The neurobiological basis of bias;
A mechanism implicated in visual spatial attention.

For the development of better pharmacological treatment of various pathologies
in which attention and impulsivity
are implicated, such as ADHD, it is crucial to gain knowledge about the
neurobiological basis.
Two neurobiological mechanisms are implicated in visuospatial attention, bias
and disengagement. bias refers to
increased sensory information processing due to the orientation of attention.
Disengagement refers to the
interruption of that attentional set, making processing of non attended stimuli
possible. The dominant theory
posits that bias rests on cholinergic functioning and disengagement depends on
noradrenergic functioning.
Results of pharmacological research are inconsistent and suggest the opposite.
In this research, the noradrenergic part of an alternative model which states
the opposite of the dominant model but accounts beter for pharmacological
results is
proposed and evaluated.

The goal of the current investigation is to test the noradrenergic part of a
new model that accounts better for results of pharmacological research. This
model states that the cholinergic system underlies disengagement, and that the
noradrenergic
system underlies bias. Two assumptions are made in this model: 1) Two opposing
mechanisms underlie bias and
disengagement, 2) Sedators impair but do not enhance these mechanisms, and
stimulants do the exact opposite.
Clonidine will be used to selectively inhibit activity in the noradrenergic
system. In line with the new model, it is expected that noradrenergic
inhibition specifically results in a decrease in bias. In this research,
explicit reference to brainactivity indices is made which is necessary since
disengagement and biasmechanisms are not dissociable in only behavior measures.

A double blind placebocontrolled, crossover design will be incorporated in
which the order of the conditions
(placebo and clonidine) and of the computertasks (Visual Spatial Cuing task and
Stop task) are
counterbalanced across participants.

A pilot is envisaged, this pilot is aimed on veryfing the ERPs in the
computertasks. If unexpected
results are found in the pilot, the experiment is either ceased or an addendum
of the protocol will be
submitted to the METC before the experiment is continued.

For the medication study an interim analysis is planned after 6 participants
completed both sessions.
The effect size will be calculated pertaining to the effect of 100 microgram
Clonidine on the dependent electrophysiological variables.
We continue the experiment with the 100 microgram dose if the effect of
Clonidine on at least one electrophysiological variable results in a power
above 80% with alpha set at 0.05. If the interim analysis suggests the sample
size must be increased, we submit another amendment.

Clonidine results in less noradrenaline turnover and in effect inhibits the
noradrenergic system.
Each participants receives all conditions, 1x clonidine, and 1x placebo, spread
across two days.

Participants will perform in a relatively long experiment. For the
medicationstudy, the experiment consists of two sessions each lasting about 5.5
hour + 1 hour medical screening. During these sessions, participants perform on
two short and two long computer tasks.
EEG will be recorded during the long computertasks. The duration of the short
computer tasks is in total approximately 30 minutes whereas the duration of the
long computer tasks is in total approximately 2 hours including short breaks.
After the short computer tasks, Clonidine or placebo will be adminstered. No
serious adverse events have been reported following 200 microgram Clonidine.
However, our researchgroup experienced that side effects, plausibly in
combination with the specific procedures, have resulted in a significant burden
for participants. As a result, 100 microgram Clonidine will be administered to
participants as significantly less side effects are expected with half of the
original dose. The medicationstudy will take place in the UMC Utrecht. At the
start of the experiment, participants will be informed (again) that they may
withdraw at any time from the experiment.