A neostriatal habit learning system in humans

Science

Volumn 273, Issue 5280, 1996, Pages 1399-1402

  Knowlton, Barbara J ^a   Mangels, Jennifer A ^b,c   Squire, Larry R ^d,e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b ROTMAN RESEARCH INSTITUTE   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

^d VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMNESIA; ARTICLE; ASSOCIATION; CLINICAL ARTICLE; CONTROLLED STUDY; DISSOCIATION; HABIT; HUMAN; LEARNING; NEOSTRIATUM; PARKINSON DISEASE; PRIORITY JOURNAL; TASK PERFORMANCE; TRAINING;

EID: 0029815726     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.273.5280.1399     Document Type: Article

References (63)

1. In a double dissociation, one lesion group is intact at task A and impaired at task B, relative to a second lesion group, whereas the second group is impaired at task A and intact at task B. H.-L. Teuber, Annu. Rev. Psychol. 9, 267 (1955); L. Weiskrantz, in Analysis of Behavioral Change, L. Weiskrantz, Ed. (Harper & Row, New York, 1968), pp. 415-429; T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
2. In a double dissociation, one lesion group is intact at task A and impaired at task B, relative to a second lesion group, whereas the second group is impaired at task A and intact at task B. H.-L. Teuber, Annu. Rev. Psychol. 9, 267 (1955); L. Weiskrantz, in Analysis of Behavioral Change, L. Weiskrantz, Ed. (Harper & Row, New York, 1968), pp. 415-429; T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
3. In a double dissociation, one lesion group is intact at task A and impaired at task B, relative to a second lesion group, whereas the second group is impaired at task A and intact at task B. H.-L. Teuber, Annu. Rev. Psychol. 9, 267 (1955); L. Weiskrantz, in Analysis of Behavioral Change, L. Weiskrantz, Ed. (Harper & Row, New York, 1968), pp. 415-429; T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
4. M. G. Packard, R, Hirsh, N. M. White, J. Neurosci. 9, 1465 (1989); M. G. Packard and J. L, McGaugh, Behav. Neurosci. 106, 439 (1992); R. J. McDonald and N. M. White, ibid. 107, 3 (1993). For an early proposal about the neostriatum and habit learning in experimental animals, see M. Mishkin, B. Malamut, J. Bachevalier, in Neurobiology of Learning and Memory, G. Lynch, J. L. McGaugh, N. M. Weinberger, Eds. (Guilford, New York, 1984), pp. 65-77.
5. M. G. Packard, R, Hirsh, N. M. White, J. Neurosci. 9, 1465 (1989); M. G. Packard and J. L, McGaugh, Behav. Neurosci. 106, 439 (1992); R. J. McDonald and N. M. White, ibid. 107, 3 (1993). For an early proposal about the neostriatum and habit learning in experimental animals, see M. Mishkin, B. Malamut, J. Bachevalier, in Neurobiology of Learning and Memory, G. Lynch, J. L. McGaugh, N. M. Weinberger, Eds. (Guilford, New York, 1984), pp. 65-77.
6. M. G. Packard, R, Hirsh, N. M. White, J. Neurosci. 9, 1465 (1989); M. G. Packard and J. L, McGaugh, Behav. Neurosci. 106, 439 (1992); R. J. McDonald and N. M. White, ibid. 107, 3 (1993). For an early proposal about the neostriatum and habit learning in experimental animals, see M. Mishkin, B. Malamut, J. Bachevalier, in Neurobiology of Learning and Memory, G. Lynch, J. L. McGaugh, N. M. Weinberger, Eds. (Guilford, New York, 1984), pp. 65-77.
7. M. G. Packard, R, Hirsh, N. M. White, J. Neurosci. 9, 1465 (1989); M. G. Packard and J. L, McGaugh, Behav. Neurosci. 106, 439 (1992); R. J. McDonald and N. M. White, ibid. 107, 3 (1993). For an early proposal about the neostriatum and habit learning in experimental animals, see M. Mishkin, B. Malamut, J. Bachevalier, in Neurobiology of Learning and Memory, G. Lynch, J. L. McGaugh, N. M. Weinberger, Eds. (Guilford, New York, 1984), pp. 65-77.
8. L. R. Squire, B. Knowlton, G. Musen, Annu. Rev. Psychol. 44, 453 (1993); D. L. Schacter and E. Tulving, Eds., Memory Systems 1994 (MIT Press, Cambridge, MA, 1994); L, Weiskrantz, Philos. Trans. R. Soc. London Ser. B 329, 99 (1990).
9. L. R. Squire, B. Knowlton, G. Musen, Annu. Rev. Psychol. 44, 453 (1993); D. L. Schacter and E. Tulving, Eds., Memory Systems 1994 (MIT Press, Cambridge, MA, 1994); L, Weiskrantz, Philos. Trans. R. Soc. London Ser. B 329, 99 (1990).
