The Prefrontal Cortex as a Model System to Understand Representation and Processing of Information

  • Shintaro Funahashi


Working memory includes temporary active maintenance of information as well as processing of maintained information. Delay-period activity observed in the prefrontal cortex has been shown to be a neural correlate of the mechanism for short-term active maintenance of information. Using spatial working memory tasks, it was found that a great majority of delay-period activity represents retrospective information (e.g., the location of the visual cue) whereas a minority represents prospective information (e.g., the direction of the forthcoming movement). In addition, using population vector analysis using a population of prefrontal activities, the temporal progression of information processing can be seen as a temporal change of the direction as well as the length of the population vector during the delay period. The mechanism participating in the gradual change of information represented by a population of activities remains unresolved. However, functional interactions among neighboring neurons representing different information and dynamic modulation of these interactions depending on the context of the trial could be a mechanism of this process.


Prefrontal Cortex Delay Period Neuron Pair DLPFC Activity DLPFC Neuron 
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  1. Aertsen AMHJ, Gerstein GL, Habib MK, Palm G (1989) Dynamics of neuronal firing correlation: modulation of “effective connectivity.” J Neurophysiol 61:900–917PubMedGoogle Scholar
  2. Amemori K, Sawaguchi T (2006) Rule-dependent shifting of sensorimotor representation in the primate prefrontal cortex. Eur J Neurosci 23:1895–1909PubMedCrossRefGoogle Scholar
  3. Baddeley A (1986) Working memory. Oxford University Press, OxfordGoogle Scholar
  4. Baddeley AD, Hitch G (1974) Working memory. In: Bower GH (ed) The psychology of learning and motivation: advances in research and theory. Academic Press, New York, pp 47–89Google Scholar
  5. Barone P, Joseph JP (1989) Prefrontal cortex and spatial sequencing in macaque monkey. Exp Brain Res 78:447–464PubMedCrossRefGoogle Scholar
  6. Boch RA, Goldberg ME (1989) Participation of prefrontal neurons in the preparation of visually guided eye movements in the rhesus monkey. J Neurophysiol 61:1064–1084PubMedGoogle Scholar
  7. Brody CD, Hernandez A, Zainos A, Romo R (2003) Timing and neural encoding of somatosensory parametric working memory in macaque prefrontal cortex. Cereb Cortex 13:1196–1207PubMedCrossRefGoogle Scholar
  8. Brown MRG, DeSouza JFX, Goltz HC, Ford K, Menon RS, Goodale MA, Everling S (2004) Comparison of memory-and visually guided saccades using event-related fMRI. J Neurophysiol 91:873–889PubMedCrossRefGoogle Scholar
  9. Bruce CJ, Goldberg ME (1985) Primate frontal eye fields. I. Single neurons discharging before saccades. J Neurophysiol 53:603–635PubMedGoogle Scholar
  10. Butters N, Pandya D, Sanders K, Dye P (1971) Behavioral deficits in monkeys after selective lesions within the middle third of sulcus principalis. J Comp Physiol Psychol 76:8–14PubMedCrossRefGoogle Scholar
  11. Carlson S, Rämä P, Tanila H, Linnankoski I, Mansikka H (1997) Dissociation of mnemonic coding and other functional neuronal processing in the monkey prefrontal cortex. J Neurophysiol 77:761–774PubMedGoogle Scholar
  12. Chelazzi L, Duncan J, Miller EK, Desimone R (1998) Responses of neurons in inferior temporal cortex during memory-guided visual search. J Neurophysiol 80:2918–2940PubMedGoogle Scholar
  13. Constantinidis C, Franowicz MN, Goldman-Rakic PS (2001) Coding specificity in cortical microcircuits: a multiple-electrode analysis of primate prefrontal cortex. J Neurosci 21:3646–3655PubMedGoogle Scholar
