Experimental Brain Research

, Volume 107, Issue 3, pp 479–485 | Cite as

The role of the dorsolateral prefrontal cortex in implicit procedural learning

  • Alvaro Pascual-Leone
  • Eric M. Wassermann
  • Jordan Grafman
  • Mark Hallett
Research Article


We studied the role of the dorsolateral prefrontal cortex in procedural learning. Normal subjects completed several blocks of a serial reaction time task using only one hand without or with concurrent non-invasive repetitive transcranial magnetic stimulation. To disrupt their function transiently, stimulation was applied at low intensity over the supplementary motor area or over the dorsolateral prefrontal cortex contralateral or ipsilateral to the hand used for the test. Stimulation to the contralateral dorsolateral prefrontal cortex markedly impaired procedural implicit learning, as documented by the lack of significant change in response times during the task. Stimulation over the other areas did not interfere with learning. These results support the notion of a critical role of contralateral dorsolateral prefrontal structures in learning of motor sequences.

Key words

Transcranial magnetic stimulation Learning and memory Cortical physiology Human 


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  1. Baddeley A (1992) Working memory. Science 255: 556–559Google Scholar
  2. Brasil-Neto JP, Pascual-Leone A, Valls-Solé J, Cohen LG, Hallett M (1992) Focal transcranial magnetic stimulation and response bias in a forced-choice task. J Neurol Neurosurg Psychiatry 55: 964–966Google Scholar
  3. Fuster JM (1985) The prefrontal cortex, mediator of cross-temporal contingencies. Hum Neurobiol 4: 169–179Google Scholar
  4. Fuster JM (1989) The prefrontal cortex: anatomy, physiology, and neuropsychology of the frontal lobe, 2nd edn. Raven Press, New YorkGoogle Scholar
  5. Fuster JM, Alexander GE (1970) Neuron activity related to shortterm memory. Science 173: 652–654Google Scholar
  6. Goldman-Rakic PS (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In: Plum F (ed) Handbook of physiology. Nervous system, vol V, Higher functions of the brain, part 1. American Physiological Society, Bethesda, MdGoogle Scholar
  7. Gordon B (1988) Preserved learning of novel information in amnesia: evidence multiple memory systems. Brain Cogn 7: 257–282Google Scholar
  8. Grafman J, Weingartner H, Newhouse PA, Thompson K, Lalonde F, Litvan I, Molchan S, Sunderland T (1990) Implicit learning in patients with Alzheimer's disease. Pharmacopsychiatry 23: 94–101Google Scholar
  9. Harrington DL, Haaland KY, Yeo R A, Marder E (1990) Procedural memory in Parkinson's disease: impaired motor but visuoperceptual learning. J Clin Exp Neuropsychol 12: 323–339Google Scholar
  10. Ivry RL, Keele SW (1989) Timing function of the cerebellum. J Cogn Neurosci 1: 136–152Google Scholar
  11. Knopman DS (1991) Long-term retention of implicitly acquired learning in patients with Alzheimer's disease. J Clin Exp Neuropsychol 13: 880–894Google Scholar
  12. Knopman DS, Nissen MJ (1987) Implicit learning in patients with probable Alzheimer's disease. Neurology 37: 784–788Google Scholar
  13. Knopman DS, Nissen MJ (1991) Procedural learning is impaired in Huntington's disease: from the serial reaction time task. Neuropsychologia 29: 245–254Google Scholar
  14. Leiner HC, Leiner AL, Dow RS (1991) The human cerebro-cerebellar system: its computing, cognitive, and language skills. Behav Brain Res 44: 113–128Google Scholar
  15. Nissen MJ, Bullemer P (1987) Attentional requirements of learning: evidence from performance measures. Cogn Psychol 19: 1–32Google Scholar
  16. Nissen MJ, Knopman DS, Schacter DL (1987) Neurochemical dissociation of memory systems. Neurology 37: 789–794Google Scholar
