Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2005 Feb;76(2):169–175. doi: 10.1136/jnnp.2004.039818

The cerebral correlates of different types of perseveration in the Wisconsin Card Sorting Test

Y Nagahama 1, T Okina 1, N Suzuki 1, H Nabatame 1, M Matsuda 1
PMCID: PMC1739495  PMID: 15654026

Abstract

Objectives: To explore the neural substrates corresponding to the perseverative errors in the Wisconsin Card Sorting Test (WCST).

Methods: The study examined the correlations between the WCST performances and the SPECT measurements of regional cerebral blood flow (rCBF) in subjects with neurodegenerative dementia. Negative non-linear correlations between the rCBF and the two different types of the perseverative errors ("stuck-in-set" and "recurrent" perseverative errors) were calculated on a voxel basis and volume-of-interest basis in the mixed groups of 72 elderly and dementia patients.

Results: The stuck-in-set perseverative error was associated with the reduced rCBF in the rostrodorsal prefrontal cortex, whereas the recurrent perseverative error was related to the left parietal activity but not to the prefrontal activity.

Conclusions: These findings augment evidence that the rostrodorsal prefrontal cortex crucially mediates attentional set shifting, and suggest that the stuck-in-set perseverative errors would be a true pathognomonic sign of frontal dysfunction. Moreover, this study shows that the recurrent perseverative errors may not be associated closely with the prefrontal function, suggesting that this error and the stuck-in-set error should be differentially estimated in the WCST.

