Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Prefrontal–amygdala circuits in social decision-making

Nature Neuroscience volume 24, pages 5–18 (2021)Cite this article

Subjects

Abstract

An increasing amount of research effort is being directed toward investigating the neural bases of social cognition from a systems neuroscience perspective. Evidence from multiple animal species is beginning to provide a mechanistic understanding of the substrates of social behaviors at multiple levels of neurobiology, ranging from those underlying high-level social constructs in humans and their more rudimentary underpinnings in monkeys to circuit-level and cell-type-specific instantiations of social behaviors in rodents. Here we review literature examining the neural mechanisms of social decision-making in humans, non-human primates and rodents, focusing on the amygdala and the medial and orbital prefrontal cortical regions and their functional interactions. We also discuss how the neuropeptide oxytocin impacts these circuits and their downstream effects on social behaviors. Overall, we conclude that regulated interactions of neuronal activity in the prefrontal–amygdala pathways critically contribute to social decision-making in the brains of primates and rodents.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Behavioral ecology of social interaction and brain regions commonly recruited by social behaviors in humans, non-human primates and rodents.
Fig. 2: Illustrations of selected results demonstrating the importance of PFC and amygdala in social behaviors.
Fig. 3: Illustrations of selected results demonstrating the importance of PFC–amygdala interactions in social behaviors.
Fig. 4: Illustrations of selected findings showing neuromodulation by OT in PFC–amygdala pathways.
Fig. 5: A hypothesized mechanism by which OT may enhance social functions in the PFC–amygdala pathways.

References

  1. Chang, S. W. C. et al. Neuroethology of primate social behavior. Proc. Natl. Acad. Sci. USA 110 Suppl 2. 10387–10394 (2013).

    CAS  PubMed  Google Scholar 

  2. Ruff, C. C. & Fehr, E. The neurobiology of rewards and values in social decision making. Nat. Rev. Neurosci. 15, 549–562 (2014).

    CAS  PubMed  Google Scholar 

  3. Giese, M. A. & Rizzolatti, G. Neural and computational mechanisms of action processing: interaction between visual and motor representations. Neuron 88, 167–180 (2015).

    CAS  PubMed  Google Scholar 

  4. Apps, M. A. J., Rushworth, M. F. S. & Chang, S. W. C. The anterior cingulate gyrus and social cognition: tracking the motivation of others. Neuron 90, 692–707 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Chang, S.W.C. An emerging field of primate social neurophysiology: current developments. eNeuro https://doi.org/10.1523/ENEURO.0295-17.2017 (2017).

  6. Chen, P. & Hong, W. Neural circuit mechanisms of social behavior. Neuron 98, 16–30 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Wittmann, M. K., Lockwood, P. L. & Rushworth, M. F. S. Neural mechanisms of social cognition in primates. Annu. Rev. Neurosci. 41, 99–118 (2018).

    CAS  PubMed  Google Scholar 

  8. Galvan, A. et al. Non-human primate optogenetics: Recent advances and future directions. J. Neurosci. 37, 10894–10903 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Piva, M. & Chang, S. W. C. An integrated framework for the role of oxytocin in multistage social decision-making. Am. J. Primatol. 80, e22735 (2018).

    PubMed  PubMed Central  Google Scholar 

  10. Sliwa, J. & Freiwald, W. A. A dedicated network for social interaction processing in the primate brain. Science 356, 745–749 (2017). This functional neuroimaging study in macaques uncovered a set of brain regions that are selectively recruited for perceiving scenes of dynamic social interactions over object interactions and noninteracting conspecifics, demonstrating how social interaction is processed uniquely in the primate brain.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lee, E. et al. Enhanced neuronal activity in the medial prefrontal cortex during social approach behavior. J. Neurosci. 36, 6926–6936 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Jennings, J. H. et al. Interacting neural ensembles in orbitofrontal cortex for social and feeding behaviour. Nature 565, 645–649 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Gothard, K. M., Battaglia, F. P., Erickson, C. A., Spitler, K. M. & Amaral, D. G. Neural responses to facial expression and face identity in the monkey amygdala. J. Neurophysiol. 97, 1671–1683 (2007).

    CAS  PubMed  Google Scholar 

  14. Putnam, P.T. & Gothard, K.M. Multi-dimensional neural selectivity in the primate amygdala. eNeuro https://doi.org/10.1523/ENEURO.0153-19.2019 (2019).

