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

doi:10.1002/mds.28967

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	1187-1192
Number of pages	6
Journal	Movement Disorders
Volume	37
Issue number	6
Early online date	21 Mar 2022
DOIs	https://doi.org/10.1002/mds.28967
Publication status	Published - Jun 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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Cite this

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title = "A critical investigation of cerebellar associative learning in isolated dystonia",

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. {\textcopyright} 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",

author = "Anna Sadnicka and Lorenzo Rocchi and Anna Latorre and Elena Antelmi and James Teo and Isabel Pare{\'e}s and Hoffland, {Britt S} and Kristian Brock and Katja Kornysheva and Edwards, {Mark J} and Bhatia, {Kailash P} and Rothwell, {John C}",

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: {\textcopyright} 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.",

year = "2022",

month = jun,

doi = "10.1002/mds.28967",

language = "English",

volume = "37",

pages = "1187--1192",

journal = "Movement Disorders",

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T1 - A critical investigation of cerebellar associative learning in isolated dystonia

AU - Sadnicka, Anna

AU - Rocchi, Lorenzo

AU - Latorre, Anna

AU - Antelmi, Elena

AU - Teo, James

AU - Pareés, Isabel

AU - Hoffland, Britt S

AU - Brock, Kristian

AU - Kornysheva, Katja

AU - Edwards, Mark J

AU - Bhatia, Kailash P

AU - Rothwell, John C

N1 - 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.

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - associative learning

KW - cerebellum

KW - dystonia

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DO - 10.1002/mds.28967

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SN - 0885-3185

VL - 37

SP - 1187

EP - 1192

JO - Movement Disorders

JF - Movement Disorders

IS - 6

ER -

A critical investigation of cerebellar associative learning in isolated dystonia

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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