Cerebellar Sequencing for Cognitive Processing

  • Marco Molinari
  • Maria G. Leggio


The idea that cerebellar processing is required in a variety of cognitive functions is well accepted in the neuroscience community. Nevertheless, the definition of the cerebellar role in the different cognitive domains remains obscure. Current data from lesion studies in humans and from experimental lesion in rats on perceptual and cognitive processing are reviewed with special emphasis on cerebellar sequencing properties. Evidence converges in highlighting sequence detection as the key stone of cerebellar functioning across modalities. The hypothesis that sequence detection might represent the main contribution of cerebellar physiology to brain functioning is presented and discussed.


Morris Water Maze Somatosensory Evoke Potential Cerebellar Lesion Cerebellar Function Deviant Stimulus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Akatsuka K, Wasaka T, Nakata H, Inui K, Hoshiyama M, Kakigi R (2005) Mismatch responses related to temporal discrimination of somatosensory stimulation. Clin Neurophysiol 116:1930–1937PubMedCrossRefGoogle Scholar
  2. Alain C, Woods DL, Knight RT (1998) A distributed cortical network for auditory sensory memory in humans. Brain Res 812:23–37PubMedCrossRefGoogle Scholar
  3. Ardila A, Rosselli M (1993) Spatial agraphia. Brain Cogn 22:137–147PubMedCrossRefGoogle Scholar
  4. Bastian AJ (2006) Learning to predict the future: the cerebellum adapts feedforward movement control. Curr Opin Neurobiol 16:645–649PubMedCrossRefGoogle Scholar
  5. Bo J, Block HJ, Clark JE, Bastian AJ (2008) A cerebellar deficit in sensorimotor prediction explains movement timing variability. J Neurophysiol 100:2825–2832PubMedCrossRefGoogle Scholar
  6. Bower JM (1997) Control of sensory data acquisition. Int Rev Neurobiol 41:489–513PubMedCrossRefGoogle Scholar
  7. Bower JM, Parsons LM (2003) Rethinking the “lesser brain”. Sci Am 289:50–57PubMedCrossRefGoogle Scholar
  8. Braitenberg V, Heck D, Sultan F (1997) The detection and generation of sequences as a key to cerebellar function: experiments and theory. Behav Brain Sci 20:229–277PubMedGoogle Scholar
  9. Chiricozzi FR, Clausi S, Molinari M, Leggio MG (2008) Phonological short-term store impairment after cerebellar lesion: a single case study. Neuropsychologia 46:1940–1953PubMedCrossRefGoogle Scholar
  10. Crozier S, Sirigu A, Lehericy S, Van de Moortele PF, Pillon B, Grafman J, Agid Y, Dubois B, LeBihan D (1999) Distinct prefrontal activations in processing sequence at the sentence and script level: an fMRI study. Neuropsychologia 37:1469–1476PubMedCrossRefGoogle Scholar
  11. Cubelli R, Guiducci A, Consolmagno P (2000) Afferent dysgraphia after right cerebral stroke: an autonomous syndrome? Brain Cogn 44:629–644PubMedCrossRefGoogle Scholar
  12. Dirnberger G, Novak J, Nasel C, Zehnter M (2010) Separating coordinative and executive dysfunction in cerebellar patients during motor skill acquisition. Neuropsychologia 48:1200–1208PubMedCrossRefGoogle Scholar
  13. Ellis AW (1988) Normal writing processes and peripheral acquired dysgraphias. Lang Cognit Process 3:99–127CrossRefGoogle Scholar
  14. Fabbro F, Moretti R, Bava A (2000) Language impairments in patients with cerebellar lesions. J Neurolinguistics 13:173–188CrossRefGoogle Scholar
  15. Fiez JA, Petersen SE, Cheney MK, Raichle ME (1992) Impaired non-motor learning and error detection associated with cerebellar damage. A single case study. Brain 115(1):155–178PubMedCrossRefGoogle Scholar
