Cerebellar motor dysfunction in schizophrenia and psychosis risk: The importance of regional cerebellar analysis approaches

Frontiers in Psychiatry

Volumn 5, Issue OCT, 2014, Pages

  Bernard, Jessica A ^a   Mitta, Vijay A ^a  

^a UNIVERSITY OF COLORADO   (United States)

Author keywords

Balance; Cerebellum; Morphology; Motor abnormalities; Motor learning; Psychosis risk; Schizophrenia; Timing

Indexed keywords

BRAIN CORTEX; BRAIN SIZE; CEREBELLAR MOTOR DYSFUNCTION; CEREBELLO CORTICAL NETWORK; CEREBELLUM; CEREBELLUM VERMIS; DIFFUSION TENSOR IMAGING; FUNCTIONAL CONNECTIVITY MAGNETIC RESONANCE IMAGING; FUNCTIONAL MAGNETIC RESONANCE IMAGING; FUNCTIONAL NEUROIMAGING; GENETIC RISK; HEMISPHERE; HIGH RISK POPULATION; HUMAN; MOTOR DYSFUNCTION; NONHUMAN; PSYCHOSIS; RESTING STATE NETWORK; REVIEW; SCHIZOPHRENIA; SCHIZOTYPAL PERSONALITY DISORDER; TASK PERFORMANCE;

EID: 84909943672     PISSN: None     EISSN: 16640640     Source Type: Journal    
DOI: 10.3389/fpsyt.2014.00160     Document Type: Review

References (157)

1. Bernard JA, Dean DJ, Kent JS, Orr JM, Pelletier-Baldelli A, Lunsford-Avery J, Gupta T, Mittal VA. Cerebellar Networks in Individuals at Ultra High-Risk of Psychosis: Impact on Postural Sway and Symptom Severity. Hum Brain Mapp (2014) 35:4064-4078.
2. Dean DJ, Bernard JA, Orr JM, Pelletier-Baldelli A, Gupta T, Carol EE, Mittal V a. Cerebellar Morphology and Procedural Learning Impairment in Neuroleptic-Naive Youth at Ultrahigh Risk of Psychosis. Clin Psychol Sci (2013) 2:152-164. doi:10.1177/2167702613500039
3. Mittal VA, Dean DJ, Bernard JA, Orr JM, Pelletier-Baldelli A, Carol EE, Gupta T, Turner J, Leopold DR, Robustelli BL, et al. Neurological Soft Signs Predict Abnormal Cerebellar-Thalamic Tract Development and Negative Symptoms in Adolescents at High Risk for Psychosis: A Longitudinal Perspective. Schizophr Bull (2013)1-12. doi:10.1093/schbul/sbt199
4. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a metaanalysis of neuroimaging studies. Neuroimage (2009) 44:489-501. doi:10.1016/j.neuroimage.2008.08.039
5. Andreasen NC, Olsen S. Negative v Positive Schizophrenia. Arch Gen Psychiatry (1982) 39:789-794.
6. Mittal VA, Walker EF. "Movement Abnormalities: A Putative Biomarker of Risk for Psychosis," in Neuropsychiatric Biomarkes, Endophenotypes, and Genes, ed. M. S. Ritsner (Springer Science + Business Media LLC), 239-258.
7. Docx L, Morrens M, Bervoets C, Hulstijn W, Fransen E, De Hert M, Baeken C, Audenaert K, Sabbe B. Parsing the components of the psychomotor syndrome in schizophrenia. Acta Psychiatr Scand (2012) 126:256-65. doi:10.1111/j.1600-0447.2012.01846.x
8. Morrens M, Hulstijn W, Sabbe B. Psychomotor slowing in schizophrenia. Schizophr Bull (2007) 33:1038-53. doi:10.1093/schbul/sbl051
9. Morrens M, Docx L, Walther S. Beyond boundaries: In search of an integrative view on motor symptoms in. Front Psychiatry Schizophr doi:10.3389/fpsyt.2014.00145
10. Peralta V, Campos MS, De Jalón EG, Cuesta MJ. Motor behavior abnormalities in drugnaïve patients with schizophrenia spectrum disorders. Mov Disord (2010) 25:1068-76. doi:10.1002/mds.23050
11. Mittal VA, Walker EF, Bearden CE, Walder D, Trottman H, Daley M, Simone A, Cannon TD. Markers of basal ganglia dysfunction and conversion to psychosis: neurocognitive deficits and dyskinesias in the prodromal period. Biol Psychiatry (2010) 68:93-99. doi:10.1016/j.biopsych.2010.01.021.Markers
12. Walker EF, Savoie T, Davis D. Neuromotor precursors of schizophrenia. Schizophr Bull (1994) 20:441-51. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7526446
13. Pappa S, Dazzan P. Spontaneous movement disorders in antipsychotic-naive patients with first-episode psychoses: a systematic review. Psychol Med (2009) 39:1065-76. doi:10.1017/S0033291708004716
14. Mittal VA, Daley M, Shiode MF, Bearden CE, O'Neill J, Cannon TD. Striatl volumes and dyskinetic movements in youth at high-risk for psychosis. Schizophr Res (2010) 123:68-70. doi:10.1016/j.schres.2010.08.002.Striatal
15. Mittal VA, Dhruv S, Tessner KD, Walder DJ, Walker EF. The relations among putative biorisk markers in schizotypal adolescents: minor physical anomalies, movement abnormalities, and salivary cortisol. Biol Psychiatry (2007) 61:1179-86. doi:10.1016/j.biopsych.2006.08.043
