The Cerebellum

, Volume 18, Issue 2, pp 178–187 | Cite as

Repeated Spiral Drawings in Essential Tremor: a Possible Limb-Based Measure of Motor Learning

  • Christine Y. Kim
  • Lan Luo
  • Qiping Yu
  • Ana Mirallave
  • Rachel Saunders-Pullman
  • Richard B. Lipton
  • Elan D. Louis
  • Seth L. PullmanEmail author
Original Paper


To investigate changes in tremor severity over repeated spiral drawings to assess whether learning deficits can be evaluated directly in a limb in essential tremor (ET). A motor learning deficit in ET, possibly mediated by cerebellar pathways, has been established in eye-blink conditioning studies, but not paradigms measuring from an affected, tremulous limb. Computerized spiral analysis captures multiple characteristics of Archimedean spirals and quantifies performance through calculated indices. Sequential spiral drawing has recently been suggested to demonstrate improvement across trials among ET subjects. One hundred and sixty-one ET and 80 age-matched control subjects drew 10 consecutive spirals on a digitizing tablet. Degree of severity (DoS), a weighted, computational score of spiral execution that takes into account spiral shape and line smoothness, previously validated against a clinical rating scale, was calculated in both groups. Tremor amplitude (Ampl), an independent index of tremor size, measured in centimeters, was also calculated. Changes in DoS and Ampl across trials were assessed using linear regression with slope evaluations. Both groups demonstrated improvement in DoS across trials, but with less improvement in the ET group compared to controls. Ampl demonstrated a tendency to worsen across trials in ET subjects. ET subjects demonstrated less improvement than controls when drawing sequential spirals, suggesting a possible motor learning deficit in ET, here captured in an affected limb. DoS improved independently of Ampl, showing that DoS and Ampl are separable motor physiologic components in ET that may be independently mediated.


Computerized spiral analysis Movement disorders Essential tremor Motor learning Cerebellum 



The authors wish to thank Amelia Boehme, PhD, for her guidance and expertise with statistical analyses and interpretation.

Author Contributions

Christine Y. Kim: Writing the manuscript, data analysis, and critical revision of the manuscript for important intellectual content.

Lan Luo: Data analysis, statistical analysis, and critical revision of the manuscript.

Qiping Yu: Statistical analysis and interpretation, acquisition, and analysis of data.

Ana Mirallave: Study design and data analysis.

Elan D. Louis: Study concept and design, acquisition of data and interpretation, writing, and critical revision of the manuscript for important intellectual content.

Seth L. Pullman: Study concept and design, acquisition, analysis and interpretation of data, writing, and critical revision of the manuscript for important intellectual content.


This work was supported by the National Institutes of Health R01 NS042859 and R01 NS088257 (EDL), National Institutes of Health T32-NS07153 (LL), the Parkinson’s Disease Foundation (LL, SLP, QY), the Michael J. Fox Foundation for Parkinson’s Research Edmond J. Safra Fellowship (CK), and the National Institutes of Health U01NS094148-01 (RS-P and RBL) and AG03949 (RBL).

Postdoctoral Fellow Christine Y. Kim is funded by Michael J. Fox Foundation for Parkinson's Research and Edmund J. Safra Fellowship.

Prof Elan D Louis is funded by National Institutes of Health (R01 NS042859 and R01 NS088257).

Prof Seth L Pullman is funded by National Institutes of Health (R01 NS042859) and Parkinson's Disease Foundation (PG005860-31).

Postdoctoral Fellow Lan Luo is funded by National Institutes of Health (T32 NS07153) and Parkinson's Disease Foundation (PG005860-31).

Research Associate Qiping Yu is funded by Parkinson's Disease Foundation (PG005860-31).

Prof Rachel Saunders-Pullman is funded by National Institutes of Health (K23 NS047256, K02 NS073836 and U01NS094148-01) and Marcled and Bigglesworth Foundation.

Prof Richard B. Lipton is funded by National Institutes of Health (U01NS094148-01, AG03949, 2PO1 AG003949, 5U10 NS077308, 1RO1 AG042595, K23 NS09610 and K23 AG049466).

Compliance with Ethical Standards

The study was conducted in accordance with the Institutional Review Board of Albert Einstein College of Medicine. Informed consent was obtained from all individual participants included in the study.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Full Financial Disclosures of All Authors for the Past Year

Stock Ownership: eNeura Therapeutics (RBL).