10. L. R. Squire, B. Knowlton, G. Musen, Annu. Rev. Psychol. 44, 453 (1993); D. L. Schacter and E. Tulving, Eds., Memory Systems 1994 (MIT Press, Cambridge, MA, 1994); L, Weiskrantz, Philos. Trans. R. Soc. London Ser. B 329, 99 (1990).
11. L R. Squire, Psychol. Rev. 99, 195 (1992); D. L. Schacter, C.-Y. Chiu, K. N. Ochsner, Annu. Rev. Neurosci. 16, 159 (1993).
12. L R. Squire, Psychol. Rev. 99, 195 (1992); D. L. Schacter, C.-Y. Chiu, K. N. Ochsner, Annu. Rev. Neurosci. 16, 159 (1993).
13. An exception is a double dissociation of declarative memory and emotional conditioning (hippocampal formation versus amygdala) in two patients (A. Bechara et al., Science 269, 1115 (1995)]. Also, declarative memory and perceptual priming were dissociated in two other patients (hippocampal formation versus neocortex) [J. D. E. Gabrieli, D. A. Fleischman, M. M. Keane, S. L. Reminger, F. Morrell, Psychol. Sci. 6, 76 (1995); M. M. Keane, J. D. E. Gabrieli, H. C. Mapstone, K. A. Johnson, S. Corkin, Brain 118, 1129 (1995)]. For a review, seeL. R. Squire and B. J. Knowlton, in The Cognitive Neurosciences, M. Gazzaniga, Ed. (MIT Press, Cambridge, MA, 1994), pp. 825-837.
14. An exception is a double dissociation of declarative memory and emotional conditioning (hippocampal formation versus amygdala) in two patients (A. Bechara et al., Science 269, 1115 (1995)]. Also, declarative memory and perceptual priming were dissociated in two other patients (hippocampal formation versus neocortex) [J. D. E. Gabrieli, D. A. Fleischman, M. M. Keane, S. L. Reminger, F. Morrell, Psychol. Sci. 6, 76 (1995); M. M. Keane, J. D. E. Gabrieli, H. C. Mapstone, K. A. Johnson, S. Corkin, Brain 118, 1129 (1995)]. For a review, seeL. R. Squire and B. J. Knowlton, in The Cognitive Neurosciences, M. Gazzaniga, Ed. (MIT Press, Cambridge, MA, 1994), pp. 825-837.
15. An exception is a double dissociation of declarative memory and emotional conditioning (hippocampal formation versus amygdala) in two patients (A. Bechara et al., Science 269, 1115 (1995)]. Also, declarative memory and perceptual priming were dissociated in two other patients (hippocampal formation versus neocortex) [J. D. E. Gabrieli, D. A. Fleischman, M. M. Keane, S. L. Reminger, F. Morrell, Psychol. Sci. 6, 76 (1995); M. M. Keane, J. D. E. Gabrieli, H. C. Mapstone, K. A. Johnson, S. Corkin, Brain 118, 1129 (1995)]. For a review, seeL. R. Squire and B. J. Knowlton, in The Cognitive Neurosciences, M. Gazzaniga, Ed. (MIT Press, Cambridge, MA, 1994), pp. 825-837.
16. An exception is a double dissociation of declarative memory and emotional conditioning (hippocampal formation versus amygdala) in two patients (A. Bechara et al., Science 269, 1115 (1995)]. Also, declarative memory and perceptual priming were dissociated in two other patients (hippocampal formation versus neocortex) [J. D. E. Gabrieli, D. A. Fleischman, M. M. Keane, S. L. Reminger, F. Morrell, Psychol. Sci. 6, 76 (1995); M. M. Keane, J. D. E. Gabrieli, H. C. Mapstone, K. A. Johnson, S. Corkin, Brain 118, 1129 (1995)]. For a review, seeL. R. Squire and B. J. Knowlton, in The Cognitive Neurosciences, M. Gazzaniga, Ed. (MIT Press, Cambridge, MA, 1994), pp. 825-837.
17. D. R. Shanks and M. F. St. John, Behav. Brain Sci. 17 , 367 (1994); A. L. Ostergaard, Q. J. Exp. Psychol. 47,331; (1994).
18. D. R. Shanks and M. F. St. John, Behav. Brain Sci. 17 , 367 (1994); A. L. Ostergaard, Q. J. Exp. Psychol. 47,331; (1994).
