The pharmacology of visuospatial attention and inhibition

Abstract

Attention and inhibition are of vital importance in everyday functioning. Problems of attention and inhibition are central to disorders such as Attention Deficit/Hyperactivity Disorder (ADHD). Both bias and disengagement key components of visuospatial attention. Bias refers to neuronal signals that modulate the sensitivity of the sensory cortex. Disengagement refers to the decoupling of attention, in case of a (relevant) stimulus occurring at an unattended location. Inhibitory functioning is conceptually tightly linked to disengagement related processing. Although implicated in mechanisms of attention and inhibition, the roles of noradrenergic, cholinergic, and dopaminergic neurotransmission are still unclear. This is an important issue to resolve. For example, in ADHD, methylphenidate, which affects both noradrenaline and dopamine, is a standard pharmacological treatment. However, in a significant number of patients, the balance between clinical effect and side effects is suboptimal. More knowledge pertaining to how these different neurotransmitter systems relate to mechanisms of bias, disengagement and inhibition may fuel more optimal treatment. The aim of the current project was to elucidate the roles of the noradrenergic, cholinergic, and dopaminergic neurotransmitter systems in bias, disengagement and inhibition. Brain activity indices pertaining to these mechanisms were assessed using the visuospatial cueing (VSC) task (to assess bias and disengagement) and stop signal task (SST; to assess inhibition) in combination with EEG. The noradrenergic, cholinergic and dopaminergic systems were manipulated by respectively, clonidine, nicotine and haloperidol (in separate studies), and the effect of these manipulations was assessed on brain activity indices of bias, disengagement and inhibition. Results showed that 1) noradrenergic attenuation by clonidine resulted in attenuation of the result of bias (the biasing signals themselves were unaffected), attenuation of disengagement related activity, and a reduction of inhibitory related activity; 2) facilitation of cholinergic neurotransmission by nicotine resulted in a reduction of the result of bias, and enhancement of inhibitory processing; 3) lastly, preliminary performance data suggest that attenuation of dopaminergic neurotransmission by haloperidol may reduce bias related processing, without affecting inhibitory related processing