| Touch,as a crucial form of nonverbal communication during social interaction,facilitates the establishment and maintenance of social bonds through emotional communication.Unlike discriminative touch(serves to identify physical aspects of touch),affective touch hasn’t been recognized until the last 20 years with the identification of a class of unmyelinated C-touch(CT)afferent fibers that are associated with the perceived pleasantness of touch.The neuropeptide oxytocin(OT)promotes attachment and social bonding and reduces anxiety,similar to the positive effects of affective touch on human interaction,and affective touch can enhance OT release.It has previously been shown that intranasal OT facilitates the pleasantness of social touch and activation of brain reward and social processing regions,but it is unclear if it influences responses to gentle stroking touch mediated by cutaneous CT fibers or pressure touch mediated by other types of fibers.And the primary treatment routes via which OT exerts its effects remain unclear.Additionally,previous studies examining OT effects on affective touch have only focused on individual responses to other-administered touch.In fact,self-administered touch is also often used to self-regulate stress and emotions,and our ability to discriminate between self-and other-administered touch may play a crucial role in developing our sense of self.However,it is unclear whether OT has similar modulatory effects on selfversus other-administered touch.To further investigate the neural mechanism involved in the modulatory effects of OT on different types of affective touch as well as its primary routes of action,the current study thus conducted three experiments: Study 1 mainly examined which types of skin afferent fibers are involved in the OT effects on affective touch and the related primary routes;Study 2 further explored whether OT has similar or different functional effects on self-and other-administered touch based on the determined targeting afferents and action routes in Study 1;Study 3 employed a resting-state functional MRI and the connectome-based predictive modeling(CPM)to explore the different predictive models related to self-versus other-administered touch according to the revealed different effects of OT on these two types of touch in Study 2.Study 1 aimed at investigating OT effects on CT-targeted gentle stroking and nonCT-targeted medium pressure massage,as well as the primary routes involved.In a randomized placebo-controlled between-subject design,combined with behavioral rating,physiological,functional near-infrared spectroscopy(f NIRS)and plasma OT concentration measures,we compared effects of intranasal(via direct entry into the brain and increased peripheral concentrations,n = 56)and oral(lingual spray: only via peripheral increases)OT on behavioral and neural responses to social touch targeting CT(gentle stroking touch)or other(medium pressure massage without stroking)cutaneous receptors.Although both types of touch were perceived as pleasant,intranasal and oral OT equivalently enhanced pleasantness ratings and responses of reward(orbitofrontal cortex,OFC)and social processing(superior temporal sulcus)regions only to gentlestroking not medium pressure massage.Furthermore,increased blood OT concentrations predicted the pleasantness of gentle stroking touch.The specificity of neural effects of OT on CT-targeted gentle stroking touch was confirmed by time-course extraction and classification analysis.Overall,the study findings suggested that increased peripheral concentrations of OT primarily modulate its behavioral and neural responses to CTtargeted gentle social touch.Study 2 employed task-dependent functional MRI to investigate OT effects on self versus other touch distinction.Based on the findings in Study 1 that oral and intranasal OT had similar effects on CT-targeted affective touch processing,Study 2 used oral medicated lollipops containing the same dose of OT or placebo(PLC).In a double-blind placebo-controlled within-subject design,39 participants participated in a self-other touch paradigm 45 minutes following the oral administration.Consistent with the findings of study 1,oral OT increased the perceived pleasantness for other-administered touch in parallel with enhanced functional connectivity between brain regions involved in reward(OFC)and salience processing(anterior insula,AI).Furthermore,OT significantly decreased neural responses in regions such as the AI,posterior insula(PI),anterior cingulate cortex(ACC)and inferior frontal gyrus,as well as the functional connectivity between the PI and posterior cingulate cortex for other-relative to self-administered touch.At the same time,multivoxel pattern analysis revealed that following the OT administration,the neural patterns that effectively discriminated between self-and otheradministered touch conditions contained fewer significant weighted voxels but achieved similar accuracy compared with PLC,suggesting that OT possibly increased the efficiency of discriminating self-and other-administered touch.These findings indicated that OT augmented self versus other touch distinction and specifically enhanced the reward value and salience of other touch.Based on the above findings,Study 3 employed a resting-state functional MRI and CPM to investigate the identification of spontaneous functional connectivity networks that could effectively predict individual responses to affective touch,to provide more evidence from a new perspective to support the mechanism underlying the different treatment effects on self-versus other-administered touch.Results demonstrated that the pleasantness ratings of other-administered touch following oral OT administration could be correctly predicted by functional connectivity networks.Specifically,the prefrontal lobe(PFC)predominantly contributed to the predictive power of the model,and related brain connectivity of PFC and the limbic system also played an important role in model prediction.But no significant results were found for self-administered touch and both touch conditions under PLC.This further supported the findings in study 2 that oral OT specifically enhanced the pleasantness of other-administered touch,and has been additionally suggested a potential association with an enhanced resting-state functional connectivity between reward(OFC)and salience processing regions(e.g.,ACC).In addition,the functional connectivity network identified in this study could be generalized to successfully predict the behavioral effects of intranasal OT on other-administered affective touch in a separate sample,further demonstrating that intranasal and oral administered OT produce similar effects on CT-targeted affective touch.Taken together,the present study with 3 experiments has revealed the functional effects of neuropeptide OT on facilitating the pleasantness of affective touch targeting CT fibers and brain activations of regions involved in reward,salience,and social cognitive processing.This modulatory effect has been additionally shown to primarily respond to other-administered affective touch.OT also augments the distinction of modulatory effects on self-and other-administered touch.In addition,the similar effects of oral and intranasal OT in modulating CT-targeted other-touch processing suggest that the peripheral routes of action primarily mediate the functional effects of OT during affective touch processing.These findings contribute to a broader understanding of the mechanisms underlying effects of the neuropeptide OT on affective touch processing.They may also have potential implications for using OT therapeutically in disorders or conditions where affective touch is perceived as unpleasant. |
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