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

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 

作者机构：Department of NeurologyCenter of Expertise for Parkinson and Movement DisordersRadboud University Medical CentreDonders Institute for BrainCognition and BehaviourNijmegenThe Netherlands Department of RehabilitationCenter 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 SciencesUniversity of WaterlooWaterlooONCanada Department of Neuropsychology and Rehabilitation PsychologyDonders Institute for BrainCognition and BehaviourRadboud UniversityNijmegenThe Netherlands Department of Medical Psychology and Radboudumc Alzheimer CenterRadboud University Medical CentreDonders Institute for BrainCognition and BehaviourNijmegenThe Netherlands Vincent Van Gogh Institute for PsychiatryVenrayThe Netherlands Klimmendaal Rehabili-tation CenterArnhemThe Netherlands Brain and Mind CentreParkinson’s Disease Research ClinicSchool of Medical SciencesUniversity of SydneyCamperdownNSWAustralia Centre for Complex SystemsThe University of SydneyCamperdownNSWAustralia Department of RehabilitationSint MaartenskliniekNijmegenThe Netherlands. 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2023年第12卷第1期

页      面：666-676页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by an Academy Van Leersum grant of the Academy Medical Sciences Fund,Royal Netherlands Academy of Arts&Sciences supported by a Parkinson Canada New Investigator grant,as well as a Natural Sciences and Engineering Research Council of Canada Discovery grant.RCH was supported by a research grant(VIDI,#09150172010044)from the Netherlands Organization for Scientific Research He has acted as consultant for UCB(unrelated to this work) supported by a grant from the European Regional Development Fund(ERDF/EFRO,grant number PROJ-00928)outside the submitted work supported by the National Health and Medical Research Council(1193857) supported by the Australian Government Research Training Program(RTP)Scholarship.GW reports no disclosures.SJGL was supported by a National Health and Medical Research Council Leadership Fellowship(1195830) supported by a ZonMW Veni grant(16.196.022) 

主　　题：Arousal Gait Parkinson’s disease Freezing of gait Locus coeruleus 

摘      要：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