The neurobiological basis of bias and disengagement;
Two neurotransmitter mechanisms implicated in visual spatial attention.

For the development of beter 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, 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 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.

Two drugs, Clonidine and Mecamylamine are used to selectively inhibit activity
in respectively the noradrenergic or the cholinergic system. In line with the
new model, it is expected that noradrenergic inhibition, in contrast to
cholinergic inhibition, results in a decrease in bias. Likewise it is expected
that cholinergic inhibition, but not noradrenergic inhibition, results in an
impairment of disengagement.

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, clonidine, mecamylamine) and of the
computertasks (Visual Spatial Cuing task and Stop task) are counterbalanced
across participants.

Two pilots are envisaged, one pilot is aimed on veryfing the ERPs in the
computertasks, the other pilot's aim is to estimate the least sufficient dose
for mecamylamine to render an effect in our paradigm.

Clonidine results in less noradrenaline turnover and in effect inhibits the
noradrenergic system.
Mecamylamine is a nicotinic acetylcholine receptor antagonist and hence,
inhibits the cholinergic system.

Each participants receives all conditions, 1x mecamylamine, 1x clonidine, and
1x placebo, spread across three days.

Participants receive three conditions, each lasting 300 minutes, and in two of
these conditions a drug is administered. Side effects of the drugs may occur.
Although these side effects seem trivial, especially clonidine may cause a
sensation of sedation, fatigue and a dry mouth. Participants will be
extensively informed about possible adverse effects.
Risks are thought to be minimal, no serious adverse events have been reported
and furthermore, all research with medication will be done at the UMCU. The
experiments are relatively long (300 min for eacht condition), and participants
have to perform a rather monotonous task. At the start of the experiment,
participants will be informed (again) that
they may withdraw at any time from the experiment.