Thiel C M, Bentley P, Dolan R J
Wellcome Department of Imaging Neuroscience, Institute of Neurology, 12 Queen Square, London, WC1 3BG, UK.
Eur J Neurosci. 2002 Dec;16(11):2199-206. doi: 10.1046/j.1460-9568.2002.02272.x.
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.
先前的研究表明，胆碱能阻断可减弱人类听觉皮层中与条件反射相关的神经元反应。本研究旨在探讨胆碱能增强对这种经验依赖性皮层反应的影响。在差异厌恶条件反射过程中，将胆碱酯酶抑制剂毒扁豆碱或安慰剂对照持续注入健康年轻志愿者体内，同时使用事件相关功能磁共振成像（fMRI）测量大脑活动。向志愿者呈现两种音调，其中一种（CS +）通过与电击配对进行条件反射，而另一种则始终在无电击的情况下呈现（CS -）。在安慰剂作用下，左侧听觉皮层出现了与条件反射相关的激活，表现为对显著的CS +的血氧水平依赖（BOLD）反应增强，而在毒扁豆碱作用下则未出现。与安慰剂相比，毒扁豆碱作用下CS -的反应增强导致了毒扁豆碱作用下与条件反射相关的激活缺失。我们认为，胆碱能系统过度活跃会导致对行为无关刺激的处理增加，从而减弱与差异条件反射相关的皮层激活。