  14. Curtis CE, D’Esposito M (2006) Selection and maintenance of saccade goals in the human frontal eye fields. J Neurophysiol 95:3923–3927PubMedCrossRefGoogle Scholar
  15. Curtis CE, Rao VY, D’Esposito M (2004) Maintenance of spatial and motor codes during oculomotor delayed response tasks. J Neurosci 24:3944–3952PubMedCrossRefGoogle Scholar
  16. D’Esposito M, Detre JA, Alsop DC, Shin RK, Atlas S, Grossman M (1995) The neural basis of the central executive system of working memory. Nature (Lond) 378:279–281PubMedCrossRefGoogle Scholar
  17. Freedman DJ, Riesenhuber M, Poggio T, Miller EK (2001) Categorical representation of visual stimuli in the primate prefrontal cortex. Science 291:312–316PubMedCrossRefGoogle Scholar
  18. Freedman M, Oscar-Berman M (1986) Bilateral frontal lobe disease and selective delayed response deficits in humans. Behav Neurosci 100:337–342PubMedCrossRefGoogle Scholar
  19. Fukushima T, Hasegawa I, Miyashita Y (2004) Prefrontal neuronal activity encodes spatial target representations sequentially updated after nonspatial target-shift cues. J Neurophysiol 91:1367–1380PubMedCrossRefGoogle Scholar
  20. Funahashi S (2001) Neuronal mechanisms of executive control by the prefrontal cortex. Neurosci Res 39:147–165PubMedCrossRefGoogle Scholar
  21. Funahashi S, Inoue M (2000) Neuronal interactions related to working memory processes in the primate prefrontal cortex revealed by cross-correlation analysis. Cereb Cortex 10:535–551PubMedCrossRefGoogle Scholar
  22. Funahashi S, Kubota K (1994) Working memory and prefrontal cortex. Neurosci Res 21:1–11PubMedCrossRefGoogle Scholar
  23. Funahashi S, Takeda K (2002) Information processes in the primate prefrontal cortex in relation to working memory processes. Rev Neurosci 13:313–345PubMedGoogle Scholar
  24. Funahashi S, Bruce CJ, Goldman-Rakic PS (1989) Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. J Neurophysiol 61:331–349PubMedGoogle Scholar
  25. Funahashi S, Bruce CJ, Goldman-Rakic PS (1990) Visuospatial coding in primate prefrontal neurons revealed by oculomotor paradigms. J Neurophysiol 63:814–831PubMedGoogle Scholar
  26. Funahashi S, Bruce CJ, Goldman-Rakic PS (1991) Neuronal activity related to saccadic eye movements in the monkey’s dorsolateral prefrontal cortex. J Neurophysiol 65:1464–1483.PubMedGoogle Scholar
  27. Funahashi S, Bruce CJ, Goldman-Rakic PS (1993a) Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic “scotomas.” J Neurosci 13:1479–1497PubMedGoogle Scholar
  28. Funahashi S, Chafee MV, Goldman-Rakic PS (1993b) Prefrontal neuronal activity in rhesus monkeys performing a delayed anti-saccade task. Nature (Lond) 365:753–756PubMedCrossRefGoogle Scholar
  29. Funahashi S, Inoue M, Kubota K (1997) Delay-period activity in the primate prefrontal cortex encoding multiple spatial positions and their order of presentation. Behav Brain Res 84:203–223PubMedCrossRefGoogle Scholar
  30. Fuster JM (1973) Unit activity in prefrontal cortex during delayed-response performance: neuronal correlates of transient memory. J Neurophysiol 36:61–78PubMedGoogle Scholar
  31. Fuster JM (1997) The prefrontal cortex: anatomy, physiology, and neuropsychology of the frontal lobe, 3rd edn. Lippincott-Raven, PhiladelphiaGoogle Scholar
  32. Genovesio A, Brasted PJ, Wise SP (2006) Representation of future and previous spatial goals by separate neural populations in prefrontal cortex. J Neurosci 26:7305–7316PubMedCrossRefGoogle Scholar
  33. Gerstein GL, Perkel DH (1969) Simultaneously recorded trains of action potentials: analysis and functional interpretation. Science 164:828–830PubMedCrossRefGoogle Scholar
