Jt. Coull et al., THE NEURAL CORRELATES OF THE NORADRENERGIC MODULATION OF HUMAN ATTENTION, AROUSAL AND LEARNING, European journal of neuroscience, 9(3), 1997, pp. 589-598
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.