Cholinergic modulation of cognition: Insights from human pharmacological functional neuroimaging

被引:124
作者
Bentley, Paul [1 ,2 ]
Driver, Jon [1 ,3 ]
Dolan, Raymond J. [1 ]
机构
[1] UCL, Wellcome Ctr Neuroimaging UCL, London WC1N 3BG, England
[2] Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Charing Cross Hosp, London W6 8RF, England
[3] UCL, UCL Inst Cognit Neurosci, London WC1N 3AR, England
基金
英国惠康基金;
关键词
Cholinergic; Pharmacological; Functional imaging; fMRI; PET; Attention; Memory; Sensory; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; CORTICAL ACETYLCHOLINE-RELEASE; MEDIAL PREFRONTAL CORTEX; LONG-TERM POTENTIATION; VERBAL WORKING-MEMORY; CUED TARGET DETECTION; NUCLEUS BASALIS; VISUAL-CORTEX; NEURAL ACTIVITY;
D O I
10.1016/j.pneurobio.2011.06.002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Evidence from lesion and cortical-slice studies implicate the neocortical cholinergic system in the modulation of sensory, attentional and memory processing. In this review we consider findings from sixty-three healthy human cholinergic functional neuroimaging studies that probe interactions of cholinergic drugs with brain activation profiles, and relate these to contemporary neurobiological models. Consistent patterns that emerge are: (1) the direction of cholinergic modulation of sensory cortex activations depends upon top-down influences; (2) cholinergic hyperstimulation reduces top-down selective modulation of sensory cortices; (3) cholinergic hyperstimulation interacts with task-specific frontoparietal activations according to one of several patterns, including: suppression of parietal-mediated reorienting; decreasing 'effort'-associated activations in prefrontal regions; and deactivation of a 'resting-state network' in medial cortex, with reciprocal recruitment of dorsolateral frontoparietal regions during performance-challenging conditions; (4) encoding-related activations in both neocortical and hippocampal regions are disrupted by cholinergic blockade, or enhanced with cholinergic stimulation, while the opposite profile is observed during retrieval; (5) many examples exist of an 'inverted-U shaped' pattern of cholinergic influences by which the direction of functional neural activation (and performance) depends upon both task (e.g. relative difficulty) and subject (e.g. age) factors. Overall, human cholinergic functional neuroimaging studies both corroborate and extend physiological accounts of cholinergic function arising from other experimental contexts, while providing mechanistic insights into cholinergic-acting drugs and their potential clinical applications. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:360 / 388
页数:29
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