Abstract
The effects of experimental lesions of the monkey prefrontal cortex have played a predominant role in current conceptualizations of the functional organization of the lateral prefrontal cortex, especially with regard to working memory. The loss or sparing of certain performance abilities has been shown to be attributable to differences in the specific requirements of behavioral testing (e.g., spatial vs. nonspatial memoranda) along with differences in the specific locations of applied ablations (e.g., dorsal vs. ventral prefrontal cortex). Such findings, which have accumulated now for over a century, have led to widespread acceptance that the dorsolateral and ventrolateral aspects of the prefrontal cortex may perform different, specialized roles in higher order cognition. Nonetheless, it remains unclear and controversial how the lateral prefrontal cortex is functionally organized. Two main views propose different types of functional specialization of the dorsal and ventral prefrontal cortex. The first contends that the lateral prefrontal cortex is segregated according to the processing of spatial and nonspatial domains of information. The second contends that domain specialization is not the key to the organization of the prefrontal cortex, but that instead, the dorsal and ventral prefrontal cortices perform qualitatively different operations. This report critically reviews all relevant monkey lesion studies that have served as the foundation for current theories regarding the functional organization of the prefrontal cortex. Our goals are to evaluate how well the existing lesion data support each theory and to enumerate caveats that must be considered when interpreting the relevant literature.
Article PDF
Similar content being viewed by others
References
Bachevalier, J., & Mishkin, M. (1986). Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys. Behavioral & Brain Research, 20, 249–261.
Bauer, R. H., & Fuster, J. M. (1976). Delayed-matching and delayedresponse deficit from cooling dorsolateral prefrontal cortex in monkeys. Journal of Comparative & Physiological Psychology, 90, 293–302.
Bianchi, L. (1922). The mechanism of the brain and the function of the frontal lobes. Edinburgh: E. & S. Livingstone.
Blum, R. A. (1952). Effects of subtotal lesions of frontal granular cortex on delay reaction in monkeys. Archives of Neurology & Psychiatry, 67, 375–386.
Bussey, T. J., Wise, S. P., & Murray, E. A. (2001). The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta). Behavioral Neuroscience, 115, 971–982.
Butters, N., & Pandya, D. (1969, September 19). Retention of delayedalternation: Effect of selective lesions of sulcus principalis. Science, 165, 1271–1273.
Butters, N., Pandya, D., Stein, D., & Rosen, J. (1972). A search for the spatial engram within the frontal lobes of monkeys. Acta Neurobiologiae Experimentalis, 32, 305–329.
Curtis, C. E., & D’Esposito, M. (2003). Persistent activity in the prefrontal cortex during working memory. Trends in Cognitive Sciences, 7, 415–423.
Curtis, C. E., Zald, D. H., Lee, J. T., & Pardo, J. V. (2000). Object and spatial alternation tasks with minimal delays activate the right anterior hippocampus proper in humans. NeuroReport, 11, 2203–2207.
D’Esposito, M., Postle, B. R., & Rypma, B. (2000). Prefrontal cortical contributions to working memory: Evidence from event-related fMRI studies. Experimental Brain Research, 133, 3–11.
Eacott, M. J., & Gaffan, D. (1992). Inferotemporal-frontal disconnection: The uncinate fascicle and visual associative learning in monkeys. European Journal of Neuroscience, 4, 1320–1332.
Ferrier, D. (1886). The functions of the brain (2nd. ed.). London: Smith, Elder, & Co.
Franz, S. I. (1907). On the functions of the cerebrum: The frontal lobes. New York: Science Press.
Funahashi, S. (2001). Neuronal mechanisms of executive control by the prefrontal cortex. Neuroscience Research, 39, 147–165.
Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1989). Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. Journal of Neurophysiology, 61, 331–349.
Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1990). Visuospatial coding in primate prefrontal neurons revealed by oculomotor paradigms. Journal of Neurophysiology, 63, 814–831.
Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1991). Neuronal activity related to saccadic eye movements in the monkey’s dorsolateral prefrontal cortex. Journal of Neurophysiology, 65, 1464–1483.
Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1993). Dorsolateral prefrontal lesions and oculomotor delayed-response performance: Evidence for mnemonic “scotomas.” Journal of Neuroscience, 13, 1479–1497.
Fuster, J. M. (2001). The prefrontal cortex—an update: Time is of the essence. Neuron, 30, 319–333.
Fuster, J. M., & Alexander, G. E. (1970). Delayed response deficit by cryogenic depression of frontal cortex. Brain Research, 20, 85–90.
Fuster, J. M., & Bauer, R. H. (1974). Visual short-term memory deficit from hypothermia of frontal cortex. Brain Research, 81, 393–400.
Fuster, J. M., Bauer, R. H., & Jervey, J. P. (1982). Cellular discharge in the dorsolateral prefrontal cortex of the monkey in cognitive tasks. Experimental Neurology, 77, 679–694.
Gaffan, D., & Harrison, S. (1988). Inferotemporal-frontal disconnection and fornix transection in visuomotor conditional learning by monkeys. Behavioral & Brain Research, 31, 149–163.
