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Article: Noradrenergic enhancement improves motor network connectivity in stroke patients

TitleNoradrenergic enhancement improves motor network connectivity in stroke patients
Authors
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/76507645
Citation
Annals of Neurology, 2011, v. 69 n. 2, p. 375-388 How to Cite?
AbstractOBJECTIVE: Both animal and human data suggest that noradrenergic stimulation may enhance motor performance after brain damage. We conducted a placebo-controlled, double-blind and crossover design study to investigate the effects of noradrenergic stimulation on the cortical motor system in hemiparetic stroke patients. METHODS: Stroke patients (n = 11) in the subacute or chronic stage with mild-to-moderate hand paresis received a single oral dose of 6 mg reboxetine (RBX), a selective noradrenaline reuptake inhibitor. We used functional magnetic resonance imaging and dynamic causal modeling to assess changes in neural activity and interregional effective connectivity while patients moved their paretic hand. RESULTS: RBX stimulation significantly increased maximum grip power and index finger-tapping frequency of the paretic hand. Enhanced motor performance was associated with a reduction of cortical 'hyperactivity' toward physiological levels as observed in healthy control subjects, especially in the ipsilesional ventral premotor cortex (vPMC) and supplementary motor area (SMA), but also in the temporoparietal junction and prefrontal cortex. Connectivity analyses revealed that in stroke patients neural coupling with SMA or vPMC was significantly reduced compared with healthy controls. This 'hypoconnectivity' was partially normalized when patients received RBX, especially for the coupling of ipsilesional SMA with primary motor cortex. INTERPRETATION: The data suggest that noradrenergic stimulation by RBX may help to modulate the pathologically altered motor network architecture in stroke patients, resulting in increased coupling of ipsilesional motor areas and thereby improved motor function.
Persistent Identifierhttp://hdl.handle.net/10722/139700
ISSN
2015 Impact Factor: 9.638
2015 SCImago Journal Rankings: 5.584
ISI Accession Number ID
Funding AgencyGrant Number
Human Brain ProjectR01-MH074457-01A1
Helmholtz Association
Funding Information:

This research was supported by a grant from the Human Brain Project (R01-MH074457-01A1 to S.B.E.) and the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (Human Brain Model to S.B.E.).

 

DC FieldValueLanguage
dc.contributor.authorWang, LEen_US
dc.contributor.authorFink, GRen_US
dc.contributor.authorDiekhoff, Sen_US
dc.contributor.authorRehme, AKen_US
dc.contributor.authorEickhoff, SBen_US
dc.contributor.authorGrefkes, Cen_US
dc.date.accessioned2011-09-23T05:54:30Z-
dc.date.available2011-09-23T05:54:30Z-
dc.date.issued2011en_US
dc.identifier.citationAnnals of Neurology, 2011, v. 69 n. 2, p. 375-388en_US
dc.identifier.issn0364-5134en_US
dc.identifier.urihttp://hdl.handle.net/10722/139700-
dc.description.abstractOBJECTIVE: Both animal and human data suggest that noradrenergic stimulation may enhance motor performance after brain damage. We conducted a placebo-controlled, double-blind and crossover design study to investigate the effects of noradrenergic stimulation on the cortical motor system in hemiparetic stroke patients. METHODS: Stroke patients (n = 11) in the subacute or chronic stage with mild-to-moderate hand paresis received a single oral dose of 6 mg reboxetine (RBX), a selective noradrenaline reuptake inhibitor. We used functional magnetic resonance imaging and dynamic causal modeling to assess changes in neural activity and interregional effective connectivity while patients moved their paretic hand. RESULTS: RBX stimulation significantly increased maximum grip power and index finger-tapping frequency of the paretic hand. Enhanced motor performance was associated with a reduction of cortical 'hyperactivity' toward physiological levels as observed in healthy control subjects, especially in the ipsilesional ventral premotor cortex (vPMC) and supplementary motor area (SMA), but also in the temporoparietal junction and prefrontal cortex. Connectivity analyses revealed that in stroke patients neural coupling with SMA or vPMC was significantly reduced compared with healthy controls. This 'hypoconnectivity' was partially normalized when patients received RBX, especially for the coupling of ipsilesional SMA with primary motor cortex. INTERPRETATION: The data suggest that noradrenergic stimulation by RBX may help to modulate the pathologically altered motor network architecture in stroke patients, resulting in increased coupling of ipsilesional motor areas and thereby improved motor function.-
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/76507645-
dc.relation.ispartofAnnals of Neurologyen_US
dc.rightsAnnals of Neurology. Copyright © John Wiley & Sons, Inc.-
dc.subject.meshAdrenergic Uptake Inhibitors - therapeutic use-
dc.subject.meshMorpholines - therapeutic use-
dc.subject.meshMotor Cortex - drug effects - physiopathology-
dc.subject.meshParesis - drug therapy - etiology - physiopathology-
dc.subject.meshStroke - complications - drug therapy - physiopathology-
dc.titleNoradrenergic enhancement improves motor network connectivity in stroke patientsen_US
dc.typeArticleen_US
dc.identifier.emailWang, LE: lingwang@hku.hken_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ana.22237-
dc.identifier.pmid21387380-
dc.identifier.scopuseid_2-s2.0-79952523489-
dc.identifier.hkuros194555en_US
dc.identifier.hkuros201732-
dc.identifier.volume69en_US
dc.identifier.issue2en_US
dc.identifier.spage375en_US
dc.identifier.epage388en_US
dc.identifier.isiWOS:000288284900020-
dc.publisher.placeUnited States-

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