16. Mittal VA, Tessner KD, Trottman HD, Esterberg M, Dhrub SH, Simeonova DI, McMillan AL, Murphy E, Saczawa ME, Walker EF. Movement abnormalities and the progression of prodromal symptomatology in adolescents at risk for psychotic disorders. J Abnorm Psychol (2007) 116:260-7. doi:10.1037/0021-843X.116.2.260
17. Mittal VA, Walker EF. Movement abnormalities predict conversion to Axis I psychosis among prodromal adolescents. J Abnorm Psychol (2007) 116:796-803. doi:10.1037/0021-843X.116.4.796
18. Mittal VA, Neumann C, Saczawa M, Walker EF. Longitudinal progression of movement abnormalities in relation to psychotic symptoms in adolescents at high risk of schizophrenia. Arch Gen Psychiatry (2008) 65:165-71. doi:10.1001/archgenpsychiatry.2007.23
19. Mittal VA, Walker EF, Bearden CE, Walder D, Trottman H, Daley M, Simone A, Cannon TD. Markers of basal ganglia dysfunction and conversion to psychosis: neurocognitive deficits and dyskinesias in the prodromal period. Biol Psychiatry (2010) 68:93-9. doi:10.1016/j.biopsych.2010.01.021
20. Mittal VA, Walker EF. Movement abnormalities and schizophrenia in DSM-V. Psychol Med (2010) 40:1581-3. doi:10.1017/S0033291710001352
21. Mittal VA, Jalbrzikowski M, Daley M, Roman C, Bearden CE, Cannon TD. Abnormal movements are associated with poor psychosocial functioning in adolescents at high risk for psychosis. Schizophr Res (2011) 130:164-9. doi:10.1016/j.schres.2011.05.007
22. Mittal VA, Walker EF. Dyskinesias, tics, and psychosis: issues for the next diagnostic and statistical manual of mental disorders. Psychiatry Res (2013) 189:158-159. doi:10.1016/j.psychres.2011.06.006.Dyskinesias
23. Dean DJ, Teulings H-L, Caligiuri M, Mittal VA. Handwriting analysis indicates spontaneous dyskinesias in neuroleptic naïve adolescents at high risk for psychosis. J Vis Exp (2014) 81:e50852. doi:10.3791/50852.Handwriting
24. Mittal VA, Orr JM, Turner J a, Pelletier AL, Dean DJ, Lunsford-Avery J, Gupta T. Striatal abnormalities and spontaneous dyskinesias in non-clinical psychosis. Schizophr Res (2013) 151:141-7. doi:10.1016/j.schres.2013.10.003
25. Angyal A, Sherman MA. Postural reactions to vestibular stimulation in schizophrenic and normal subjects. Am J Psychiatry (1942)857-862.
26. Marvel CL, Schwartz BL, Rosse RB. A quantitative measure of postural sway deficits in schizophrenia. Schizophr Res (2004) 68:363-72. doi:10.1016/j.schres.2003.09.003
27. Carroll CA, O'Donnell BF, Shekhar A, Hetrick WP. Timing dysfunctions in schizophrenia as measured by a repetitive finger tapping task. Brain Cogn (2009) 71:345-53. doi:10.1016/j.bandc.2009.06.009
28. Green MF, Kern RS, Williams O, McGurk S, Kee K. Procedural Learning in Schizophrenia: Evidence from Serial Reaction Time. Cogn Neuropsychiatry (1997) 2:123-134. doi:10.1080/135468097396360
29. Bolbecker AR, Mehta CS, Edwards CR, Steinmetz JE, O'Donnell BF, Hetrick WP. Eyeblink conditioning deficits indicate temporal processing abnormalities in schizophrenia. Schizophr Res (2009) 111:182-91. doi:10.1016/j.schres.2009.03.016
30. Andreasen NC, O'Leary DS, Cizadlo T, Arndt S, Rezai K, Ponto LL, Watkins GL, Hichwa RD. Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proc Natl Acad Sci U S A (1996) 93:9985-90. Available at:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=38542&tool=pmcentrez&rendertype=abstract
31. Andreasen NC, Paradiso S, O'Leary DS. "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull (1998) 24:203-18. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9613621
32. Picard H, Amado I, Mouchet-Mages S, Olié J-P, Krebs M-O. The role of the cerebellum in schizophrenia: an update of clinical, cognitive, and functional evidences. Schizophr Bull (2008) 34:155-72. doi:10.1093/schbul/sbm049
33. Barch DM. Cerebellar-Thalamic Connectivity in Schizophrenia. Schizophr Bull (2014)1-3. doi:10.1093/schbul/sbu076
34. Bernard JA, Mittal VA. Dysfunctional activation of the cerebellum in schizophrenia: a functional neuroimaging meta-analysis. Clin Psychol Sci
