TY - JOUR T1 - Free Energy, Precision and Learning: The Role of Cholinergic Neuromodulation JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8227 LP - 8236 DO - 10.1523/JNEUROSCI.4255-12.2013 VL - 33 IS - 19 AU - Rosalyn J. Moran AU - Pablo Campo AU - Mkael Symmonds AU - Klaas E. Stephan AU - Raymond J. Dolan AU - Karl J. Friston Y1 - 2013/05/08 UR - http://www.jneurosci.org/content/33/19/8227.abstract N2 - 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. ER -