Cognitive, Affective, & Behavioral Neuroscience

, Volume 13, Issue 4, pp 900–915 | Cite as

Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory

  • Robert S. RossEmail author
  • Matthew L. LoPresti
  • Karin Schon
  • Chantal E. Stern


Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses.


Prefrontal Social interaction fMRI Delayed match-to-sample 


Author note

This work was supported by the National Science Foundation Science of Learning Center (Grant No. SMA-0835976), the National Institutes of Health (Grant No. P50 MH071702), and the Department of Psychology at Boston University. Functional magnetic resonance imaging was conducted at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, Grant No. P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program and the High-End Instrumentation Grant Program; specifically, Grant No. S10RR021110. We thank Matthew Grace for his assistance developing and piloting the behavioral task, and Michael Hasselmo and David Somers for helpful discussions about the study. We also thank Ruben Gur’s Brain Behavior Laboratory at the University of Pennsylvania for supplying the majority of the face stimuli used in this study.


  1. Agster, K. L., Fortin, N. J., & Eichenbaum, H. (2002). The hippocampus and disambiguation of overlapping sequences. Journal of Neuroscience, 22, 5760–5768.PubMedGoogle Scholar
  2. Axmacher, N., Elger, C. E., & Fell, J. (2009). Working memory-related hippocampal deactivation interferes with long-term memory formation. Journal of Neuroscience, 29, 1052–1960.PubMedCrossRefGoogle Scholar
  3. Barbas, H., & Blatt, G. J. (1995). Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey. Hippocampus, 5, 511–533.PubMedCrossRefGoogle Scholar
  4. Berlin, H. A., Rolls, E. T., & Kischka, U. (2004). Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions. Brain, 127, 1108–1126.PubMedCrossRefGoogle Scholar
  5. Bower, M. R., Euston, D. R., & McNaughton, B. L. (2005). Sequential-context-dependent hippocampal activity is not necessary to learn sequences with repeated elements. Journal of Neuroscience, 25, 1313–1323.PubMedCrossRefGoogle Scholar
  6. Boynton, G. M., Engel, S. A., Glover, G. H., & Heeger, D. J. (1996). Linear systems analysis of functional magnetic resonance imaging in human V1. Journal of Neuroscience, 16, 4207–4221.PubMedGoogle Scholar
  7. Brown, T. I., Ross, R. S., Keller, J. B., Hasselmo, M. E., & Stern, C. E. (2010). Which way was I going? Contextual retrieval supports the disambiguation of well learned overlapping navigational routes. Journal of Neuroscience, 30, 7414–7422.PubMedCentralPubMedCrossRefGoogle Scholar
  8. Brown, T. I., Ross, R. S., Tobyne, S. M., & Stern, C. E. (2012). Cooperative interactions between hippocampal and striatal systems support flexible navigation. NeuroImage, 60, 1316–1330.PubMedCentralPubMedCrossRefGoogle Scholar
  9. Caplan, J. B., McIntosh, A. R., & De Rosa, E. (2007). Two distinct functional networks for successful resolution of proactive interference. Cerebral Cortex, 17, 1650–1663.PubMedCrossRefGoogle Scholar
  10. Cavada, C., Company, T., Tejedor, J., Cruz-Rizzolo, R. J., & Reinoso-Suarez, F. (2000). The anatomical connections of the macaque monkey orbitofrontal cortex: A review. Cerebral Cortex, 10, 220–242.PubMedCrossRefGoogle Scholar
  11. Chudasama, Y., & Robbins, T. W. (2003). Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: Further evidence for the functional heterogeneity of the rodent frontal cortex. Journal of Neuroscience, 23, 8771–8780.PubMedGoogle Scholar
