Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Different time courses of learning-related activity in the prefrontal cortex and striatum


To navigate our complex world, our brains have evolved a sophisticated ability to quickly learn arbitrary rules such as ‘stop at red’. Studies in monkeys using a laboratory test of this capacity—conditional association learning—have revealed that frontal lobe structures (including the prefrontal cortex) as well as subcortical nuclei of the basal ganglia are involved in such learning1,2,3,4,5. Neural correlates of associative learning have been observed in both brain regions6,7,8,9,10,11,12,13,14, but whether or not these regions have unique functions is unclear, as they have typically been studied separately using different tasks. Here we show that during associative learning in monkeys, neural activity in these areas changes at different rates: the striatum (an input structure of the basal ganglia) showed rapid, almost bistable, changes compared with a slower trend in the prefrontal cortex that was more in accordance with slow improvements in behavioural performance. Also, pre-saccadic activity began progressively earlier in the striatum but not in the prefrontal cortex as learning took place. These results support the hypothesis that rewarded associations are first identified by the basal ganglia, the output of which ‘trains’ slower learning mechanisms in the frontal cortex15.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Task and behaviour.
Figure 2: Change in peri-cue saccade direction selectivity in prefrontal cortex and caudate nucleus with learning.
Figure 3: Change in saccade direction selectivity at the time of saccade execution during the learning process.


  1. Petrides, M. in Handbook of Neuropsychology (eds Boller, F. & Grafman, J.) 59–82 (Elsevier, Amsterdam, 1994)

    Google Scholar 

  2. Passingham, R. E. The Frontal Lobes and Voluntary Action (Oxford Univ. Press, Oxford, 1995)

    Google Scholar 

  3. Fuster, J. M. The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe (Lippincott-Raven, Philadelphia, 1997)

    Google Scholar 

  4. Wise, S. P., Murray, E. A. & Gerfen, C. R. The frontal cortex-basal ganglia system in primates. Crit. Rev. Neurobiol. 10, 317–356 (1996)

    CAS  Article  Google Scholar 

  5. Murray, E. A., Bussey, T. J. & Wise, S. P. Role of prefrontal cortex in a network for arbitrary visuomotor mapping. Exp. Brain Res. 133, 114–129 (2000)

    CAS  Article  Google Scholar 

  6. Tremblay, L., Hollerman, J. R. & Schultz, W. Modifications of reward expectation-related neuronal activity during learning in primate striatum. J. Neurophysiol. 80, 964–977 (1998)

    CAS  Article  Google Scholar 

  7. Asaad, W. F., Rainer, G. & Miller, E. K. Neural activity in the primate prefrontal cortex during associative learning. Neuron 21, 1399–1407 (1998)

    CAS  Article  Google Scholar 

  8. White, I. M. & Wise, S. P. Rule-dependent neuronal activity in the prefrontal cortex. Exp. Brain Res. 126, 315–335 (1999)

    CAS  Article  Google Scholar 

  9. Toni, I. & Passingham, R. E. Prefrontal-basal ganglia pathways are involved in the learning of arbitrary visuomotor associations: a PET study. Exp. Brain Res. 127, 19–32 (1999)

    CAS  Article  Google Scholar 

  10. Lauwereyns, J., Watanabe, K., Coe, B. & Hikosaka, O. A neural correlate of response bias in monkey caudate nucleus. Nature 418, 413–417 (2002)

    ADS  CAS  Article  Google Scholar 

  11. Hadj-Bouziane, F. & Boussaoud, D. Neuronal activity in the monkey striatum during conditional visuomotor learning. Exp. Brain Res. 153, 190–196 (2003)

    Article  Google Scholar 

  12. Schumacher, E. H., Elston, P. A. & D'Esposito, M. Neural evidence for representation-specific response selection. J. Cogn. Neurosci. 15, 1111–1121 (2003)

    Article  Google Scholar 

  13. Brasted, P. J. & Wise, S. P. Comparison of learning-related neuronal activity in the dorsal premotor cortex and striatum. Eur. J. Neurosci. 19, 721–740 (2004)

    Article  Google Scholar 

  14. Hoshi, E. & Tanji, J. Area-selective neuronal activity in the dorsolateral prefrontal cortex for information retrieval and action planning. J. Neurophysiol. 91, 2707–2722 (2004)

    Article  Google Scholar 

  15. Houk, J. C. & Wise, S. P. Distributed modular architectures linking basal ganglia, cerebellum, and cerebral cortex: their role in planning and controlling action. Cereb. Cortex 5, 95–110 (1995)