  16. Frings M, Boenisch R, Gerwig M, Diener HC, Timmann D (2004) Learning of sensory sequences in cerebellar patients. Learn Mem 11:347–355PubMedCrossRefGoogle Scholar
  17. Frings M, Maschke M, Gerwig M, Diener HC, Timmann D (2006) Acquisition of simple auditory and visual sequences in cerebellar patients. Cerebellum 5:206–211PubMedCrossRefGoogle Scholar
  18. Gao JH, Parsons LM, Bower JM, Xiong J, Li J, Fox PT (1996) Cerebellum implicated in sensory acquisition and discrimination rather than motor control. Science 272:482–483CrossRefGoogle Scholar
  19. Gebhart AL, Petersen SE, Thach WT (2002) Role of the posterolateral cerebellum in language. Ann N Y Acad Sci 978:318–333PubMedCrossRefGoogle Scholar
  20. Gomez-Beldarrain M, Garcia-Monco JC, Rubio B, Pascual-Leone A (1998) Effect of focal cerebellar lesions on procedural learning in the serial reaction time task. Exp Brain Res 120:25–30PubMedCrossRefGoogle Scholar
  21. Graziano A, Leggio MG, Mandolesi L, Neri P, Molinari M, Petrosini L (2002) Learning power of single behavioral units in acquisition of a complex spatial behavior: an observational learning study in cerebellar-lesioned rats. Behav Neurosci 116:116–125PubMedCrossRefGoogle Scholar
  22. Ito M (2006) Cerebellar circuitry as a neuronal machine. Prog Neurobiol 78:272–303PubMedCrossRefGoogle Scholar
  23. Ito M (2008) Control of mental activities by internal models in the cerebellum. Nat Rev Neurosci 9:304–313PubMedCrossRefGoogle Scholar
  24. Ivry R (2000) Exploring the role of the cerebellum in sensory anticipation and timing: commentary on Tesche and Karhu (comment). Hum Brain Mapp 9:115–118PubMedCrossRefGoogle Scholar
  25. Ivry RB, Spencer RM, Zelaznik HN, Diedrichsen J (2002) The cerebellum and event timing. Ann N Y Acad Sci 978:302–317PubMedCrossRefGoogle Scholar
  26. Leggio MG, Neri P, Graziano A, Mandolesi L, Molinari M, Petrosini L (1999) Cerebellar contribution to spatial event processing: characterization of procedural learning. Exp Brain Res 127:1–11PubMedCrossRefGoogle Scholar
  27. Leggio MG, Molinari M, Neri P, Graziano A, Mandolesi L, Petrosini L (2000a) Representation of actions in rats: the role of cerebellum in learning spatial performances by observation. Proc Natl Acad Sci USA 97:2320–2325PubMedCrossRefGoogle Scholar
  28. Leggio MG, Silveri MC, Petrosini L, Molinari M (2000b) Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study. J Neurol Neurosurg Psychiatry 69:102–106PubMedCrossRefGoogle Scholar
  29. Leggio MG, Tedesco AM, Chiricozzi FR, Clausi S, Orsini A, Molinari M (2008) Cognitive sequencing impairment in patients with focal or atrophic cerebellar damage. Brain 131:1332–1343PubMedCrossRefGoogle Scholar
  30. Leggio MG, Chiricozzi FR, Clausi S, Tedesco AM, Molinari M (2011) The neuropsychological profile of cerebellar damage: the sequencing hypothesis. Cortex 47:137–144PubMedCrossRefGoogle Scholar
  31. Marien P, Engelborghs S, Pickut BA, De Deyn PP (2000) Aphasia following cerebellar damage: fact or fallacy? J Neurolinguistics 13:145–171CrossRefGoogle Scholar
  32. Marien P, Verhoeven J, Brouns R, De Witte L, Dobbeleir A, De Deyn PP (2007) Apraxic agraphia following a right cerebellar hemorrhage. Neurology 69:926–929PubMedCrossRefGoogle Scholar
  33. Martin A, Wiggs CL, Lalonde F, Mack C (1994) Word retrieval to letter and semantic cues: a double dissociation in normal subjects using interference tasks. Neuropsychologia 32:1487–1494PubMedCrossRefGoogle Scholar
