Neuropeptides are critical for social cognition, and are actively being pursued as a therapeutic agent for treating diseases with marked social deficits, such as autism spectrum disorders (ASD), schizophrenia, and psychopathy. Oxytocin (OT) is an evolutionarily conserved neuropeptide involved in social processing in multiple species. Despite numerous demonstrations of OT-induced social behavior, it remains unclear how OT modulates networks of neurons involved in social decision-making. Using the reward donation task involving donor and recipient monkeys, we reported that inhaled OT enhances vicarious reinforcement of the donor when the choice is between rewarding another and no one, whereas it amplifies self reinforcement when the choice is between rewarding himself and another. OT in this task also enhances the looking behavior at the recipient following reward donations. Empathy-related processing might be mediated by a cohort of networks involving amygdala, anterior cingulate (ACC), and orbitofrontal cortices (OFC). In the reward donation task, we also found that ACC neurons predominantly represent rewards delivered to another, whereas OFC neurons predominantly represent rewards delivered to self. Amygdala contains a high number of OT receptors, and mediates affective and social processing. Amygdala, especially the basolateral portion, is reciprocally connected with ACC and OFC, and is involved in evaluating both positive and negative rewards. OT directly gates information processing in amygdala with other structures, and influences amygdala activations during social evaluations in humans. Critically, OT receptor risk allele carriers for ASD show altered amygdala activations in social emotional tasks. Given these observations, we seek to elucidate the following by capitalizing upon the reward donation task: 1) activity of single amygdala neurons during reward allocation decisions;2) neural mechanisms of OT-induced responses in amygdala neurons;and 3) specific modulations of ACC and OFC neurons due to OT-mediated processes by amygdala. We hypothesize that amygdala contains both vicarious and self reinforcement signals, and these are both amplified by inhaled OT. We further hypothesize that local OT delivery to amygdala neurons enhances self reward signals in OFC and vicarious reward signals in ACC. Our results have a potential to advance our knowledge on neuropsychiatric diseases with social deficits, and our understanding of OT-based therapeutics.

Public Health Relevance

Despite a broad continuum of phenotypic variation in behavior, individuals with autism spectrum disorders (ASD) share core deficits in social interaction. Here we propose that social dysfunction in ASD results, in part, from problems in deriving vicarious reward from others, and that this process may depend on neuropeptide oxytocin, which is implicated in various social processes. We will use our animal model of vicarious reward to discover how oxytocin, a potential therapy for ASD, mediates social processing in the brain, and discover its role in brain dysfunction.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Transition Award (R00)
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Simmons, Janine M
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Yale University
Schools of Arts and Sciences
New Haven
United States
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Apps, Matthew A J; Rushworth, Matthew F S; Chang, Steve W C (2016) The Anterior Cingulate Gyrus and Social Cognition: Tracking the Motivation of Others. Neuron 90:692-707
Dal Monte, Olga; Piva, Matthew; Morris, Jason A et al. (2016) Live interaction distinctively shapes social gaze dynamics in rhesus macaques. J Neurophysiol 116:1626-1643
Chang, Steve W C; Calton, Jeffrey L; Lawrence, Bonnie M et al. (2016) Region-Specific Summation Patterns Inform the Role of Cortical Areas in Selecting Motor Plans. Cereb Cortex 26:2154-66
Du, Emily; Chang, Steve W C (2015) Neural components of altruistic punishment. Front Neurosci 9:26
Chang, Steve W C; Fagan, Nicholas A; Toda, Koji et al. (2015) Neural mechanisms of social decision-making in the primate amygdala. Proc Natl Acad Sci U S A 112:16012-7
Chang, Steve W C; Platt, Michael L (2014) Oxytocin and social cognition in rhesus macaques: implications for understanding and treating human psychopathology. Brain Res 1580:57-68
Brent, Lauren J N; Chang, Steve W C; Gariépy, Jean-François et al. (2014) The neuroethology of friendship. Ann N Y Acad Sci 1316:1-17
Chang, Steve W C; Isoda, Masaki (2014) Toward a better understanding of social learning, social deciding, and other-regarding preferences. Front Neurosci 8:362
Chang, Steve W C; Platt, Michael L (2014) Amygdala: eyes wide open. Curr Biol 24:R1000-2
Pedersen, Cort A; Chang, Steven W C; Williams, Christina L (2014) Evolutionary perspectives on the role of oxytocin in human social behavior, social cognition and psychopathology. Brain Res 1580:1-7

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