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Development of a novel startle response task in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle respons...

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Autores principales: Maresh, Kate, Papageorgiou, Andriani, Ridout, Deborah, Harrison, Neil, Mandy, William, Skuse, David, Muntoni, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017900/
https://www.ncbi.nlm.nih.gov/pubmed/35439255
http://dx.doi.org/10.1371/journal.pone.0264091
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author Maresh, Kate
Papageorgiou, Andriani
Ridout, Deborah
Harrison, Neil
Mandy, William
Skuse, David
Muntoni, Francesco
author_facet Maresh, Kate
Papageorgiou, Andriani
Ridout, Deborah
Harrison, Neil
Mandy, William
Skuse, David
Muntoni, Francesco
author_sort Maresh, Kate
collection PubMed
description Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle responses to threat which normalise when dystrophin is restored in the brain. We hypothesised that startle responses may also be increased in humans with DMD, which would have potential translational therapeutic implications. To investigate this, we first designed a novel discrimination fear-conditioning task and tested it in six healthy volunteers, followed by male DMD (n = 11) and Control (n = 9) participants aged 7–12 years. The aims of this methodological task development study were to: i) confirm the task efficacy; ii) optimise data processing procedures; iii) determine the most appropriate outcome measures. In the task, two neutral visual stimuli were presented: one ‘safe’ cue presented alone; one ‘threat’ cue paired with a threat stimulus (aversive noise) to enable conditioning of physiological startle responses (skin conductance response, SCR, and heart rate). Outcomes were the unconditioned physiological startle responses to the initial threat, and retention of conditioned responses in the absence of the threat stimulus. We present the protocol development and optimisation of data processing methods based on empirical data. We found that the task was effective in producing significantly higher physiological startle SCR in reinforced ‘threat’ trials compared to ‘safe’ trials (P < .001). Different data extraction methods were compared and optimised, and the optimal sampling window was derived empirically. SCR amplitude was the most effective physiological outcome measure when compared to SCR area and change in heart rate, with the best profile on data processing, the least variance, successful conditioned response retention (P = .01) and reliability assessment in test-retest analysis (rho = .86). The definition of this novel outcome will allow us to study this response in a DMD population.
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spelling pubmed-90179002022-04-20 Development of a novel startle response task in Duchenne muscular dystrophy Maresh, Kate Papageorgiou, Andriani Ridout, Deborah Harrison, Neil Mandy, William Skuse, David Muntoni, Francesco PLoS One Research Article Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle responses to threat which normalise when dystrophin is restored in the brain. We hypothesised that startle responses may also be increased in humans with DMD, which would have potential translational therapeutic implications. To investigate this, we first designed a novel discrimination fear-conditioning task and tested it in six healthy volunteers, followed by male DMD (n = 11) and Control (n = 9) participants aged 7–12 years. The aims of this methodological task development study were to: i) confirm the task efficacy; ii) optimise data processing procedures; iii) determine the most appropriate outcome measures. In the task, two neutral visual stimuli were presented: one ‘safe’ cue presented alone; one ‘threat’ cue paired with a threat stimulus (aversive noise) to enable conditioning of physiological startle responses (skin conductance response, SCR, and heart rate). Outcomes were the unconditioned physiological startle responses to the initial threat, and retention of conditioned responses in the absence of the threat stimulus. We present the protocol development and optimisation of data processing methods based on empirical data. We found that the task was effective in producing significantly higher physiological startle SCR in reinforced ‘threat’ trials compared to ‘safe’ trials (P < .001). Different data extraction methods were compared and optimised, and the optimal sampling window was derived empirically. SCR amplitude was the most effective physiological outcome measure when compared to SCR area and change in heart rate, with the best profile on data processing, the least variance, successful conditioned response retention (P = .01) and reliability assessment in test-retest analysis (rho = .86). The definition of this novel outcome will allow us to study this response in a DMD population. Public Library of Science 2022-04-19 /pmc/articles/PMC9017900/ /pubmed/35439255 http://dx.doi.org/10.1371/journal.pone.0264091 Text en © 2022 Maresh et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Maresh, Kate
Papageorgiou, Andriani
Ridout, Deborah
Harrison, Neil
Mandy, William
Skuse, David
Muntoni, Francesco
Development of a novel startle response task in Duchenne muscular dystrophy
title Development of a novel startle response task in Duchenne muscular dystrophy
title_full Development of a novel startle response task in Duchenne muscular dystrophy
title_fullStr Development of a novel startle response task in Duchenne muscular dystrophy
title_full_unstemmed Development of a novel startle response task in Duchenne muscular dystrophy
title_short Development of a novel startle response task in Duchenne muscular dystrophy
title_sort development of a novel startle response task in duchenne muscular dystrophy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017900/
https://www.ncbi.nlm.nih.gov/pubmed/35439255
http://dx.doi.org/10.1371/journal.pone.0264091
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