19. The human neostriatum has been linked to motor behavior, motor learning (23), and the kinds of problem-solving and procedural learning tasks also associated with frontal lobe function [J. A. Saint-Cyr, A. E. Taylor, L. L. Trepanier, A. E. Lang, in Neuropsychological Disorders Associated with Subcortical Lesions, G. Vallan, S. F. Cappa, C. Wallesch, Eds. (Oxford Univ. Press, Oxford, 1992), pp. 204-226]. For example, patients with neostriatal dysfunction due to Parkinson's disease were impaired at the Tower of Toronto puzzle [J. A. Saint-Cyr, A. E. Taylor, A. E. Lang, Brain 111, 941 (1988)] and at learning to recognize fragmented pictures (M. W. Bondi and A. Kaszniak, J. Clin. Exp. Neuropsychol. 13, 339 (1991)].
20. The human neostriatum has been linked to motor behavior, motor learning (23), and the kinds of problem-solving and procedural learning tasks also associated with frontal lobe function [J. A. Saint-Cyr, A. E. Taylor, L. L. Trepanier, A. E. Lang, in Neuropsychological Disorders Associated with Subcortical Lesions, G. Vallan, S. F. Cappa, C. Wallesch, Eds. (Oxford Univ. Press, Oxford, 1992), pp. 204-226]. For example, patients with neostriatal dysfunction due to Parkinson's disease were impaired at the Tower of Toronto puzzle [J. A. Saint-Cyr, A. E. Taylor, A. E. Lang, Brain 111, 941 (1988)] and at learning to recognize fragmented pictures (M. W. Bondi and A. Kaszniak, J. Clin. Exp. Neuropsychol. 13, 339 (1991)].
21. The human neostriatum has been linked to motor behavior, motor learning (23), and the kinds of problem-solving and procedural learning tasks also associated with frontal lobe function [J. A. Saint-Cyr, A. E. Taylor, L. L. Trepanier, A. E. Lang, in Neuropsychological Disorders Associated with Subcortical Lesions, G. Vallan, S. F. Cappa, C. Wallesch, Eds. (Oxford Univ. Press, Oxford, 1992), pp. 204-226]. For example, patients with neostriatal dysfunction due to Parkinson's disease were impaired at the Tower of Toronto puzzle [J. A. Saint-Cyr, A. E. Taylor, A. E. Lang, Brain 111, 941 (1988)] and at learning to recognize fragmented pictures (M. W. Bondi and A. Kaszniak, J. Clin. Exp. Neuropsychol. 13, 339 (1991)].
22. Seven (six men, one woman) patients had medial temporal lobe amnesia and five (three men, two women) had diencephalic amnesia. Damage to the hippocampal formation or diencephalon was confirmed by quantitative neuroimaging for 11 of the 12 patients (n = 8 [A. P. Shimamura, T. L. Jernigan, L. R. Squire, J. Neurosci. 8, 4400 (1988); L. R. Squire, D. G, Amaral, G. A. Press, ibid. 10, 3106 (1990); J. Polich and L. R, Squire, Bectroencephalogr. Clin. Neurophysiol. 86, 408 (1993)]; for n = 3 (L R. Squire, unpublished observations)). The remaining patient was suspected to have hippocampal damage on the basis of etiology (anoxia). The patients averaged 66 years of age (range, 54 to 77) with an average of 14.0 years of education. They averaged 104.3 on the Wechsler Adult Intelligence Scale-Revised ( WAIS-R; mean subscale scores = 18.9 for the information subscale and 53.0 for the vocabulary subscale), and they averaged 101.3, 72.4, 79.0, 68.5, and 55.3 on the five indices of the Wechsler Memory Scale-Revised (attention-concentration, verbal memory, nonverbal memory, general memory, and delayed memory). These scores have a mean of 100 in the normal population (standard deviation = 15).
23. Seven (six men, one woman) patients had medial temporal lobe amnesia and five (three men, two women) had diencephalic amnesia. Damage to the hippocampal formation or diencephalon was confirmed by quantitative neuroimaging for 11 of the 12 patients (n = 8 [A. P. Shimamura, T. L. Jernigan, L. R. Squire, J. Neurosci. 8, 4400 (1988); L. R. Squire, D. G, Amaral, G. A. Press, ibid. 10, 3106 (1990); J. Polich and L. R, Squire, Bectroencephalogr. Clin. Neurophysiol. 86, 408 (1993)]; for n = 3 (L R. Squire, unpublished observations)). The remaining patient was suspected to have hippocampal damage on the basis of etiology (anoxia). The patients averaged 66 years of age (range, 54 to 77) with an average of 14.0 years of education. They averaged 104.3 on the Wechsler Adult Intelligence Scale-Revised ( WAIS-R; mean subscale scores = 18.9 for the information subscale and 53.0 for the vocabulary subscale), and they averaged 101.3, 72.4, 79.0, 68.5, and 55.3 on the five indices of the Wechsler Memory Scale-Revised (attention-concentration, verbal memory, nonverbal memory, general memory, and delayed memory). These scores have a mean of 100 in the normal population (standard deviation = 15).
