintain the homeostasis.Given the activity of vagus nerve is highly related to human physical and mental health,vagus nerve stimulation has been continuously developed.Recently,transcutaneous auricular vagus nerve stimulation(ta VNS)has increasingly developed due to its non-invasiveness and easy administration.It has been assumed that ta VNS can modulate specific neurophysiological activities along the extensive brain-body projections of vagus nerve,thereby affecting multiple cognitive functions in humans.Currently,a small number of studies have shown that ta VNS has a beneficial effect on fundamental cognitive functions such as emotion processing and executive control.However,as an emerging neuromodulation technology,studies regarding ta VNS are not sufficient,and results are inconclusive.Four studies were conducted to comprehensively investigate the modulatory effects of ta VNS on brain,behavior and endocrine responses.Current studies combined behavioral experiment,eye-tracking and neuroimaging techniques with enzyme-linked immunoassay method to explore the underlying neurophysiological mechanism of the effects of ta VNS on face emotion processing and emotional inhibitory control.Study 1 aims to investigate the impact of ta VNS on gaze toward emotional faces in combination with eye-tracking and on the release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation.A total of 54 subjects were enrolled in a sham-controlled,participant-blind,crossover experiment,consisting of two treatment sessions 1 week apart.In one session participants received ta VNS,and in the other,they received sham stimulation with the treatment order counterbalanced.The proportion of time spent viewing the faces and facial features(i.e.,eyes,nose,and mouth)was measured.Additionally,saliva samples were taken for the measurement of oxytocin concentrations.Saliva oxytocin concentrations increased significantly after ta VNS compared to sham stimulation.In addition,ta VNS increased time spent viewing the nose region irrespective of face emotion,and this was positively correlated with increased saliva oxytocin concentrations.These findings suggest that ta VNS biases visual attention toward socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release.To further verify the stable effect of ta VNS on oxytocin release,and to explore the neural mechanism underlying the impact of ta VNS on social cognition,Study 2 employed functional near-infrared spectroscopy(f NIRS)imaging technology to measure ta VNS effects on functional coupling changes using the resting state data.A randomized,shamcontrolled between-subject design was adopted.A total of 91 participants were randomly allocated into experimental group(receiving ta VNS)and control group(receiving sham stimulation).Saliva samples were also collected for the measurement of oxytocin concentrations.Results showed that oxytocin concentration increased significantly after ta VNS compared to sham stimulation,and functional couplings within the frontal brain regions increased,including the inferior frontal gyrus(IFG),orbitofrontal cortex(OFC),dorsolateral prefrontal cortex and the medial prefrontal cortex(m PFC),which are proposed to be highly associated with the ability of emotional inhibitory control.Based on the results of above studies,Study 3 employed an emotional face Go/NoGo f NIRS paradigm combined with computational modeling to investigate the underlying neurocomputational mechanism of the impact of ta VNS on inhibitory control to emotional faces.Eight-seven subjects were recruited in this study.Results revealed that accuracy of response inhibition of emotional face was significantly increased while drift rate of correct Go response decreased after ta VNS in comparison to sham stimulation.Additionally,ta VNS increased the activation of right IFG for response inhibition on emotional faces and functional coupling between IFG and OFC.Parallel mediation analysis revealed that ta VNS could increase the accuracy of response inhibition on emotional faces by reducing the drift rate of correct Go response and enhancing the functional coupling between IFG and OFC.Moreover,Study 4 aims to further investigate the effect of ta VNS on emotional inhibitory control.This study employed an emotional scene Go/No-Go f NIRS paradigm with 90 subjects being enrolled,and the methods and data analysis procedures were consistent with Study 3.It has been found that ta VNS increased the accuracy of response inhibition on emotional scenes.Notably,response time of correct Go response also increased after ta VNS,and this was positively correlated with increased accuracy of response inhibition on emotional scenes.More importantly,drift rate for correct Go response decreased after ta VNS compared to sham stimulation.Furthermore,ta VNS significantly enhanced the activation of left and right IFG for response inhibition on emotional scenes response inhibition.Functional coupling between IFG and OFC was significantly enhanced while functional coupling between IFG and m PFC was reduced after ta VNS,and they parallelly mediated the effect of ta VNS on increased accuracy of response inhibition on emotional scenes.Combined with the results of Study 3,these findings indicated that ta VNS can improve the inhibitory control on both emotional faces and scenes,but the underlying neurocomputational mechanisms may be distinct.In summary,this dissertation revealed the beneficial effects of ta VNS on face emotion processing and emotional inhibitory control from behavioral experiments,brain and endocrine responses.It helps enrich the research evidence of the modulatory effects of ta VNS on social cognition,and provides more evidences about therapeutic potentials of ta VNS as the treatment of neurodevelopmental and psychiatric disorders characterized by deficits in face emotion recognition and inhibitory control,such as autism spectrum disorders and attention deficit hyperactivity disorder.