  15. Allison, T., Puce, A. & McCarthy, G. Social perception from visual cues: role of the STS region. Trends Cogn. Sci. 4, 267–278 (2000).

    CAS  PubMed  Google Scholar 

  16. Chang, L. & Tsao, D. Y. The code for facial identity in the primate brain. Cell 169, 1013–1028.e14 (2017).

    CAS  PubMed  Google Scholar 

  17. Freiwald, W., Duchaine, B. & Yovel, G. Face processing systems: from neurons to real-world social perception. Annu. Rev. Neurosci. 39, 325–346 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tsao, D. Y., Moeller, S. & Freiwald, W. A. Comparing face patch systems in macaques and humans. Proc. Natl. Acad. Sci. USA 105, 19514–19519 (2008).

    CAS  PubMed  Google Scholar 

  19. Kanwisher, N., McDermott, J. & Chun, M. M. The fusiform face area: a module in human extrastriate cortex specialized for face perception. J. Neurosci. 17, 4302–4311 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bilalić, M., Langner, R., Ulrich, R. & Grodd, W. Many faces of expertise: fusiform face area in chess experts and novices. J. Neurosci. 31, 10206–10214 (2011).

    PubMed  PubMed Central  Google Scholar 

  21. Bergan, J. F., Ben-Shaul, Y. & Dulac, C. Sex-specific processing of social cues in the medial amygdala. eLife 3, e02743 (2014).

    PubMed  PubMed Central  Google Scholar 

  22. Li, Y. et al. Neuronal representation of social information in the medial amygdala of awake behaving mice. Cell 171, 1176–1190.e17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Gothard, K. M. Multidimensional processing in the amygdala. Nat. Rev. Neurosci. 21, 565–575 (2020).

    PubMed  PubMed Central  Google Scholar 

  24. Bliss-Moreau, E., Moadab, G., Bauman, M. D. & Amaral, D. G. The impact of early amygdala damage on juvenile rhesus macaque social behavior. J. Cogn. Neurosci. 25, 2124–2140 (2013).

    PubMed  PubMed Central  Google Scholar 

  25. Emery, N. J. et al. The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta). Behav. Neurosci. 115, 515–544 (2001).

    CAS  PubMed  Google Scholar 

  26. Machado, C. J. & Bachevalier, J. The impact of selective amygdala, orbital frontal cortex, or hippocampal formation lesions on established social relationships in rhesus monkeys (Macaca mulatta). Behav. Neurosci. 120, 761–786 (2006).

    PubMed  Google Scholar 

  27. Dal Monte, O., Costa, V. D., Noble, P. L., Murray, E. A. & Averbeck, B. B. Amygdala lesions in rhesus macaques decrease attention to threat. Nat. Commun. 6, 10161 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Adolphs, R., Tranel, D., Damasio, H. & Damasio, A. Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature 372, 669–672 (1994).

    CAS  PubMed  Google Scholar 

  29. Adolphs, R. et al. A mechanism for impaired fear recognition after amygdala damage. Nature 433, 68–72 (2005).

    CAS  PubMed  Google Scholar 

  30. Kennedy, D. P., Gläscher, J., Tyszka, J. M. & Adolphs, R. Personal space regulation by the human amygdala. Nat. Neurosci. 12, 1226–1227 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Hirstein, W. & Ramachandran, V. S. Capgras syndrome: a novel probe for understanding the neural representation of the identity and familiarity of persons. Proc. Biol. Sci. 264, 437–444 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Tanimizu, T. et al. Functional connectivity of multiple brain regions required for the consolidation of social recognition memory. J. Neurosci. 37, 4103–4116 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ferretti, V. et al. Oxytocin signaling in the central amygdala modulates emotion discrimination in mice. Curr. Biol. 29, 1938–1953.e6 (2019).

    CAS  PubMed  Google Scholar 

  34. Livneh, U., Resnik, J., Shohat, Y. & Paz, R. Self-monitoring of social facial expressions in the primate amygdala and cingulate cortex. Proc. Natl. Acad. Sci. USA 109, 18956–18961 (2012).

    CAS  PubMed  Google Scholar 

  35. Wang, S. et al. The human amygdala parametrically encodes the intensity of specific facial emotions and their categorical ambiguity. Nat. Commun. 8, 14821 (2017). This study uniquely combines multiple imaging methods, including functional MRI, single-neuron recording and lesions, finding evidence for the amygdala’s core role in perceiving affective facial expressions and their ambiguity.