  34. Gerstein GL, Perkel DH (1972) Mutual temporal relationships among neuronal spike trains. Statistical techniques for display and analysis. Biophys J 12:453–473PubMedCrossRefGoogle Scholar
  35. Georgopoulos A, Kettner RE, Schwartz AB (1988) Primate motor cortex and free arm movements to visual targets in three-dimensional space. II. Coding of the direction of movement by a neuronal population. J Neurosci 8:2928–2937PubMedGoogle Scholar
  36. Georgopoulos AP, Schwartz AB, Kettner RE (1986) Neuronal population coding of movement direction. Science 233:1416–1419PubMedCrossRefGoogle Scholar
  37. Goldman-Rakic PS (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In: Plum F (ed) Higher functions of the brain, part 1. Handbook of physiology, section 1: the nervous system, vol V. American Physiological Society, Bethesda, MD, pp 373–417Google Scholar
  38. Goldman-Rakic PS (1998) The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. In: Roberts AC, Robbins TW, Weiskrantz L (eds) The prefrontal cortex: executive and cognitive functions. Oxford University Press, Oxford, pp 87–102Google Scholar
  39. Goldman-Rakic PS (1999) The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol Psychiatry 46:650–661PubMedCrossRefGoogle Scholar
  40. Goldman-Rakic PS, Funahashi S, Bruce CJ (1990) Neocortical memory circuits. Cold Spring Harbor Symp Quant Biol 55:1025–1038PubMedGoogle Scholar
  41. Hasegawa I, Fukushima T, Ihara T, Miyashita Y (1998) Callosal window between prefrontal cortices: cognitive interaction to retrieve long-term memory. Science 281:814–818PubMedCrossRefGoogle Scholar
  42. Hikosaka O, Wurtz RH (1983) Visual and oculomotor functions of monkey substantia nigra pars reticulata. III. Memory-contingent visual and saccade responses. J Neurophysiol 49:1268–1284PubMedGoogle Scholar
  43. Hoshi E (2006) Functional specialization within the dorsolateral prefrontal cortex: a review of anatomical and physiological studies of non-human primates. Neurosci Res 54:73–84PubMedCrossRefGoogle Scholar
  44. Hoshi E, Shima K, Tanji J (2000) Neuronal activity in the primate prefrontal cortex in the process of motor selection based on two behavioral rules. J Neurophysiol 83:2355–2373PubMedGoogle Scholar
  45. Hoshi E, Tanji J (2004) Area-selective neuronal activity in the dorsolateral prefrontal cortex for information retrieval and action planning. J Neurophysiol 91:2707–2722PubMedCrossRefGoogle Scholar
  46. Inoue M, Mikami A (2006) Prefrontal activity during serial probe reproduction task: encoding, mnemonic, and retrieval processes. J Neurophysiol 95:1008–1041PubMedCrossRefGoogle Scholar
  47. Jacobsen CF (1936) Studies of cerebral function in primates. I. The functions of the frontal association areas in monkeys. Comp Psychol Monogr 13:1–60Google Scholar
  48. Johnston K, Everling S (2006) Monkey dorsolateral prefrontal cortex sends task-selective signals directly to the superior colliculus. J Neurosci 26:12471–12478PubMedCrossRefGoogle Scholar
  49. Kettner RE, Schwartz AB, Georgopoulos AP (1988) Primate motor cortex and free arm movements to visual targets in three-dimensional space. III. Positional gradients and population coding of movement direction from various movement origins. J Neurosci 8:2938–2947PubMedGoogle Scholar
  50. Kojima S, Goldman-Rakic PS (1982) Delay-related activity of prefrontal neurons in rhesus monkeys performing delayed response. Brain Res 248:43–49PubMedCrossRefGoogle Scholar
  51. Lauwereyns J, Sakagami M, Tsutsui K, Kobayashi S, Koizumi M, Hikosaka O (2001) Responses to task-irrelevant visual features by primate prefrontal neurons. J Neurophysiol 86:2001–2010PubMedGoogle Scholar
  52. Lumer E, Rees G (1999) Covariation of activity in visual and prefrontal cortex associated with subjective visual perception. Proc Natl Acad Sci U S A 96:1669–1673PubMedCrossRefGoogle Scholar