Goldman, P. S., & Rosvold, H. E. (1970). Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey. Experimental Neurology, 27, 291–304.
Goldman, P. S., Rosvold, H. E., Vest, B., & Galkin, T. W. (1971). Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey. Journal of Comparative & Physiological Psychology, 77, 212–220.
Gross, C. G., & Weiskrantz, L. (1962). Evidence for dissociation of impairment on auditory discrimination and delayed response following lateral frontal lesions in monkeys. Experimental Neurology, 5, 453–476.
Hitzig, E. (1874). Untersuchungen über das Gehirn [Investigations of the brain]. Berlin: A. Hirschwald.
Hunter, W. S. (1913). The delayed reaction in animals. Behavioral Monographs, 2, 21–30.
Iversen, S. D., & Mishkin, M. (1970). Perseverative interference in monkeys following selective lesions of the inferior prefrontal convexity. Experimental Brain Research, 11, 376–386.
Jacobsen, C. F. (1936). Studies of cerebral function in primates: I. The functions of the frontal association areas in monkeys. Comparative Psychology Monographs, 13, 1–60.
Kowalska, D. M., Bachevalier, J., & Mishkin, M. (1991). The role of the inferior prefrontal convexity in performance of delayed nonmatching-to-sample. Neuropsychologia, 29, 583–600.
Levy, R., & Goldman-Rakic, P. S. (1999). Association of storage and processing functions in the dorsolateral prefrontal cortex of the nonhuman primate. Journal of Neuroscience, 19, 5149–5158.
Levy, R., & Goldman-Rakic, P. S. (2000). Segregation of working memory functions within the dorsolateral prefrontal cortex. Experimental Brain Research, 133, 23–32.
Miller, E. K. (2000). The prefrontal cortex and cognitive control. Nature Reviews Neuroscience, 1, 59–65.
Miller, M. H., & Orbach, J. (1972). Retention of spatial alternation following frontal lobe resections in stump-tailed macaques. Neuropsychologia, 10, 291–298.
Mishkin, M. (1954). Visual discrimination performance following partial ablations of the temporal lobe: II. Ventral surface vs. hippocampus. Journal of Comparative & Physiological Psychology, 47, 187–193.
Mishkin, M. (1957). Effects of small frontal lesions on delayed alternation in monkeys. Journal of Neurophysiology, 20, 615–622.
Mishkin, M., & Manning, F. J. (1978). Non-spatial memory after selective prefrontal lesions in monkeys. Brain Research, 143, 313–323.
Mishkin, M., & Pribram, K. H. (1954). Visual discrimination performance following partial ablations of the temporal lobe: I. Ventral vs. lateral. Journal of Comparative & Physiological Psychology, 47, 14–20.
Mishkin, M., & Pribram, K. H. (1955). Analysis of the effects of frontal lesions in monkey: I. Variations of delayed alternation. Journal of Comparative & Physiological Psychology, 48, 492–495.
Mishkin, M., & Pribram, K. H. (1956). Analysis of the effects of frontal lesions in monkey: II. Variations of delayed response. Journal of Comparative & Physiological Psychology, 49, 36–40.
Mishkin, M., Vest, B., Waxler, M., & Rosvold, H. E. (1969). A reexamination of the effects of frontal lesions on object alternation. Neuropsychologia, 7, 357–364.
Murray, E. A., Bussey, T. J., & Wise, S. P. (2000). Role of prefrontal cortex in a network for arbitrary visuomotor mapping. Experimental Brain Research, 133, 114–129.
Ö Scalaidhe, S. P., Wilson, F. A., & Goldman-Rakic, P. S. (1999). Face-selective neurons during passive viewing and working memory performance of rhesus monkeys: Evidence for intrinsic specialization of neuronal coding. Cerebral Cortex, 9, 459–475.
Oscar-Berman, M. (1975). The effects of dorsolateral-frontal and ventrolateral-orbitofrontal lesions on spatial discrimination learning and delayed response in two modalities. Neuropsychologia, 13, 237–246.
Owen, A. M. (2000). The role of the lateral frontal cortex in mnemonic processing: The contribution of functional neuroimaging. Experimental Brain Research, 133, 33–43.
Owen, A. M., Stern, C. E., Look, R. B., Tracey, I., Rosen, B. R., & Petrides, M. (1998). Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex. Proceedings of the National Academy of Sciences, 95, 7721–7726.
Parker, A., & Gaffan, D. (1998). Memory after frontal/temporal disconnection in monkeys: Conditional and nonconditional tasks, unilateral and bilateral frontal lesions. Neuropsychologia, 36, 259–271.
Passingham, R. [E.] (1975). Delayed matching after selective prefrontal lesions in monkeys (Macaca mulatta). Brain Research, 92, 89–102.
Passingham, R. E., Toni, I., & Rushworth, M. F. (2000). Specialization within the prefrontal cortex: The ventral prefrontal cortex and associative learning. Experimental Brain Research, 133, 103–113.
