TY  - JOUR
AU  - Wang, L.E.
AU  - Fink, G. R.
AU  - Diekhoff, S.
AU  - Rehmke, A.K.
AU  - Eickhoff, S. B.
AU  - Grefkes, C.
TI  - Noradrenergic enhancement improves motor network connectivity in stroke patients
JO  - Annals of neurology
VL  - 69
SN  - 0364-5134
CY  - Hoboken, NJ
PB  - Wiley-Blackwell
M1  - PreJuSER-12585
SP  - 375 - 388
PY  - 2011
N1  - 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.).
AB  - 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.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.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.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.
KW  - Adrenergic Uptake Inhibitors: therapeutic use
KW  - Adult
KW  - Aged
KW  - Cross-Over Studies
KW  - Double-Blind Method
KW  - Hand Strength: physiology
KW  - Humans
KW  - Magnetic Resonance Imaging
KW  - Male
KW  - Middle Aged
KW  - Morpholines: therapeutic use
KW  - Motor Cortex: drug effects
KW  - Motor Cortex: physiopathology
KW  - Paresis: drug therapy
KW  - Paresis: etiology
KW  - Paresis: physiopathology
KW  - Psychomotor Performance: drug effects
KW  - Recovery of Function: drug effects
KW  - Stroke: complications
KW  - Stroke: drug therapy
KW  - Stroke: physiopathology
KW  - Adrenergic Uptake Inhibitors (NLM Chemicals)
KW  - Morpholines (NLM Chemicals)
KW  - reboxetine (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21387380
UR  - <Go to ISI:>//WOS:000288284900020
DO  - DOI:10.1002/ana.22237
UR  - https://juser.fz-juelich.de/record/12585
ER  -