    PubMed  PubMed Central  Google Scholar 

  36. Wang, S. et al. Neurons in the human amygdala selective for perceived emotion. Proc. Natl. Acad. Sci. USA 111, E3110–E3119 (2014).

    CAS  PubMed  Google Scholar 

  37. Richeson, J. A., Todd, A. R., Trawalter, S. & Baird, A. A. Eye-gaze direction modulates race-related amygdala activity. Group Process. Intergroup Relat. 11, 233–246 (2008).

    Google Scholar 

  38. Baron, S. G., Gobbini, M. I., Engell, A. D. & Todorov, A. Amygdala and dorsomedial prefrontal cortex responses to appearance-based and behavior-based person impressions. Soc. Cogn. Affect. Neurosci. 6, 572–581 (2011).

    PubMed  Google Scholar 

  39. Engell, A. D., Haxby, J. V. & Todorov, A. Implicit trustworthiness decisions: automatic coding of face properties in the human amygdala. J. Cogn. Neurosci. 19, 1508–1519 (2007).

    PubMed  Google Scholar 

  40. Kumaran, D., Banino, A., Blundell, C., Hassabis, D. & Dayan, P. Computations underlying social hierarchy learning: distinct neural mechanisms for updating and representing self-relevant information. Neuron 92, 1135–1147 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Zink, C. F. et al. Know your place: neural processing of social hierarchy in humans. Neuron 58, 273–283 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Noonan, M. P. et al. A neural circuit covarying with social hierarchy in macaques. PLoS Biol. 12, e1001940 (2014).

    PubMed  PubMed Central  Google Scholar 

  43. Munuera, J., Rigotti, M. & Salzman, C. D. Shared neural coding for social hierarchy and reward value in primate amygdala. Nat. Neurosci. 21, 415–423 (2018). This macaque study found that the same neuronal ensembles in the amygdala encode both the value associated with juice rewards and the hierarchical rank of conspecifics, demonstrating a link between non-social and social value processing.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. So, N., Franks, B., Lim, S. & Curley, J. P. A social network approach reveals associations between mouse social dominance and brain gene expression. PLoS One 10, e0134509 (2015).

    PubMed  PubMed Central  Google Scholar 

  45. Sallet, J. et al. Social network size affects neural circuits in macaques. Science 334, 697–700 (2011). Utilizing neuroimaging in macaques, this work revealed how anatomical structures and intrinsic coupling between areas in the primate brain become altered as a function of changing one’s social network size, documenting neural adaptations to new social environments.

    CAS  PubMed  Google Scholar 

  46. Chang, S. W. C., Gariépy, J.-F. & Platt, M. L. Neuronal reference frames for social decisions in primate frontal cortex. Nat. Neurosci. 16, 243–250 (2013). This research capitalized on vicarious reward in macaques to reveal a specialized function of ACCg neurons in signaling the reward received by a conspecific, demonstrating other-referenced reward processing in this brain region.

    CAS  PubMed  Google Scholar 

  47. Dal Monte, O., Chu, C. C. J., Fagan, N. A. & Chang, S. W. C. Specialized medial prefrontal-amygdala coordination in other-regarding decision preference. Nat. Neurosci. 23, 565–574 (2020). This work examined how neurons in the basolateral amygdala and the ACCg interact in social decision-making in macaques and found that enhanced neuronal synchrony between the two areas underlies prosocial decision-making, establishing a role of inter-regional synchrony in primate social behavior.

    CAS  PubMed  Google Scholar 

  48. Rudebeck, P. H., Buckley, M. J., Walton, M. E. & Rushworth, M. F. A role for the macaque anterior cingulate gyrus in social valuation. Science 313, 1310–1312 (2006).

    CAS  PubMed  Google Scholar 

  49. Bickart, K. C., Hollenbeck, M. C., Barrett, L. F. & Dickerson, B. C. Intrinsic amygdala-cortical functional connectivity predicts social network size in humans. J. Neurosci. 32, 14729–14741 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Cremers, H. R. et al. Neuroticism modulates amygdala-prefrontal connectivity in response to negative emotional facial expressions. Neuroimage 49, 963–970 (2010).

