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Modulating arousal to overcome gait impairments in Parkinson’s disease:how the noradrenergic system may act as a double-edged sword

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Translational Neurodegeneration 2023年第1期12卷 666-676页

作者： Anouk Tosserams Bastiaan R.Bloem kaylena a.ehgoetz martens Rick C.Helmich Roy P.C.Kessels James M.Shine Natasha L.Taylor Gabriel Wainstein Simon J.G.Lewis Jorik Nonnekes Department of Neurology Center of Expertise for Parkinson and Movement DisordersRadboud University Medical CentreDonders Institute for BrainCognition and BehaviourNijmegenThe Netherlands Department of Rehabilitation Center of Expertise for Parkinson and Movement DisordersRadboud University Medical CentreDonders Institute for BrainCognition and BehaviourPO Box 91016500 HB NijmegenThe Netherlands Department of Kinesiology and Health Sciences University of WaterlooWaterlooONCanada Department of Neuropsychology and Rehabilitation Psychology Donders Institute for BrainCognition and BehaviourRadboud UniversityNijmegenThe Netherlands Department of Medical Psychology and Radboudumc Alzheimer Center Radboud University Medical CentreDonders Institute for BrainCognition and BehaviourNijmegenThe Netherlands Vincent Van Gogh Institute for Psychiatry VenrayThe Netherlands Klimmendaal Rehabili-tation Center ArnhemThe Netherlands Brain and Mind Centre Parkinson’s Disease Research ClinicSchool of Medical SciencesUniversity of SydneyCamperdownNSWAustralia Centre for Complex Systems The University of SydneyCamperdownNSWAustralia Department of Rehabilitation Sint MaartenskliniekNijmegenThe Netherlands.

In stressful or anxiety-provoking situations,most people with Parkinson’s disease(PD)experience a general worsening of motor symptoms,including their gait ***,a proportion of patients actually report benefits from experiencing-or even purposely inducing-stressful or high-arousal *** 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 ***,these strategies differ along an axis of arousal-some act to heighten,whereas others diminish,overall sympathetic ***,our observations suggest that arousal may act as a double-edged sword for gait control in *** 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 ***,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 *** 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 *** the presence of suboptimal arousal,compensatory networks may be too segregated to allow for adequate ***,with supraoptimal arousal,increased cross-talk between competing inputs of these complementary networks may emerge and become dysf

关键词： Arousal Gait Parkinson’s disease Freezing of gait Locus coeruleus

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