title: Free energy, precision and learning: the role of cholinergic neuromodulation.
abstract: 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.
authors: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom. rosalynj@vtc.vt.edu
authors: Rosalyn J
authors: RJ
authors: Moran
authors: Pablo
authors: P
authors: Campo
authors: Mkael
authors: M
authors: Symmonds
authors: Klaas E
authors: KE
authors: Stephan
authors: Raymond J
authors: RJ
authors: Dolan
authors: Karl J
authors: KJ
authors: Friston
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003198:Computer Simulation; D004311:Double-Blind Method; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D005260:Female; D005702:Galantamine / Q000494:pharmacology; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009483:Neuropsychological Tests; D010465:Perception / Q000187:drug effects / Q000502:physiology*; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D005702:Galantamine; D000109:Acetylcholine
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