Objective markers of drug effects on brain function from recordings of scalp potential in healthy volunteers

In order to stress the importance of P300 responses in drug development, we describe the spatiotemporal characteristics of this objective, evoked event-related potential. These brain activations reflect mnemonic function, in which limbic structures play a role. It is demonstrated that a pharmacological challenge concerning, for example, the cholinergic system in young healthy volunteers induces modifications in P300 reminiscent of the aging brain. We use this type of observation to build a model in which it can be verified whether the deterioration can be counteracted by treatment with “cognition-enhancing” drugs. If we accept the extrapolation of the pharmacological effects to symptomatology, scalp potential analysis offers an appropriate tool for the study of drug interactions in early proof-of-concept models.