Wellcome Trust Centre for Neuroimaging, University College London, WC1N 3BG London, United Kingdom, Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, 52425 Juelich Germany,
Wellcome Trust Centre for Neuroimaging, University College London, WC1N 3BG London, United Kingdom, School of Psychology, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
J Neurosci. 2014 Nov 19;34(47):15735-42. doi: 10.1523/JNEUROSCI.0091-14.2014.
The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision.
胆碱能神经递质系统如何有助于注意力处理，其确切机制仍知之甚少。在这里，我们应用计算模型分析了在胆碱酯酶抑制剂加兰他敏（Reminyl）的精神药理学挑战下的心理物理数据（从空间注意任务中获得）。这使我们能够以分层贝叶斯推断的形式正式描述胆碱能对选择性注意的调节。在安慰剂对照、个体内交叉设计中，16 名健康人类受试者进行了 Posner 位置提示任务的修改版本，其中有效和无效提示目标的比例（提示有效性百分比，%CV）随时间变化。扫视反应速度用于估计分层贝叶斯模型的参数，以测试胆碱能刺激是否影响注意力分配的概率信念的逐个试验更新，或者加兰他敏是否改变了从这些信念到随后的眼球运动的映射。行为上，加兰他敏导致概率上下文（%CV）对反应速度的影响大于安慰剂。至关重要的是，计算模型表明，这种效应是由于对提示有效性的信念更新率增加（而不是行为反应对这些信念的敏感性增加）所致。我们讨论了这些发现与胆碱能对分层皮质处理的影响以及与预期不确定性或精度的编码有关。