Full Text

The Full Text of this article is available as a PDF (226.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson S. W., Damasio H., Jones R. D., Tranel D. Wisconsin Card Sorting Test performance as a measure of frontal lobe damage. J Clin Exp Neuropsychol. 1991 Nov;13(6):909–922. doi: 10.1080/01688639108405107. [DOI] [PubMed] [Google Scholar]
  2. Berman K. F., Ostrem J. L., Randolph C., Gold J., Goldberg T. E., Coppola R., Carson R. E., Herscovitch P., Weinberger D. R. Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study. Neuropsychologia. 1995 Aug;33(8):1027–1046. doi: 10.1016/0028-3932(95)00035-2. [DOI] [PubMed] [Google Scholar]
  3. Bokde A. L., Pietrini P., Ibáez V., Furey M. L., Alexander G. E., Graff-Radford N. R., Rapoport S. I., Schapiro M. B., Horwitz B. The effect of brain atrophy on cerebral hypometabolism in the visual variant of Alzheimer disease. Arch Neurol. 2001 Mar;58(3):480–486. doi: 10.1001/archneur.58.3.480. [DOI] [PubMed] [Google Scholar]
  4. Bookheimer S. Y., Strojwas M. H., Cohen M. S., Saunders A. M., Pericak-Vance M. A., Mazziotta J. C., Small G. W. Patterns of brain activation in people at risk for Alzheimer's disease. N Engl J Med. 2000 Aug 17;343(7):450–456. doi: 10.1056/NEJM200008173430701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradley K. M., O'Sullivan V. T., Soper N. D. W., Nagy Z., King E. M-F, Smith A. D., Shepstone B. J. Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease. Brain. 2002 Aug;125(Pt 8):1772–1781. doi: 10.1093/brain/awf185. [DOI] [PubMed] [Google Scholar]
  6. Bäckman L., Andersson J. L., Nyberg L., Winblad B., Nordberg A., Almkvist O. Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease. Neurology. 1999 Jun 10;52(9):1861–1870. doi: 10.1212/wnl.52.9.1861. [DOI] [PubMed] [Google Scholar]
  7. Cools Roshan, Clark Luke, Owen Adrian M., Robbins Trevor W. Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging. J Neurosci. 2002 Jun 1;22(11):4563–4567. doi: 10.1523/JNEUROSCI.22-11-04563.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Costello C. G. Research on symptoms versus research on syndromes. Arguments in favour of allocating more research time to the study of symptoms. Br J Psychiatry. 1992 Mar;160:304–308. doi: 10.1192/bjp.160.3.304. [DOI] [PubMed] [Google Scholar]
  9. DeKosky Steven T., Ikonomovic Milos D., Styren Scot D., Beckett Laurel, Wisniewski Stephen, Bennett David A., Cochran Elizabeth J., Kordower Jeffrey H., Mufson Elliott J. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol. 2002 Feb;51(2):145–155. doi: 10.1002/ana.10069. [DOI] [PubMed] [Google Scholar]
  10. Dehaene S., Changeux J. P. The Wisconsin Card Sorting Test: theoretical analysis and modeling in a neuronal network. Cereb Cortex. 1991 Jan-Feb;1(1):62–79. doi: 10.1093/cercor/1.1.62. [DOI] [PubMed] [Google Scholar]
  11. Desgranges B., Baron J. C., de la Sayette V., Petit-Taboué M. C., Benali K., Landeau B., Lechevalier B., Eustache F. The neural substrates of memory systems impairment in Alzheimer's disease. A PET study of resting brain glucose utilization. Brain. 1998 Apr;121(Pt 4):611–631. doi: 10.1093/brain/121.4.611. [DOI] [PubMed] [Google Scholar]
  12. Dias R., Robbins T. W., Roberts A. C. Dissociation in prefrontal cortex of affective and attentional shifts. Nature. 1996 Mar 7;380(6569):69–72. doi: 10.1038/380069a0. [DOI] [PubMed] [Google Scholar]
  13. Dolan R. J., Bench C. J., Liddle P. F., Friston K. J., Frith C. D., Grasby P. M., Frackowiak R. S. Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or disease specificity? J Neurol Neurosurg Psychiatry. 1993 Dec;56(12):1290–1294. doi: 10.1136/jnnp.56.12.1290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Drewe E. A. The effect of type and area of brain lesion on Wisconsin card sorting test performance. Cortex. 1974 Jun;10(2):159–170. doi: 10.1016/s0010-9452(74)80006-7. [DOI] [PubMed] [Google Scholar]
  15. Fink G. R., Dolan R. J., Halligan P. W., Marshall J. C., Frith C. D. Space-based and object-based visual attention: shared and specific neural domains. Brain. 1997 Nov;120(Pt 11):2013–2028. doi: 10.1093/brain/120.11.2013. [DOI] [PubMed] [Google Scholar]
  16. Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
  17. Grady Cheryl L., McIntosh Anthony R., Beig Sania, Keightley Michelle L., Burian Hana, Black Sandra E. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J Neurosci. 2003 Feb 1;23(3):986–993. doi: 10.1523/JNEUROSCI.23-03-00986.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grafman J., Jonas B., Salazar A. Wisconsin Card Sorting Test performance based on location and size of neuroanatomical lesion in Vietnam veterans with penetrating head injury. Percept Mot Skills. 1990 Dec;71(3 Pt 2):1120–1122. doi: 10.2466/pms.1990.71.3f.1120. [DOI] [PubMed] [Google Scholar]
