Intranasal oxytocin in rhesus monkeys alters brain networks that detect social salience and reward

Abstract

In primates, resting state functional neuroimaging (rsfcMRI) has identified several large-scale, intrinsic brain networks, including the salience network (SN), which is involved in detecting stimulus salience. Intranasal oxytocin (IN-OT) has been shown to modulate the salience and rewarding quality of social stimuli in mammals and numerous studies have shown that it can affect the functional connectivity between brain regions. Less is known, however, about how these effects unfold over time following IN-OT administration. This study used rsfcMRI in anesthetized rhesus macaques to track temporal changes in the functional connectivity between brain regions involved in the SN, including the anterior cingulate cortex (ACC), anterior insula (AI), amygdala (amy), and ventral striatum (vstr), lasting three hours after IN-OT or Placebo (saline) administration. We found significant temporal changes in the functional connectivity between all regions associated with treatment condition. IN-OT increased the functional connectivity between AI_vstr, ACC_amy (right hemisphere), ACC_vstr (left hemisphere), and amy_vstr (right hemisphere), but reduced the functional connectivity between ACC_AI, and the AI_amygdala. These results suggest that IN-OT may dampen salience detection in rhesus monkeys, consistent with previous findings of reduced social vigilance, while enhancing the connectivity between the SN and regions involved in processing reward.

Intranasal oxytocin selectively modulates the behavior of rhesus monkeys in an expression matching task

“…Although more research is needed to determine whether facial identity and expression are processed by independent neural mechanisms 38–40 , our results indicate that intranasal OT selectively alters the sensitivity of monkeys to facial expressions, possibly via an interaction with motivation and reward circuitry in the primate brain (i.e. the amygdala) 34,48,49 .…”

“…This indicates that the amygdala is involved at an early stage of information processing, when orienting and directing one’s eye movements towards salient environmental stimuli and those with emotional valence. Since a previous functional imaging study found that the response to facial expressions with negative valence in the monkey amygdala was selectively reduced by the delivery of OT 44,45 , it may be that our results from the OT treatment condition reflect a change in the subject’s viewing behavior stemming from altered amygdala activity 20,29,34,46 .…”

“…In humans and monkeys, there have been numerous reports that OT inhalation alters viewing behavior towards face stimuli 21,29–33 . In particular, the studies that have demonstrated that OT administration selectively modulates attention towards faces conveying fearful expressions has been used to argue that OT effects are stimulus-driven and social in nature 32,33 and, thus, the OT signaling pathway promotes specific operations involved in processing social stimuli 7,8,20,34 . However, these studies also suffer from the common criticism; that it would be easier to explain these findings in terms of general changes in the internal state of the subjects, such as reduced anxiety, increased motivation, or improved attention 12,13,35,36 .…”

On the Possibility to Use Oxytocin as A Potential Therapeutic Approach for Memory-Related Psychological Disorders

“…Moreover, the medial prefrontal activity in response to ingroup pain in the revenge group, but not in the control group mediates the association between endogenous oxytocin and the propensity to give painful electrical shocks to outgroup members, regardless of whether or not they were personally involved in the conflict [52]. Oxytocin also modulate rodent and monkeys' performance in memory tasks, and both increased and reduced effects were reported [53][54][55][56][57]. The effects of oxytocin on the perception and evaluation of social stimuli greatly was dependent on the emotional/social valence of stimuli [58] and it is suggested that oxytocin's effect is context-dependently in monkeys [58,59].…”

Intranasal oxytocin reduces pre-courtship aggression and increases paternal response in California mice (Peromyscus californicus)

“…Endogenous hormone and neuropeptide levels are important for biobehavioral feedback and to help animals respond appropriately to various social interactions. Oxytocin (OXT), a neuropeptide hormone, is a neuromodulator that may be important for weighing social salience and determining appropriate behavioral response to social stimuli (Shamay-Tsoory & Abu-Akel, 2016; Parr et al, 2018; Yao et al, 2018; Johnson et al, 2017; Egito et al, 2020). Previous studies on OXT show its significant effects on prosocial affiliative behaviors such as trust, social bonding, social recognition, and anxiolytic behavior in both human and animal models (Theodoridou et al, 2009; Kosfeld et al, 2005; Ring et al, 2006; Bales et al, 2003; Blocker et al, 2015; Guestella et al, 2008).…”