Cerebral Cortex Advance Access published online on August 17, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp144
Noradrenergic Modulation of Cortical Networks Engaged in Visuomotor Processing
1 Neuromodulation & Neurorehabilitation, Max Planck Institute for Neurological Research, 50931 Cologne, Germany, 2 Department of Neurology, University Hospital Cologne, 50924 Cologne, Germany, 3 Institute of Neurosciences and Medicine—Cognitive Neurology (INM3), Research Centre Jülich, 52425 Jülich, Germany, 4 International Graduate School of Neuroscience, Ruhr-Universität Bochum, 44801 Bochum, Germany, 5 Department of Psychiatry and Psychotherapy, RWTH Aachen University, 52074 Aachen, Germany
Address correspondence to Christian Grefkes, MD, Neuromodulation & Neurorehabilitation, Max-Planck-Institute for Neurological Research, Gleueler Str. 50, 50931 Köln, Germany. Email: christian.grefkes{at}uk-koeln.de.
Both animal and human data suggest that stimulation of the noradrenergic system may influence neuronal excitability in regions engaged in sensory processing and visuospatial attention. We tested the hypothesis that the neural mechanisms subserving motor performance in tasks relying on the visuomotor control of goal-directed hand movements might be modulated by noradrenergic influences. Healthy subjects were stimulated using the selective noradrenaline reuptake inhibitor reboxetine (RBX) in a placebo-controlled crossover design. Functional magnetic resonance imaging and dynamic causal modeling (DCM) were used to assess drug-related changes in blood oxygen level–dependent activity and interregional connectivity while subjects performed a joystick task requiring goal-directed movements. Improved task performance under RBX was associated with increased activity in right visual, intraparietal and superior frontal cortex (premotor/frontal eye field). DCM revealed that the neuronal coupling among these regions was significantly enhanced when subjects were stimulated with RBX. Concurrently, right intraparietal cortex and right superior frontal cortex exerted a stronger driving influence on visuomotor areas of the left hemisphere, including SMA and M1. These effects were independent from task difficulty. The data suggest that stimulating noradrenergic mechanisms may rearrange the functional network architecture within and across the hemispheres, for example, by synaptic gating, thereby optimizing motor behavior.
Key Words: effective connectivity • noradrenaline • parietofrontal circuits • pharmacological fMRI • visuomotor control
Received for publication April 21, 2009. Revision received June 2, 2009. Accepted for publication June 17, 2009.