  19. Hotz G., Helm-Estabrooks N. Perseveration. Part I: a review. Brain Inj. 1995 Feb-Mar;9(2):151–159. doi: 10.3109/02699059509008188. [DOI] [PubMed] [Google Scholar]
  20. Ibáez V., Pietrini P., Alexander G. E., Furey M. L., Teichberg D., Rajapakse J. C., Rapoport S. I., Schapiro M. B., Horwitz B. Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease. Neurology. 1998 Jun;50(6):1585–1593. doi: 10.1212/wnl.50.6.1585. [DOI] [PubMed] [Google Scholar]
  21. Iversen S. D., Mishkin M. Perseverative interference in monkeys following selective lesions of the inferior prefrontal convexity. Exp Brain Res. 1970 Nov 26;11(4):376–386. doi: 10.1007/BF00237911. [DOI] [PubMed] [Google Scholar]
  22. Konishi S., Nakajima K., Uchida I., Kikyo H., Kameyama M., Miyashita Y. Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI. Brain. 1999 May;122(Pt 5):981–991. doi: 10.1093/brain/122.5.981. [DOI] [PubMed] [Google Scholar]
  23. Konishi Seiki, Hayashi Toshihiro, Uchida Idai, Kikyo Hideyuki, Takahashi Emi, Miyashita Yasushi. Hemispheric asymmetry in human lateral prefrontal cortex during cognitive set shifting. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7803–7808. doi: 10.1073/pnas.122644899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Martin A. J., Friston K. J., Colebatch J. G., Frackowiak R. S. Decreases in regional cerebral blood flow with normal aging. J Cereb Blood Flow Metab. 1991 Jul;11(4):684–689. doi: 10.1038/jcbfm.1991.121. [DOI] [PubMed] [Google Scholar]
  25. Matsuda H. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease. Ann Nucl Med. 2001 Apr;15(2):85–92. doi: 10.1007/BF02988596. [DOI] [PubMed] [Google Scholar]
  26. Mazziotta J. C., Toga A. W., Evans A., Fox P., Lancaster J. A probabilistic atlas of the human brain: theory and rationale for its development. The International Consortium for Brain Mapping (ICBM). Neuroimage. 1995 Jun;2(2):89–101. doi: 10.1006/nimg.1995.1012. [DOI] [PubMed] [Google Scholar]
  27. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  28. Mega M. S., Lee L., Dinov I. D., Mishkin F., Toga A. W., Cummings J. L. Cerebral correlates of psychotic symptoms in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2000 Aug;69(2):167–171. doi: 10.1136/jnnp.69.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Menon V., Adleman N. E., White C. D., Glover G. H., Reiss A. L. Error-related brain activation during a Go/NoGo response inhibition task. Hum Brain Mapp. 2001 Mar;12(3):131–143. doi: 10.1002/1097-0193(200103)12:3<131::AID-HBM1010>3.0.CO;2-C. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mielke R., Kessler J., Szelies B., Herholz K., Wienhard K., Heiss W. D. Normal and pathological aging--findings of positron-emission-tomography. J Neural Transm (Vienna) 1998;105(8-9):821–837. doi: 10.1007/s007020050097. [DOI] [PubMed] [Google Scholar]
  31. Monchi O., Petrides M., Petre V., Worsley K., Dagher A. Wisconsin Card Sorting revisited: distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging. J Neurosci. 2001 Oct 1;21(19):7733–7741. doi: 10.1523/JNEUROSCI.21-19-07733.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nagahama Y., Fukuyama H., Yamauchi H., Katsumi Y., Magata Y., Shibasaki H., Kimura J. Age-related changes in cerebral blood flow activation during a Card Sorting Test. Exp Brain Res. 1997 May;114(3):571–577. doi: 10.1007/pl00005665. [DOI] [PubMed] [Google Scholar]
  33. Nagahama Y., Fukuyama H., Yamauchi H., Matsuzaki S., Konishi J., Shibasaki H., Kimura J. Cerebral activation during performance of a card sorting test. Brain. 1996 Oct;119(Pt 5):1667–1675. doi: 10.1093/brain/119.5.1667. [DOI] [PubMed] [Google Scholar]
  34. Nagahama Y., Okada T., Katsumi Y., Hayashi T., Yamauchi H., Oyanagi C., Konishi J., Fukuyama H., Shibasaki H. Dissociable mechanisms of attentional control within the human prefrontal cortex. Cereb Cortex. 2001 Jan;11(1):85–92. doi: 10.1093/cercor/11.1.85. [DOI] [PubMed] [Google Scholar]
  35. Nagahama Y., Sadato N., Yamauchi H., Katsumi Y., Hayashi T., Fukuyama H., Kimura J., Shibasaki H., Yonekura Y. Neural activity during attention shifts between object features. Neuroreport. 1998 Aug 3;9(11):2633–2638. doi: 10.1097/00001756-199808030-00038. [DOI] [PubMed] [Google Scholar]
  36. Nagahama Yasuhiro, Okina Tomoko, Suzuki Norio, Matsuzaki Shigeru, Yamauchi Hiroshi, Nabatame Hidehiko, Matsuda Minoru. Factor structure of a modified version of the wisconsin card sorting test: an analysis of executive deficit in Alzheimer's disease and mild cognitive impairment. Dement Geriatr Cogn Disord. 2003;16(2):103–112. doi: 10.1159/000070683. [DOI] [PubMed] [Google Scholar]
  37. Neary D., Snowden J. S., Gustafson L., Passant U., Stuss D., Black S., Freedman M., Kertesz A., Robert P. H., Albert M. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998 Dec;51(6):1546–1554. doi: 10.1212/wnl.51.6.1546. [DOI] [PubMed] [Google Scholar]
