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