35. Leiner HC, Leiner a L, Dow RS. Reappraising the cerebellum: what does the hindbrain contribute to the forebrain? Behav Neurosci (1989) 103:998-1008. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2679667
36. Leiner HC, Leiner a L, Dow RS. Cognitive and language functions of the human cerebellum. Trends Neurosci (1993) 16:444-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7507614
37. Leiner HC, Leiner AL, Dow RS. Does the cerebellum contribute to mental skills? Behav Neurosci (1986) 100:443-54. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3741598
38. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain (1998) 121 (Pt 4:561-79. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9577385
39. Chen SHA, Desmond JE. Temporal dynamics of cerebro-cerebellar network recruitment during a cognitive task. Neuropsychologia (2005) 43:1227-37. doi:10.1016/j.neuropsychologia.2004.12.015
40. Desmond JE, Chen SHA, Shieh PB. Cerebellar transcranial magnetic stimulation impairs verbal working memory. Ann Neurol (2005) 58:553-60. doi:10.1002/ana.20604
41. Ramnani N. The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci (2006) 7:511-22. doi:10.1038/nrn1953
42. Ito M. Control of mental activities by internal models in the cerebellum. Nat Rev Neurosci (2008) 9:304-13. doi:10.1038/nrn2332
43. Spencer RMC, Ivry RB. "Cerebellum and timing," in Handbook of the cerebellum and cerebellar disorders, eds. M. Manto, J. D. Schmahmann, F. Rossi, D. L. Gruol, N. Koibuchi (New York: Springer), 1201-1219.
44. Keele SW, Ivry RB. Does the cerebellum provide a common computation for diverse tasks? A timing hypothesis. Ann N Y Acad Sci (1990) 6-8:179-211.
45. Kim JJ, Thompson RF. Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning. Trends Neurosci (1997) 20:177-181. doi:10.1016/S0166-2236(96)10081-3
46. Gerwig M, Kolb FP, Timmann D. The involvement of the human cerebellum in eyeblink conditioning. Cerebellum (2007) 6:38-57. doi:10.1080/14734220701225904
47. Lindquist DH, Steinmetz JE, Thompson RF. "Cerebellum and eyeblink conditioning," in Handbook of the Cerebellum and Cerebellar Disorders, eds. M. Manto, J. D. Schmahmann, F. Rossi, D. L. Gruol, N. Koibuchi (Dordrecht: Springer Netherlands), 1175-1190. doi:10.1007/978-94-007-1333-8
48. Brown SM, Kieffaber PD, Carroll C a, Vohs JL, Tracy J a, Shekhar a, O'Donnell BF, Steinmetz JE, Hetrick WP. Eyeblink conditioning deficits indicate timing and cerebellar abnormalities in schizophrenia. Brain Cogn (2005) 58:94-108. doi:10.1016/j.bandc.2004.09.011
49. Edwards CR, Newman S, Bismark A, Skosnik PD, O'Donnell BF, Shekhar A, Steinmetz JE, Hetrick WP. Cerebellum volume and eyeblink conditioning in schizophrenia. Psychiatry Res (2008) 162:185-94. doi:10.1016/j.pscychresns.2007.06.001
50. Bolbecker AR, Steinmetz AB, Mehta CS, Forsyth JK, Klaunig MJ, Lazar EK, Steinmetz JE, O'Donnell BF, Hetrick WP. Exploration of cerebellar-dependent associative learning in schizophrenia: effects of varying and shifting interstimulus interval on eyeblink conditioning. Behav Neurosci (2011) 125:687-98. doi:10.1037/a0025150
51. Forsyth JK, Bolbecker AR, Mehta CS, Klaunig MJ, Steinmetz JE, O'Donnell BF, Hetrick WP. Cerebellar-dependent eyeblink conditioning deficits in schizophrenia spectrum disorders. Schizophr Bull (2012) 38:751-9. doi:10.1093/schbul/sbq148
52. Parker KL, Andreasen NC, Liu D, Freeman JH, O'Leary DS. Eyeblink conditioning in unmedicated schizophrenia patients: a positron emission tomography study. Psychiatry Res (2013) 214:402-9. doi:10.1016/j.pscychresns.2013.07.006
53. Coesmans M, Röder CH, Smit AE, Koekkoek SKE, Zeeuw CI De, Frens MA, Geest JN Van Der. Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia. J Psychiatry Neurosci (2014) 39:3-11. doi:10.1503/jpn.120205
54. Sears LL, Andreasen NC, O'Leary DS. Cerebellar functional abnormalities in schizophrenia are suggested by classical eyeblink conditioning. Biol Psychiatry (2000) 48:204-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10924663
55. Marenco S, Weinberger DR, Schreurs BG. Single-cue delay and trace classical conditioning in schizophrenia. Biol Psychiatry (2003) 53:390-402. doi:10.1016/S0002-3223(03)01506-8