    PubMed  Google Scholar 

  51. Satterthwaite, T. D. et al. Opposing amygdala and ventral striatum connectivity during emotion identification. Brain Cogn. 76, 353–363 (2011).

    PubMed  PubMed Central  Google Scholar 

  52. O’Connell, L. A. & Hofmann, H. A. Evolution of a vertebrate social decision-making network. Science 336, 1154–1157 (2012).

    PubMed  Google Scholar 

  53. Tremblay, S., Sharika, K. M. & Platt, M. L. Social decision-making and the brain: A comparative perspective. Trends Cogn. Sci. 21, 265–276 (2017).

    PubMed  PubMed Central  Google Scholar 

  54. Watson, K. K. & Platt, M. L. Social signals in primate orbitofrontal cortex. Curr. Biol. 22, 2268–2273 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Lockwood, P. L., Apps, M. A. J. & Chang, S. W. C. Is there a ‘social brain’? Implementations and algorithms. Trends Cogn. Sci. 20, 802–813 (2020).

    Google Scholar 

  56. Weinberg-Wolf, H. & Chang, S. W. C. Differences in how macaques monitor others: Does serotonin play a central role? Wiley Interdiscip. Rev. Cogn. Sci. 10, e1494 (2019).

    PubMed  PubMed Central  Google Scholar 

  57. Neubert, F.-X., Mars, R. B., Sallet, J. & Rushworth, M. F. S. Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex. Proc. Natl. Acad. Sci. USA 112, E2695–E2704 (2015).

    CAS  PubMed  Google Scholar 

  58. Basile, B. M., Schafroth, J. L., Karaskiewicz, C. L., Chang, S. W. C. & Murray, E. A. The anterior cingulate cortex is necessary for forming prosocial preferences from vicarious reinforcement in monkeys. PLoS Biol. 18, e3000677 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Apps, M. A. J., Lesage, E. & Ramnani, N. Vicarious reinforcement learning signals when instructing others. J. Neurosci. 35, 2904–2913 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Lockwood, P. L., Apps, M. A. J., Roiser, J. P. & Viding, E. Encoding of vicarious reward prediction in anterior cingulate cortex and relationship with trait empathy. J. Neurosci. 35, 13720–13727 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Lockwood, P. L. et al. Neural mechanisms for learning self and other ownership. Nat. Commun. 9, 4747 (2018). This human neuroimaging study found that BOLD signal from the ACCg selectively tracks object ownership information for strangers over self or familiar others, demonstrating a role of this brain region in other-referenced stimulus processing.

    PubMed  PubMed Central  Google Scholar 

  62. Azzi, J. C. B., Sirigu, A. & Duhamel, J.-R. Modulation of value representation by social context in the primate orbitofrontal cortex. Proc. Natl. Acad. Sci. USA 109, 2126–2131 (2012).

    CAS  PubMed  Google Scholar 

  63. Noritake, A., Ninomiya, T. & Isoda, M. Social reward monitoring and valuation in the macaque brain. Nat. Neurosci. 21, 1452–1462 (2018). This study in macaques revealed that neurons in dmPFC signal juice reward values in an agent-specific manner, whereas dopaminergic midbrain neurons signal the integrated subjective value based on relative juice amounts between self and other, demonstrating a specialized function of this region in separating agency in reward processing.

    CAS  PubMed  Google Scholar 

  64. Piva, M. et al. The dorsomedial prefrontal cortex computes task-invariant relative subjective value for self and other. eLife 8, e44939 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Nicolle, A. et al. An agent independent axis for executed and modeled choice in medial prefrontal cortex. Neuron 75, 1114–1121 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Chang, S. W. C. et al. Neural mechanisms of social decision-making in the primate amygdala. Proc. Natl. Acad. Sci. USA 112, 16012–16017 (2015).

    CAS  PubMed  Google Scholar 

  67. Grabenhorst, F., Báez-Mendoza, R., Genest, W., Deco, G. & Schultz, W. Primate amygdala neurons simulate decision processes of social partners. Cell 177, 986–998.e15 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Haruno, M. & Frith, C. D. Activity in the amygdala elicited by unfair divisions predicts social value orientation. Nat. Neurosci. 13, 160–161 (2010).

    CAS  PubMed  Google Scholar 

  69. Joiner, J., Piva, M., Turrin, C. & Chang, S. W. C. Social learning through prediction error in the brain. NPJ Sci. Learn. 2, 8 (2017).

