THE NEURAL CORRELATES OF THE NORADRENERGIC MODULATION OF HUMAN ATTENTION, AROUSAL AND LEARNING

The prefrontal cortex has been suggested as a site of action for the n oradrenergic modulation of cognition. In healthy volunteers attentiona l deficits can be induced by the alpha 2 adrenoceptor agonist clonidin e, without impairment of more explicit tests of frontal lobe function. It is therefore possible that the effects of noradrenaline cannot be localized to a specific brain area such as the prefrontal cortex, but instead involve structures in a more widespread attentional network. A 1.5 mu g/kg dose of clonidine or placebo was administered to 13 healt hy male volunteers performing the rapid visual information processing task, which places demands on both sustained attention and working mem ory. Twelve positron emission tomography measurements of regional cere bral blood flow (rCBF) were collected during performance of this task and also during a rest state. A second experiment in 12 healthy volunt eers examined the effects of a 1.3 mu g/kg dose of clonidine on the rC BF changes associated with performance of a paired associates learning task compared with passive listening to word pairs. Comparison of eac h of the experimental tasks with its respective control replicated pre vious findings. A significant drug x task interaction, common to the t wo studies, was found in the right thalamus, Inspection of the adjuste d rCBF values showed that the effect was due to attenuation of thalami c rCBF during the control states rather than to any effects of clonidi ne during performance of the cognitive tasks, although the effect was stronger in the rapid visual information processing study than in the paired associates learning study, The significant effect of clonidine during the control as opposed to the 'cognitive' activation state is c onsistent with previous findings in animals and humans demonstrating g reater effects of clonidine during states of relatively low arousal. T he results suggest neuroanatomical dissociation of the noradrenergic m odulation of arousal (via the thalamus) and attention.