REVIEWS 126,315-33 d1,4 es.393. a11,20 .R R& e.H. 51-57 nds c ⊥Ap he h r the ,549-5 tye the .C.s Pem 19开 6.31-38 5159o ws the 1-222105 51,1455-146199 良F an6 M.N n the in cortco-onta connc nan em h起,e 67,1 TURE REVIEWS NEUROSCIENC 2000 Macmillan Magazines Lto21. White, I. M. & Wise, S. P. Rule-dependent neuronal activity in the prefrontal cortex. Exp. Brain Res. 126, 315–335 (1999). Demonstration of ‘rule-tuned’ neurons in the primate prefrontal cortex. Monkeys were trained to acquire a target using either a ‘spatial’ or ‘associative’ rule. 22. Rainer, G., Asaad, W. F. & Miller, E. K. Selective representation of relevant information by neurons in the primate prefrontal cortex. Nature 393, 577–579 (1998). 23. Petrides, M. Deficits in non-spatial conditional associative learning after periarcuate lesions in the monkey. Behav. Brain Res. 16, 95–101 (1985). 24. Petrides, M. Nonspatial conditional learning impaired in patients with unilateral frontal but not unilateral temporal lobe excisions. Neuropsychologia 28, 137–149 (1990). 25. Gaffan, D. & Harrison, S. Inferotemporal-frontal disconnection and fornix transection in visuomotor conditional learning by monkeys. Behav. Brain Res. 31, 149–163 (1988). 26. Eacott, M. J. & Gaffan, D. Inferotemporal-frontal disconnection — the uncinate fascicle and visual associative learning in monkeys. Eur. J. Neurosci. 4, 1320–1332 (1992). 27. Parker, A. & Gaffan, D. Memory after frontal/temporal disconnection in monkeys: conditional and non-conditional tasks, unilateral and bilateral frontal lesions. Neuropsychologia 36, 259–271 (1998). 28. Watanabe, M. Prefrontal unit activity during associative learning in the monkey. Exp. Brain Res. 80, 296–309 (1990). 29. Asaad, W. F., Rainer, G. & Miller, E. K. Neural activity in the primate prefrontal cortex during associative learning. Neuron 21, 1399–1407 (1998). Neural information about a cue object and the saccade it instructed merged together in prefrontal activity in this neurophysiological study of associative learning. 30. Fuster, J. M., Bodner, M. & Kroger, J. K. Cross-modal and cross-temporal association in neurons of frontal cortex. Nature 405, 347–351 (2000). Demonstration that prefrontal neurons reflect learned cross-modal associations. Many prefrontal neurons were selectively responsive to a visual stimulus and the auditory stimulus with which it was associated. 31. Bichot, N. P., Schall, J. D. & Thompson, K. G. Visual feature selectivity in frontal eye fields induced by experience in mature macaques. Nature 381, 697–699 (1996). Neurophysiological study showing learning-induced response properties for neurons in the frontal eye fields. Monkeys trained to look for a particular colour developed neurons sensitive to that colour. 32. Bichot, N. P. & Schall, J. D. Effects of similarity and history on neural mechanisms of visual selection. Nature Neurosci. 2, 549–554 (1999). 33. Hoshi, E., Shima, K. & Tanji, J. Task-dependent selectivity of movement-related neuronal activity in the primate prefrontal cortex. J. Neurophysiol. 80, 3392–3397 (1998). 34. Asaad, W. F., Rainer, G. & Miller, E. K. Task-specific neural activity in the primate prefrontal cortex. J. Neurophysiol. 84, 451–459 (2000). Demonstration that the responses of prefrontal neurons to cues and actions are highly task-specific. This indicates that prefrontal neurons may participate in neural ensembles that represent tasks, not just stimuli and forthcoming motor acts. 35. Wallis, J. D., Anderson, K. C. & Miller, E. K. Neuronal representation of abstract rules in the orbital and lateral prefrontal cortices (PFC). Soc. Neurosci. Abstr. (in the press). 36. Dehaene, S., Kerszeberg, M. & Changeux, J. P. A neuronal model of a global workspace in effortful cognitive tasks. Proc. Natl Acad. Sci. USA 95, 14529–14534 (1998). 37. Watanabe, M. Reward expectancy in primate prefrontal neurons. Nature 382, 629–632 (1996). 38. Tremblay, L. & Schultz, W. Relative reward preference in primate orbitofrontal cortex. Nature 398, 704–708 (1999). 39. Leon, M. I. & Shadlen, M. N. Effect of expected reward magnitude on the response of neurons in the dorsolateral prefrontal cortex of the macaque. Neuron 24, 415–425 (1999). 40. Mirenowicz, J. & Schultz, W. Importance of unpredictability for reward responses in primate dopamine neurons. J. Neurophysiol. 72, 1024–1027 (1994). 41. Mirenowicz, J. & Schultz, W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature 379, 449–451 (1996). 