PT  - JOURNAL ARTICLE
AU  - Rosalyn J. Moran
AU  - Pablo Campo
AU  - Mkael Symmonds
AU  - Klaas E. Stephan
AU  - Raymond J. Dolan
AU  - Karl J. Friston
TI  - Free Energy, Precision and Learning: The Role of Cholinergic Neuromodulation
AID  - 10.1523/JNEUROSCI.4255-12.2013
DP  - 2013 May 08
TA  - The Journal of Neuroscience
PG  - 8227--8236
VI  - 33
IP  - 19
4099  - http://www.jneurosci.org/content/33/19/8227.short
4100  - http://www.jneurosci.org/content/33/19/8227.full
SO  - J. Neurosci.2013 May 08; 33
AB  - 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.