Cargando…
Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword
In stressful or anxiety-provoking situations, most people with Parkinson’s disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, a proportion of patients actually report benefits from experiencing—or even purposely inducing—stressful or high-arousa...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040128/ https://www.ncbi.nlm.nih.gov/pubmed/36967402 http://dx.doi.org/10.1186/s40035-023-00347-z |
_version_ | 1784912414329798656 |
---|---|
author | Tosserams, Anouk Bloem, Bastiaan R. Ehgoetz Martens, Kaylena A. Helmich, Rick C. Kessels, Roy P. C. Shine, James M. Taylor, Natasha L. Wainstein, Gabriel Lewis, Simon J. G. Nonnekes, Jorik |
author_facet | Tosserams, Anouk Bloem, Bastiaan R. Ehgoetz Martens, Kaylena A. Helmich, Rick C. Kessels, Roy P. C. Shine, James M. Taylor, Natasha L. Wainstein, Gabriel Lewis, Simon J. G. Nonnekes, Jorik |
author_sort | Tosserams, Anouk |
collection | PubMed |
description | In stressful or anxiety-provoking situations, most people with Parkinson’s disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, a proportion of patients actually report benefits from experiencing—or even purposely inducing—stressful or high-arousal situations. Using data from a large-scale international survey study among 4324 people with PD and gait impairments within the online Fox Insight (USA) and ParkinsonNEXT (NL) cohorts, we demonstrate that individuals with PD deploy an array of mental state alteration strategies to cope with their gait impairment. Crucially, these strategies differ along an axis of arousal—some act to heighten, whereas others diminish, overall sympathetic tone. Together, our observations suggest that arousal may act as a double-edged sword for gait control in PD. We propose a theoretical, neurobiological framework to explain why heightened arousal can have detrimental effects on the occurrence and severity of gait impairments in some individuals, while alleviating them in others. Specifically, we postulate that this seemingly contradictory phenomenon is explained by the inherent features of the ascending arousal system: namely, that arousal is related to task performance by an inverted u-shaped curve (the so-called Yerkes and Dodson relationship). We propose that the noradrenergic locus coeruleus plays an important role in modulating PD symptom severity and expression, by regulating arousal and by mediating network-level functional integration across the brain. The ability of the locus coeruleus to facilitate dynamic ‘cross-talk’ between distinct, otherwise largely segregated brain regions may facilitate the necessary cerebral compensation for gait impairments in PD. In the presence of suboptimal arousal, compensatory networks may be too segregated to allow for adequate compensation. Conversely, with supraoptimal arousal, increased cross-talk between competing inputs of these complementary networks may emerge and become dysfunctional. Because the locus coeruleus degenerates with disease progression, finetuning of this delicate balance becomes increasingly difficult, heightening the need for mental strategies to self-modulate arousal and facilitate shifting from a sub- or supraoptimal state of arousal to improve gait performance. Recognition of this underlying mechanism emphasises the importance of PD-specific rehabilitation strategies to alleviate gait disability. |
format | Online Article Text |
id | pubmed-10040128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100401282023-03-27 Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword Tosserams, Anouk Bloem, Bastiaan R. Ehgoetz Martens, Kaylena A. Helmich, Rick C. Kessels, Roy P. C. Shine, James M. Taylor, Natasha L. Wainstein, Gabriel Lewis, Simon J. G. Nonnekes, Jorik Transl Neurodegener Review In stressful or anxiety-provoking situations, most people with Parkinson’s disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, a proportion of patients actually report benefits from experiencing—or even purposely inducing—stressful or high-arousal situations. Using data from a large-scale international survey study among 4324 people with PD and gait impairments within the online Fox Insight (USA) and ParkinsonNEXT (NL) cohorts, we demonstrate that individuals with PD deploy an array of mental state alteration strategies to cope with their gait impairment. Crucially, these strategies differ along an axis of arousal—some act to heighten, whereas others diminish, overall sympathetic tone. Together, our observations suggest that arousal may act as a double-edged sword for gait control in PD. We propose a theoretical, neurobiological framework to explain why heightened arousal can have detrimental effects on the occurrence and severity of gait impairments in some individuals, while alleviating them in others. Specifically, we postulate that this seemingly contradictory phenomenon is explained by the inherent features of the ascending arousal system: namely, that arousal is related to task performance by an inverted u-shaped curve (the so-called Yerkes and Dodson relationship). We propose that the noradrenergic locus coeruleus plays an important role in modulating PD symptom severity and expression, by regulating arousal and by mediating network-level functional integration across the brain. The ability of the locus coeruleus to facilitate dynamic ‘cross-talk’ between distinct, otherwise largely segregated brain regions may facilitate the necessary cerebral compensation for gait impairments in PD. In the presence of suboptimal arousal, compensatory networks may be too segregated to allow for adequate compensation. Conversely, with supraoptimal arousal, increased cross-talk between competing inputs of these complementary networks may emerge and become dysfunctional. Because the locus coeruleus degenerates with disease progression, finetuning of this delicate balance becomes increasingly difficult, heightening the need for mental strategies to self-modulate arousal and facilitate shifting from a sub- or supraoptimal state of arousal to improve gait performance. Recognition of this underlying mechanism emphasises the importance of PD-specific rehabilitation strategies to alleviate gait disability. BioMed Central 2023-03-26 /pmc/articles/PMC10040128/ /pubmed/36967402 http://dx.doi.org/10.1186/s40035-023-00347-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Tosserams, Anouk Bloem, Bastiaan R. Ehgoetz Martens, Kaylena A. Helmich, Rick C. Kessels, Roy P. C. Shine, James M. Taylor, Natasha L. Wainstein, Gabriel Lewis, Simon J. G. Nonnekes, Jorik Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword |
title | Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword |
title_full | Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword |
title_fullStr | Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword |
title_full_unstemmed | Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword |
title_short | Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword |
title_sort | modulating arousal to overcome gait impairments in parkinson’s disease: how the noradrenergic system may act as a double-edged sword |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040128/ https://www.ncbi.nlm.nih.gov/pubmed/36967402 http://dx.doi.org/10.1186/s40035-023-00347-z |
work_keys_str_mv | AT tosseramsanouk modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT bloembastiaanr modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT ehgoetzmartenskaylenaa modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT helmichrickc modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT kesselsroypc modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT shinejamesm modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT taylornatashal modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT wainsteingabriel modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT lewissimonjg modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword AT nonnekesjorik modulatingarousaltoovercomegaitimpairmentsinparkinsonsdiseasehowthenoradrenergicsystemmayactasadoubleedgedsword |