  34. Marvel C, Desmond J (2010) Functional topography of the cerebellum in verbal working memory. Neuropsychol Rev 20:271PubMedCrossRefGoogle Scholar
  35. Maschke M, Drepper J, Burgerhoff K, Calabrese S, Kolb FP, Daum I, Diener HC, Timmann D (2002) Differences in trace and delay visuomotor associative learning in cerebellar patients. Exp Brain Res 147:538–548PubMedCrossRefGoogle Scholar
  36. Moberget T, Karns CM, Deouell LY, Lindgren M, Knight RT, Ivry RB (2008) Detecting violations of sensory expectancies following cerebellar degeneration: a mismatch negativity study. Neuropsychologia 46:2569–2579PubMedCrossRefGoogle Scholar
  37. Molinari M, Petrosini L (1997) Is sequence in/sequence out a cerebellar mode of operation in cognition too? Behav Brain Sci 20:259–260CrossRefGoogle Scholar
  38. Molinari M, Leggio MG, Solida A, Ciorra R, Misciagna S, Silveri MC, Petrosini L (1997) Cerebellum and procedural learning: evidence from focal cerebellar lesions. Brain 120:1753–1762PubMedCrossRefGoogle Scholar
  39. Molinari M, Filippini V, Leggio MG (2002) Neuronal plasticity of interrelated cerebellar and cortical networks. Neuroscience 111:863–870PubMedCrossRefGoogle Scholar
  40. Molinari M, Chiricozzi F, Clausi S, Tedesco A, De Lisa M, Leggio M (2008) Cerebellum and detection of sequences, from perception to cognition. Cerebellum 7:611–615PubMedCrossRefGoogle Scholar
  41. Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60PubMedCrossRefGoogle Scholar
  42. Naatanen R, Michie PT (1979) Early selective-attention effects on the evoked potential: a critical review and reinterpretation. Biol Psychol 8:81–136PubMedCrossRefGoogle Scholar
  43. Nissen MJ, Bullemer P (1987) Attentional requirements of learning: evidence from performance measures. Cogn Psychol 19:1–32CrossRefGoogle Scholar
  44. Nixon PD (2003) The role of the cerebellum in preparing responses to predictable sensory events. Cerebellum 2:114–122PubMedCrossRefGoogle Scholar
  45. Orsini A, Laicardi C (2000) Factor structure of the Italian version of the WAIS-R compared with the American standardization. Percept Mot Skills 90:1091–1100PubMedGoogle Scholar
  46. Pascual-Leone A, Grafman J, Clark K, Stewart M, Massaquoi S, Lou JS, Hallett M (1993) Procedural learning in Parkinson’s disease and cerebellar degeneration. Ann Neurol 34:594–602PubMedCrossRefGoogle Scholar
  47. Petersen SE, Fox PT, Posner MI, Mintun M, Raichle ME (1988) Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature 331:585–589PubMedCrossRefGoogle Scholar
  48. Petrosini L, Leggio MG, Molinari M (1998) The cerebellum in the spatial problem solving: a co-star or a guest star? Prog Neurobiol 56:191–210PubMedCrossRefGoogle Scholar
  49. Raichle ME, Fiez JA, Videen TO, MacLeod AM, Pardo JV, Fox PT, Petersen SE (1994) Practice-related changes in human brain functional anatomy during nonmotor learning. Cereb Cortex 4:8–26PubMedCrossRefGoogle Scholar
  50. Restuccia D, Della MG, Valeriani M, Leggio MG, Molinari M (2007) Cerebellar damage impairs detection of somatosensory input changes. A somatosensory mismatch-negativity study. Brain 130:276–287PubMedCrossRefGoogle Scholar
  51. Richter S, Matthies K, Ohde T, Dimitrova A, Gizewski E, Beck A, Aurich V, Timmann D (2004) Stimulus–response versus stimulus-stimulus–response learning in cerebellar patients. Exp Brain Res 158:438–449PubMedCrossRefGoogle Scholar
