A critical investigation of cerebellar associative learning in isolated dystonia

Anna Sadnicka, Lorenzo Rocchi, Anna Latorre, Elena Antelmi, James Teo, Isabel Pareés, Britt S Hoffland, Kristian Brock, Katja Kornysheva, Mark J Edwards, Kailash P Bhatia, John C Rothwell

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Abstract

BACKGROUND: Impaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia yet the results from individual studies are conflicting and underpowered.

OBJECTIVE: To systematically examine the influence of dystonia, dystonia subtype, and clinical features over eyeblink conditioning within a statistical model which controlled for the covariates age and sex.

METHODS: Original neurophysiological data from all published studies (until 2019) were shared and compared to an age- and sex-matched control group. Two raters blinded to participant identity rescored all recordings (6732 trials). After higher inter-rater agreement was confirmed, mean conditioning per block across raters was entered into a mixed repetitive measures model.

RESULTS: Isolated dystonia (P = 0.517) and the subtypes of isolated dystonia (cervical dystonia, DYT-TOR1A, DYT-THAP1, and focal hand dystonia) had similar levels of eyeblink conditioning relative to controls. The presence of tremor did not significantly influence levels of eyeblink conditioning. A large range of eyeblink conditioning behavior was seen in both health and dystonia and sample size estimates are provided for future studies.

CONCLUSIONS: The similarity of eyeblink conditioning behavior in dystonia and controls is against a global cerebellar learning deficit in isolated dystonia. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains an open research question. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Original languageEnglish
JournalMovement Disorders
Early online date21 Mar 2022
DOIs
Publication statusE-pub ahead of print - 21 Mar 2022

Bibliographical note

Funding Information:
A.S. is supported by a Chadburn Clinical Lectureship in Medicine and a project grant from the Royal Society. Funding agency:

Publisher Copyright:
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Keywords

  • associative learning
  • cerebellum
  • dystonia
  • eyeblink conditioning

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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