  12. Courtney, S. M., Ungerleider, L. G., Keil, K., & Haxby, J. V. (1996). Object and spatial visual working memory activate separate neural systems in human cortex. Cerebral Cortex, 6, 39–49.PubMedCrossRefGoogle Scholar
  13. Damasio, H. (2005). Human brain anatomy in computerized images (2nd ed.). New York, NY: Oxford University Press.CrossRefGoogle Scholar
  14. Eichenbaum, H. (2000). A cortical-hippocampal system for declarative memory. Nature Reviews Neuroscience, 1, 41–50.PubMedCrossRefGoogle Scholar
  15. Ekman, P., & Friesen, W. (1976). Pictures of facial affect. Palo Alto, CA: Consulting Psychologists Press.Google Scholar
  16. Fellows, L. K., & Farah, M. J. (2003). Ventromedial frontal cortex mediates affective shifting in humans: Evidence from a reversal learning paradigm. Brain, 126, 1830–1837.PubMedCrossRefGoogle Scholar
  17. Finke, C., Braun, M., Ostendorf, F., Lehmann, T. N., Hoffmann, K. T., Kopp, U., & Ploner, C. J. (2008). The human hippocampal formation mediates short-term memory of colour–location associations. Neuropsychologia, 46, 614–623.Google Scholar
  18. Ginther, M. R., Walsh, D. F., & Ramus, S. J. (2011). Hippocampal neurons encode different episodes in an overlapping sequence of odors task. Journal of Neuroscience, 31, 2706–2711.PubMedCentralPubMedCrossRefGoogle Scholar
  19. Gur, R. C., Sara, R., Hagendoorn, M., Marom, O., Hughett, P., Macy, L., . . . Gur, R. E. (2002). A method for obtaining 3-dimensional facial expressions and its standardization for use in neurocognitive studies. Journal of Neuroscience Methods, 115, 137–143.Google Scholar
  20. Hannula, D. E., Tranel, D., & Cohen, N. J. (2006). The long and the short of it: Relational memory impairments in amnesia, even at short lags. Journal of Neuroscience, 26, 8352–8359.PubMedCrossRefGoogle Scholar
  21. Hartley, T., Bird, C. M., Chan, D., Cipolotti, L., Husain, M., Vargha-Khadem, F., & Burgess, N. (2007). The hippocampus is required for short-term topographical memory in humans. Hippocampus, 17, 34–48.Google Scholar
  22. Haxby, J. V., Petit, L., Ungerleider, L. G., & Courtney, S. M. (2000). Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory. NeuroImage, 11, 380–391.PubMedCrossRefGoogle Scholar
  23. Hornak, J., O’Doherty, J., Bramham, J., Rolls, E. T., Morris, R. G., Bullock, P. R., & Polkey, C. E. (2004). Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans. Journal of Cognitive Neuroscience, 16, 463–478.Google Scholar
  24. Insausti, R., & Munoz, M. (2001). Cortical projections of the non-entorhinal hippocampal formation in the cynomolgus monkey (Macaca fascicularis). European Journal of Neuroscience, 14, 435–451.PubMedCrossRefGoogle Scholar
  25. Jeneson, A., Mauldin, K. N., & Squire, L. R. (2010). Intact working memory for relational information after medial temporal lobe damage. Journal of Neuroscience, 30, 13624–13629.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Kringelbach, M. L., & Rolls, E. T. (2003). Neural correlates of rapid reversal learning in a simple model of human social interaction. NeuroImage, 20, 1371–1383.PubMedCrossRefGoogle Scholar
  27. Kumaran, D., & Maguire, E. A. (2006). The dynamics of hippocampal activation during encoding of overlapping sequences. Neuron, 49, 617–629.PubMedCrossRefGoogle Scholar
  28. Kumaran, D., & Maguire, E. A. (2007). Match–mismatch processes underlie human hippocampal responses to associative novelty. Journal of Neuroscience, 27, 8517–8524.PubMedCentralPubMedCrossRefGoogle Scholar