24. Seven (six men, one woman) patients had medial temporal lobe amnesia and five (three men, two women) had diencephalic amnesia. Damage to the hippocampal formation or diencephalon was confirmed by quantitative neuroimaging for 11 of the 12 patients (n = 8 [A. P. Shimamura, T. L. Jernigan, L. R. Squire, J. Neurosci. 8, 4400 (1988); L. R. Squire, D. G, Amaral, G. A. Press, ibid. 10, 3106 (1990); J. Polich and L. R, Squire, Bectroencephalogr. Clin. Neurophysiol. 86, 408 (1993)]; for n = 3 (L R. Squire, unpublished observations)). The remaining patient was suspected to have hippocampal damage on the basis of etiology (anoxia). The patients averaged 66 years of age (range, 54 to 77) with an average of 14.0 years of education. They averaged 104.3 on the Wechsler Adult Intelligence Scale-Revised ( WAIS-R; mean subscale scores = 18.9 for the information subscale and 53.0 for the vocabulary subscale), and they averaged 101.3, 72.4, 79.0, 68.5, and 55.3 on the five indices of the Wechsler Memory Scale-Revised (attention-concentration, verbal memory, nonverbal memory, general memory, and delayed memory). These scores have a mean of 100 in the normal population (standard deviation = 15).
25. The diagnosis of Parkinson's disease (17 men and 3 women) was confirmed by a senior staff neurologist at the University of California Medical Center, San Diego. The patients averaged 65.2 years of age (range, 46 to 79) and an average of 16.0 years of education. They scored 54.2 and 25.1 on the vocabulary and information subscales, respectively, of the WAIS-R [compare with (8, 10)]. Their mean score on the Dementia Rating Scale was 137.7, indicating an absence of dementing illness [maximum score = 144, S. Mattis, in Geriatric Psychiatry, R. Bellack and B. Keraso, Eds. (Grune and Straften, New York, 1976)]. The mean severity of Parkinsonian symptoms was stage 2.8 as rated by the Hoehn and Yahr Scale, 1 = least severe, 5 = most severe [M. M. Hoehn and M. D. Yahr, Neurology 17, 427 (1967)], and was 10.5 as rated by the Unified Parkinson's Disease Rating Scale, hand and foot subscale, O = normal, 32 = most severe [S. Fahn et al., in Recent Developments in Parkinson's Disease, S. Fahn, C. D. Marsden, M. Goldstein, D. B. Calne, Eds. (Macmillan, New York, 1987)]. The mean score on the Beck Depression Inventory was 5.4 (maximum = 63), indicating an absence of clinical depression [A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, I. Erbaugh, Arch. Gen. Psychiatry 56, 561 (1961)]. At the time of testing, all patients were under the care of a neurologist and were optimally medicated. All of the patients were receiving dopamine precursor treatment (Sinemet). In addition, 12 patients were taking a monoamine oxidase inhibitor (Eldepryl), 8 were taking a dopamine enhancing drug (Partodel, Permax, or Amantadine), and 3 were taking an anticholinergic drug (Arlane). Removing the latter three patients did not noticeably affect the results.
26. The diagnosis of Parkinson's disease (17 men and 3 women) was confirmed by a senior staff neurologist at the University of California Medical Center, San Diego. The patients averaged 65.2 years of age (range, 46 to 79) and an average of 16.0 years of education. They scored 54.2 and 25.1 on the vocabulary and information subscales, respectively, of the WAIS-R [compare with (8, 10)]. Their mean score on the Dementia Rating Scale was 137.7, indicating an absence of dementing illness [maximum score = 144, S. Mattis, in Geriatric Psychiatry, R. Bellack and B. Keraso, Eds. (Grune and Straften, New York, 1976)]. The mean severity of Parkinsonian symptoms was stage 2.8 as rated by the Hoehn and Yahr Scale, 1 = least severe, 5 = most severe [M. M. Hoehn and M. D. Yahr, Neurology 17, 427 (1967)], and was 10.5 as rated by the Unified Parkinson's Disease Rating Scale, hand and foot subscale, O = normal, 32 = most severe [S. Fahn et al., in Recent Developments in Parkinson's Disease, S. Fahn, C. D. Marsden, M. Goldstein, D. B. Calne, Eds. (Macmillan, New York, 1987)]. The mean score on the Beck Depression Inventory was 5.4 (maximum = 63), indicating an absence of clinical depression [A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, I. Erbaugh, Arch. Gen. Psychiatry 56, 561 (1961)]. At the time of testing, all patients were under the care of a neurologist and were optimally medicated. All of the patients were receiving dopamine precursor treatment (Sinemet). In addition, 12 patients were taking a monoamine oxidase inhibitor (Eldepryl), 8 were taking a dopamine enhancing drug (Partodel, Permax, or Amantadine), and 3 were taking an anticholinergic drug (Arlane). Removing the latter three patients did not noticeably affect the results.
