Noradrenergically Mediated Plasticity in a Human Attentional Neuronal Network

Noradrenaline is implicated in the modulation of attention and arousal, but the neuroanatomical basis of this effect in humans is unknown. A previous functional neuroimaging study failed to find clear effects of clonidine (alpha2 adrenoceptor agonist) on activity of brain regions implicated in attention. Therefore, we now investigate whether clonidine affects the functional integration of a neuroanatomical attentional network, by modulating connectivity between brain regions rather than activity within discrete regions. Following infusion of either clonidine or placebo, positron emission tomography measurements of brain activity were collected in 13 normal subjects while they were either resting or performing an attentional task. Effective connectivity analysis showed that during rest, clonidine decreased the functional strength of connections both from frontal cortex to thalamus and in pathways to and from visual cortex. Conversely, during the attentional task, functional integration generally increased, with changes being centered on parietal cortex (increased connectivity from locus coeruleus to parietal cortex and from parietal cortex to thalamus and frontal cortex). A drug-induced increase in the modulatory effects of frontal cortex on projections from locus coeruleus to parietal cortex was also observed. Collectively, these results highlight cognitively dissociable effects of clonidine on interactions among functionally integrated brain regions and implicate the noradrenergic system in mediating the functional integration of attentional brain systems. The context-sensitive nature of the changes are consistent with observations that noradrenergic drugs have differential effects on brain processes depending on subjects' underlying arousal levels. More generally, the results illustrate the dynamic plasticity of cognitive brain systems following neurochemical challenge.