Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, UK.
Neuroimage. 2012 Aug 1;62(1):239-49. doi: 10.1016/j.neuroimage.2012.04.041. Epub 2012 Apr 28.
The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A(1) and A(2A) adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG-FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19% reduction over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG-FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis.
咖啡因的作用是通过其对腺苷 A(1)和 A(2A) 腺苷受体的非选择性拮抗作用介导的，导致神经元活动增加，但也导致大脑血管收缩。因此，咖啡因可以通过其神经和血管作用来改变 BOLD fMRI 信号反应，具体取决于不同脑区的受体分布。在这项研究中，我们旨在使用同时进行的 EEG-FMRI 来区分单次剂量咖啡因对任务相关脑活动测量的神经和血管影响。我们选择比较低水平的视觉和运动（有节奏的手指敲击）任务与认知（听觉Oddball）任务，期望咖啡因会根据这些任务对大脑反应产生不同的影响。为了避免慢性咖啡因摄入的影响，我们在一项双盲安慰剂对照交叉研究中检查了 250 毫克口服咖啡因对 14 名非习惯性和非习惯性咖啡因消费者的影响。我们的结果表明，咖啡因显著降低了视觉和初级运动皮层的任务相关 BOLD 信号变化，而枕叶皮层的视觉诱发电位的幅度和潜伏期保持不变。然而，在听觉 Oddball 任务（目标与非目标刺激）中，咖啡因显著增加了额叶皮层的 BOLD 信号。相应地，咖啡因也有显著的效果，可以减少 Oddball 任务中目标诱发反应电位（P300）的潜伏期，并且这与额叶皮层上的正电位有关。行为数据表明，咖啡因也改善了 Oddball 任务的表现，使错过的反应数量明显减少。我们的结果与早期研究一致，即在我们观察到的动脉自旋标记（灰质减少 19%）显示的一般咖啡因引起的脑血流减少的情况下，咖啡因给药后会改变血流代谢偶联。我们能够通过改变低水平任务 fMRI 反应来识别血管效应，从而改变神经血管偶联，同时保留视觉诱发电位。然而，我们的数据也表明，咖啡因具有认知作用，因为它对额叶 BOLD 信号有积极影响，与 Oddball EEG 反应潜伏期缩短一致。EEG-FMRI 的联合使用是一种很有前途的方法，可以研究药物和疾病研究中脑功能的改变，在这些研究中，神经血管偶联可能会在区域基础上发生改变。