56. Stevens A, Schwarz J, Schwarz B, Ruf I, Kolter T, Czekalla J. Implicit and explicit learning in schizophrenics treated with olanzapine and with classic neuroleptics. Psychopharmacology (Berl) (2002) 160:299-306. doi:10.1007/s00213-001-0974-1
57. Lubow RE. Classical eyeblink conditioning and schizophrenia: a short review. Behav Brain Res (2009) 202:1-4. doi:10.1016/j.bbr.2009.03.006
58. Bolbecker AR, Kent JS, Petersen IT, Klaunig MJ, Forsyth JK, Howell JM, Westfall DR, O'Donnell BF, Hetrick WP. Impaired Cerebellar-Dependent Eyeblink Conditioning in First-Degree Relatives of Individuals With Schizophrenia. Schizophr Bull (2013)1-10. doi:10.1093/schbul/sbt112
59. Cheng DT, Disterhoft JF, Power JM, Ellis D a, Desmond JE. Neural substrates underlying human delay and trace eyeblink conditioning. Proc Natl Acad Sci U S A (2008) 105:8108-13. doi:10.1073/pnas.0800374105
60. Cheng DT, Meintjes EM, Stanton ME, Desmond JE, Pienaar M, Dodge NC, Power JM, Molteno CD, Disterhoft JF, Jacobson JL, et al. Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults. Hum Brain Mapp (2014) 35:1390-403. doi:10.1002/hbm.22261
61. Holmes G. The cerebellum of man. Brain (1939) 62:1-30.
62. Diener HC, Dichgans J, Bacher M, Gompf B. Quantification of postural sway in normals and patients with cerebellar diseases. Electroencephalogr Clin Neurophysiol (1984) 57:134-142.
63. Ouchi Y, Okada H, Yoshikawa E, Nobezawa S, Futatsubashi M. Brain activation during maintenance of standing postures in humans. Brain (1999) 122:329-338.
64. Bernard JA, Seidler RD. Relationships Between Regional Cerebellar Volume and Sensorimotor and Cognitive Function in Young and Older Adults. Cerebellum (2013) doi:10.1007/s12311-013-0481-z
65. Sullivan E V, Rose J, Pfefferbaum A. Physiological and focal cerebellar substrates of abnormal postural sway and tremor in alcoholic women. Biol Psychiatry (2010) 67:44-51. doi:10.1016/j.biopsych.2009.08.008
66. Sullivan E V, Rohlfing T, Pfefferbaum A. Pontocerebellar volume deficits and ataxia in alcoholic men and women: no evidence for "telescoping". Psychopharmacology (Berl) (2010) 208:279-90. doi:10.1007/s00213-009-1729-7
67. Ho B-C, Mola C, Andreasen NC. Cerebellar dysfunction in neuroleptic naive schizophrenia patients: clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs. Biol Psychiatry (2004) 55:1146-53. doi:10.1016/j.biopsych.2004.02.020
68. Sullivan E V, Rosenbloom MJ, Pfefferbaum A. Balance and gait deficits in schizophrenia compounded by the comorbidity of alcoholism. Am J Psychiatry (2004) 161:751-5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15056526
69. Kent JS, Hong SL, Bolbecker AR, Klaunig MJ, Forsyth JK, O'Donnell BF, Hetrick WP. Motor deficits in schizophrenia quantified by nonlinear analysis of postural sway. PLoS One (2012) 7:e41808. doi:10.1371/journal.pone.0041808
70. Stensdotter A-K, Wanvik AK, Lorås HW. Postural control in quiet standing with a concurrent cognitive task in psychotic conditions. J Mot Behav (2013) 45:279-87. doi:10.1080/00222895.2013.791241
71. Ahlgrén-Rimpiläinen A, Lauerma H, Kähkönen S, Aalto H, Pyykkö I, Palmgren K, Rimpiläinen I. Effect of visual information on postural control in patients with schizophrenia. J Nerv Ment Dis (2010) 198:601-3. doi:10.1097/NMD.0b013e3181ea16bc
72. Ivry RB, Keele SW. Timing functions of the cerebellum. J Cogn Neurosci (1989) 1:136-52. doi:10.1162/jocn.1989.1.2.136
73. Spencer RMC, Zelaznik HN, Diedrichsen J, Ivry RB. Disrupted timing of discontinuous but not continuous movements by cerebellar lesions. Science (2003) 300:1437-9. doi:10.1126/science.1083661
74. Jueptner M, Rijntjes M, Weiller C, Faiss JH, Timmann D, Mueller SP, Diener HC. Localization of a cerebellar timing process using PET. Neurology (1995) 45:1540-1545. doi:10.1212/WNL.45.8.1540
75. Lewis P., Miall R. Brain activation patterns during measurement of sub- and supra-second intervals. Neuropsychologia (2003) 41:1583-1592. doi:10.1016/S0028-3932(03)00118-0
76. Ivry RB, Spencer RMC. The neural representation of time. Curr Opin Neurobiol (2004) 14:225-32. doi:10.1016/j.conb.2004.03.013
77. Carroll CA, Boggs J, O'Donnell BF, Shekhar A, Hetrick WP. Temporal processing dysfunction in schizophrenia. Brain Cogn (2008) 67:150-61. doi:10.1016/j.bandc.2007.12.005