    PubMed  PubMed Central  Google Scholar 

  70. Rosenberger, L. A. et al. The human basolateral amygdala is indispensable for social experiential learning. Curr. Biol. 29, 3532–3537.e3 (2019).

    CAS  PubMed  Google Scholar 

  71. Yoshida, K., Saito, N., Iriki, A. & Isoda, M. Representation of others’ action by neurons in monkey medial frontal cortex. Curr. Biol. 21, 249–253 (2011).

    CAS  PubMed  Google Scholar 

  72. Yoshida, K., Saito, N., Iriki, A. & Isoda, M. Social error monitoring in macaque frontal cortex. Nat. Neurosci. 15, 1307–1312 (2012).

    CAS  PubMed  Google Scholar 

  73. Falcone, R., Cirillo, R., Ferraina, S. & Genovesio, A. Neural activity in macaque medial frontal cortex represents others’ choices. Sci. Rep. 7, 12663 (2017).

    PubMed  PubMed Central  Google Scholar 

  74. Burgos-Robles, A., Gothard, K. M., Monfils, M. H., Morozov, A. & Vicentic, A. Conserved features of anterior cingulate networks support observational learning across species. Neurosci. Biobehav. Rev. 107, 215–228 (2019).

    PubMed  PubMed Central  Google Scholar 

  75. Debiec, J. & Olsson, A. Social fear learning: from animal models to human function. Trends Cogn. Sci. 21, 546–555 (2017).

    PubMed  PubMed Central  Google Scholar 

  76. Jeon, D. et al. Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Nat. Neurosci. 13, 482–488 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Allsop, S. A. et al. Corticoamygdala transfer of socially derived information gates observational learning. Cell 173, 1329–1342.e18 (2018). Using an observational fear learning paradigm in mice, this research revealed an important function of ACC neurons projecting to the basolateral amygdala in learning from others’ outcomes, demonstrating a circuit-specific mechanism of observational learning.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Behrens, T. E. J., Hunt, L. T., Woolrich, M. W. & Rushworth, M. F. S. Associative learning of social value. Nature 456, 245–249 (2008). This human neuroimaging study revealed a specialized computational function of the ACCg in evaluating another’s advice to guide one’s reward-maximizing decisions, demonstrating other-referenced learning signals in this brain region.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Buzsáki, G., Logothetis, N. & Singer, W. Scaling brain size, keeping timing: evolutionary preservation of brain rhythms. Neuron 80, 751–764 (2013).

    PubMed  PubMed Central  Google Scholar 

  80. Fries, P. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence. Trends Cogn. Sci. 9, 474–480 (2005).

    PubMed  Google Scholar 

  81. Friston, K. J., Bastos, A. M., Pinotsis, D. & Litvak, V. LFP and oscillations-what do they tell us? Curr. Opin. Neurobiol. 31, 1–6 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Young, L. J. & Wang, Z. The neurobiology of pair bonding. Nat. Neurosci. 7, 1048–1054 (2004).

    CAS  PubMed  Google Scholar 

  83. Amadei, E. A. et al. Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles. Nature 546, 297–301 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Murray, E. A. & Izquierdo, A. Orbitofrontal cortex and amygdala contributions to affect and action in primates. Ann. NY Acad. Sci. 1121, 273–296 (2007).

    PubMed  Google Scholar 

  85. Haroush, K. & Williams, Z. M. Neuronal prediction of opponent’s behavior during cooperative social interchange in primates. Cell 160, 1233–1245 (2015). In pairs of macaques engaged in the prisoner’s dilemma task, this research discovered that neurons in the ACC are involved in predictively signaling cooperative decisions based on cooperation history and, further, that microstimulating these neurons reduced reciprocating cooperation, demonstrating a role of this region in reciprocal social interaction.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Decety, J., Jackson, P. L., Sommerville, J. A., Chaminade, T. & Meltzoff, A. N. The neural bases of cooperation and competition: an fMRI investigation. Neuroimage 23, 744–751 (2004).