  52. Rosser A, Hodges JR (1994) Initial letter and semantic category fluency in Alzheimer’s disease, Huntington’s disease, and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 57:1389–1394PubMedCrossRefGoogle Scholar
  53. Schmahmann JD (1997) Rediscovery of an early concept. Int Rev Neurobiol 41:3–27PubMedCrossRefGoogle Scholar
  54. Schmahmann J (2010) The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev 20:236PubMedCrossRefGoogle Scholar
  55. Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome (see comments). Brain 121(Pt 4):561–579PubMedCrossRefGoogle Scholar
  56. Shin JC, Ivry RB (2003) Spatial and temporal sequence learning in patients with Parkinson’s disease or cerebellar lesions. J Cogn Neurosci 15:1232–1243PubMedCrossRefGoogle Scholar
  57. Silveri MC, Leggio MG, Molinari M (1994) The cerebellum contributes to linguistic production: a case of agrammatic speech following a right cerebellar lesion (see comments). Neurology 44:2047–2050PubMedCrossRefGoogle Scholar
  58. Silveri MC, Misciagna S, Leggio MG, Molinari M (1997) Spatial dysgraphia and cerebellar lesion: a case report. Neurology 48:1529–1532PubMedCrossRefGoogle Scholar
  59. Silveri MC, Misciagna S, Leggio MG, Molinari M (1999) Cerebellar spatial dysgraphia: further evidence (letter). J Neurol 246:312–313PubMedCrossRefGoogle Scholar
  60. Stoodley CJ, Schmahmann JD (2009) Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage 44:489–501PubMedCrossRefGoogle Scholar
  61. Takegata R, Paavilainen P, Naatanen R, Winkler I (2001) Preattentive processing of spectral, temporal, and structural characteristics of acoustic regularities: a mismatch negativity study. Psychophysiology 38:92–98PubMedCrossRefGoogle Scholar
  62. Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M, Leggio MG (2011) The cerebellar cognitive profile. Brain. doi:10.1093/brain/awr266.2011PubMedGoogle Scholar
  63. Tesche CD, Karhu JJ (2000) Anticipatory cerebellar responses during somatosensory omission in man (see comments). Hum Brain Mapp 9:119–142PubMedCrossRefGoogle Scholar
  64. Thach WT, Goodkin HP, Keating JG (1992) The cerebellum and the adaptive coordination of movement. Annu Rev Neurosci 15:403–442PubMedCrossRefGoogle Scholar
  65. Timmann D, Daum I (2007) Cerebellar contributions to cognitive functions: a progress report after two decades of research. Cerebellum 6:159–162PubMedCrossRefGoogle Scholar
  66. Timmann D, Drepper J, Calabrese S, Burgerhoff K, Maschke M, Kolb FP, Daum I, Diener HC (2004) Use of sequence information in associative learning in control subjects and cerebellar patients. Cerebellum 3:75–82PubMedCrossRefGoogle Scholar
  67. Tinaz S, Schendan HE, Schon K, Stern CE (2006) Evidence for the importance of basal ganglia output nuclei in semantic event sequencing: an fMRI study. Brain Res 1067:239–249PubMedCrossRefGoogle Scholar
  68. Ullman MT (2004) Contributions of memory circuits to language: the declarative/procedural model. Cognition 92:231–270PubMedCrossRefGoogle Scholar
  69. White M, Lalonde R, Botez M (2000) Neuropsychologic and neuropsychiatric characteristics of patients with Friedreich’s ataxia. Acta Neurol Scand 102:222–226PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Laboratory of Experimental Neurorehabilitation Unit A – Ataxia LaboratoryI.R.C.C.S. Santa Lucia FoundationRomeItaly
  2. 2.Neurorehabilitation Unit A – Ataxia LaboratoryI.R.C.C.S. Santa Lucia FoundationRomeItaly
  3. 3.Department of PsychologyUniversity of Rome La SapienzaRomeItaly

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