Effects Of Intranasal Oxytocin On Attention And Emotion Regulation

Oxytocin(OXT)is a peptide hormone and neuropeptide,which is synthesized in the magnocellular neurons of the paraventricular nucleus(PVN)and supraoptic nucleus(SON)of the mammalian hypothalamus and released into the bloodstream and peripheral circulation via the posterior lobe of the pituitary gland(i.e.the neurohypophysial system)to facilitate uterine contractions and lactating in nursing female animals.Oxytocin,synthesized by smaller parvocellular neurons in the paraventricular nucleus of the hypothalamus,is projected into the brain stem and limbic system,including the hippocampus,amygdala,hypothalamus and nucleus accumbens.Oxytocin acts to influence an immense number of complex central and peripheral physiological functions.In neurotypical adults,a large body of research suggests benefits of intranasal oxytocin for improving social cognition,including eye gaze,emotion recognition,trust,in-group preference,memory of socially relevant cues,and attenuating anxiety and stress responses,along with neural underpinnings of these benefits.To account for the variegated roles of oxytocin in human behavior,an important theoretical framework(i.e.social salience hypothesis)was proposed,which suggests the salience effect of oxytocin modulates attentional orienting responses to external contextual social cues.By combining resting-state fMRI(rsfMRI),the first goal of this study is to verify the social salience hypothesis of oxytocin and investigate whether oxytocin has already modulated attentional control during the task-free state.Attentional control plays an important role in the process of emotional regulation,and these two cognitive processes are in a complementary relationship.Attentional control is considered as the core of adaptive emotional regulation.Based on previous findings,oxytocin may attenuate the fear response and improve the ability of fear regulation by initially upregulating prefrontal cortex responses to fear-associated stimuli and by unspecifically downregulating amygdala responses.Therefore,the second goal of this study is to examine the effects of oxytocin on the top-down emotional regulation system,and the effects on functional interactions between the prefrontal cortex and corresponding subcortical regions(e.g.amygdala,insula).Accumulating evidence suggests that the interplay between competing attentional processes is mirrored in the intrinsic temporal anti-correlations between the default network(DN),engaged during rest and internally-oriented processes and networks engaged during external attentional demands such as the dorsal attention network(DAN)and salience network(SN).Against this background,study 1 employed a randomized,between-subject,placebo-controlled pharmacological fMRI study in a large sample of healthy male and female participants(N = 187)aimed at determining the modulatory effects of OXT on the intrinsic organization within-and the dynamic interplay betweenthe DAN–SN–DN systems.OXT increased the functional integration between subsystems within SN and DN and increased functional segregation of the DN with both attentional control networks(SN and DAN).Whereas no sex differences were observed,OXT effects on the DN–SN interaction were modulated by autistic traits.Together,the findings of study 1 suggest that OXT may facilitate efficient attention allocation by modulating the intrinsic functional dynamics between DN components and large-scale networks involved in external attentional demands(SN and DAN).The findings of the resting-state study showed the modulatory effects of oxytocin on both the top-down and bottom-up attention-related brain networks.Against this background,study 2 employed a randomized,between-subject,placebo-controlled pharmacological fMRI study in healthy male participants(N = 88)aimed at determining modulatory effects of OXT on top-down and bottom-up processing during task performance.The participants performed an implicit(emotional Go/NoGo task)and explicit emotion regulation(distancing task)during the fMRI scanning.Oxytocin did not produce significant influences on both the implicit and explicit emotion regulation tasks in the behavioral performance.However,cognitive emotion regulation via distancing significantly decrease negative affect during encoding and in turn abolished the subsequent emotional memory effect in terms of enhanced memory for negative information in the domains of short-term(Day 0).In contrast to previously reported effects of OXT on implicit emotion regulation,it did not affect explicit cognitive emotion regulation per se.However,in line with previous animal models OXT generally improved the emotional memory of the neutral condition.fMRI results showed that oxytocin decreased the activity of the regions involved in face processing during the stimuli presentation periods both in the emotional Go/NoGo task and the distancing task,suggesting that oxytocin increased the salience of social stimuli.Therefore,the participants after oxytocin treatment can perform the task normally without recruiting regions a lot involved in face processing.Meta-analyses have shown that anticipation and regulation of clearly or potentially aversive events are both associated with increased activation of the amygdala.We,therefore,examined OXT effects on both the anticipation and regulation periods in the emotion regulation task.OXT attenuated amygdala responses during the reappraisal anticipation period(top-down attentional control)but increased the amygdala responses during the look anticipation period(bottom-up attentional control).Moreover,OXT effects on the amygdala responses were modulated by self-reported state and trait anxiety as well as action control ability.These findings suggest that OXT may attenuate the threat-related attention of high anxious participants during the top-down attentional processing,but increase the threat-related attention of low anxious participants during the bottom-up attentional processing.Together,these results suggest that the OXT system may promote efficient attentional allocation by modulating both top-down orientation in response to task demands as well as bottom-up reorientation towards salient stimuli in the environment.