    CAS  Article  Google Scholar 

  16. Miller, E. K. & Cohen, J. D. An integrative theory of prefrontal cortex function. Annu. Rev. Neurosci. 24, 167–202 (2001)

    CAS  Article  Google Scholar 

  17. Graybiel, A. M. The basal ganglia and the initiation of movement. Rev. Neurol. (Paris) 146, 570–574 (1990)

    CAS  Google Scholar 

  18. Hikosaka, O., Takikawa, Y. & Kawagoe, R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev. 80, 953–978 (2000)

    CAS  Article  Google Scholar 

  19. DeLong, M. R. & Georgopoulos, A. P. in Handbook of Physiology—Nervous System (eds Brookhart, J. M. & Mountcastle, V. B.) 1017–1061 (American Physiological Society, Bethesda, 1981)

    Google Scholar 

  20. Middleton, F. A. & Strick, P. L. Basal-ganglia ‘projections’ to the prefrontal cortex of the primate. Cereb. Cortex 12, 926–935 (2002)

    Article  Google Scholar 

  21. Packard, M. G. & Knowlton, B. J. Learning and memory functions of the basal ganglia. Annu. Rev. Neurosci. 25, 563–593 (2002)

    CAS  Article  Google Scholar 

  22. Graybiel, A. M. The basal ganglia and chunking of action repertoires. Neurobiol. Learn. Mem. 70, 119–136 (1998)

    CAS  Article  Google Scholar 

  23. Bar-Gad, I., Morris, G. & Bergman, H. Information processing, dimensionality reduction and reinforcement learning in the basal ganglia. Prog. Neurobiol. 71, 439–473 (2003)

    Article  Google Scholar 

  24. Reynolds, J. N., Hyland, B. I. & Wickens, J. R. A cellular mechanism of reward-related learning. Nature 413, 67–70 (2001)

    ADS  CAS  Article  Google Scholar 

  25. Wilson, C. J. & Kawaguchi, Y. The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons. J. Neurosci. 16, 2397–2410 (1996)

    CAS  Article  Google Scholar 

  26. O'Reilly, R. C. & Munakata, Y. Computational Explorations in Cognitive Neuroscience: Understanding the Mind by Stimulating the Brain (MIT Press, Cambridge, Massachusetts, 2000)

    Google Scholar 

  27. Schultz, W. & Dickinson, A. Neuronal coding of prediction errors. Annu. Rev. Neurosci. 23, 473–500 (2000)

    CAS  Article  Google Scholar 

  28. McClure, S. M., Berns, G. S. & Montague, P. R. Temporal prediction errors in a passive learning task activate human striatum. Neuron 38, 339–346 (2003)

    CAS  Article  Google Scholar 

  29. Wirth, S. et al. Single neurons in the monkey hippocampus and learning of new associations. Science 300, 1578–1581 (2003)

    ADS  CAS  Article  Google Scholar 

  30. Hanes, D. P. & Schall, J. D. Neural control of voluntary movement initiation. Science 274, 427–430 (1996)

    ADS  CAS  Article  Google Scholar 

Download references


We thank M. H. Histed for valuable discussions; K. J. MacCully for technical assistance; W. F. Asaad, A. J. Bastian, T. Buschman, A. C. Diogo, J. Feingold, D. J. Freedman, M. Machon, J. McDermott, J. E. Roy and M. Wicherski for helpful comments. This work was supported by a grant from the N.I.N.D.S. A.P. was supported by the Tourette's Syndrome Association.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Anitha Pasupathy.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1

Demonstration of peri-cue epoch saccade direction selectivity and its development with learning in single PFC and Cd neurons. (PDF 701 kb)

Supplementary Figure 2

Example of a single Cd neuron showing rapid backward progression of direction selectivity within a few correct trials. (PDF 520 kb)

Supplementary Figure 3

This file contains the supplementary figure comparing population direction selectivity on correct and error trials for the prefrontal (PFC) cortex and the caudate nucleus (Cd). Peri-cue direction selectivity on error trials is significantly weaker than on correct trials in the PFC but not Cd. (PDF 237 kb)

Supplementary Figure 4

Comparison of the evolution of average direction selectivity as a function of correct trials between the PFC and Cd populations. (PDF 189 kb)

Supplementary Figure Legends

This file contains legends for Supplementary figures 1-4. (DOC 30 kb)

Supplementary Notes

This file contains twelve supplementary notes that report results and methods that could not be fit in the main body. (DOC 43 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pasupathy, A., Miller, E. Different time courses of learning-related activity in the prefrontal cortex and striatum. Nature 433, 873–876 (2005).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing