Experimental Brain Research

, Volume 205, Issue 3, pp 375–385 | Cite as

Movement chunking during sequence learning is a dopamine-dependant process: a study conducted in Parkinson’s disease

  • Pierre-Luc Tremblay
  • Marc-Andre Bedard
  • Dominic Langlois
  • Pierre J. Blanchet
  • Martin Lemay
  • Maxime Parent
Research Article


Chunking of single movements into integrated sequences has been described during motor learning, and we have recently demonstrated that this process involves a dopamine-dependant mechanism in animal (Levesque et al. in Exp Brain Res 182:499–508, 2007; Tremblay et al. in Behav Brain Res 198:231–239, 2009). However, there is no such evidence in human. The aim of the present study was to assess this question in Parkinson’s disease (PD), a neurological condition known for its dopamine depletion in the striatum. Eleven PD patients were tested under their usual levodopa medication (ON state), and following a 12-h levodopa withdrawal (OFF state). Patients were compared with 12 healthy participants on a motor learning sequencing task, requiring pressing fourteen buttons in the correct order, which was determined by visual stimuli presented on a computer screen. Learning was assessed from three blocks of 20 trials administered successively. Chunks of movements were intrinsically created by each participant during this learning period. Then, the sequence was shuffled according to the participant’s own chunks, generating two new sequences, with either preserved or broken chunks. Those new motor sequences had to be performed separately in a fourth and fifth blocks of 20 trials. Results showed that execution time improved in every group during the learning period (from blocks 1 to 3). However, while motor chunking occurred in healthy controls and ON-PD patients, it did not in OFF-PD patients. In the shuffling conditions, a significant difference was seen between the preserved and the broken chunks conditions for both healthy participants and ON-PD patients, but not for OFF-PD patients. These results suggest that movement chunking during motor sequence learning is a dopamine-dependent process in human.