    PubMed  PubMed Central  Google Scholar 

  87. Rilling, J. et al. A neural basis for social cooperation. Neuron 35, 395–405 (2002).

    CAS  PubMed  Google Scholar 

  88. Unger, E. K. et al. Medial amygdalar aromatase neurons regulate aggression in both sexes. Cell Reports 10, 453–462 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Hong, W., Kim, D.-W. & Anderson, D. J. Antagonistic control of social versus repetitive self-grooming behaviors by separable amygdala neuronal subsets. Cell 158, 1348–1361 (2014). By comparing aggressive social behaviors and repetitive non-social behaviors in mice, this work revealed that excitatory and inhibitory neurons in the medial amygdala are involved in antagonistically regulating social and non-social behaviors, providing evidence for how these behaviors are regulated in the brain.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Felix-Ortiz, A. C., Burgos-Robles, A., Bhagat, N. D., Leppla, C. A. & Tye, K. M. Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex. Neuroscience 321, 197–209 (2016). This study in mice discovered that social behaviors and anxiety-like behaviors are regulated by projections from the amygdala to the mPFC, demonstrating how the same pathways can regulate social and non-social functions.

    CAS  PubMed  Google Scholar 

  91. Lin, D. et al. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470, 221–226 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Yizhar, O. et al. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477, 171–178 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Selimbeyoglu, A. et al. Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in CNTNAP2-deficient mice. Sci. Transl. Med. 9, eaah6733 (2017).

    PubMed  PubMed Central  Google Scholar 

  94. Huang, W.-C., Chen, Y. & Page, D. T. Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome. Nat. Commun. 7, 13421 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Zhou, Y. et al. Atypical behaviour and connectivity in SHANK3-mutant macaques. Nature 570, 326–331 (2019).

    CAS  PubMed  Google Scholar 

  96. Kingsbury, L. et al. Correlated neural activity and encoding of behavior across brains of socially interacting animals. Cell 178, 429–446.e16 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Zhang, W. & Yartsev, M. M. Correlated neural activity across the brains of socially interacting bats. Cell 178, 413–428.e22 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Hasson, U., Ghazanfar, A. A., Galantucci, B., Garrod, S. & Keysers, C. Brain-to-brain coupling: a mechanism for creating and sharing a social world. Trends Cogn. Sci. 16, 114–121 (2012).

    PubMed  PubMed Central  Google Scholar 

  99. Donaldson, Z. R. & Young, L. J. Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322, 900–904 (2008).

    CAS  PubMed  Google Scholar 

  100. Eisenegger, C., Haushofer, J. & Fehr, E. The role of testosterone in social interaction. Trends Cogn. Sci. 15, 263–271 (2011).

    CAS  PubMed  Google Scholar 

  101. Pedersen, C. A., Chang, S. W. C. & Williams, C. L. Evolutionary perspectives on the role of oxytocin in human social behavior, social cognition and psychopathology. Brain Res. 1580, 1–7 (2014).

    CAS  PubMed  Google Scholar 

  102. Neumann, I. D. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J. Neuroendocrinol. 20, 858–865 (2008).

    CAS  PubMed  Google Scholar 

  103. Freeman, S.M. & Young, L.J. Comparative perspectives on oxytocin and vasopressin receptor research in rodents and primates: translational implications. J. Neuroendocrinol. https://doi.org/10.1111/jne.12382 (2016).

  104. Marlin, B. J., Mitre, M., D’amour, J. A., Chao, M. V. & Froemke, R. C. Oxytocin enables maternal behaviour by balancing cortical inhibition. Nature 520, 499–504 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Gamer, M., Zurowski, B. & Büchel, C. Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans. Proc. Natl. Acad. Sci. USA 107, 9400–9405 (2010).

    CAS  PubMed  Google Scholar 

  106. Petrovic, P., Kalisch, R., Singer, T. & Dolan, R. J. Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J. Neurosci. 28, 6607–6615 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Dölen, G., Darvishzadeh, A., Huang, K. W. & Malenka, R. C. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501, 179–184 (2013).

    PubMed  PubMed Central  Google Scholar 

  108. Chang, S. W. C., Barter, J. W., Ebitz, R. B., Watson, K. K. & Platt, M. L. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta). Proc. Natl. Acad. Sci. USA 109, 959–964 (2012).

    CAS  PubMed  Google Scholar 

  109. Dal Monte, O., Noble, P. L., Costa, V. D. & Averbeck, B. B. Oxytocin enhances attention to the eye region in rhesus monkeys. Front. Neurosci. 8, 41 (2014).

