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 (al pha 2 adrenoceptor agonist) on activity of brain regions implicated in atte ntion. Therefore, we now investigate whether clonidine affects the function al integration of a neuroanatomical attentional network, by modulating conn ectivity between brain regions rather than activity within discrete regions . Following infusion of either clonidine or placebo, positron emission tomo graphy 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 fun ctional strength of connections both from frontal cortex to thalamus and in pathways to and from visual cortex. Conversely, during the attentional tas k, 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-in duced increase in the modulatory effects of frontal cortex on projections f rom locus coeruleus to parietal cortex was also observed. Collectively, the se results highlight cognitively dissociable effects of clonidine on intera ctions among functionally integrated brain regions and implicate the noradr energic system in mediating the functional integration of attentional brain systems. The context-sensitive nature of the changes are consistent with o bservations that noradrenergic drugs have differential effects on brain pro cesses depending on subjects' underlying arousal levels. More generally, th e results illustrate the dynamic plasticity of cognitive brain systems foll owing neurochemical challenge. (C) 1999 Academic Press.