27. The diagnosis of Parkinson's disease (17 men and 3 women) was confirmed by a senior staff neurologist at the University of California Medical Center, San Diego. The patients averaged 65.2 years of age (range, 46 to 79) and an average of 16.0 years of education. They scored 54.2 and 25.1 on the vocabulary and information subscales, respectively, of the WAIS-R [compare with (8, 10)]. Their mean score on the Dementia Rating Scale was 137.7, indicating an absence of dementing illness [maximum score = 144, S. Mattis, in Geriatric Psychiatry, R. Bellack and B. Keraso, Eds. (Grune and Straften, New York, 1976)]. The mean severity of Parkinsonian symptoms was stage 2.8 as rated by the Hoehn and Yahr Scale, 1 = least severe, 5 = most severe [M. M. Hoehn and M. D. Yahr, Neurology 17, 427 (1967)], and was 10.5 as rated by the Unified Parkinson's Disease Rating Scale, hand and foot subscale, O = normal, 32 = most severe [S. Fahn et al., in Recent Developments in Parkinson's Disease, S. Fahn, C. D. Marsden, M. Goldstein, D. B. Calne, Eds. (Macmillan, New York, 1987)]. The mean score on the Beck Depression Inventory was 5.4 (maximum = 63), indicating an absence of clinical depression [A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, I. Erbaugh, Arch. Gen. Psychiatry 56, 561 (1961)]. At the time of testing, all patients were under the care of a neurologist and were optimally medicated. All of the patients were receiving dopamine precursor treatment (Sinemet). In addition, 12 patients were taking a monoamine oxidase inhibitor (Eldepryl), 8 were taking a dopamine enhancing drug (Partodel, Permax, or Amantadine), and 3 were taking an anticholinergic drug (Arlane). Removing the latter three patients did not noticeably affect the results.
28. The diagnosis of Parkinson's disease (17 men and 3 women) was confirmed by a senior staff neurologist at the University of California Medical Center, San Diego. The patients averaged 65.2 years of age (range, 46 to 79) and an average of 16.0 years of education. They scored 54.2 and 25.1 on the vocabulary and information subscales, respectively, of the WAIS-R [compare with (8, 10)]. Their mean score on the Dementia Rating Scale was 137.7, indicating an absence of dementing illness [maximum score = 144, S. Mattis, in Geriatric Psychiatry, R. Bellack and B. Keraso, Eds. (Grune and Straften, New York, 1976)]. The mean severity of Parkinsonian symptoms was stage 2.8 as rated by the Hoehn and Yahr Scale, 1 = least severe, 5 = most severe [M. M. Hoehn and M. D. Yahr, Neurology 17, 427 (1967)], and was 10.5 as rated by the Unified Parkinson's Disease Rating Scale, hand and foot subscale, O = normal, 32 = most severe [S. Fahn et al., in Recent Developments in Parkinson's Disease, S. Fahn, C. D. Marsden, M. Goldstein, D. B. Calne, Eds. (Macmillan, New York, 1987)]. The mean score on the Beck Depression Inventory was 5.4 (maximum = 63), indicating an absence of clinical depression [A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, I. Erbaugh, Arch. Gen. Psychiatry 56, 561 (1961)]. At the time of testing, all patients were under the care of a neurologist and were optimally medicated. All of the patients were receiving dopamine precursor treatment (Sinemet). In addition, 12 patients were taking a monoamine oxidase inhibitor (Eldepryl), 8 were taking a dopamine enhancing drug (Partodel, Permax, or Amantadine), and 3 were taking an anticholinergic drug (Arlane). Removing the latter three patients did not noticeably affect the results.
29. The controls (seven men and eight women) averaged 65.1 years of age (range, 54 to 77) and 14.2 years of education. They scored 54.0 and 20.9 on the vocabulary and information subscales of the WAIS-R, respectively.
30. B. J. Knowlton, L. R. Squire, M. Gluck, Learn. Mem. 1,106 (1994); P. Reber, B. J. Knowlton, L. R Squire, Behav. Neurosci., in press.
31. B. J. Knowlton, L. R. Squire, M. Gluck, Learn. Mem. 1,106 (1994); P. Reber, B. J. Knowlton, L. R Squire, Behav. Neurosci., in press.
32. The amnesic patients and controls performed 67.2 and 70.3% correct, respectively, during trials 41 through 50, which was well above chance levels (t values > 3.3, P values < 0.01). Learning was evident in each group across the five trial blocks (analysis of linear trend for amnesic patients, F(1,11) = 5.9, P < 0.04; for controls, F[1,14) = 4.3, P < 0.06). Data for trie controls and 10 of the 12 amnesic patients were reported in (11).
