Effects of cholinergic enhancement on conditioning‐related responses in human auditory cortex

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Abstract
It has previously been shown that cholinergic blockade attenuates conditioning‐related neuronal responses in human auditory cortex. The present study was conducted to investigate the effect of cholinergic enhancement on such experience‐dependent cortical responses. The cholinesterase inhibitor physostigmine, or a placebo control, were continuously infused into healthy young volunteers, during differential aversive conditioning whilst brain activity was measured using event‐related functional magnetic resonance imaging (fMRI). Volunteers were presented with two tones, one of which (CS+) was conditioned by pairing with an electrical shock whereas the other was always presented without the shock (CS–). Conditioning‐related activations, expressed as an enhanced blood oxygenation level dependent (BOLD) response to the salient CS+, were evident in left auditory cortex under placebo but not under physostigmine. This absence of conditioning‐related activations under physostigmine was due to enhanced responses to the CS– under physostigmine as compared to placebo. We suggest that an overactive cholinergic system leads to increased processing of behaviourally irrelevant stimuli and thus attenuates differential conditioning‐related cortical activations.