title: Effects of cholinergic enhancement on conditioning-related responses in human auditory cortex.
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.
authors.affiliation: Wellcome Department of Imaging Neuroscience, Institute of Neurology, 12 Queen Square, London, WC1 3BG, UK. c.thiel@fz-juelich.de
authors.forename: C M
authors.initials: CM
authors.lastname: Thiel
authors.forename: P
authors.initials: P
authors.lastname: Bentley
authors.forename: R J
authors.initials: RJ
authors.lastname: Dolan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000161:Acoustic Stimulation; D000328:Adult; D001303:Auditory Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology*; D020532:Basal Nucleus of Meynert / Q000378:metabolism*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D002799:Cholinergic Fibers / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D016292:Procedural Sedation; D004558:Electric Stimulation; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010830:Physostigmine / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D000109:Acetylcholine