78. Densen ME. Time perception and schizophrenia. Percept Mot Skills (1977) 44:436-438.
79. Johnson JE, Petzel TP. Temporal orientation and time estimation in chornic schizophrenics. J Clin Psychol (1971) 27:194-196.
80. Volz HP, Nenadic I, Gaser C, Rammsayer T, Häger F, Sauer H. Time estimation in schizophrenia: an fMRI study at adjusted levels of difficulty. Neuroreport (2001) 12:313-6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11209941
81. Elvevåg B, McCormack T, Glibert A, Brown GDA, Wienberger DR, Goldberg TE. Duration judgements in patients with schizophrenia. Psychol Med (2003) 33:1249-1261.
82. Davalos DB, Kisley M a., Ross RG. Effects of interval duration on temporal processing in schizophrenia. Brain Cogn (2003) 52:295-301. doi:10.1016/S0278-2626(03)00157-X
83. Waters F, Jablensky A. Time discrimination deficits in schizophrenia patients with firstrank (passivity) symptoms. Psychiatry Res (2009) 167:12-20. doi:10.1016/j.psychres.2008.04.004
84. Carroll CA, O'Donnell BF, Shekhar A, Hetrick WP. Timing dysfunctions in schizophrenia span from millisecond to several-second durations. Brain Cogn (2009) 70:181-90. doi:10.1016/j.bandc.2009.02.001
85. Buchsbaum MS. The frontal lobes, basal ganglia, and temporal lobes as sites for schizophrenia. Schizophr Bull (1990) 16:379-89. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2287929
86. Penney TB, Meck WH, Roberts S a, Gibbon J, Erlenmeyer-Kimling L. Interval-timing deficits in individuals at high risk for schizophrenia. Brain Cogn (2005) 58:109-18. doi:10.1016/j.bandc.2004.09.012
87. Lee K-H, Dixon JK, Spence S a., WoodruffPWR. Time perception dysfunction in psychometric schizotypy. Pers Individ Dif (2006) 40:1363-1373. doi:10.1016/j.paid.2005.10.021
88. Imamizu H, Miyauchi S, Tamada T, Sasaki Y, Takino R, Pütz B, Yoshioka T, Kawato M. Human cerebellar activity reflecting an acquired internal model of a new tool. Nature (2000) 403:192-5. doi:10.1038/35003194
89. Jenkins IH, Brooks DJ, Frackowiak RSJ, Passingham FE. Motor Sequence Tomography Learning: A Study with Positron. (1994) 14:
90. Doyon J, Song AW, Karni A, Lalonde F, Adams MM, Ungerleider LG. Experiencedependent changes in cerebellar contributions to motor sequence learning. Proc Natl Acad Sci U S A (2002) 99:1017-22. doi:10.1073/pnas.022615199
91. Doyon J, Benali H. Reorganization and plasticity in the adult brain during learning of motor skills. Curr Opin Neurobiol (2005) 15:161-7. doi:10.1016/j.conb.2005.03.004
92. Seidler RD, Noll DC, Chintalapati P. Bilateral basal ganglia activation associated with sensorimotor adaptation. Exp brain Res (2006) 175:544-55. doi:10.1007/s00221-006-0571-y
93. Schendan HE, Searl MM, Melrose RJ, Stern CE. An FMRI study of the role of the medial temporal lobe in implicit and explicit sequence learning. Neuron (2003) 37:1013-25. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12670429
94. Bernard JA, Seidler RD. Cerebellar contributions to visuomotor adaptation and motor sequence learning: an ALE meta-analysis. Front Hum Neurosci (2013) 7:27. doi:10.3389/fnhum.2013.00027
95. Schwartz BL, Rosse RB, Veazey C, Deutsch SI. Impaired motor skill learning in schizophrenia: implications for corticostriatal dysfunction. Biol Psychiatry (1996) 39:241-8. doi:10.1016/0006-3223(95)00130-1
96. Pedersen A, Siegmund A, Ohrmann P, Rist F, Rothermundt M, Suslow T, Arolt V. Reduced implicit and explicit sequence learning in first-episode schizophrenia. Neuropsychologia (2008) 46:186-95. doi:10.1016/j.neuropsychologia.2007.07.021
97. Bédard M-A, Scherer H, Delorimier J, Stip E, Lalonde P. Differential effects of D2-and D4-blocking neuroleptics on the procedural learning of schizophrenic patients. Can J Psychiatry (1996) 41:S21-S24.