Consultancies: Consultant to Denali Therapeutics (RS-P).

Expert Testimony: NONE.

Advisory Boards: Dystonia Medical Research Foundation: Musicians with Dystonia, Scientific Advisory Board (SP); Tremor and Other Hyperkinetic Movement Disorders, Editorial Board (SP); National Headache Foundation (RBL), Neurology and the National Headache Foundation (RBL).

Employment: Columbia University Medical Center (CK, LL, SP, QY); Yale School of Medicine (EL); Queen’s Hospital, Barking Redbridge and Havering Trust, Romford, London UK (AM), Mount Sinai Beth Israel, Icahn School of Medicine Mount Sinai (RS-P), Albert Einstein College of Medicine (RBL).

Partnerships: NONE.

Contracts: Consultant Clinical Neurophysiology permanent staff (AM).

Honoraria: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Colucid, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKlein, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, and Vedanta (all RBL).

Royalties: Wolff’s Headache, 8th Edition, Oxford Press University, 2009, Wiley and Informa (RBL).

Grants: NIH R01 NS042859 (SP); NIH T32 NS07153 (LL); NINDS R01 NS094607 (EL: principal investigator), NINDS R01 NS085136 (EL: principal investigator), NINDS R01 NS073872 (EL: principal investigator), NINDS R01 NS085136 (EL: principal investigator), NINDS R01 NS088257 (EL: principal investigator); Claire O’Neil Essential Tremor Research Fund (Yale University) (EL); Michael J. Fox Foundation for Parkinson’s Research, Edmund J. Safra Fellowship (CK); Parkinson Disease Foundation (LL, SP, QY); Dystonia Medical Research Foundation James C. Kilik Memorial Research Award (CK); Smart Foundation Gift for Parkinson’s Disease Research (CK); National Institutes of Health U01NS094148-01 (RS-P and RBL) and AG03949 (RBL), PO1 AG003949 (RBL; program director), 5 U10 NS077308 (RBL: PI), 1RO1 AG042595 (RBL; investigator), RO1 NS082432 (EBL: investigator), K23 NS09610 (RBL: mentor), and K23 AG049466 (RBL: mentor), the National Migraine Headache Foundation (RBL).