  53. Mansouri FA, Matsumoto K, Tanaka K (2006) Prefrontal cell activities related to monkeys’ success and failure in adapting to rule changes in a Wisconsin card sorting test analog. J Neurosci 26:2745–2756PubMedCrossRefGoogle Scholar
  54. Mikami A, Ito S, Kubota K (1982) Visual response properties of dorsolateral prefrontal neurons during visual fixation task. J Neurophysiol 47:593–605PubMedGoogle Scholar
  55. Miller EK (2000) The prefrontal cortex and cognitive control. Nat Rev Neurosci 1:59–65PubMedCrossRefGoogle Scholar
  56. Miller EK, Cohen JD (2001) An integrative theory of prefrontal cortex function. Annu Rev Neurosci 24:167–202PubMedCrossRefGoogle Scholar
  57. Miller EK, Erickson CA, Desimone R (1996) Neural mechanisms of visual working memory in prefrontal cortex of the macaque. J Neurosci 16:5154–5167PubMedGoogle Scholar
  58. Morris R, Pandya DN, Petrides M (1999) Fiber system linking the mid-dorsolateral frontal cortex with the retrosplenial/presubicular region in the rhesus monkey. J Comp Neurol 407:183–192PubMedCrossRefGoogle Scholar
  59. Mushiake H, Saito N, Sakamoto K, Itoyama Y, Tanji J (2006) Activity in the lateral prefrontal cortex reflects multiple steps of future events in action plans. Neuron 50: 631–641PubMedCrossRefGoogle Scholar
  60. O’Scalaidhe SP, Wilson FAW, Goldman-Rakic PS (1999) Face-selective neurons during passive viewing and working memory performance of rhesus monkeys: evidence for intrinsic specialization of neuronal coding. Cereb Cortex 9:459–475CrossRefGoogle Scholar
  61. Pandya DN, Barnes CL (1987) Architecture and connections of the frontal lobe. In: Perecman E (ed) The frontal lobes revisited. IRBN Press, New York, pp 41–72Google Scholar
  62. Perkel DH, Gerstein GL, Moore GP (1967a) Neuronal spike trains and stochastic point processes. I. The single spike train. Biophys J 7:391–418PubMedCrossRefGoogle Scholar
  63. Perkel DH, Gerstein L, Moore GP (1967b) Neuronal spike trains and stochastic point processes. II. Simultaneous spike trains. Biophys J 7:419–440PubMedCrossRefGoogle Scholar
  64. Petrides M (1994) Frontal lobes and working memory: evidence from investigations of the effects of cortical excisions in nonhuman primates. In: Boller F, Spinnler H, Hendler JA (eds) Handbook of neuropsychology, vol 9. Elsevier, Amsterdam, pp 59–82Google Scholar
  65. Postle BR, Berger JS, Taich AM, D’Esposito M (2000) Activity in human frontal cortex associated with spatial working memory and saccadic behavior. J Cognit Neurosci 12:2–14CrossRefGoogle Scholar
  66. Quintana J, Fuster JM (1999) From perception to action: temporal integrative functions of prefrontal and parietal neurons. Cereb Cortex 9:213–221PubMedCrossRefGoogle Scholar
  67. Rainer G, Asaad WF, Miller EK (1998) Memory fields of neurons in the primate prefrontal cortex. Proc Natl Acad Sci U S A 95:15008–15013PubMedCrossRefGoogle Scholar
  68. Rainer G, Miller EK (2000) Effects of visual experience on the representation of objects in the prefrontal cortex. Neuron 27:179–189PubMedCrossRefGoogle Scholar
  69. Rainer G, Miller EK (2002) Time-course of object-related neural activity in the primate prefrontal cortex during a short-term memory task. Eur J Neurosci 15:1244–1254PubMedCrossRefGoogle Scholar
  70. Rainer G, Rao SC, Miller EK (1999) Prospective coding for objects in primate prefrontal cortex. J Neurosci 19:5493–5505PubMedGoogle Scholar
  71. Rao SC, Rainer G, Miller EK (1997) Integration of what and where in the primate prefrontal cortex. Science 276:821–824.PubMedCrossRefGoogle Scholar
  72. Rao SG, Williams GV, Goldman-Rakic PS (1999) Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: evidence for microcolumnar organization in PFC. J Neurophysiol 81:1903–1916PubMedGoogle Scholar
