The Pharmacology of Attention.

For the development of better pharmacological treatment of various disorders in which attention and impulsivity are implicated, such as ADHD, it is of crucial importance to acquire more knowledge on their neurobiological basis. Two functional brain mechanisms that are implicated in visual spatial attention are bias and disengagement. Here, 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 cholinergic neurotransmission underlies bias, and disengagement rests on noradrenergic neurotransmission. However, results of pharmacological studies are inconsistent. Scrutinizing the results of pharmacological research suggests the opposite of the dominant model. Therefore a new model is proposed which specifically states that bias rests on noradrenergic neurotransmission and that disengagement rests on cholinergic neurotransmission. Since behavioral outcome reflects activity in both mechanisms, studying brain activity is crucial. Therefore, hypotheses will be tested by evaluating the effects of cholinergic and noradrenergic antagonism not only on behavioral measures, but explicitly on bias and disengagement associated functional brain indices (i.e., event-related potentials; ERPs).

In line with results from recent pharmacological studies, it is expected that:

1. Inhibiting the cholinergic system by Inversine (Mecamylamine Hydrochloride) results in an impairment of disengagement, but will not affect bias;

2. Inhibiting the noradrenergic neurotransmitter system by Clonidine will result in an impairment in Bias, but will not affect disengagement.

At approximately t=120 min. post drug ingestion, computertasks are performed and EEG is simultaneously recorded.

Pilot is a drug-free pilot aimed to verify results (ERPs / behavioral data) of previous studies, 12 participants will be included.



The final study will contrast clonidine (0.1mg) and placebo. Like the pilot, the duration of each condition is 4.5 hours. In this study, 24 participants will be included. The minimal time between conditions is one week.