Emotional Inhibitory Control And The Modulatory Roles Of Oxytocin And Vasopressin

Inhibitory control,as a key component of executive control,refers to the ability to suppress inappropriate or prepotent responses and supports flexible and goal-directed behavior in ever-changing environments.Accumulating evidence from animal models and human studies demonstrated a modulatory influence of emotional context,genes and neuropeptides on inhibitory control.While several neuroimaging studies examined the specific circuits and regions that mediate the influence of emotional context on inhibition,results have remained inconsistent.A large body of research has shown that the evolutionary conserved neuropeptides oxytocin(OXT)and arginine vasopressin(AVP)play an important role in modulating emotional and cognitive functions.However,the specific role of these two peptides in emotional inhibitory control including their common and different effects have not been systematically established.To determine the neural mechanism underlying the interaction between emotion and inhibitory control and the two peptides OXT and AVP’s modulatory effect on it four studies were conducted.These studies combined behavioral and neuroimaging assessments with genetic and pharmacological methods to explore(1)the specific neural circuits and regions that underlying emotional inhibitory control,(2)effects of genetic variations of the OXT receptor on emotional inhibitory control,and(3)OXT and AVP’s modulatory effect on it.Study 1 aimed at separating brain regions and circuits that specifically mediate domain-general and emotional context-specific inhibitory control.The present study employed a validated emotional linguistic Go/No Go f MRI paradigm and a large cohort of healthy subjects(N = 250)were recruited.In addition to task-based activation changes,the network-level analyses including a data-driven approach(ICC)that operates on the voxel-level and independent of pre-specified regions of interest and the generalized psychophysiological interaction analyses(g PPI)on the seed to voxel level were employed.Behavioral results reflected successful emotional modulation of inhibitory control.Both BOLD level and ICC analysis showed separated domain-general and emotional-specific regions mainly encompassing VS and PFC circuits.Follow-up functional connectivity analyses revealed significant VS-PFC connectivity duting emotion and inhibition interaction.Together,these findings indicate separable domain general as well emotional context specific inhibitory brain systems.To investigate the modulatory role of the neuropeptide OXT on the interaction between emotion and inhibitory control,Study 2 explored the influence of genetic variations of common OXT receptor genes(OXTR,OXTR rs53576,OXTR rs237887,OXTR rs2254298,OXTR rs2268498 and OXTR rs2268491)on the neural activation reported in Study 1.Behavioral results found no association between variations in the OXT receptor genetics and inhibitory control in different emotional contexts was found.Neural results showed a significant interaction effect specifically between OXTR rs53576 polymorphism and emotional inhibitory control,mainly located in the right paracentral lobule/precuneus.Based on the results from Study 2,Study 3 combined an emotional inhibitory control eye tracking paradigm(emotional anti-saccade task)that we used in a previous study to establish modulatory effects of intranasal OXT to explore intranasal AVP’s effect on topdown emotional inhibitory control and the common and distinguishable effects between these two peptides.Our findings suggested that both AVP and OXT decrease goal-directed top-down inhibitory control to social emotional stimuli but that AVP more potently increased bottom-up social attentional processing.Study 4 aimed to explore oral OXT’s effect on emotional inhibitory control and its similar/different effects with the intranasal route,based on previous studies which have reported that OXT’s effect on social cognition varied according to administration route.Our findings suggested that OXT via oral and intranasal administration has similar effects on top-down inhibitory control but oral OXT produced more potent effect on bottom-up social attention.Taken together,the current study combined behavioral and f MRI neuroimaging with genetic and pharmacological methods to determine the neural mechanism underlying emotional inhibitory control and modulatory effects of the neuropeptides OXT and AVP in this domain.Our findings showed that specifically the connections between the ventral striatum and medial prefrontal regions are involved in the modulatory role of emotional contexts on inhibitory control and that both OXT and AVP play an important modulatory role in emotional inhibitory control.The current study may provide more information for OXT and AVP’s potential use in the intervention and treatment of neurodevelopmental and psychiatric disorder charactered by deficits in inhibitory control.