42. Schultz, W., Apicella, P. & Ljungberg, T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J. Neurosci. 13, 900–913 (1993). 43. Schultz, W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1–27 (1998). 44. Hollerman, J. R. & Schultz, W. Dopamine neurons report an error in the temporal prediction of reward during learning. Nature Neurosci. 1, 304–309 (1998). 45. Schultz, W. & Dickinson, A. Neuronal coding of prediction errors. Annu. Rev. Neurosci. 23, 473–500 (2000). A review of evidence that dopamine neurons provide a ‘prediction error’ signal that can orchestrate learning of the means to acquire rewards. 46. Cepeda, C., Buchwald, N. A. & Levine, M. S. Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated. Proc. Natl Acad. Sci. USA 90, 9576–9580 (1993). 47. Williams, G. V. & Goldman-Rakic, P. S. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376, 572–575 (1995). 48. Braver, T. S. & Cohen, J. D. in Attention and Performance 18 (eds Monsell, S. & Driver, J.) (MIT Press, Cambridge, Massachusetts, in the press). 49. Fuster, J. M. Unit activity in prefrontal cortex during delayedresponse performance: neuronal correlates of transient memory. J. Neurophysiol. 36, 61–78 (1973). 50. Niki, H. Differential activity of prefrontal units during right and left delayed response trials. Brain Res. 70, 346–349 (1974). 51. Funahashi, S., Bruce, C. J. & Goldman-Rakic, P. S. Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. J. Neurophysiol. 61, 331–349 (1989). 52. Miller, E. K., Erickson, C. A. & Desimone, R. Neural mechanisms of visual working memory in prefrontal cortex of the macaque. J. Neurosci. 16, 5154–5167 (1996). 53. Romo, R., Brody, C. D., Hernandez, A. & Lemus, L. Neuronal correlates of parametric working memory in the prefrontal cortex. Nature 399, 470–473 (1999). 54. Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599 (1997). 55. Duncan, J., Emslie, H., Williams, P., Johnson, R. & Freer, C. Intelligence and the frontal lobe: The organization of goaldirected behavior. Cogn. Psychol. 30, 257–303 (1996). 56. Miller, E. K., Li, L. & Desimone, R. Activity of neurons in anterior inferior temporal cortex during a short-term memory task. J. Neurosci. 13, 1460–1478 (1993). 57. Constantinidis, C. & Steinmetz, M. A. Neuronal activity in posterior parietal area 7a during the delay periods of a spatial memory task. J. Neurophysiol. 76, 1352–1355 (1996). 58. Zipser, D., Kehoe, B., Littlewort, G. & Fuster, J. A spiking network model of short-term active memory. J. Neurosci. 13, 3406–3420 (1993). 59. Durstewitz, D., Kelc, M. & Gunturkun, O. A neurocomputational theory of the dopaminergic modulation of working memory functions. J. Neurosci. 19, 2807–2822 (1999). 60. Wang, X. J. Synaptic basis of cortical persistent activity: the importance of NMDA receptors to working memory. J. Neurosci. 19, 9587–9603 (1999). 61. Durstewitz, D., Seamans, J. K. & Sejnowski, T. J. Dopamine-mediated stabilization of delay-period activity in a network model of the prefrontal cortex. J. Neurophysiol. 83, 1733–1750 (2000). 62. Desimone, R. & Duncan, J. Neural mechanisms of selective visual attention. Ann. Rev. Neurosci. 18, 193–222 (1995). A review of the neural mechanisms for focal attention. The authors suggest that bias signals from the PFC resolve neural competition between items vying to reach awareness. 63. Miller, E. K. in Attention and Performance 18 (eds Monsell, S. & Driver, J.) (MIT Press, Cambridge, Massachusetts, in the press). 64. Fuster, J. M., Bauer, R. H. & Jervey, J. P. Functional interactions between inferotemporal and prefrontal cortex in a cognitive task. Brain Res. 330, 299–307 (1985). 65. Chafee, M. V. & Goldman-Rakic, P. S. Inactivation of parietal and prefrontal cortex reveals interdependence of neural activity during memory-guided saccades. J. Neurophysiol. 83, 1550–1566 (2000). 66. Tomita, H., Ohbayashi, M., Nakahara, K., Hasegawa, I. & Miyashita, Y. Top-down signal from prefrontal cortex in executive control of memory retrieval. Nature 401, 699–703 (1999). Neurophysiological study showing that ‘top-down’ signals from the PFC are required to activate longterm memories stored in the inferior temporal cortex. 67. Miller, E. K. & Desimone, R. Parallel neuronal mechanisms for short-term memory. Science 263, 520–522 (1994). 68. Recanzone, G. H., Merzenich, M. M. & Jenkins, W. M. Frequency discrimination training engaging a restricted skin surface results in an emergence of a cutaneous response zone in cortical area 3a. J. Neurophysiol. 