Parkinson Dopamine Striatum Motor learning Movement Sequence learning 


  1. Aosaki T, Tsubokawa H, Ishida A, Watanabe K, Graybiel AM, Kimura M (1994) Responses of tonically active neurons in the primate’s striatum undergo systematic changes during behavioral sensorimotor conditioning. J Neurosci 14:3969–3984PubMedGoogle Scholar
  2. Badgaiyan RD, Fischman AJ, Alpert NM (2007) Striatal dopamine release in sequential learning. Neuroimage 38:549–556CrossRefPubMedGoogle Scholar
  3. Badgaiyan RD, Fischman AJ, Alpert NM (2008) Explicit motor memory activates the striatal dopamine system. Neuroreport 19:409–412CrossRefPubMedGoogle Scholar
  4. Berridge KC, Whishaw IQ (1992) Cortex, striatum and cerebellum: control of serial order in a grooming sequence. Exp Brain Res 90:275–290CrossRefPubMedGoogle Scholar
  5. Boyd LA, Edwards JD, Siengsukon CS, Vidoni ED, Wessel BD, Linsdell MA (2009) Motor sequence chunking is impaired by basal ganglia stroke. Neurobiol Learn Mem 92:35–44CrossRefPubMedGoogle Scholar
  6. Centonze D, Picconi B, Gubellini P, Bernardi G, Calabresi P (2001) Dopaminergic control of synaptic plasticity in the dorsal striatum. Eur J Neurosci 13:1071–1077CrossRefPubMedGoogle Scholar
  7. Charpier S, Deniau JM (1997) In vivo activity-dependent plasticity at cortico-striatal connections: evidence for physiological long-term potentiation. Proc Natl Acad Sci USA 94:7036–7040CrossRefPubMedGoogle Scholar
  8. Contin M, Riva R, Martinelli P, Albani F, Avoni P, Baruzzi A (2001) Levodopa therapy monitoring in patients with Parkinson disease: a kinetic-dynamic approach. Ther Drug Monit 23:621–629CrossRefPubMedGoogle Scholar
  9. Contreras-Vidal JL, Buch ER (2003) Effects of Parkinson’s disease on visuomotor adaptation. Exp Brain Res 150:25–32PubMedGoogle Scholar
  10. Costa RM (2007) Plastic corticostriatal circuits for action learning: what’s dopamine got to do with it? Ann N Y Acad Sci 1104:172–191CrossRefPubMedGoogle Scholar
  11. Cromwell HC, Berridge KC, Drago J, Levine MS (1998) Action sequencing is impaired in D1A-deficient mutant mice. Eur J Neurosci 10:2426–2432CrossRefPubMedGoogle Scholar
  12. Domenger D, Schwarting RK (2008) Effects of neostriatal 6-OHDA lesion on performance in a rat sequential reaction time task. Neurosci Lett 444:212–216CrossRefPubMedGoogle Scholar
  13. Eckart MT, Huelse-Matia MC, McDonald RS, Schwarting RK (2010) 6-Hydroxydopamine lesions in the rat neostriatum impair sequential learning in a serial reaction time task. Neurotox Res 17:287–298CrossRefPubMedGoogle Scholar
  14. Erixon-Lindroth N, Farde L, Wahlin TB, Sovago J, Halldin C, Backman L (2005) The role of the striatal dopamine transporter in cognitive aging. Psychiatry Res 138:1–12CrossRefPubMedGoogle Scholar
  15. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMedGoogle Scholar
  16. Graybiel AM (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31:359–387CrossRefPubMedGoogle Scholar
  17. Hikosaka O, Rand MK, Miyachi S, Miyashita K (1995) Learning of sequential movements in the monkey: process of learning and retention of memory. J Neurophysiol 74:1652–1661PubMedGoogle Scholar
  18. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMedGoogle Scholar
  19. Koerts J, Leenders KL, Brouwer WH (2009) Cognitive dysfunction in non-demented Parkinson’s disease patients: controlled and automatic behavior. Cortex 45:922–929CrossRefPubMedGoogle Scholar
  20. Levesque M, Bedard MA, Courtemanche R, Tremblay PL, Scherzer P, Blanchet PJ (2007) Raclopride-induced motor consolidation impairment in primates: role of the dopamine type-2 receptor in movement chunking into integrated sequences. Exp Brain Res 182:499–508CrossRefPubMedGoogle Scholar
  21. Matsumoto N, Hanakawa T, Maki S, Graybiel AM, Kimura M (1999) Role of [corrected] nigrostriatal dopamine system in learning to perform sequential motor tasks in a predictive manner. J Neurophysiol 82:978–998PubMedGoogle Scholar
  22. Messier J, Adamovich S, Jack D, Hening W, Sage J, Poizner H (2007) Visuomotor learning in immersive 3D virtual reality in Parkinson’s disease and in aging. Exp Brain Res 179:457–474CrossRefPubMedGoogle Scholar
  23. Nakamura T, Ghilardi MF, Mentis M, Dhawan V, Fukuda M, Hacking A, Moeller JR, Ghez C, Eidelberg D (2001) Functional networks in motor sequence learning: abnormal topographies in Parkinson’s disease. Hum Brain Mapp 12:42–60CrossRefPubMedGoogle Scholar
  24. Paquet F, Bedard MA, Levesque M, Tremblay PL, Lemay M, Blanchet PJ, Scherzer P, Chouinard S, Filion J (2008) Sensorimotor adaptation in Parkinson’s disease: evidence for a dopamine dependent remapping disturbance. Exp Brain Res 185:227–236CrossRefPubMedGoogle Scholar
  25. Pisani A, Centonze D, Bernardi G, Calabresi P (2005) Striatal synaptic plasticity: implications for motor learning and Parkinson’s disease. Mov Disord 20:395–402CrossRefPubMedGoogle Scholar
  26. Reynolds JN, Hyland BI, Wickens JR (2001) A cellular mechanism of reward-related learning. Nature 413:67–70CrossRefPubMedGoogle Scholar
  27. Sakai K, Kitaguchi K, Hikosaka O (2003) Chunking during human visuomotor sequence learning. Exp Brain Res 152:229–242CrossRefPubMedGoogle Scholar
  28. Seidler RD (2006) Differential effects of age on sequence learning and sensorimotor adaptation. Brain Res Bull 70:337–346CrossRefPubMedGoogle Scholar
  29. Seidler RD, Tuite P, Ashe J (2007) Selective impairments in implicit learning in Parkinson’s disease. Brain Res 1137:104–110CrossRefPubMedGoogle Scholar
  30. Siegert RJ, Taylor KD, Weatherall M, Abernethy DA (2006) Is implicit sequence learning impaired in Parkinson’s disease? A meta-analysis. Neuropsychology 20:490–495CrossRefPubMedGoogle Scholar
  31. Stark AK, Pakkenberg B (2004) Histological changes of the dopaminergic nigrostriatal system in aging. Cell Tissue Res 318:81–92CrossRefPubMedGoogle Scholar
  32. Suri RE, Schultz W (1998) Learning of sequential movements by neural network model with dopamine-like reinforcement signal. Exp Brain Res 121:350–354CrossRefPubMedGoogle Scholar
  33. Tremblay PL, Bedard MA, Levesque M, Chebli M, Parent M, Courtemanche R, Blanchet PJ (2009) Motor sequence learning in primate: role of the D2 receptor in movement chunking during consolidation. Behav Brain Res 198:231–239CrossRefPubMedGoogle Scholar
  34. Verwey WB, Eikelboom T (2003) Evidence for lasting sequence segmentation in the discrete sequence-production task. J Mot Behav 35:171–181CrossRefPubMedGoogle Scholar
  35. Verwey WB (2010) Diminished motor skill development in elderly: indications for limited motor chunk use. Acta Psychol (Amst) 134:206–214CrossRefGoogle Scholar
  36. Wickens JR, Horvitz JC, Costa RM, Killcross S (2007) Dopaminergic mechanisms in actions and habits. J Neurosci 27:8181–8183CrossRefPubMedGoogle Scholar
  37. Wu T, Hallett M (2005) A functional MRI study of automatic movements in patients with Parkinson’s disease. Brain 128:2250–2259CrossRefPubMedGoogle Scholar
  38. Wu T, Chan P, Hallett M (2010) Effective connectivity of neural networks in automatic movements in Parkinson’s disease. Neuroimage 49:2581–2587CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Pierre-Luc Tremblay
    • 1
  • Marc-Andre Bedard
    • 1
  • Dominic Langlois
    • 1
  • Pierre J. Blanchet
    • 2
    • 3
  • Martin Lemay
    • 4
    • 5
  • Maxime Parent
    • 1
  1. 1.Department of Psychology, Cognitive Pharmacology Research UnitUniversity of Quebec in Montreal (UQAM)MontrealCanada
  2. 2.André-Barbeau Movement Disorder CentreCHUMMontrealCanada
  3. 3.Département de Stomatologie, Faculté de Médecine DentaireUniversité de MontréalMontrealCanada
  4. 4.Département de kinésiologieUQAMMontrealCanada
  5. 5.Centre de Réadaptation Marie-Enfant (CHU Sainte-Justine)MontrealCanada

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