Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers

J. van Gaalen, R. P. P. W. M. Maas, E. F. Ippel, M. W. Elting, K. Y. van Spaendonck-Zwarts, S. Vermeer, C. Verschuuren-Bemelmans, D. Timmann, Bart P. van de Warrenburg

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Spinocerebellar ataxias (SCAs) are a group of autosomal dominantly inherited degenerative diseases. As the pathological process probably commences years before the first appearance of clinical symptoms, preclinical carriers of a SCA mutation offer the opportunity to study the earliest stages of cerebellar dysfunction and degeneration. Eyeblink classical conditioning (EBCC) is a motor learning paradigm, crucially dependent on the integrity of the olivocerebellar circuit, and has been shown to be able to detect subtle alterations of cerebellar function, which might already be present in preclinical carriers. Methods: In order to acquire conditioned responses, we performed EBCC, delay paradigm, in 18 preclinical carriers of a SCA3 mutation and 16 healthy, age-matched controls by presenting repeated pairings of an auditory tone with a supraorbital nerve stimulus with a delay interval of 400 ms. Results: Preclinical carriers acquired significantly less conditioned eyeblink responses than controls and learning rates were significantly reduced. This motor learning defect was, however, not associated with the predicted time to onset. Conclusions: EBCC is impaired in preclinical carriers of a SCA3 mutation, as a result of impaired motor learning capacities of the cerebellum and is thus suggestive of cerebellar dysfunction. EBCC can be used to detect but probably not monitor preclinical cerebellar dysfunction in genetic ataxias, such as SCA3.
Original languageEnglish
JournalExperimental Brain Research
DOIs
Publication statusE-pub ahead of print - 2018

Cite this

van Gaalen, J., Maas, R. P. P. W. M., Ippel, E. F., Elting, M. W., van Spaendonck-Zwarts, K. Y., Vermeer, S., ... van de Warrenburg, B. P. (2018). Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers. Experimental Brain Research. https://doi.org/10.1007/s00221-018-5424-y
van Gaalen, J. ; Maas, R. P. P. W. M. ; Ippel, E. F. ; Elting, M. W. ; van Spaendonck-Zwarts, K. Y. ; Vermeer, S. ; Verschuuren-Bemelmans, C. ; Timmann, D. ; van de Warrenburg, Bart P. / Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers. In: Experimental Brain Research. 2018.
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title = "Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers",
abstract = "Background: Spinocerebellar ataxias (SCAs) are a group of autosomal dominantly inherited degenerative diseases. As the pathological process probably commences years before the first appearance of clinical symptoms, preclinical carriers of a SCA mutation offer the opportunity to study the earliest stages of cerebellar dysfunction and degeneration. Eyeblink classical conditioning (EBCC) is a motor learning paradigm, crucially dependent on the integrity of the olivocerebellar circuit, and has been shown to be able to detect subtle alterations of cerebellar function, which might already be present in preclinical carriers. Methods: In order to acquire conditioned responses, we performed EBCC, delay paradigm, in 18 preclinical carriers of a SCA3 mutation and 16 healthy, age-matched controls by presenting repeated pairings of an auditory tone with a supraorbital nerve stimulus with a delay interval of 400 ms. Results: Preclinical carriers acquired significantly less conditioned eyeblink responses than controls and learning rates were significantly reduced. This motor learning defect was, however, not associated with the predicted time to onset. Conclusions: EBCC is impaired in preclinical carriers of a SCA3 mutation, as a result of impaired motor learning capacities of the cerebellum and is thus suggestive of cerebellar dysfunction. EBCC can be used to detect but probably not monitor preclinical cerebellar dysfunction in genetic ataxias, such as SCA3.",
author = "{van Gaalen}, J. and Maas, {R. P. P. W. M.} and Ippel, {E. F.} and Elting, {M. W.} and {van Spaendonck-Zwarts}, {K. Y.} and S. Vermeer and C. Verschuuren-Bemelmans and D. Timmann and {van de Warrenburg}, {Bart P.}",
year = "2018",
doi = "10.1007/s00221-018-5424-y",
language = "English",
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van Gaalen, J, Maas, RPPWM, Ippel, EF, Elting, MW, van Spaendonck-Zwarts, KY, Vermeer, S, Verschuuren-Bemelmans, C, Timmann, D & van de Warrenburg, BP 2018, 'Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers' Experimental Brain Research. https://doi.org/10.1007/s00221-018-5424-y

Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers. / van Gaalen, J.; Maas, R. P. P. W. M.; Ippel, E. F.; Elting, M. W.; van Spaendonck-Zwarts, K. Y.; Vermeer, S.; Verschuuren-Bemelmans, C.; Timmann, D.; van de Warrenburg, Bart P.

In: Experimental Brain Research, 2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers

AU - van Gaalen, J.

AU - Maas, R. P. P. W. M.

AU - Ippel, E. F.

AU - Elting, M. W.

AU - van Spaendonck-Zwarts, K. Y.

AU - Vermeer, S.

AU - Verschuuren-Bemelmans, C.

AU - Timmann, D.

AU - van de Warrenburg, Bart P.

PY - 2018

Y1 - 2018

N2 - Background: Spinocerebellar ataxias (SCAs) are a group of autosomal dominantly inherited degenerative diseases. As the pathological process probably commences years before the first appearance of clinical symptoms, preclinical carriers of a SCA mutation offer the opportunity to study the earliest stages of cerebellar dysfunction and degeneration. Eyeblink classical conditioning (EBCC) is a motor learning paradigm, crucially dependent on the integrity of the olivocerebellar circuit, and has been shown to be able to detect subtle alterations of cerebellar function, which might already be present in preclinical carriers. Methods: In order to acquire conditioned responses, we performed EBCC, delay paradigm, in 18 preclinical carriers of a SCA3 mutation and 16 healthy, age-matched controls by presenting repeated pairings of an auditory tone with a supraorbital nerve stimulus with a delay interval of 400 ms. Results: Preclinical carriers acquired significantly less conditioned eyeblink responses than controls and learning rates were significantly reduced. This motor learning defect was, however, not associated with the predicted time to onset. Conclusions: EBCC is impaired in preclinical carriers of a SCA3 mutation, as a result of impaired motor learning capacities of the cerebellum and is thus suggestive of cerebellar dysfunction. EBCC can be used to detect but probably not monitor preclinical cerebellar dysfunction in genetic ataxias, such as SCA3.

AB - Background: Spinocerebellar ataxias (SCAs) are a group of autosomal dominantly inherited degenerative diseases. As the pathological process probably commences years before the first appearance of clinical symptoms, preclinical carriers of a SCA mutation offer the opportunity to study the earliest stages of cerebellar dysfunction and degeneration. Eyeblink classical conditioning (EBCC) is a motor learning paradigm, crucially dependent on the integrity of the olivocerebellar circuit, and has been shown to be able to detect subtle alterations of cerebellar function, which might already be present in preclinical carriers. Methods: In order to acquire conditioned responses, we performed EBCC, delay paradigm, in 18 preclinical carriers of a SCA3 mutation and 16 healthy, age-matched controls by presenting repeated pairings of an auditory tone with a supraorbital nerve stimulus with a delay interval of 400 ms. Results: Preclinical carriers acquired significantly less conditioned eyeblink responses than controls and learning rates were significantly reduced. This motor learning defect was, however, not associated with the predicted time to onset. Conclusions: EBCC is impaired in preclinical carriers of a SCA3 mutation, as a result of impaired motor learning capacities of the cerebellum and is thus suggestive of cerebellar dysfunction. EBCC can be used to detect but probably not monitor preclinical cerebellar dysfunction in genetic ataxias, such as SCA3.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30430184

U2 - 10.1007/s00221-018-5424-y

DO - 10.1007/s00221-018-5424-y

M3 - Article

JO - Experimental Brain Research

JF - Experimental Brain Research

SN - 0014-4819

ER -