33. S. Zola-Morgan and L. R. Squire, Annu. Rev. NeuroSci. 16, 547 (1993).
34. Both scores were above the level that would be expected by guessing [t(19) values > 3.2, P values < 0.01]. The 10 patients with severe symptoms also learned with extended training (47.8 ± 3.9% correct for trials 1 through 50, 61.1 ± 4.5% correct for trials 101 through 150).
35. Ten of the 12 amnesic patients were given trials 51 through 150. The probabilistic structure of the task encourages "probability matching," whereby individuals come to select each alternative in proportion to its reinforcement history [W. K. Estes, J. Am. Stat. Assoc. 67, 81 (1972)]. In our task, probability matching would result in a maximum score of 79% correct.
36. B. Scatton, L. Roquier, F. Javoy-Agid, Y. Agid. Neurology 32, 1039 (1982); J. S. Perlmutter and M. E. Raichle, ibid. 35, 1127 (1985); A. J. Lees and E. Smith, Brain 106, 257 (1983); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang. ibid. 109, 845 (1986). For the anatomical basis of a striatal-frontal link, see G. Alexander, M. Delong, P. Strick, Annu. Rev. Neurosci, 9, 357 (1986).
37. B. Scatton, L. Roquier, F. Javoy-Agid, Y. Agid. Neurology 32, 1039 (1982); J. S. Perlmutter and M. E. Raichle, ibid. 35, 1127 (1985); A. J. Lees and E. Smith, Brain 106, 257 (1983); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang. ibid. 109, 845 (1986). For the anatomical basis of a striatal-frontal link, see G. Alexander, M. Delong, P. Strick, Annu. Rev. Neurosci, 9, 357 (1986).
38. B. Scatton, L. Roquier, F. Javoy-Agid, Y. Agid. Neurology 32, 1039 (1982); J. S. Perlmutter and M. E. Raichle, ibid. 35, 1127 (1985); A. J. Lees and E. Smith, Brain 106, 257 (1983); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang. ibid. 109, 845 (1986). For the anatomical basis of a striatal-frontal link, see G. Alexander, M. Delong, P. Strick, Annu. Rev. Neurosci, 9, 357 (1986).
39. B. Scatton, L. Roquier, F. Javoy-Agid, Y. Agid. Neurology 32, 1039 (1982); J. S. Perlmutter and M. E. Raichle, ibid. 35, 1127 (1985); A. J. Lees and E. Smith, Brain 106, 257 (1983); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang. ibid. 109, 845 (1986). For the anatomical basis of a striatal-frontal link, see G. Alexander, M. Delong, P. Strick, Annu. Rev. Neurosci, 9, 357 (1986).
40. B. Scatton, L. Roquier, F. Javoy-Agid, Y. Agid. Neurology 32, 1039 (1982); J. S. Perlmutter and M. E. Raichle, ibid. 35, 1127 (1985); A. J. Lees and E. Smith, Brain 106, 257 (1983); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang. ibid. 109, 845 (1986). For the anatomical basis of a striatal-frontal link, see G. Alexander, M. Delong, P. Strick, Annu. Rev. Neurosci, 9, 357 (1986).
41. The 20 patients with Parkinson's disease achieved 3.7 categories (maximum = 6) on the Wisconsin Card Sorting Test ( WCST ) with an average of 19.2% perseverative errors, that is, errors that would have been correct responses in the previous phase of the test [R. K. Heaton, G. Chelune, J. Talley, G. Kay, G. Curtiss, Wisconsin Card Sorting Test Manual (Psychological Assessment Resources, Odessa, FL, 1993)]. Individuals from the Heaton ef al, normative sample (n = 169, age = 50 to 79 years) achieved 4.6 ± 0.1 categories correct with 16.1 ± 0.7% perseverative errors.
42. The patients with frontal lobe lesions (six men and four women) averaged 68 years of age (range, 62 to 76 years) and 13.7 years of education. Six had sustained left frontal lesions, three had sustained right frontal lesions, and one had bilateral frontal lobe lesions. On the WCST (17), they achieved 3.6 categories and made 32.8% perseverative errors, marginally more than the Parkinson patients, t(28) = 1.76, P = 0.09. For reconstructions of the frontal lesions and examples of their impaired performance on other tests, see J. S. Janowsky, A. P Shimamura, M. Kritchevsky, L. R. Squire, Behav. Neurosci. 103, 548 (1989) (patients JD. MD, JV); A. P. Shimamura, P. J. Jurica, J. A. Mangels, F. B. Gershberg, R. T. Knight, J. Cognit. Neurosci. 7, 144 (1995) (patients EB, AL, MM, RM); J. A. Mangels, F. B. Gershberg. A. P. Shimamura, R. T. Knight, Neuropsychology 10, 32 (1996) (patients OA, JD); L. L. Chao and R. T. Knight, Neuroreport 6, 1605 (1995) (patient JC).
