Neural correlates of improved motor function following noradrenergic stimulation in stroke patients
Introduction
Evidence from studies in both animals and humans suggests that stimulation of the noradrenergic system may enhance motor recovery after brain damage by changing the excitability of the cerebral cortex. In the present study, we tested the hypothesis that stimulating the noradrenergic system by means of reboxetine (RBX), a selective noradrenaline reuptake inhibitor, may modulate the neural networks driving motor function in stroke patients with motor deficits. A double-blind, placebo-controlled within-subject design with drug-naive stroke patients was applied.
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Methods
12 chronic stroke patients with unilateral motor deficits received either a single dose of 6 mg RBX or placebo (PBO) on two testing days separated by one week. For behavioral testing, we used four motor tasks with different complexity: (i) the action research arm test, (ii) hand grip strength, (iii) index finger tapping and (iv) rapid horizontal pointing movements. Movements were analyzed using an ultrasound-based 3-D motion system (Zebris CMS 20). For fMRI, we employed an index finger tapping
Results
Data analysis of the behavioral results revealed improvements in maximum grip power and finger tapping frequency of the affected, but not of the unaffected hand (P <0.05). The fMRI results displayed pathological overactivity in related motor areas when patients moved the index finger of the affected hand (PBO ∩ RBX, P <0.05, FWE corrected, SPM5). Regions of interest analyses (ROI, Fig. 1) revealed that under reboxetine neural overactivity was significantly reduced in the ipsilesional ventral
Conclusions
Noradrenergic stimulation by RBX mediates a complex rearrangement in the network architecture of the motor system in patients suffering from stroke-induced motor deficits. Pathological overactivity in key motor areas observed under PBO was significantly reduced when subjects were stimulated with RBX. The connectivity analyses imply that the disinhibition of contralesional M1 might constitute the neural basis for improved motor performance observed for RBX. In conclusion, our results suggest