Time estimation and arousal responses in dopa-responsive dystonia
Abstract Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17545-w |
| _version_ | 1811188849615831040 |
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| author | Leonie F. Becker Sinem Tunc Peter Murphy Tobias Bäumer Anne Weissbach Martje G. Pauly Duha M. Al-Shorafat Gerard Saranza Anthony E. Lang Christian Beste Tobias H. Donner Julius Verrel Alexander Münchau |
| author_facet | Leonie F. Becker Sinem Tunc Peter Murphy Tobias Bäumer Anne Weissbach Martje G. Pauly Duha M. Al-Shorafat Gerard Saranza Anthony E. Lang Christian Beste Tobias H. Donner Julius Verrel Alexander Münchau |
| author_sort | Leonie F. Becker |
| collection | DOAJ |
| description | Abstract Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such as timing, action preparation and feedback processing, have not been investigated so far. In an active time estimation task with trial-by-trial feedback, participants indicated a target interval (1200 ms) by a motor response. We compared 12 patients tested (in fixed order) under their current levodopa medication ("ON") and after levodopa withdrawal ("OFF") to matched healthy controls (HC), measured twice to control for repetition effects. We assessed time estimation accuracy, trial-to-trial adjustment, as well as task- and feedback-related pupil-linked arousal responses. Patients showed comparable time estimation accuracy ON medication as HC but reduced performance OFF medication. Task-related pupil responses showed the reverse pattern. Trial-to-trial adjustments of response times were reduced in DRD, particularly OFF medication. Our results indicate differential alterations of time estimation accuracy and task-related arousal dynamics in DRD patients as a function of dopaminergic medication state. A medication-independent alteration of task repetition effects in DRD cannot be ruled out with certainty but is discussed as less likely. |
| first_indexed | 2024-04-11T14:25:04Z |
| format | Article |
| id | doaj.art-06c8a7b3c4a44af0832037c6d5c69403 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:25:04Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-06c8a7b3c4a44af0832037c6d5c694032022-12-22T04:18:53ZengNature PortfolioScientific Reports2045-23222022-08-0112111010.1038/s41598-022-17545-wTime estimation and arousal responses in dopa-responsive dystoniaLeonie F. Becker0Sinem Tunc1Peter Murphy2Tobias Bäumer3Anne Weissbach4Martje G. Pauly5Duha M. Al-Shorafat6Gerard Saranza7Anthony E. Lang8Christian Beste9Tobias H. Donner10Julius Verrel11Alexander Münchau12Institute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu LübeckInstitute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu LübeckSection Computational Cognitive Neuroscience, Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-EppendorfInstitute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu LübeckInstitute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu LübeckInstitute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu LübeckEdmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western HospitalEdmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western HospitalEdmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western HospitalCognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU DresdenSection Computational Cognitive Neuroscience, Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-EppendorfInstitute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu LübeckInstitute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu LübeckAbstract Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such as timing, action preparation and feedback processing, have not been investigated so far. In an active time estimation task with trial-by-trial feedback, participants indicated a target interval (1200 ms) by a motor response. We compared 12 patients tested (in fixed order) under their current levodopa medication ("ON") and after levodopa withdrawal ("OFF") to matched healthy controls (HC), measured twice to control for repetition effects. We assessed time estimation accuracy, trial-to-trial adjustment, as well as task- and feedback-related pupil-linked arousal responses. Patients showed comparable time estimation accuracy ON medication as HC but reduced performance OFF medication. Task-related pupil responses showed the reverse pattern. Trial-to-trial adjustments of response times were reduced in DRD, particularly OFF medication. Our results indicate differential alterations of time estimation accuracy and task-related arousal dynamics in DRD patients as a function of dopaminergic medication state. A medication-independent alteration of task repetition effects in DRD cannot be ruled out with certainty but is discussed as less likely.https://doi.org/10.1038/s41598-022-17545-w |
| spellingShingle | Leonie F. Becker Sinem Tunc Peter Murphy Tobias Bäumer Anne Weissbach Martje G. Pauly Duha M. Al-Shorafat Gerard Saranza Anthony E. Lang Christian Beste Tobias H. Donner Julius Verrel Alexander Münchau Time estimation and arousal responses in dopa-responsive dystonia Scientific Reports |
| title | Time estimation and arousal responses in dopa-responsive dystonia |
| title_full | Time estimation and arousal responses in dopa-responsive dystonia |
| title_fullStr | Time estimation and arousal responses in dopa-responsive dystonia |
| title_full_unstemmed | Time estimation and arousal responses in dopa-responsive dystonia |
| title_short | Time estimation and arousal responses in dopa-responsive dystonia |
| title_sort | time estimation and arousal responses in dopa responsive dystonia |
| url | https://doi.org/10.1038/s41598-022-17545-w |
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