  38. Nebu A., Ikeda M., Fukuhara R., Shigenobu K., Maki N., Hokoishi K., Komori K., Yasuoka T., Tanabe H. Relationship between blood flow kinetics and severity of Alzheimer's disease: assessment of severity using a questionnaire-type examination, Alzheimer's disease assessment scale, cognitive sub-scale (ADAS(cog)). Dement Geriatr Cogn Disord. 2001 Sep-Oct;12(5):318–325. doi: 10.1159/000051277. [DOI] [PubMed] [Google Scholar]
  39. Nelson H. E. A modified card sorting test sensitive to frontal lobe defects. Cortex. 1976 Dec;12(4):313–324. doi: 10.1016/s0010-9452(76)80035-4. [DOI] [PubMed] [Google Scholar]
  40. 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. 1996 Jan-Feb;6(1):31–38. doi: 10.1093/cercor/6.1.31. [DOI] [PubMed] [Google Scholar]
  41. Perani D., Bressi S., Cappa S. F., Vallar G., Alberoni M., Grassi F., Caltagirone C., Cipolotti L., Franceschi M., Lenzi G. L. Evidence of multiple memory systems in the human brain. A [18F]FDG PET metabolic study. Brain. 1993 Aug;116(Pt 4):903–919. doi: 10.1093/brain/116.4.903. [DOI] [PubMed] [Google Scholar]
  42. Petersen R. C., Stevens J. C., Ganguli M., Tangalos E. G., Cummings J. L., DeKosky S. T. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001 May 8;56(9):1133–1142. doi: 10.1212/wnl.56.9.1133. [DOI] [PubMed] [Google Scholar]
  43. Petrides M. 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. J Neurosci. 1995 Jan;15(1 Pt 1):359–375. doi: 10.1523/JNEUROSCI.15-01-00359.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Pollmann S., Weidner R., Müller H. J., von Cramon D. Y. A fronto-posterior network involved in visual dimension changes. J Cogn Neurosci. 2000 May;12(3):480–494. doi: 10.1162/089892900562156. [DOI] [PubMed] [Google Scholar]
  45. Price C. J., Mummery C. J., Moore C. J., Frakowiak R. S., Friston K. J. Delineating necessary and sufficient neural systems with functional imaging studies of neuropsychological patients. J Cogn Neurosci. 1999 Jul;11(4):371–382. doi: 10.1162/089892999563481. [DOI] [PubMed] [Google Scholar]
  46. Robinson A. L., Heaton R. K., Lehman R. A., Stilson D. W. The utility of the Wisconsin Card Sorting Test in detecting and localizing frontal lobe lesions. J Consult Clin Psychol. 1980 Oct;48(5):605–614. doi: 10.1037//0022-006x.48.5.605. [DOI] [PubMed] [Google Scholar]
  47. Rogers R. D., Andrews T. C., Grasby P. M., Brooks D. J., Robbins T. W. Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans. J Cogn Neurosci. 2000 Jan;12(1):142–162. doi: 10.1162/089892900561931. [DOI] [PubMed] [Google Scholar]
  48. Rubia K., Russell T., Overmeyer S., Brammer M. J., Bullmore E. T., Sharma T., Simmons A., Williams S. C., Giampietro V., Andrew C. M. Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks. Neuroimage. 2001 Feb;13(2):250–261. doi: 10.1006/nimg.2000.0685. [DOI] [PubMed] [Google Scholar]
  49. Rushworth M. F., Nixon P. D., Eacott M. J., Passingham R. E. Ventral prefrontal cortex is not essential for working memory. J Neurosci. 1997 Jun 15;17(12):4829–4838. doi: 10.1523/JNEUROSCI.17-12-04829.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Sandson J., Albert M. L. Perseveration in behavioral neurology. Neurology. 1987 Nov;37(11):1736–1741. doi: 10.1212/wnl.37.11.1736. [DOI] [PubMed] [Google Scholar]
  51. Seidman L. J., Pepple J. R., Faraone S. V., Kremen W. S., Cassens G., McCarley R. W., Tsuang M. T. Wisconsin Card Sorting Test performance over time in schizophrenia. Preliminary evidence from clinical follow-up and neuroleptic reduction studies. Schizophr Res. 1991 Oct;5(3):233–242. doi: 10.1016/0920-9964(91)90081-2. [DOI] [PubMed] [Google Scholar]
  52. Slansky I., Herholz K., Pietrzyk U., Kessler J., Grond M., Mielke R., Heiss W. D. Cognitive impairment in Alzheimer's disease correlates with ventricular width and atrophy-corrected cortical glucose metabolism. Neuroradiology. 1995 May;37(4):270–277. doi: 10.1007/BF00588331. [DOI] [PubMed] [Google Scholar]
  53. Stuss D. T., Levine B., Alexander M. P., Hong J., Palumbo C., Hamer L., Murphy K. J., Izukawa D. Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes. Neuropsychologia. 2000;38(4):388–402. doi: 10.1016/s0028-3932(99)00093-7. [DOI] [PubMed] [Google Scholar]
  54. Wojciulik E., Kanwisher N. The generality of parietal involvement in visual attention. Neuron. 1999 Aug;23(4):747–764. doi: 10.1016/s0896-6273(01)80033-7. [DOI] [PubMed] [Google Scholar]
  55. van den Broek M. D., Bradshaw C. M., Szabadi E. Utility of the Modified Wisconsin Card Sorting Test in neuropsychological assessment. Br J Clin Psychol. 1993 Sep;32(Pt 3):333–343. doi: 10.1111/j.2044-8260.1993.tb01064.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES