Human and monkey P3-like responses in a mixed modality paradigm: effects of context and context-dependent noradrenergic influences.

Previous studies in non-human primates have reported that noradrenergic agents, such as the alpha 2 agonist clonidine, affect auditory but not visual P3 responses. One explanation for these effects may be that distinct modalities are differentially susceptible to noradrenergic influences--a modality-dependent effect. Another possibility is that noradrenergic effects are modality-independent but context-dependent. Two separate experiments, in humans and monkeys, examined the role of stimulus modality, context and noradrenergic activity in an attempt to elucidate the nature of the relationship between P3 and the action of this catecholamine neurotransmitter. In Experiment 1, human subjects were exposed to two versions of a mixed modality oddball paradigm. In one version, the context or background activity was auditory, while in the other it was visual. In both versions of the paradigm, the same auditory and visual rare targets occurred. The results indicated that N2 and P3 to visual targets were more sensitive to changes in context than those to auditory targets. In both cases, N2 and P3 amplitudes to targets were enhanced when the eliciting event and context differed. A modality-specific N2b, on the other hand, was enhanced when the context matched the modality of the eliciting event. In Experiment 2, monkeys received systemic injections of a saline placebo or one of three doses of the adrenergic antagonist L657,743 prior to presentation of a mixed modality oddball paradigm in a visual context. Drug effects were observed on earlier components such as N1, P2 and N2 but not on later P3-like responses. The combined findings complement previous ones from our laboratory and suggest that P3 reflects context-dependent processes and specifically context-dependent, not modality-specific, noradrenergic activity.