    PubMed  PubMed Central  Google Scholar 

  110. Putnam, P. T., Roman, J. M., Zimmerman, P. E. & Gothard, K. M. Oxytocin enhances gaze-following responses to videos of natural social behavior in adult male rhesus monkeys. Psychoneuroendocrinology 72, 47–53 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Leng, G. & Ludwig, M. Intranasal oxytocin: Myths and delusions. Biol. Psychiatry 79, 243–250 (2016).

    CAS  PubMed  Google Scholar 

  112. Walum, H., Waldman, I. D. & Young, L. J. Statistical and methodological considerations for the interpretation of intranasal oxytocin studies. Biol. Psychiatry 79, 251–257 (2016).

    CAS  PubMed  Google Scholar 

  113. Bethlehem, R. A. I., van Honk, J., Auyeung, B. & Baron-Cohen, S. Oxytocin, brain physiology, and functional connectivity: a review of intranasal oxytocin fMRI studies. Psychoneuroendocrinology 38, 962–974 (2013).

    CAS  PubMed  Google Scholar 

  114. Kirsch, P. et al. Oxytocin modulates neural circuitry for social cognition and fear in humans. J. Neurosci. 25, 11489–11493 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Ebner, N. C. et al. Oxytocin’s effect on resting-state functional connectivity varies by age and sex. Psychoneuroendocrinology 69, 50–59 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Dodhia, S. et al. Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder. Neuropsychopharmacology 39, 2061–2069 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Riem, M. M. E. et al. No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter. Neuropsychopharmacology 37, 1257–1266 (2012).

    CAS  PubMed  Google Scholar 

  118. Lukas, M., Toth, I., Veenema, A. H. & Neumann, I. D. Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: male juvenile versus female adult conspecifics. Psychoneuroendocrinology 38, 916–926 (2013).

    CAS  PubMed  Google Scholar 

  119. Ferguson, J. N. et al. Social amnesia in mice lacking the oxytocin gene. Nat. Genet. 25, 284–288 (2000).

    CAS  PubMed  Google Scholar 

  120. Ferguson, J. N., Aldag, J. M., Insel, T. R. & Young, L. J. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J. Neurosci. 21, 8278–8285 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Dumais, K. M., Bredewold, R., Mayer, T. E. & Veenema, A. H. Sex differences in oxytocin receptor binding in forebrain regions: correlations with social interest in brain region- and sex- specific ways. Horm. Behav. 64, 693–701 (2013).

    CAS  PubMed  Google Scholar 

  122. Yao, S., Bergan, J., Lanjuin, A. & Dulac, C. Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues. eLife 6, e31373 (2017). By examining oxytocin signaling in the mouse medial amygdala, this work discovered that oxytocin receptors expressed on aromatase-expressing neurons in males mediate preferred social interaction with females, demonstrating how oxytocin regulates sex-specific behaviors in this region.

    PubMed  PubMed Central  Google Scholar 

  123. Pisansky, M. T., Hanson, L. R., Gottesman, I. I. & Gewirtz, J. C. Oxytocin enhances observational fear in mice. Nat. Commun. 8, 2102 (2017).

    PubMed  PubMed Central  Google Scholar 

  124. Burkett, J. P. et al. Oxytocin-dependent consolation behavior in rodents. Science 351, 375–378 (2016). This work in prairie voles revealed that activity in the ACC and oxytocin processing in this brain region enables partner-directed consolation behaviors toward conspecifics in distress, uncovering how empathy related behaviors are controlled by this brain region and oxytocin.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Owen, S. F. et al. Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature 500, 458–462 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Murugan, M. et al. Combined social and spatial coding in a descending projection from the prefrontal cortex. Cell 171, 1663–1677.e16 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Anderson, D. J. Circuit modules linking internal states and social behaviour in flies and mice. Nat. Rev. Neurosci. 17, 692–704 (2016).

    CAS  PubMed  Google Scholar 

  128. Hosokawa, T. & Watanabe, M. Prefrontal neurons represent winning and losing during competitive video shooting games between monkeys. J. Neurosci. 32, 7662–7671 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Nummela, S. U., Jovanovic, V., de la Mothe, L. & Miller, C. T. Social context-dependent activity in marmoset frontal cortex populations during natural conversations. J. Neurosci. 37, 7036–7047 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Poldrack, R. A. et al. Scanning the horizon: towards transparent and reproducible neuroimaging research. Nat. Rev. Neurosci. 18, 115–126 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Botvinik-Nezer, R. et al. Variability in the analysis of a single neuroimaging dataset by many teams. Nature 582, 84–88 (2020).