Petrides, M. (1991). Monitoring of selections of visual stimuli and the primate frontal cortex. Proceedings of the Royal Society of London: Series B, 246, 293–298.
Petrides, M. (1995). Impairments on nonspatial self-ordered and externally ordered working memory tasks after lesions of the mid-dorsal part of the lateral frontal cortex in the monkey. Journal of Neuroscience, 15, 359–375.
Petrides, M. (2000a). Dissociable roles of mid-dorsolateral prefrontal and anterior inferotemporal cortex in visual working memory. Journal of Neuroscience, 20, 7496–7503.
Petrides, M. (2000b). The role of the mid-dorsolateral prefrontal cortex in working memory. Experimental Brain Research, 133, 44–54.
Petrides, M., & Milner, B. (1982). Deficits on subject-ordered tasks after frontal- and temporal-lobe lesions in man. Neuropsychologia, 20, 249–262.
Petrides, M., & Pandya, D. N. (1994). Comparative architectonic analysis of the human and macaque frontal cortex. In F. Boller & J. Grafman (Eds.), Handbook of neuropsychology (Vol. 9, pp. 17–58). Amsterdam: Elsevier.
Petrides, M., & Pandya, D. N. (2002). Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey. European Journal of Neuroscience, 16, 291–310.
Pribram, K. H., & Mishkin, M. (1956). Analysis of the effects of frontal lesions in monkey: III. Object alternation. Journal of Comparative & Physiological Psychology, 49, 41–45.
Quintana, J., & Fuster, J. M. (1992). Mnemonic and predictive functions of cortical neurons in a memory task. NeuroReport, 3, 721–724.
Quintana, J., & Fuster, J. M. (1993). Spatial and temporal factors in the role of prefrontal and parietal cortex in visuomotor integration. Cerebral Cortex, 3, 122–132.
Quintana, J., Yajeya, J., & Fuster, J. M. (1988). Prefrontal representation of stimulus attributes during delay tasks: I. Unit activity in cross-temporal integration of sensory and sensory-motor information. Brain Research, 474, 211–221.
Rao, S. C., Rainer, G., & Miller, E. K. (1997, May 2). Integration of what and where in the primate prefrontal cortex. Science, 276, 821–824.
Rosenkilde, C. E., Rosvold, H. E., & Mishkin, M. (1981). Time discrimination with positional responses after selective prefrontal lesions in monkeys. Brain Research, 210, 129–144.
Rushworth, M. F., Nixon, P. D., Eacott, M. J., & Passingham, R. E. (1997). Ventral prefrontal cortex is not essential for working memory. Journal of Neuroscience, 17, 4829–4838.
Shindy, W. W., Posley, K. A., & Fuster, J. M. (1994). Reversible deficit in haptic delay tasks from cooling prefrontal cortex. Cerebral Cortex, 4, 443–450.
Stamm, J. S. (1973). Functional dissociation between the inferior and arcuate segments of dorsolateral prefrontal cortex in the monkey. Neuropsychologia, 11, 181–190.
Stamm, J. S., & Weber-Levine, M. L. (1971). Delayed alternation impairments following selective prefrontal cortical ablations in monkeys. Experimental Neurology, 33, 263–278.
Ungerleider, L. G., Courtney, S. M., & Haxby, J. V. (1998). A neural system for human visual working memory. Proceedings of the National Academy of Sciences, 95, 883–890.
Ungerleider, L. G., & Mishkin, M. (1982). Two cortical visual systems. In R. J. W. Mansfield (Ed.), Analysis of visual behavior (pp. 549–586). Cambridge, MA: MIT Press.
Volgushev, M., Vidyasagar, T. R., Chistiakova, M., & Eysel, U. T. (2000). Synaptic transmission in the neocortex during reversible cooling. Neuroscience, 98, 9–22.
Walker, A. E. (1940). A cytoarchitectural study of the prefrontal area of the macaque monkey. Journal of Comparative Neurology, 73, 59–86.
Wang, M., Zhang, H., & Li, B. M. (2000). Deficit in conditional visuomotor learning by local infusion of bicuculline into the ventral prefrontal cortex in monkeys. European Journal of Neuroscience, 12, 3787–3796.
Wilson, F. A., Ö Scalaidhe, S. P., & Goldman-Rakic, P. S. (1993, June 25). Dissociation of object and spatial processing domains in primate prefrontal cortex. Science, 260, 1955–1958.
Wise, S. P., & Murray, E. A. (2000). Arbitrary associations between antecedents and actions. Trends in Neurosciences, 23, 271–276.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by grants from the National Institutes of Health and the James S. McDonnell Foundation to C.E.C.
Rights and permissions
About this article
Cite this article
Curtis, C.E., D’esposito, M. The effects of prefrontal lesions on working memory performance and theory. Cognitive, Affective, & Behavioral Neuroscience 4, 528–539 (2004). https://doi.org/10.3758/CABN.4.4.528
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.3758/CABN.4.4.528