Altered face scanning and arousal after orbitofrontal cortex lesion in adult rhesus monkeys.

To further assess orbitofrontal cortex (OFC) contribution to the processing of socioemotional signals, spontaneous scanning patterns and pupil diameter variations were measured while adult rhesus macaques with either bilateral lesions of OFC areas 11 and 13 (Group O-asp) or sham-operations (Group C) freely viewed pictures of neutral and expressive faces of conspecifics, of other nonhuman primates and humans, and of objects with and without facial features. As compared to Group C, Group O-asp displayed (a) increased overall spontaneous visual exploration and increased scanning of primate neutral faces regardless of species and face orientation (upright/inverted), (b) longer gazes at the eyes of faces and of objects with facial features, and (c) intact ability to discriminate emotional from neutral faces, but (d) altered scanning patterns at emotional macaque faces coupled with (e) increased pupil dilation for conspecific faces according to face emotion and orientation (profile/stare). Thus, the primate OFC appears essential in the attention to and processing of faces, especially attention to the eyes and arousal self-regulation. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Mother recognition and preference after neonatal amygdala lesions in rhesus macaques (Macaca mulatta) raised in a semi-naturalistic environment.

Attachment to the caregiver, typically the biological mother, is crucial to young mammals' socio-emotional development. Although studies in nonprimate species suggest that the amygdala regulates social preference and attachment development, its role in primate filial attachment development has been little investigated and has produced mixed results. This study assessed the effects of neonatal amygdala- (Neo-A, N = 16) and sham- (Neo-C, N = 12) lesions on mother recognition and discrimination in macaques raised in species-typical social groups. Neonatal amygdalectomy did not affect social discriminative abilities and mother preference at 3 and 6 months of age, strongly suggesting that the amygdala is not involved in the cognitive processes underlying the development of filial attachment at least when the amygdala damage occurred after the third to fourth weeks of age. Nevertheless, as compared to sham-operated controls, amygdalectomized infants initiated physical contact with their mothers less frequently. The findings are discussed in relation to the known contribution of the amygdala to filial attachment in both rodents and humans.

Peripherally administered non-peptide oxytocin antagonist, L368,899, accumulates in limbic brain areas: a new pharmacological tool for the study of social motivation in non-human primates.

Central administration of oxytocin (OT) antagonists inhibits maternal and sexual behavior in non-primates, providing the strongest experimental evidence that endogenous OT facilitates these behaviors. While there have been a few reports that ICV administration of OT increases social behaviors in monkeys, no studies to date have assessed the effects of OT antagonists. Therefore, we studied in rhesus monkeys whether L368,899, a non-peptide antagonist produced by Merck that selectively blocks the human uterine OT receptor, penetrates the CNS after peripheral administration and alters female maternal and sexual behavior. In two studies in four male monkeys, L368,899 was injected iv (1 mg/kg) after which (1) CSF samples were collected at intervals over 4 h and (2) brains were collected at 60 min. Assay of samples confirmed that iv-administered L368,899 entered CSF and accumulated in the hypothalamus, septum, orbitofrontal cortex, amygdala and hippocampus, but not other areas. An adult female monkey was tested for interest in either an infant or sexual behavior, receiving a different iv treatment prior to each test (1 or 3 mg/kg of L368,899 or saline). OT antagonist treatment reduced or eliminated interest in the infant and sexual behavior. These results, although preliminary, are the first to directly implicate endogenous OT in activation of primate maternal interest and sexual behavior. While it remains to be empirically demonstrated that peripherally administered L368,899 blocks central OT receptors, our behavioral findings suggest that this non-peptide antagonist may facilitate testing OT involvement in a variety of social and other behaviors in primates.

Social attachment in juvenile monkeys with neonatal lesion of the hippocampus, amygdala and orbital frontal cortex.

Non-human primates, like humans, develop and maintain social relationships and attachments throughout their life. The first and most crucial relationship in a primate life is that with its mother. Yet, in absence of their biological mother, infant primates form attachment to surrogate mothers. Although, this early attachment is critical for the development of normal species-typical social and emotional skills, the neural substrates underlying the formation of social relationships in primates are still unclear. The present study assessed, in infant rhesus monkeys (Macaca mulatta) reared by human caregivers and social interactions with peers, the effects of bilateral neonatal (1-2 weeks of age) ibotenic acid lesions of the amygdala and hippocampus (N=6 in each group), aspiration lesions of the orbital frontal cortex (N=6) or sham lesions (N=5) on the development of a social attachment with the principal human caregiver. A specific preference for the later was assessed at 11 months of age, in a two-choice discrimination task, opposing the principal human caregiver to another familiar human, in a familiar environment. None of the lesions impaired the expression of preferential responses toward the principal human caregiver. Nevertheless, lesions of the orbital frontal cortex led to a weaker preference, suggesting that this structure may play a role in the quality and/or strength of the infant/mother relationships. The present non-human primate findings are discussed in terms of their relevance for autism.

Do neonatal bilateral ibotenic acid lesions of the hippocampal formation or of the amygdala impair HPA axis responsiveness and regulation in infant rhesus macaques (Macaca mulatta)?

In response to stressful events, the HPA axis is activated triggering the successive release of CRF, ACTH, and glucocorticoids. The glucocorticoids in turn provide a negative feedback signal to terminate the stress response. The amygdala and the hippocampus are involved in the regulation of the HPA axis. In rodents, their respective roles have been identified; the amygdala exerts a stimulatory effect, whereas the hippocampus provides negative feedback control. In primates, however, their regulatory roles are still not well defined. The present study compared HPA axis responsiveness and regulation in 3- to 5-month-old rhesus macaques that received neonatal (15 +/- 3 days old) bilateral ibotenic acid lesions of the hippocampus or amygdala, or sham lesions. Group differences in plasma cortisol response to separation from the mother and relocation in a novel environment were assessed as well as response to dexamethasone suppression and ACTH challenge. Results revealed that the initial cortisol levels after separation/relocation did not differ between groups. Subjects with hippocampus lesions did not show a suppression of cortisol in response to dexamethasone, suggesting a loss of negative feedback control of HPA regulation. Subjects with amygdala and sham lesions did not differ in response to dexamethasone. Indeed, bilateral neonatal lesions of the amygdala have little impact on HPA axis responsiveness and regulation in contrast to lesions in adult monkeys. Finally, females displayed higher cortisol levels than males, independently of their lesion, indicating that the development of sex differences in the regulation of the HPA axis does not involve the amygdala or hippocampus.