    CAS  PubMed  Google Scholar 

  132. Gordon, E. M. et al. Precision functional mapping of individual human brains. Neuron 95, 791–807.e7 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Poldrack, R. A. et al. Long-term neural and physiological phenotyping of a single human. Nat. Commun. 6, 8885 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Rudebeck, P. H., Saunders, R. C., Prescott, A. T., Chau, L. S. & Murray, E. A. Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating. Nat. Neurosci. 16, 1140–1145 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Vaidya, A. R., Pujara, M. S., Petrides, M., Murray, E. A. & Fellows, L. K. Lesion studies in contemporary neuroscience. Trends Cogn. Sci. 23, 653–671 (2019).

    PubMed  PubMed Central  Google Scholar 

  136. Carmichael, S. T. & Price, J. L. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. J. Comp. Neurol. 363, 615–641 (1995).

    CAS  PubMed  Google Scholar 

  137. Ghashghaei, H. T., Hilgetag, C. C. & Barbas, H. Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. Neuroimage 34, 905–923 (2007).

    CAS  PubMed  Google Scholar 

  138. Janak, P. H. & Tye, K. M. From circuits to behaviour in the amygdala. Nature 517, 284–292 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Barbas, H. Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices. Brain Res. Bull. 52, 319–330 (2000).

    CAS  PubMed  Google Scholar 

  140. Miyashita, T., Ichinohe, N. & Rockland, K. S. Differential modes of termination of amygdalothalamic and amygdalocortical projections in the monkey. J. Comp. Neurol. 502, 309–324 (2007).

    PubMed  Google Scholar 

  141. Amaral, D. G. & Price, J. L. Amygdalo-cortical projections in the monkey (Macaca fascicularis). J. Comp. Neurol. 230, 465–496 (1984).

    CAS  PubMed  Google Scholar 

  142. Carmichael, S. T. & Price, J. L. Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys. J. Comp. Neurol. 363, 642–664 (1995).

    CAS  PubMed  Google Scholar 

  143. Baxter, M. G. & Murray, E. A. The amygdala and reward. Nat. Rev. Neurosci. 3, 563–573 (2002).

    CAS  PubMed  Google Scholar 

  144. Freeman, S. M., Inoue, K., Smith, A. L., Goodman, M. M. & Young, L. J. The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta). Psychoneuroendocrinology 45, 128–141 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Loup, F., Tribollet, E., Dubois-Dauphin, M. & Dreifuss, J. J. Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study. Brain Res. 555, 220–232 (1991).

    CAS  PubMed  Google Scholar 

  146. Schorscher-Petcu, A., Dupré, A. & Tribollet, E. Distribution of vasopressin and oxytocin binding sites in the brain and upper spinal cord of the common marmoset. Neurosci. Lett. 461, 217–222 (2009).

    CAS  PubMed  Google Scholar 

  147. Putnam, P. T., Young, L. J. & Gothard, K. M. Bridging the gap between rodents and humans: The role of non-human primates in oxytocin research. Am. J. Primatol. 80, e22756 (2018).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Institute of Mental Health (R01 MH120081, R01MH110750). We thank P. Putnam, S. Fan and O. Meisner for their helpful comments on the manuscript and C. Stanton for help with the figure illustrations.

Author information

Author notes

  1. These authors contributed equally: Prabaha Gangopadhyay, Megha Chawla.

Authors and Affiliations

  1. Department of Psychology, Yale University, New Haven, CT, USA

    Prabaha Gangopadhyay, Megha Chawla, Olga Dal Monte & Steve W. C. Chang

  2. Department of Psychology, University of Turin, Torino, Italy

    Olga Dal Monte

  3. Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA

    Steve W. C. Chang

  4. Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA

    Steve W. C. Chang

Authors
  1. Prabaha Gangopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Megha Chawla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga Dal Monte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steve W. C. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steve W. C. Chang.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Peer review information Nature Neuroscience thanks Ralph Adolphs and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gangopadhyay, P., Chawla, M., Dal Monte, O. et al. Prefrontal–amygdala circuits in social decision-making. Nat Neurosci 24, 5–18 (2021). https://doi.org/10.1038/s41593-020-00738-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-020-00738-9

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing