School of Psychology, Beijing Sport University, Beijing, China.
School of Psychology, Beijing Sport University, Beijing, China; Department of Medical Psychology, Second Medical Center, General Hospital of the People's Liberation Army, China.
Sleep Med. 2024 Oct;122:71-83. doi: 10.1016/j.sleep.2024.08.007. Epub 2024 Aug 8.
Studies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear.
A double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil.
The subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus.
After 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.
研究发现，临床批准的咖啡因和莫达非尼的使用在一定程度上可以缓解睡眠剥夺（SD）引起的认知障碍。然而，这两种认知增强剂对抗 SD 对认知障碍影响的神经机制仍不清楚。
设计了一项使用静息态功能磁共振成像（rs-fMRI）的双盲、自身对照实验。参与者经历了三次 36 小时的 SD 试验，每次在 SD 的第 28 小时和第 32 小时服用 200mg 咖啡因、莫达非尼或安慰剂。选择丘脑的 16 个亚区作为感兴趣区，并在参与者服用咖啡因或莫达非尼后探索丘脑与其他脑区之间的功能连接（FC）的变化。
参与者的主观困倦感随 SD 持续时间的增加而增加。与安慰剂相比，莫达非尼和咖啡因对觉醒或困倦状态没有显著影响。然而，在神经 FC 方面，我们发现丘脑与其他区域之间的 FC 存在不同程度的减弱或增强。与安慰剂相比，SD 期间服用咖啡因会减弱右侧额状颞叶丘脑（rTtha）亚区与左侧舌回之间的 FC。咖啡因增强了丘脑的三个亚区，即左侧感觉丘脑、左侧 rTtha 和右侧外侧前额叶丘脑，以及右侧下颞叶、左侧眶额回和右侧上顶叶回之间的 FC。莫达非尼减弱了右侧顶后丘脑与左侧颞中回之间的 FC，并增强了左侧内侧前额叶丘脑、左侧 rTtha 和右侧枕叶丘脑与左侧额中回之间的 FC。
在总 SD 36 小时后，与安慰剂相比，莫达非尼和咖啡因的给药增强或减弱了健康成年人丘脑各亚区与额颞叶脑区之间的时域相关性。这些结果为进一步揭示咖啡因和莫达非尼的神经药理学机制提供了有价值的证据，并为探索针对 SD 的有效药物干预策略提供了重要的见解。