43. The patients with frontal lobe lesions (six men and four women) averaged 68 years of age (range, 62 to 76 years) and 13.7 years of education. Six had sustained left frontal lesions, three had sustained right frontal lesions, and one had bilateral frontal lobe lesions. On the WCST (17), they achieved 3.6 categories and made 32.8% perseverative errors, marginally more than the Parkinson patients, t(28) = 1.76, P = 0.09. For reconstructions of the frontal lesions and examples of their impaired performance on other tests, see J. S. Janowsky, A. P Shimamura, M. Kritchevsky, L. R. Squire, Behav. Neurosci. 103, 548 (1989) (patients JD. MD, JV); A. P. Shimamura, P. J. Jurica, J. A. Mangels, F. B. Gershberg, R. T. Knight, J. Cognit. Neurosci. 7, 144 (1995) (patients EB, AL, MM, RM); J. A. Mangels, F. B. Gershberg. A. P. Shimamura, R. T. Knight, Neuropsychology 10, 32 (1996) (patients OA, JD); L. L. Chao and R. T. Knight, Neuroreport 6, 1605 (1995) (patient JC).
44. The patients with frontal lobe lesions (six men and four women) averaged 68 years of age (range, 62 to 76 years) and 13.7 years of education. Six had sustained left frontal lesions, three had sustained right frontal lesions, and one had bilateral frontal lobe lesions. On the WCST (17), they achieved 3.6 categories and made 32.8% perseverative errors, marginally more than the Parkinson patients, t(28) = 1.76, P = 0.09. For reconstructions of the frontal lesions and examples of their impaired performance on other tests, see J. S. Janowsky, A. P Shimamura, M. Kritchevsky, L. R. Squire, Behav. Neurosci. 103, 548 (1989) (patients JD. MD, JV); A. P. Shimamura, P. J. Jurica, J. A. Mangels, F. B. Gershberg, R. T. Knight, J. Cognit. Neurosci. 7, 144 (1995) (patients EB, AL, MM, RM); J. A. Mangels, F. B. Gershberg. A. P. Shimamura, R. T. Knight, Neuropsychology 10, 32 (1996) (patients OA, JD); L. L. Chao and R. T. Knight, Neuroreport 6, 1605 (1995) (patient JC).
45. The patients with frontal lobe lesions (six men and four women) averaged 68 years of age (range, 62 to 76 years) and 13.7 years of education. Six had sustained left frontal lesions, three had sustained right frontal lesions, and one had bilateral frontal lobe lesions. On the WCST (17), they achieved 3.6 categories and made 32.8% perseverative errors, marginally more than the Parkinson patients, t(28) = 1.76, P = 0.09. For reconstructions of the frontal lesions and examples of their impaired performance on other tests, see J. S. Janowsky, A. P Shimamura, M. Kritchevsky, L. R. Squire, Behav. Neurosci. 103, 548 (1989) (patients JD. MD, JV); A. P. Shimamura, P. J. Jurica, J. A. Mangels, F. B. Gershberg, R. T. Knight, J. Cognit. Neurosci. 7, 144 (1995) (patients EB, AL, MM, RM); J. A. Mangels, F. B. Gershberg. A. P. Shimamura, R. T. Knight, Neuropsychology 10, 32 (1996) (patients OA, JD); L. L. Chao and R. T. Knight, Neuroreport 6, 1605 (1995) (patient JC).
46. In addition, analysis of variance (severe PD patients compared with frontal patients and three 50-trial blocks: trials 1 through 50, 51 through 100, and 101 through 150) revealed a significant group × trial block interaction [F(2,34) = 3.52. P < 0.04). The interaction resulted from the fact that the frontal patients, like the amnesic patients and controls, scored about the same overall in each of the three 50-trial blocks (frontals: 60.5, 56.5, and 66.1%; amnesics; 58.5, 61.2, and 59.2%; controls: 65.9, 67.3, and 66.1%). In contrast, the severely affected PD patients scored 47.8% correct (at chance) on trials 1 through 50, 58.2% on trials 51 through 100, and 61.1 % on trials 101 through 150.
47. A. M. Gotham. R. G. Brown, C. S. Marsden, Brain 111, 229 (1988); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang, Brain Cognition 13, 211 (1990); E. R. Vriezen and M. Moscovitch, Neuropsychologia 28, 1283 (1990); M. W. Bondi, A. W. Kaszniak, K. A. Bayles, K. T. Vance, Neuropsychology 7. 89 (1993).