67, 1057–1070 (1992). 69. Merzenich, M. M. & Sameshima, K. Cortical plasticity and memory. Curr. Opin. Neurobiol. 3, 187–196 (1993). 70. Gilbert, C. D. Plasticity in visual perception and physiology. Curr. Opin. Neurobiol. 6, 269–274 (1996). 71. Rushworth, M. F., Nixon, P. D., Eacott, M. J. & Passingham, R. E. Ventral prefrontal cortex is not essential for working memory. J. Neurosci. 17, 4829–4838 (1997). 72. Knight, R. T. Decreased response to novel stimuli after prefrontal lesions in man. Clin. Neurophys. 59, 9–20 (1984). 73. Yamaguchi, S. & Knight, R. T. Anterior and posterior association cortex contributions to the somatosensory P300. J. Neurosci. 11, 2039–2054 (1991). 74. Knight, R. T. Distributed cortical network for visual attention. J. Cogn. Neurosci. 9, 75–91 (1997). 75. Shadmehr, R. & Holcomb, H. Neural correlates of motor memory consolidation. Science 277, 821–824 (1997). 76. Riches, I. P., Wilson, F. A. & Brown, M. W. The effects of visual stimulation and memory on neurons of the hippocampal formation and the neighboring parahippocampal gyrus and inferior temporal cortex of the primate. J. Neurosci. 11, 1763–1779 (1991). 77. Miller, E. K., Gochin, P. M. & Gross, C. G. Habituation-like decrease in the responses of neurons in inferior temporal cortex of the macaque. Vis. Neurosci. 7, 357–362 (1991). 78. Li, L., Miller, E. K. & Desimone, R. The representation of stimulus familiarity in anterior inferior temporal cortex. J. Neurophysiol. 69, 1918–1929 (1993). 79. Miller, E. K., Li, L. & Desimone, R. A neural mechanism for working and recognition memory in inferior temporal cortex. Science 254, 1377–1379 (1991). 80. Rainer, G., Rao, S. C. & Miller, E. K. Prospective coding for objects in primate prefrontal cortex. J. Neurosci. 19, 5493–5505 (1999). 81. Squire, L. R. & Zola-Morgan, S. The medial temporal lobe memory system. Science 253, 1380–1386 (1991). 82. Eichenbaum, H., Dudchenko, P., Wood, E., Shapiro, M. & Tanila, H. The hippocampus, memory, and place cells: Is it spatial memory or a memory space? Neuron 23, 209–226 (1999). 83. Ivry, R. B. The representation of temporal information in perception and motor control. Curr. Opin. Neurobiol. 6, 851–857 (1996). 84. Graybiel, A. M. The basal ganglia and chunking of action sequences. Neurobiol. Learn. Mem. 70, 119–136 (1998). 85. Botvinick, M., Nystrom, L. E., Fissell, K., Carter, C. S. & Cohen, J. D. Conflict monitoring versus selection-for-action in anterior cingulate cortex. Nature 402, 179–181 (1999). 86. Fuster, J. M. Memory in the Cerebral Cortex (MIT Press, Cambridge, Massachusetts, 1995). 87. Petrides, M. Functional organization of the human frontal cortex for mnemonic processing — Evidence from neuroimaging studies. Ann. NY Acad. Sci. 769, 85–96 (1995). 88. Owen, A. M., Evans, A. C. & Petrides, M. Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: A positron emission tomography study. Cereb. Cortex 6, 31–38 (1996). Evidence from human functional imaging that different prefrontal regions are involved in simple maintenance versus the monitoring and manipulation of information held ‘in mind’. 89. Petrides, M. Specialized systems for the processing of mnemonic information within the primate frontal cortex. Phil. Trans. R. Soc. Lond. B 351, 1455–1461 (1996). 90. Goldman-Rakic, P. S. in Vision and Movement Mechanisms in the Cerebral Cortex (eds Caminiti, R., Hoffman, K. P., Lacquaniti, F. & Altman, J.) 162–172 (HFSP, Strasbourg, 1996). 91. Milner, B. Effects of different brain lesions on card sorting. Arch. Neurol. 9, 90 (1963). 92. Dias, R., Robbins, T. W. & Roberts, A. C. Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav. Neurosci. 110, 872–886 (1996). 93. Shallice, T. & Burgess, P. W. Deficits in strategy application following frontal lobe damage in man. Brain 114, 727–741 (1991). 94. Jones, E. G. & Powell, T. P. S. An anatomical study of converging sensory pathways within the cerebral cortex of the monkey. Brain 93, 793–820 (1970). 95. Chavis, D. A. & Pandya, D. N. Further observations on cortico–frontal connections in the rhesus monkey. Brain Res. 117, 369–386 (1976). Acknowledgements I thank Wael Asaad, Jonathan Cohen, Peter Dayan, John Duncan, Howard Eichenbaum, David Freedman, Tomaso Poggio, Maximilian Riesenhuber and Marlene Wicherski for valuable comments and discussions. NATURE REVIEWS | NEUROSCIENCE VOLUME 1 | OCTOBER 2000 | 6 5 REVIEWS © 2000 Macmillan Magazines Ltd