98. Bédard M-A, Shérer H, Stip E, Cohen H, Rodriguez J-P, Richer F. Procedural learning in schizophrenia: Further consideration on the deleterious effect of neuroleptics. Brain Cogn (2000) 43:31-39.
99. Scherer H, Bedard M-A, Stip E, Paquet F, Richer F, Bériault M, Rodriguez J-P, Motard JP. Procedural learning in schizophrenia can reflect the pharmacologic properties of the antipsychotic treatments. Cogn Behav Neurol (2004) 17:32-40. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15209223
100. Kumari V, Gray J a, Honey GD, Soni W, Bullmore ET, Williams SCR, Ng VW, Vythelingum GN, Simmons A, Suckling J, et al. Procedural learning in schizophrenia: a functional magnetic resonance imaging investigation. Schizophr Res (2002) 57:97-107. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12165380
101. Marvel CL, Turner BM, O'Leary DS, Johnson HJ, Pierson RK, Ponto LLB, Andreasen NC. The neural correlates of implicit sequence learning in schizophrenia. Neuropsychology (2007) 21:761-77. doi:10.1037/0894-4105.21.6.761
102. Kasparek T, Rehulova J, Kerkovsky M, Sprlakova A, Mechl M, Mikl M. Corticocerebellar functional connectivity and sequencing of movements in schizophrenia. BMC Psychiatry (2012) 12:17. doi:10.1186/1471-244X-12-17
103. Hüttlova J, Kikinis Z, Kerkovsky M, Bouix S, Vu M-A, Makris N, Shenton M, Kasparek T. Abnormalities in myelination of the superior cerebellar peduncle in patients with schizophrenia and deficits in movement sequencing. Cerebellum (2014) 13:415-24. doi:10.1007/s12311-014-0550-y
104. Exner C, Weniger G, Schmidt-Samoa C, Irle E. Reduced size of the pre-supplementary motor cortex and impaired motor sequence learning in first-episode schizophrenia. Schizophr Res (2006) 84:386-96. doi:10.1016/j.schres.2006.03.013
105. Zedkova L, Woodward ND, Harding I, Tibbo PG, Purdon SE. Procedural learning in schizophrenia investigated with functional magnetic resonance imaging. Schizophr Res (2006) 88:198-207. doi:10.1016/j.schres.2006.06.039
106. Kasparek T, Prikryl R, Rehulova J, Marecek R, Mikl M, Prikrylova H, Vanicek J, Ceskova E. Brain functional connectivity of male patients in remission after the first episode of schizophrenia. Hum Brain Mapp (2012) 00:n/a-n/a. doi:10.1002/hbm.21469
107. Siegert RJ, Weatherall M, Bell EM. Is implicit sequence learning impaired in schizophrenia? A meta-analysis. Brain Cogn (2008) 67:351-9. doi:10.1016/j.bandc.2008.02.005
108. Pedersen A, Rist F. Implicit memory in schizotypal subjects and normal controls: effects of a secondary task on sequence learning. Percept Mot Skills (2001) 92:349-367.
109. Ferraro FR, Okerlund M. Implicit memory of nonclinicla schizotypal individuals. Percept Mot Skills (1995) 80:371-376.
110. Bernard JA, Seidler RD, Hassevoort KM, Benson BL, Welsh RC, Wiggins JL, Jaeggi SM, Buschkuehl M, Monk CS, Jonides J, et al. Resting state cortico-cerebellar functional connectivity networks: a comparison of anatomical and self-organizing map approaches. Front Neuroanat (2012) 6:31. doi:10.3389/fnana.2012.00031
111. Schlerf JE, Verstynen TD, Ivry RB, Spencer RMC. Evidence of a novel somatopic map in the human neocerebellum during complex actions. J Neurophysiol (2010) 103:3330-6. doi:10.1152/jn.01117.2009
112. Block H, Celnik P. Stimulating the Cerebellum Affects Visuomotor Adaptation but not Intermanual Transfer of Learning. Cerebellum (2013) doi:10.1007/s12311-013-0486-7
113. Schlerf JE, Galea JM, Bastian AJ, Celnik P a. Dynamic modulation of cerebellar excitability for abrupt, but not gradual, visuomotor adaptation. J Neurosci (2012) 32:11610-7. doi:10.1523/JNEUROSCI.1609-12.2012
114. Anguera JA, Bernard JA, Jaeggi SM, Buschkuehl M, Benson BL, Jennett S, Humfleet J, Reuter-lorenz P. The effects of working memory resource depletion and training on sensorimotor adaptation. Behav Brain Res (2013) 228:107-115. doi:10.1016/j.bbr.2011.11.040.The
115. Anguera JA, Reuter-Lorenz PA, Willingham DT, Seidler RD. Failure to engage spatial working memory contributes to age-related declines in visuomotor learning. J Cogn Neurosci (2011) 23:11-25. doi:10.1162/jocn.2010.21451
116. Stoodley CJ, Valera EM, Schmahmann JD. Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage (2012) 59:1560-70. doi:10.1016/j.neuroimage.2011.08.065
117. Leiner HC, Leiner AL, Dow RS. The human cerebro-cerebellar system: its computing, cognitive, and language skills. Behav Brain Res (1991) 44:113-128.