  29. LoPresti, M. L., Schon, K., Tricarico, M. D., Swisher, J. D., Celone, K. A., & Stern, C. E. (2008). Working memory for social cues recruits orbitofrontal cortex and amygdala: A functional magnetic resonance imaging study of delayed matching to sample for emotional expressions. Journal of Neuroscience, 28, 3718–3728.PubMedCentralPubMedCrossRefGoogle Scholar
  30. Lyons, M. J., Akamatsu, S., Kamachi, M., & Gyoba, J. (1998, April). Coding facial expressions with Gabor wavelets. Paper presented at the Third IEEE International Conference on Automatic Face and Gesture Recognition, Nara, Japan.Google Scholar
  31. McAlonan, K., & Brown, V. J. (2003). Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat. Behavioural Brain Research, 146, 97–103.PubMedCrossRefGoogle Scholar
  32. McIntosh, A. R., Grady, C. L., Haxby, J. V., Ungerleider, L. G., & Horwitz, B. (1996). Changes in limbic and prefrontal functional interactions in a working memory task for faces. Cerebral Cortex, 6, 571–584.PubMedCrossRefGoogle Scholar
  33. Meunier, M., Bachevalier, J., & Mishkin, M. (1997). Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys. Neuropsychologia, 35, 999–1015.PubMedCrossRefGoogle Scholar
  34. Newmark, R. E., Schon, K., Ross, R. S., & Stern, C. E. (2013). Contributions of the hippocampal subfields and entorhinal cortex to disambiguation during working memory. Hippocampus. doi: 10.1002/hipo.22106
  35. Nichols, E. A., Kao, Y. C., Verfaellie, M., & Gabrieli, J. D. E. (2006). Working memory and long-term memory for faces: Evidence from fMRI and global amnesia for involvement of the medial temporal lobes. Hippocampus, 16, 604–616.PubMedCentralPubMedCrossRefGoogle Scholar
  36. Olsen, R. K., Nichols, E. A., Chen, J., Hunt, J. F., Glover, G. H., Gabrieli, J. D. E., & Wagner, A. D. (2009). Performance-related sustained and anticipatory activity in human medial temporal lobe during delayed match-to-sample. Journal of Neuroscience, 29, 11880–11890.Google Scholar
  37. Olson, I. R., Moore, K. S., Stark, M., & Chatterjee, A. (2006). Visual working memory is impaired when the medial temporal lobe is damaged. Journal of Cognitive Neuroscience, 18, 1087–1097.PubMedCrossRefGoogle Scholar
  38. Olson, I. R., Page, K., Moore, K. S., Chatterjee, A., & Verfaellie, M. (2006). Working memory for conjunctions relies on the medial temporal lobe. Journal of Neuroscience, 26, 4596–4601.PubMedCentralPubMedCrossRefGoogle Scholar
  39. Ongur, D., Ferry, A. T., & Price, J. L. (2003). Architectonic subdivision of the human orbital and medial prefrontal cortex. The Journal of Comparative Neurology, 460, 425–449.PubMedCrossRefGoogle Scholar
  40. Otto, T., & Eichenbaum, H. (1992). Complementary roles of the orbital prefrontal cortex and the perirhinal–entorhinal cortices in an odor-guided delayed-nonmatching-to-sample task. Behavioral Neuroscience, 106, 762–775.PubMedCrossRefGoogle Scholar
  41. Pantic, M., Valstar, M. F., Rademaker, R., & Maat, L. (2005, July). Web-based database for facial expression analysis. Paper presented at the IEEE Int’l Conference on Multimedia and Expo, Amsterdam, The Netherlands.Google Scholar
  42. Petrides, M. (2005). Lateral prefrontal cortex: Architectonic and functional organization. Philosophical Transactions of the Royal Society B, 360, 781–795.CrossRefGoogle Scholar
  43. Ranganath, C., Cohen, M. X., & Brozinsky, C. J. (2005). Working memory maintenance contributes to long-term memory formation: Neural and behavioral evidence. Journal of Cognitive Neuroscience, 17, 994–1010.PubMedCrossRefGoogle Scholar