  1. 1.
    Louis ED. Essential tremor. Lancet Neurol. 2005;4(2):100–10.CrossRefGoogle Scholar
  2. 2.
    Deuschl G, Wenzelburger R, Loffler K, Raethjen J, Stolze H. Essential tremor and cerebellar dysfunction clinical and kinematic analysis of intention tremor. Brain. 2000;123(Pt 8):1568–80.CrossRefGoogle Scholar
  3. 3.
    Kronenbuerger M, Konczak J, Ziegler W, Buderath P, Frank B, Coenen VA, et al. Balance and motor speech impairment in essential tremor. Cerebellum. 2009;8(3):389–98.CrossRefGoogle Scholar
  4. 4.
    Rao AK, Gillman A, Louis ED. Quantitative gait analysis in essential tremor reveals impairments that are maintained into advanced age. Gait Posture. 2011;34(1):65–70.CrossRefGoogle Scholar
  5. 5.
    Helmchen C, Hagenow A, Miesner J, Sprenger A, Rambold H, Wenzelburger R, et al. Eye movement abnormalities in essential tremor may indicate cerebellar dysfunction. Brain. 2003;126(Pt 6):1319–32.CrossRefGoogle Scholar
  6. 6.
    Benito-Leon J, Labiano-Fontcuberta A. Linking essential tremor to the cerebellum: clinical evidence. Cerebellum. 2016;15(3):253–62.CrossRefGoogle Scholar
  7. 7.
    Louis ED, Huang CC, Dyke JP, Long Z, Dydak U. Neuroimaging studies of essential tremor: how well do these studies support/refute the neurodegenerative hypothesis? Tremor Other Hyperkinet Mov (N Y). 2014;4:235.Google Scholar
  8. 8.
    Buijink AW, Broersma M, van der Stouwe AM, van Wingen GA, Groot PF, Speelman JD, et al. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor. Parkinsonism Relat Disord. 2015;21(4):383–8.CrossRefGoogle Scholar
  9. 9.
    Louis ED, Faust PL, Vonsattel JP, Honig LS, Rajput A, Robinson CA, et al. Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain. 2007;130(Pt 12):3297–307.CrossRefGoogle Scholar
  10. 10.
    Shill HA, Adler CH, Sabbagh MN, Connor DJ, Caviness JN, Hentz JG, et al. Pathologic findings in prospectively ascertained essential tremor subjects. Neurology. 2008;70(16 Pt 2):1452–5.CrossRefGoogle Scholar
  11. 11.
    Axelrad JE, Louis ED, Honig LS, Flores I, Ross GW, Pahwa R, et al. Reduced Purkinje cell number in essential tremor: a postmortem study. Arch Neurol. 2008;65(1):101–7.CrossRefGoogle Scholar
  12. 12.
    Kuo SH, Wang J, Tate WJ, Pan MK, Kelly GC, Gutierrez J, et al. Cerebellar pathology in early onset and late onset essential tremor. Cerebellum. 2017;16(2):473–82.CrossRefGoogle Scholar
  13. 13.
    Lin CY, Louis ED, Faust PL, Koeppen AH, Vonsattel JP, Kuo SH. Abnormal climbing fibre-Purkinje cell synaptic connections in the essential tremor cerebellum. Brain. 2014;137(Pt 12):3149–59.CrossRefGoogle Scholar
  14. 14.
    Shmuelof L, Krakauer JW, Mazzoni P. How is a motor skill learned? Change and invariance at the levels of task success and trajectory control. J Neurophysiol. 2012;108(2):578–94.CrossRefGoogle Scholar
  15. 15.
    Gutierrez-Castellanos N, Da Silva-Matos CM, Zhou K, Canto CB, Renner MC, Koene LMC, et al. Motor learning requires Purkinje cell synaptic potentiation through activation of AMPA-receptor subunit GluA3. Neuron. 2017;93(2):409–24.CrossRefGoogle Scholar
  16. 16.
    Spampinato D, Celnik P. Deconstructing skill learning and its physiological mechanisms. Cortex. 2018;104:90–102.CrossRefGoogle Scholar
  17. 17.
    Herzfeld DJ, Kojima Y, Soetedjo R, Shadmehr R. Encoding of error and learning to correct that error by the Purkinje cells of the cerebellum. Nat Neurosci. 2018;21(5):736–43.CrossRefGoogle Scholar
  18. 18.
    Nixon PD, Passingham RE. The cerebellum and cognition: cerebellar lesions impair sequence learning but not conditional visuomotor learning in monkeys. Neuropsychologia. 2000;38(7):1054–72.CrossRefGoogle Scholar
  19. 19.
    Kronenbuerger M, Gerwig M, Brol B, Block F, Timmann D. Eyeblink conditioning is impaired in subjects with essential tremor. Brain. 2007;130(Pt 6):1538–51.CrossRefGoogle Scholar
  20. 20.
    Shill HA, De La Vega FJ, Samanta J, Stacy M. Motor learning in essential tremor. Mov Disord. 2009;24(6):926–8.CrossRefGoogle Scholar
  21. 21.
    Schuhmayer N, Weber C, Kieler M, Pirker W, Auff E, Haubenberger D. Improvement of repeated Archimedes spirals in essential tremor: evidence for a learning effect? Mov Disord. 2015;30(Suppl 1):4204.Google Scholar
  22. 22.
    Van Gemmert AW, Teulings HL. Advances in graphonomics: studies on fine motor control, its development and disorders. Hum Mov Sci. 2006;25(4–5):447–53.CrossRefGoogle Scholar