118. Kelly RM, Strick PL. Cerebellar Loops with Motor Cortex and Prefrontal Cortex of a Nonhuman Primate. J Neurosci (2003) 23:8432-8444.
119. Akkal D, Dum RP, Strick PL. Supplementary motor area and presupplementary motor area: targets of basal ganglia and cerebellar output. J Neurosci (2007) 27:10659-73. doi:10.1523/JNEUROSCI.3134-07.2007
120. Dum RP, Strick PL. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J Neurophysiol (2003) 89:634-9. doi:10.1152/jn.00626.2002
121. Strick PL, Dum RP, Fiez JA. Cerebellum and Nonmotor Function. Annu Rev Neurosci (2009) 32:413-434. doi:10.1146/annurev.neuro.31.060407.125606
122. Krienen FM, Buckner RL. Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cereb Cortex (2009) 19:2485-97. doi:10.1093/cercor/bhp135
123. Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V, Greicius MD. Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci (2009) 29:8586-94. doi:10.1523/JNEUROSCI.1868-09.2009
124. O'Reilly JX, Beckmann CF, Tomassini V, Ramnani N, Johansen-Berg H. Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity. Cereb Cortex (2010) 20:953-65. doi:10.1093/cercor/bhp157
125. Bernard JA, Peltier SJ, Benson BL, Wiggins JL, Jaeggi SM, Buschkuehl M, Jonides J, Monk CS, Seidler RD. Dissociable Functional Networks of the Human Dentate Nucleus. Cereb Cortex (2014) 24:2151-2159. doi:10.1093/cercor/bht065
126. Bernard JA, Seidler RD, Hassevoort KM, Benson BL, Welsh RC, Wiggins JL, Jaeggi SM, Buschkuehl M, Monk CS, Jonides J, et al. Resting state cortico-cerebellar functional connectivity networks: a comparison of anatomical and self-organizing map approaches. Front Neuroanat (2012) 6:31. doi:10.3389/fnana.2012.00031
127. Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BTT. The organization of the human cerebellum estimated by intrinsic functional connectivity. (2011) 02138:2322-2345. doi:10.1152/jn.00339.2011.
128. Salmi J, Pallesen KJ, Neuvonen T, Brattico E, Korvenoja A, Salonen O, Carlson S. Cognitive and motor loops of the human cerebro-cerebellar system. J Cogn Neurosci (2010) 22:2663-76. doi:10.1162/jocn.2009.21382
129. Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex (2010) 46:831-44. doi:10.1016/j.cortex.2009.11.008
130. Balsters JH, Whelan CD, Robertson IH, Ramnani N. Cerebellum and cognition: evidence for the encoding of higher order rules. Cereb Cortex (2013) 23:1433-43. doi:10.1093/cercor/bhs127
131. Strakowski SM, Delbello MP, Adler CM. The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Mol Psychiatry (2005) 10:105-16. doi:10.1038/sj.mp.4001585
132. DelBello MP, Strakowski SM, Zimmerman ME, Hawkins JM, Sax KW. MRI analysis of the cerebellum in bipolar disorder: a pilot study. Neuropsychopharmacology (1999) 21:63-8. doi:10.1016/S0893-133X(99)00026-3
133. Mills NP, Delbello MP, Adler CM, Strakowski SM. MRI analysis of cerebellar vermal abnormalities in bipolar disorder. Am J Psychiatry (2005) 162:1530-2. doi:10.1176/appi.ajp.162.8.1530
134. Escalona PR, Early B, McDonald WM, Doraiswamy M, Shah SA, Husain MM, Bokyo OB, Figiel GS, Ellinwood EH, NemereoffCB, et al. Reduction of cerebellar volume in major depression: a controlled MRI study. Depression (1993) 1:156-158.