  44. Ranganath, C., & D’Esposito, M. (2001). Medial temporal lobe activity associated with active maintenance of novel information. Neuron, 31, 865–873.PubMedCrossRefGoogle Scholar
  45. Rissman, J., Gazzaley, A., & D’Esposito, M. (2004). Measuring functional connectivity during distinct stages of a cognitive task. NeuroImage, 23, 752–763.PubMedCrossRefGoogle Scholar
  46. Roberts, A. C., Tomic, D. L., Parkinson, C. H., Roeling, T. A., Cutter, D. J., Robbins, T. W., & Everitt, B. J. (2007). Forebrain connectivity of the prefrontal cortex in the marmoset monkey (Callithrix jacchus): An anterograde and retrograde tract-tracing study. Journal of Comparative Neurology, 502, 86–112.Google Scholar
  47. Rolls, E. T. (2004). The functions of the orbitofrontal cortex. Brain and Cognition, 55, 11–29.PubMedCrossRefGoogle Scholar
  48. Rolls, E. T. (2007). The representation of information about faces in the temporal and frontal lobes. Neuropsychologia, 45, 124–143.PubMedCrossRefGoogle Scholar
  49. Ross, R. S., Brown, T. I., & Stern, C. E. (2009). The retrieval of learned sequences engages the hippocampus: Evidence from fMRI. Hippocampus, 19, 790–799.PubMedCentralPubMedCrossRefGoogle Scholar
  50. Ross, R. S., Sherrill, K. R., & Stern, C. E. (2011). The hippocampus is functionally connected to the striatum and orbitofrontal cortex during context dependent decision making. Brain Research, 1423, 53–66.PubMedCentralPubMedCrossRefGoogle Scholar
  51. Rudebeck, P. H., & Murray, E. A. (2008). Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning. Journal of Neuroscience, 28, 8338–8343.PubMedCentralPubMedCrossRefGoogle Scholar
  52. Sala, J. B., Rama, P., & Courtney, S. M. (2003). Functional topography of a distributed neural system for spatial and nonspatial information maintenance in working memory. Neuropsychologia, 41, 341–356.PubMedCrossRefGoogle Scholar
  53. Scheperjans, F., Eickhoff, S. B., Hömke, L., Mohlberg, H., Hermann, K., Amunts, K., & Zilles, K. (2008). Probabilistic maps, morphometry, and variability of cytoarchitectonic areas in the human superior parietal cortex. Cerebral Cortex, 18, 2141–2157.Google Scholar
  54. Schluppeck, D., Curtis, C. E., Glimcher, P. W., & Heeger, D. J. (2006). Sustained activity in topographic areas of human posterior parietal cortex during memory-guided saccades. Journal of Neuroscience, 26, 5098–5108.PubMedCentralPubMedCrossRefGoogle Scholar
  55. Schoenbaum, G., Setlow, B., Nugent, S. L., Saddoris, M. P., & Gallagher, M. (2003). Lesions of orbitofrontal cortex and basolateral amygdala complex disrupt acquisition of odor-guided discriminations and reversals. Learning and Memory, 10, 129–140.PubMedCentralPubMedCrossRefGoogle Scholar
  56. Schon, K., Atri, A., Hasselmo, M. E., Tricarico, M. D., LoPresti, M. L., & Stern, C. E. (2005). Scopolamine reduces persistent activity related to long-term encoding in the parahippocampal gyrus during delayed matching in humans. Journal of Neuroscience, 25, 9112–9123.PubMedCrossRefGoogle Scholar
  57. Schon, K., Hasselmo, M. E., Lopresti, M. L., Tricarico, M. D., & Stern, C. E. (2004). Persistence of parahippocampal representation in the absence of stimulus input enhances long-term encoding: A functional magnetic resonance imaging study of subsequent memory after a delayed match-to-sample task. Journal of Neuroscience, 24, 11088–11097. doi: 10.1523/JNEUROSCI.3807-04.2004 PubMedCrossRefGoogle Scholar