48. A. M. Gotham. R. G. Brown, C. S. Marsden, Brain 111, 229 (1988); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang, Brain Cognition 13, 211 (1990); E. R. Vriezen and M. Moscovitch, Neuropsychologia 28, 1283 (1990); M. W. Bondi, A. W. Kaszniak, K. A. Bayles, K. T. Vance, Neuropsychology 7. 89 (1993).
49. A. M. Gotham. R. G. Brown, C. S. Marsden, Brain 111, 229 (1988); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang, Brain Cognition 13, 211 (1990); E. R. Vriezen and M. Moscovitch, Neuropsychologia 28, 1283 (1990); M. W. Bondi, A. W. Kaszniak, K. A. Bayles, K. T. Vance, Neuropsychology 7. 89 (1993).
50. A. M. Gotham. R. G. Brown, C. S. Marsden, Brain 111, 229 (1988); A. E. Taylor, J. A. Saint-Cyr, A. E. Lang, Brain Cognition 13, 211 (1990); E. R. Vriezen and M. Moscovitch, Neuropsychologia 28, 1283 (1990); M. W. Bondi, A. W. Kaszniak, K. A. Bayles, K. T. Vance, Neuropsychology 7. 89 (1993).
51. Also see A. M. Owen et al., Brain 116, 1159 (1993); A. M. Owen et al., Neuropsychology 9. 126 (1995). Despite these differences between the effects on cognition of frontal lobe lesions and Parkinson's disease, the cognitive impairment in Parkinson's disease presumably arises from the effect that neostriatal lesions exert on the targets of the basal ganglia, which include frontal cortex.
52. Also see A. M. Owen et al., Brain 116, 1159 (1993); A. M. Owen et al., Neuropsychology 9. 126 (1995). Despite these differences between the effects on cognition of frontal lobe lesions and Parkinson's disease, the cognitive impairment in Parkinson's disease presumably arises from the effect that neostriatal lesions exert on the targets of the basal ganglia, which include frontal cortex.
53. The PD patients who performed poorest on tne classification task (percent correct score during trials 1 through 50) also obtained the highest Hoehn and Yahr Scale scores of symptom severity (9) correlation coefficient, r = -0.55, P < 0.02). In contrast, in the case of the frontal patients, performance on the first 50 trials of the classification test was slightly and nonsignificantly better for those patients with the most severe frontal symptoms [measured by the number of categories achieved correctly on the WCST (17) and by the percent perseverative error score,r = -0.14 and r = 0.22, respectively]. Interestingly, for the PD patients, poor classification learning also correlated with frontal lobe symptoms (r = 0.63, P < 0.01 for categories; r = -0.69, P < 0.01 for perseverative errors), as would be expected if increasing frontal lobe dysfunction reflects the progression of the primary disease in the neostriaturn. However, the overall pattern of correlations suggests that the neostriatal symptoms, not the frontal lobe symptoms, best predicted classification learning. This conclusion depends on the assumption that frontal lobe dysfunction in the PD patients was no more severe than in the patients with frontal lobe lesions. The neuropsychological findings (17, 18) are consistent with this idea.
54. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
55. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
56. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
57. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
58. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
59. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
60. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
61. D. P. Salmon and N. Butters, Curr. Opin. Neurobiol. 5,184 (1995): J. Pauisen, N. Butters, D. P. Salmon, W C. Heindel, M. R. Swensen Neuropsychobgy 7, 73 (1993); D. Knopman and M, J Nissen, Neuropsychologia 29, 245 (1991); D. B. Willingham and W. J. Koroshatz, Psychobiology 21, 173 (1993); D. L. Harrington, K. Y. Haaland, R. A. Yeo, E. Marder, J. Clin, Exp. Neuropsychol. 12, 323 (1990); N. Butters, W, C. Heindel, D. P. Salmon, Bull. Psychonomic Soc. 28,359 (1990). For a review of oasal ganglia function in the context of the formation and expression of action repertoires, see A. M. Graybiel, Curr. Opin. Neurobiol. 5, 733 (1995). Also see S. P. Wise. Semin. Neurosci. 8, 39 (1996).
62. Patients with Huntirgton's disease also did not learn the probabilistic classification task (B. J. Knowlton et al., Neuropsychology, in press). However, it is difficult to isolate this deficit to the basal ganglia because of the dementia and widespread neuropathology associated with Huntington's disease.
63. We thank J. Zouzounis and J. Moore for research assistance, A. Shimamura for referral of patients with frontal lobe lesions, and C. Shultz for advice and referral of patients with Parkinson's disease. Supported by the Medical Research Service of the Department of Veterans Affairs, the National Institute of Mental Health (NIMH) (grant MH24600), and an NIMH postdoctoral fellowship (B.J.K.).