135. Schmitt A, Schulenberg W, Bernstein H-G, Steiner J, Schneider-Axmann T, Yeganeh- Doost P, Malchow B, Hasan A, Gruber O, Bogerts B, et al. Reduction of gyrification index in the cerebellar vermis in schizophrenia: a post-mortem study. World J Biol Psychiatry (2011) 12 Suppl 1:99-103. doi:10.3109/15622975.2011.598379
136. Deicken RF, Feiwell R, SchuffN, Soher B. Evidence for altered cerebellar vermis neuronal integrity in schizophrenia. Psychiatry Res (2001) 107:125-34. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11566429
137. Maloku E, Covelo IR, Hanbauer I, Guidotti A, Kadriu B, Hu Q, Davis JM, Costa E. Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression. Proc Natl Acad Sci U S A (2010) 107:4407-11. doi:10.1073/pnas.0914483107
138. Lohr JB, Jeste D V. Cerebellar pathology in schizophrenia? A neuronometric study. Biol Psychiatry (1986) 21:865-75. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3741908
139. Andersen BO, Pakkenberg B. Stereological quantitation in cerebella from people with schizophrenia Stereological quantitation in cerebella from people with schizophrenia. Br J Psychiatry (2003) 182:354-361. doi:10.1192/bjp.02.65
140. Andersen BB, Fabricius K, Gundersen HJG, Jelsing J, Stark a K. No change in neuron numbers in the dentate nucleus of patients with schizophrenia estimated with a new stereological method-the smooth fractionator. J Anat (2004) 205:313-21. doi:10.1111/j.0021-8782.2004.00337.x
141. Shenton ME, Dickey CC, Frumin M, McCarley RW. A review of MRI findings in schizophrenia. Schizophr Res (2001) 49:1-52. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2812015&tool=pmcentrez&rendertype=abstract
142. Ichimiya T, Okubo Y, Suhara T, Sudo Y. Reduced volume of the cerebellar vermis in neuroleptic-naive schizophrenia. Biol Psychiatry (2001) 49:20-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11163776
143. Keller A, Castellanos FX, Vaituzis a C, Jeffries NO, Giedd JN, Rapoport JL. Progressive loss of cerebellar volume in childhood-onset schizophrenia. Am J Psychiatry (2003) 160:128-33. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12505811
144. Bottmer C, Bachmann S, Pantel J, Essig M, Amann M, Schad LR, Magnotta V, Schröder J. Reduced cerebellar volume and neurological soft signs in first-episode schizophrenia. Psychiatry Res (2005) 140:239-50. doi:10.1016/j.pscychresns.2005.02.011
145. James AC, James S, Smith DM, Javaloyes A. Cerebellar, prefrontal cortex, and thalamic volumes over two time points in adolescent-onset schizophrenia. Am J Psychiatry (2004) 161:1023-1029.
146. Okugawa G, Sedvall GC, Agartz I. Smaller Cerebellar Vermis but not Hemisphere Volumes in Patients With Chronic Schizophrenia. Am J Psychiatry (2003) 160:1614-1617.
147. Loeber RT, Cintron CM, Yurgelun-Todd D a. Morphometry of individual cerebellar lobules in schizophrenia. Am J Psychiatry (2001) 158:952-4. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11384906
148. Greenstein D, Lenroot R, Clausen L, Chavez A, Vaituzis a C, Tran L, Gogtay N, Rapoport J. Cerebellar development in childhood onset schizophrenia and non-psychotic siblings. Psychiatry Res (2011) 193:131-7. doi:10.1016/j.pscychresns.2011.02.010
149. Borgwardt SJ, Riecher-Rössler A, Dazzan P, Chitnis X, Aston J, Drewe M, Gschwandtner U, Haller S, Pflüger M, Rechsteiner E, et al. Regional gray matter volume abnormalities in the at risk mental state. Biol Psychiatry (2007) 61:1148-56. doi:10.1016/j.biopsych.2006.08.009
150. Pantelis C, Velakoulis D, McGorry PD, Wood SJ, Suckling J, Phillips LJ, Yung AR, Bullmore ET, Brewer W, Soulsby B, et al. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet (2003) 361:281-8. doi:10.1016/S0140-6736(03)12323-9
151. Kim D-J, Kent JS, Bolbecker AR, Sporns O, Cheng H, Newman SD, Puce A, O'Donnell BF, Hetrick WP. Disrupted Modular Architecture of Cerebellum in Schizophrenia: A Graph Theoretic Analysis. Schizophr Bull (2014) i:1-11. doi:10.1093/schbul/sbu059
152. Weier K, Fonov V, Lavoie K, Doyon J, Collins DL. Rapid automatic segmentation of the human cerebellum and its lobules (RASCAL)-Implementation and application of the patch-based label-fusion technique with a template library to segment the human cerebellum. Hum Brain Mapp (2014) 00: doi:10.1002/hbm.22529
153. Park MTM, Pipitone J, Baer LH, Winterburn JL, Shah Y, Chavez S, Schira MM, Lobaugh NJ, Lerch JP, Voineskos AN, et al. Derivation of high-resolution MRI atlases of the human cerebellum at 3T and segmentation using multiple automatically generated templates. Neuroimage (2014) 95C:217-231. doi:10.1016/j.neuroimage.2014.03.037
154. Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. Neuroimage (2009) 46:39-46. doi:10.1016/j.neuroimage.2009.01.045
155. Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. Neuroimage (2006) 33:127-138. doi:10.1016/j.neuroimage.2006.05.056
156. Bernard JA, Peltier SJ, Wiggins JL, Jaeggi SM, Buschkuehl M, Fling BW, Kwak Y, Jonides J, Monk CS, Seidler RD. Disrupted cortico-cerebellar connectivity in older adults. Neuroimage (2013) doi:10.1016/j.neuroimage.2013.06.042
157. E K-H, Chen S-HA, Ho M-HR, Desmond JE. A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI studies. Hum Brain Mapp (2012) 000: doi:10.1002/hbm.22194