  58. Schon, K., Quiroz, Y. T., Hasselmo, M. E., & Stern, C. E. (2009). Greater working memory load results in greater medial temporal activity at retrieval. Cerebral Cortex, 19, 2561–2571.PubMedCentralPubMedCrossRefGoogle Scholar
  59. Schon, K., Ross, R. S., Hasselmo, M. E., & Stern, C. E. (2013). Complementary roles of medial temporal lobes and mid-dorsolateral prefrontal cortex for working memory for novel and familiar trial-unique visual stimuli. European Journal of Neuroscience, 37, 668–678. doi: 10.1111/ejn.12062 PubMedCrossRefGoogle Scholar
  60. Schon, K., Tinaz, S., Somers, D. C., & Stern, C. E. (2008). Delayed match to object or place: An event-related fMRI study of short-term stimulus maintenance and the role of stimulus pre-exposure. NeuroImage, 39, 857–872.PubMedCentralPubMedCrossRefGoogle Scholar
  61. Shohamy, D., & Wagner, A. D. (2008). Integrating memories in the human brain: Hippocampal–midbrain encoding of overlapping events. Neuron, 60, 378–389.PubMedCentralPubMedCrossRefGoogle Scholar
  62. Shrager, Y., Levy, D. A., Hopkins, R. O., & Squire, L. R. (2008). Working memory and the organization of brain systems. Journal of Neuroscience, 28, 4818–4822.PubMedCentralPubMedCrossRefGoogle Scholar
  63. Slotnick, S. D., Moo, L. R., Segal, J. B., & Hart, J., Jr. (2003). Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. Cognitive Brain Research, 17, 75–82.PubMedCrossRefGoogle Scholar
  64. Stern, C. E., Sherman, S. J., Kirchhoff, B. A., & Hasselmo, M. E. (2001). Medial temporal and prefrontal contributions to working memory tasks with novel and familiar stimuli. Hippocampus, 11, 337–346.PubMedCrossRefGoogle Scholar
  65. Tabbert, K., Stark, R., Kirsch, P., & Vaitl, D. (2005). Hemodynamic responses of the amygdala, the orbitofrontal cortex and the visual cortex during a fear conditioning paradigm. International Journal of Psychophysiology, 57, 15–23.PubMedCrossRefGoogle Scholar
  66. Tsuchida, A., Doll, B. B., & Fellows, L. K. (2010). Beyond reversal: A critical role for human orbitofrontal cortex in flexible learning from probabilistic feedback. Journal of Neuroscience, 30, 16868–16875.PubMedCrossRefGoogle Scholar
  67. Walton, M. E., Behrens, T. E., Buckley, M. J., Rudebeck, P. H., & Rushworth, M. F. (2010). Separable learning systems in the macaque brain and the role of orbitofrontal cortex in contingent learning. Neuron, 65, 927–939.PubMedCentralPubMedCrossRefGoogle Scholar
  68. Wood, E. R., Dudchenko, P. A., Robitsek, R. J., & Eichenbaum, H. (2000). Hippocampal neurons encode information about different types of memory episodes occurring in the same location. Neuron, 27, 623–633.PubMedCrossRefGoogle Scholar

Copyright information

© Psychonomic Society, Inc. 2013

Authors and Affiliations

  • Robert S. Ross
    • 1
    • 2
    • 3
    • 4
    • 6
    Email author
  • Matthew L. LoPresti
    • 1
    • 2
    • 3
    • 4
  • Karin Schon
    • 1
    • 2
    • 3
    • 4
  • Chantal E. Stern
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Center for Memory and BrainBoston UniversityBostonUSA
  2. 2.Center of Excellence for Learning in Education, Science, and Technology—CELESTBoston UniversityBostonUSA
  3. 3.Department of PsychologyBoston UniversityBostonUSA
  4. 4.Athinoula A. Martinos Center for Biomedical ImagingMassachusetts General Hospital and Harvard Medical SchoolCharlestownUSA
  5. 5.Department of RadiologyMassachusetts General Hospital and Harvard Medical SchoolCharlestownUSA
  6. 6.Boston UniversityBostonUSA

Personalised recommendations