  73. Romo R, Brody CD, Hernandez A, Lemus L (1999) Neuronal correlates of parametric working memory in the prefrontal cortex. Nature (Lond) 399:470–473PubMedCrossRefGoogle Scholar
  74. Saito N, Mushiake H, Sakamoto K, Itoyama Y, Tanji J (2005) Representation of immediate and final behavioral goals in the monkey prefrontal cortex during an instructed delay period. Cereb Cortex 15:1535–1546PubMedCrossRefGoogle Scholar
  75. Sakagami M, Niki H (1994) Encoding of behavioral significance of visual stimuli by primate prefrontal neurons: relation to relevant task conditions. Exp Brain Res 97:423–436PubMedCrossRefGoogle Scholar
  76. Sakagami M, Tsutsui K (1999) The hierarchical organization of decision making in the primate prefrontal cortex. Neurosci Res 34:79–89PubMedCrossRefGoogle Scholar
  77. Sakagami M, Tsutsui K, Lauwereyns J, Koizumi M, Kobayashi S, Hikosaka O (2001) A code for behavioral inhibition on the basis of color, but not motion, in ventrolateral prefrontal cortex of macaque monkey. J Neurosci 21:4801–4808PubMedGoogle Scholar
  78. Sakurai Y, Takahashi S (2006) Dynamic synchrony of firing in the monkey prefrontal cortex during working-memory tasks. J Neurosci 26:10141–10153PubMedCrossRefGoogle Scholar
  79. Schwartz AB, Kettner RE, Georgopoulos AP (1988) Primate motor cortex and free arm movements to visual targets in three-dimensional space. I. Relations between single cell discharge and direction of movement. J Neurosci 8:2913–2927PubMedGoogle Scholar
  80. Stuss DT, Knight RT (2002) Principles of frontal lobe function. Oxford University Press, New YorkGoogle Scholar
  81. Suzuki H, Azuma M (1983) Topographic studies on visual neurons in the dorsolateral prefrontal cortex of the monkey. Exp Brain Res 53:47–58PubMedCrossRefGoogle Scholar
  82. Takeda K, Funahashi S (2002) Prefrontal task-related activity representing visual cue location or saccade direction in spatial working memory tasks. J Neurophysiol 87:567–588PubMedGoogle Scholar
  83. Takeda K, Funahashi S (2004) Population vector analysis of primate prefrontal activity during spatial working memory. Cereb Cortex 14:1328–1339PubMedCrossRefGoogle Scholar
  84. Tomita H, Ohbayashi M, Nakahara K, Hasegawa I, Miyashita Y (1999) Top-down signal from prefrontal cortex in executive control of memory retrieval. Nature (Lond) 401:699–703PubMedCrossRefGoogle Scholar
  85. Vaadia E, Haalman I, Abeles M, Bergman H, Prut Y, Slovin H, Aertsen A (1995) Dynamics of neuronal interactions in monkey cortex in relation to behavioral events. Nature (Lond) 373:515–518PubMedCrossRefGoogle Scholar
  86. Wallis JD, Miller EK (2003) From rule to response: neuronal processes in the premotor and prefrontal cortex. J Neurophysiol 90:1790–1806PubMedCrossRefGoogle Scholar
  87. Wallis JD, Anderson KC, Miller EK (2001) Single neurons in prefrontal cortex encode abstract rules. Nature (Lond) 411:953–956PubMedCrossRefGoogle Scholar
  88. White IM, Wise SP (1999) Rule-dependent neuronal activity in the prefrontal cortex. Exp Brain Res 126:315–335PubMedCrossRefGoogle Scholar
  89. Wilson FAW, O’Scalaidhe SP, Goldman-Rakic PS (1993) Dissociation of object and spatial processing domains in primate prefrontal cortex. Science 260:1955–1958PubMedCrossRefGoogle Scholar
  90. Windmann S, Wehrmann M, Calabrese P, Gunturkun O (2006) Role of the prefrontal cortex in attentional control over bistable vision. J Cognit Neurosci 18:456–471CrossRefGoogle Scholar

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© Springer 2007

Authors and Affiliations

  • Shintaro Funahashi
    • 1
  1. 1.Department of Cognitive and Behavioral Sciences, Graduate School of Human and Environmental StudiesKyoto UniversityKyotoJapan

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