  17. Nissen MJ, Willingham D, Hartman M (1989) Explicit and implicit remembering. When is learning preserved in amnesia? Neuropsychologia 27: 341–352Google Scholar
  18. Pascual-Leone A, Grafman J, Clark K, Stewart M, Massaquoi S, Lou J-S, Hallett M (1993a) Procedural learning in Parkinson's disease and cerebellar degeneration. Ann Neurol 34: 594–602Google Scholar
  19. Pascual-Leone A, Houser CM, Reese K, Shotland LI, Grafman J, Sato S, Valls-Solé J, Brasil-Neto JP, Wassermann EM, Cohen LG, Hallett M (1993b) Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. Electroencephalogr Clin Neurophysiol 89: 120–130Google Scholar
  20. Pascual-Leone A, Grafman J, Hallett M (1994a) Modulation of cortical motor output maps during development of implicit and explicit knowledge. Science 263: 1287–1289PubMedGoogle Scholar
  21. Pascual-Leone A, Valls-Solé J, Brasil-Neto J, Grafman J, Hallett M (1994b) Akinesia in Parkinson's disease. II: Shortening of choice reaction time and movement time with subthreshold repetitive transcranial motor cortex stimulation. Neurology 44: 892–898Google Scholar
  22. Pascual-Leone A, Cohen LG, Dang N, Brasil-Neto JP, Cammarota A, Hallett M (1995a) Modulation of human cortical motor outputs during the acquisition of new fine motor skills. J Neurophysiol (in press)Google Scholar
  23. Pascual-Leone A, Grafman J, Cohen LG, Roth BJ, Hallett M (1995b) Transcranial magnetic stimulation: a new tool for the study of higher cognitive functions in humans. In: Grafman J, Boller F (eds) Handbook of neuropsychology, vol 9. Elsevier, Amsterdam (in press)PubMedGoogle Scholar
  24. Passingham R (1993) The frontal lobes and voluntary action. Oxford University Press, OxfordGoogle Scholar
  25. Phillips AG, Carr GD (1987) Cognition and the basal ganglia: a possible substrate for procedural knowledge. Can J Neurol Sci 14: 381–385Google Scholar
  26. Roth BJ, Saypol JM, Hallett M, Cohen LG (1991) A theoretical calculation of the electric field induced in the cortex during transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol 81: 47–56Google Scholar
  27. Saint CJ, Taylor AE, Lang AE (1988) Procedural learning and neostriatal dysfunction in man. Brain 111: 941–959Google Scholar
  28. Schmahmann JD (1991) An emerging concept: the cerebellar contribution to higher function. Arch Neurol 48: 1178–1187Google Scholar
  29. Squire LR (1992) Declarative and nondeclarative memory: multiple brain systems supporting learning and memory. J Cogn Neurosci 4: 232–243Google Scholar
  30. Tofts PS (1990) The distribution of induced currents in magnetic stimulation of the nervous system. Proc R Soc Lond B Biol Sci 35: 1119–1128Google Scholar
  31. Wassermann EW, Wang B, Toro C, Zeffiro T, Valls-Solé J, Pascual-Leone A Hallett M (1992) Projecting transcranial magetic Stimulation (TMS) maps into brain MRI. Soc Neurosci Abstr 18: 939Google Scholar
  32. Willingham DB, Nissen MJ, Bullemer P (1989) On the development of procedural knowledge. J Exp Psychol Learn Mem Cogn 15: 1047–1060Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Alvaro Pascual-Leone
    • 1
    • 2
  • Eric M. Wassermann
    • 1
  • Jordan Grafman
    • 3
  • Mark Hallett
    • 1
  1. 1.Human Motor Control Section, Medical Neurology BranchNational Institute of Neurological Disorders and Stroke, National Institutes of HealthBethesdaUSA
  2. 2.Consejo Superior Investigaciones Cientificas, Unidad de Neurobiología, Departamento de FisiologíaUniversidad de ValenciaValenciaSpain
  3. 3.Cognitive Neuroscience Section, Medical Neurology BranchNational Institute of Neurological Disorders and Stroke, National Institutes of HealthBethesdaUSA

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