Human electrophysiological correlates of learned irrelevance: effects of the muscarinic M1 antagonist biperiden

Int J Neuropsychopharmacol. 2012 Nov;15(10):1375-85. doi: 10.1017/S1461145711001647. Epub 2011 Nov 18.


Learned irrelevance (LIrr) refers to a reduction in associative learning after pre-exposure of the conditioned and unconditioned stimulus in a non-contingent fashion. This paradigm might serve as a translational model for (pre)attentive information processing deficits in schizophrenia. This is the first study to investigate the event-related potentials (ERPs) of a within-subject LIrr paradigm in humans. Furthermore, the effects of the muscarinic M1 antagonist biperiden on LIrr were assessed. As expected, LIrr was found to be intact in young healthy volunteers after placebo. Furthermore, in the placebo condition P3b latency was decreased for target stimuli, which were pre-cued. This suggests that the predictability of the occurrence of these stimuli is mainly reflected by this ERP component. Biperiden had no effect on the behavioural LIrr measures, although prolonged reaction times were evident. Biperiden increased the N1 amplitude of the pre-exposed predictor letters, suggesting an effect of this drug on early perceptual processing. In conclusion, the within-subject paradigm used in the current study in combination with electroencephalography can reveal brain mechanisms involved in LIrr. M1 antagonism did not affect LIrr performance but seemed to influence early information processing.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Biperiden / pharmacology
  • Biperiden / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography / methods
  • Electrophysiological Phenomena / drug effects
  • Electrophysiological Phenomena / physiology
  • Evoked Potentials / drug effects*
  • Evoked Potentials / physiology
  • Female
  • Humans
  • Learning / drug effects*
  • Learning / physiology
  • Male
  • Muscarinic Antagonists / pharmacology
  • Muscarinic Antagonists / therapeutic use*
  • Photic Stimulation / methods
  • Reaction Time / drug effects*
  • Reaction Time / physiology
  • Receptor, Muscarinic M1 / antagonists & inhibitors*
  • Receptor, Muscarinic M1 / physiology
  • Young Adult


  • Muscarinic Antagonists
  • Receptor, Muscarinic M1
  • Biperiden