Noradrenergic and cholinergic modulation of late ERP responses to deviant stimuli.
Researchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo-controlled crossover study in which we investigated how the late positive ERP response to deviant stimuli is modulated by (a) clonidine, an α2 agonist that attenuates baseline noradrenergic activity; and (b) scopolamine, a muscarinic antagonist of acetylcholine receptors. We collected EEG data from 18 healthy volunteers during the performance of an auditory oddball task with several active and passive task conditions. We then used temporospatial principal component analysis (PCA) to decompose the ERP waveforms. The PCA revealed two distinct late positive ERP components: the classic parietal P300 and the frontal novelty P3. Statistical analysis of the temporospatial factor scores indicated that in most conditions the amplitude of the classic P300 was increased by clonidine and scopolamine. In contrast, the amplitude of the novelty P3 was decreased by both drugs. The similar pattern of results for clonidine and scopolamine probably reflects the strong interactions between the noradrenergic and cholinergic systems. The results, in combination with previous pharmacological studies, suggest a critical role for both neuromodulator systems in the generation of the P300 and the novelty P3.
Cognitive Psychology Unit, Institute of Psychology, Leiden University, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
Stephen B R E
SB
Brown
Leiden Institute for Brain and Cognition, Leiden, The Netherlands.|Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Nic J A
NJ
van der Wee
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Martijn S
MS
van Noorden
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Erik J
EJ
Giltay
Cognitive Psychology Unit, Institute of Psychology, Leiden University, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
Sander
S
Nieuwenhuis
D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D025341:Principal Component Analysis; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D055815:Young Adult
D058647:Adrenergic alpha-2 Receptor Agonists; D018680:Cholinergic Antagonists; D012601:Scopolamine; D003000:Clonidine
Cognition; EEG; Pharmacology