Free energy, precision and learning: the role of cholinergic neuromodulation

Rosalyn J Moran, Pablo Campo, Mkael Symmonds, Klaas E Stephan, Raymond J Dolan, Karl J Friston

Research output: Contribution to journalArticle (Academic Journal)peer-review

139 Citations (Scopus)


Acetylcholine (ACh) is a neuromodulatory transmitter implicated in perception and learning under uncertainty. This study combined computational simulations and pharmaco-electroencephalography in humans, to test a formulation of perceptual inference based upon the free energy principle. This formulation suggests that ACh enhances the precision of bottom-up synaptic transmission in cortical hierarchies by optimizing the gain of supragranular pyramidal cells. Simulations of a mismatch negativity paradigm predicted a rapid trial-by-trial suppression of evoked sensory prediction error (PE) responses that is attenuated by cholinergic neuromodulation. We confirmed this prediction empirically with a placebo-controlled study of cholinesterase inhibition. Furthermore, using dynamic causal modeling, we found that drug-induced differences in PE responses could be explained by gain modulation in supragranular pyramidal cells in primary sensory cortex. This suggests that ACh adaptively enhances sensory precision by boosting bottom-up signaling when stimuli are predictable, enabling the brain to respond optimally under different levels of environmental uncertainty.

Original languageEnglish
Pages (from-to)8227-36
Number of pages10
JournalJournal of Neuroscience
Issue number19
Publication statusPublished - 8 May 2013


  • Acetylcholine
  • Acoustic Stimulation
  • Adolescent
  • Adult
  • Algorithms
  • Brain
  • Brain Mapping
  • Cholinesterase Inhibitors
  • Computer Simulation
  • Double-Blind Method
  • Electroencephalography
  • Evoked Potentials, Auditory
  • Female
  • Galantamine
  • Humans
  • Learning
  • Male
  • Models, Neurological
  • Neuropsychological Tests
  • Perception
  • Predictive Value of Tests
  • Young Adult


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