model of cognitive enhancement would be ofbenefit as a screening tool in the search for new thera-pies for cognitive disorders such as Alzheimer’s
disease.This article provides arguments in favor of neurophysi-ological assessments during performance in psychomet-ric tests to fulfil such aims. The first part concerns
thebasic characterization of event-related potentials (ERPs)and, in particular, the generators of the cognitiveresponse called P300, in terms of temporal and spatialproperties. Next, we investigate the effects
of both non-cholinergic and cholinergic drugs and their interactionin healthy young male and elderly subjects using theextracted ERP parameter as readout.Temporal and spatial characterization of cognitive responsesERPs are transient modifications in electromagneticbrain signals, which are time-locked to cognitive, motor,or sensory processing.They represent activity directly
atthe level of neuronal networks and hence form a goodmethod for studying the working brain and obtainingneurophysiological indices of attentional mechanismsand cognitive function. In so-called “oddball” paradigms,in which a subject is instructed to count the number
oftarget stimuli, a positive scalp potential with
a maximumamplitude of around 300 ms is recorded and is referredto as P300 (Figure 1). Before
the emergence of this typeof activation, the brain signals display a sequence
ofcomponents related to consecutive steps of informationprocessing in the central nervous system (CNS), likeencoding of stimulus, orienting reaction, etc.These
occurin certain time-windows during normal functioning, andthe term chronometry is often used. Hence, such
elec-trical responses from the scalp are relevant because
theyare the result of a coordinated synchronization in dis-tributed neuronal populations. Topographic analysis3 8 8C l i n i c a l r e s e a r c hIn order to stress the importance
of P300 responses indrug development, we describe the
spatiotemporal char-acteristics of this objective, evoked
event-related poten-tial. These brain activations reflect
mnemonic function, inwhich limbic structures play a role.
It is demonstrated thata pharmacological challenge concerning,
for example, thecholinergic system in young healthy
volunteers inducesmodifications in P300 reminiscent
of the aging brain. Weuse this type of observation to build
a model in which itcan be verified whether the deterioration
can be coun-teracted by treatment with “cognition-enhancing” drugs.If we accept the extrapolation of
the pharmacologicaleffects to symptomatology, scalp potential
analysis offersan appropriate tool for the study
of drug interactions inearly proof-of-concept models.Dialogues Clin Neurosci.
2002;4:388-394.Objective markers of drug effects
on brainfunction from recordings of scalp
potential in healthy volunteersPeter H. Boeijinga, PhDKeywords: limbic
activation; event-related response; P300; cognition; neuropsychopharmacology;
acetylcholine esterase
inhibitor; noncholinergic agentAuthor affiliations: Head of MEG and Clinical EEG Explorations, FORENAP, Institute
for Research in Neuroscience
and Neuropsychiatry, Rouffach, FranceAddress for correspondence: FORENAP,
Institute for Research in Neuroscience and Neuropsychiatry,
BP29, 68250 Rouffach, France.
(e-mail: peter.boeijinga@forenap.asso.fr)A
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