Cholinergic modulation of auditory processing, sensory gating and novelty detection in human participants.
BACKGROUND
Suppression of redundant auditory information and facilitation of deviant, novel, or salient sounds can be assessed with paired-click and oddball tasks, respectively. Electrophysiological correlates of perturbed auditory processing found in these paradigms are likely to be a trait marker or candidate endophenotype for schizophrenia.


OBJECTIVE
This is the first study to investigate the effects of the muscarinic M1 antagonist biperiden and the cholinesterase inhibitor rivastigmine on auditory-evoked potentials (AEPs), sensory gating, and mismatch negativity (MMN) in young, healthy volunteers.


RESULTS
Biperiden increased P50 amplitude and prolonged N100 and P200 latency in the paired-click task but did not affect sensory gating. Rivastigmine was able to reverse the effects of biperiden on N100 and P200 latency. Biperiden increased P50 latency in the novelty oddball task, which was reversed by concurrent administration of rivastigmine. Rivastigmine shortened N100 latency and enhanced P3a amplitude in the novelty oddball paradigm, both of which were reversed by biperiden.


CONCLUSIONS
The muscarinic M1 receptor appears to be involved in preattentive processing of auditory information in the paired-click task. Additional effects of biperiden versus rivastigmine were reversed by a combination treatment, which renders attribution of these findings to muscarinic M1 versus muscarinic M2-M5 or nicotinic receptors much more difficult. It remains to be seen whether the effects of cholinergic drugs on AEPs are specifically related to the abnormalities found in schizophrenia. Alternatively, aberrant auditory processing could also be indicative of a general disturbance in neural functioning shared by several neuropsychiatric disorders and/or neurodegenerative changes seen in aging.
Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. i.klinkenberg@alumni.maastrichtuniversity.nl
Inge
I
Klinkenberg
Arjan
A
Blokland
Wim J
WJ
Riedel
Anke
A
Sambeth
D000161:Acoustic Stimulation / Q000379:methods*; D000293:Adolescent; D000328:Adult; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology*; D001712:Biperiden / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D048448:Phenylcarbamates / Q000494:pharmacology; D000068836:Rivastigmine; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D048448:Phenylcarbamates; D001712:Biperiden; D000068836:Rivastigmine