  23. 23.
    Longstaff MG, Heath RA. Spiral drawing performance as an indicator of fine motor function in people with multiple sclerosis. Hum Mov Sci. 2006;25(4–5):474–91.CrossRefGoogle Scholar
  24. 24.
    Saunders-Pullman R, Derby C, Stanley K, Floyd A, Bressman S, Lipton RB, et al. Validity of spiral analysis in early Parkinson’s disease. Mov Disord. 2008;23(4):531–7.CrossRefGoogle Scholar
  25. 25.
    Liu X, Carroll CB, Wang SY, Zajicek J, Bain PG. Quantifying drug-induced dyskinesias in the arms using digitised spiral-drawing tasks. J Neurosci Methods. 2005;144(1):47–52.CrossRefGoogle Scholar
  26. 26.
    Hsu AW, Piboolnurak PA, Floyd AG, Yu QP, Wraith JE, Patterson MC, et al. Spiral analysis in Niemann-Pick disease type C. Mov Disord. 2009;24(13):1984–90.CrossRefGoogle Scholar
  27. 27.
    Hess CW, Hsu AW, Yu Q, Ortega R, Pullman SL. Increased variability in spiral drawing in patients with functional (psychogenic) tremor. Hum Mov Sci. 2014;38:15–22.CrossRefGoogle Scholar
  28. 28.
    Louis ED, Gillman A, Boschung S, Hess CW, Yu Q, Pullman SL. High width variability during spiral drawing: further evidence of cerebellar dysfunction in essential tremor. Cerebellum. 2012;11(4):872–9.CrossRefGoogle Scholar
  29. 29.
    Louis ED, Yu Q, Floyd AG, Moskowitz C, Pullman SL. Axis is a feature of handwritten spirals in essential tremor. Mov Disord. 2006;21(8):1294–5.CrossRefGoogle Scholar
  30. 30.
    Fahn S, UPDRS program members. Unified Parkinson’s Disease Rating Scale. In: Fahn SMC, Goldstein M, Calne DB, editors. Recent developments in Parkinson’s disease. 2. Florham Park: Macmillan Healthcare Information; 1987. p. 153–63.Google Scholar
  31. 31.
    San Luciano M, Wang C, Ortega RA, Yu Q, Boschung S, Soto-Valencia J, et al. Digitized spiral drawing: a possible biomarker for early Parkinson’s disease. PLoS One. 2016;11(10):e0162799.CrossRefGoogle Scholar
  32. 32.
    Schuhmayer N, Weber C, Kieler M, Voller B, Pirker W, Auff E, et al. Task-dependent variability of essential tremor. Parkinsonism Relat Disord. 2017;41:79–85.CrossRefGoogle Scholar
  33. 33.
    Louis ED, Borden S, Moskowitz CB. Essential tremor centralized brain repository: diagnostic validity and clinical characteristics of a highly selected group of essential tremor cases. Mov Disord. 2005;20(10):1361–5.CrossRefGoogle Scholar
  34. 34.
    Folstein MF, Robins LN, Helzer JE. The mini-mental state examination. Arch Gen Psychiatry. 1983;40(7):812.CrossRefGoogle Scholar
  35. 35.
    Lipton RB, Katz MJ, Kuslansky G, Sliwinski MJ, Stewart WF, Verghese J, et al. Screening for dementia by telephone using the memory impairment screen. J Am Geriatr Soc. 2003;51(10):1382–90.CrossRefGoogle Scholar
  36. 36.
    Machowska-Majchrzak A, Pierzchala K, Pietraszek S, Labuz-Roszak B. Essential tremor—assessment of tremor accelerometric parameters’ symmetry and the relationship between hand dominance and severity of tremor. Neurol Neurochir Pol. 2011;45(2):121–7.CrossRefGoogle Scholar
  37. 37.
    Louis ED, Wendt KJ, Pullman SL, Ford B. Is essential tremor symmetric? Observational data from a community-based study of essential tremor. Arch Neurol. 1998;55(12):1553–9.CrossRefGoogle Scholar
  38. 38.
    Pullman SL. Spiral analysis: a new technique for measuring tremor with a digitizing tablet. Mov Disord. 1998;13(Suppl 3):85–9.Google Scholar
  39. 39.
    Titley HK, Hansel C. Asymmetries in cerebellar plasticity and motor learning. Cerebellum. 2016;15(2):87–92.CrossRefGoogle Scholar
  40. 40.
    Kuo SH, Lin CY, Wang J, Sims PA, Pan MK, Liou JY, et al. Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases. Acta Neuropathol. 2017;133(1):121–38.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology, Clinical Motor Physiology LaboratoryColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Neurology, Mount Sinai Beth IsraelIcahn School of Medicine Mount SinaiNew YorkUSA
  3. 3.Department of Neurology, Albert Einstein College of MedicineYeshiva UniversityBronxUSA
  4. 4.Department of Neurology, Yale School of MedicineYale UniversityNew HavenUSA
  5. 5.Department of Chronic Disease Epidemiology, Yale School of Public HealthYale UniversityNew HavenUSA
  6. 6.Center for Neuroepidemiology and Clinical Neurological Research, Yale School of MedicineYale UniversityNew HavenUSA

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