Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Molecular Imaging and Functional Pharmacology, Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland; Singapore BioImaging Consortium, Agency for Science, Technology and Research, Singapore.
Neuroimage. 2017 Apr 1;149:190-199. doi: 10.1016/j.neuroimage.2017.01.074. Epub 2017 Feb 1.
Studies in mice using resting-state functional magnetic resonance imaging (rs-fMRI) have provided opportunities to investigate the effects of pharmacological manipulations on brain function and map the phenotypes of mouse models of human brain disorders. Mouse rs-fMRI is typically performed under anaesthesia, which induces both regional suppression of brain activity and disruption of large-scale neural networks. Previous comparative studies using rodents investigating various drug effects on long-distance functional connectivity (FC) have reported agent-specific FC patterns, however, effects of regional suppression are sparsely explored. Here we examined changes in regional connectivity under six different anaesthesia conditions using mouse rs-fMRI with the goal of refining the framework of understanding the brain activation under anaesthesia at a local level. Regional homogeneity (ReHo) was used to map local synchronization in the brain, followed by analysis of several brain areas based on ReHo maps. The results revealed high local coherence in most brain areas. The primary somatosensory cortex and caudate-putamen showed agent-specific properties. Lower local coherence in the cingulate cortex was observed under medetomidine, particularly when compared to the combination of medetomidine and isoflurane. The thalamus was associated with retained local coherence across anaesthetic levels and multiple nuclei. These results show that anaesthesia induced by the investigated anaesthetics through different molecular targets promote agent-specific regional connectivity. In addition, ReHo is a data-driven method with minimum user interaction, easy to use and fast to compute. Given that examination of the brain at a local level is widely applied in human rs-fMRI studies, our results show its sensitivity to extract information on varied neuronal activity under six different regimens relevant to mouse functional imaging. These results, therefore, will inform future rs-fMRI studies on mice and the type of anaesthetic agent used, and will help to bridge observations between this burgeoning research field and ongoing human research across analytical scales.
使用静息态功能磁共振成像 (rs-fMRI) 的小鼠研究为研究药物对大脑功能的影响以及绘制人类大脑疾病小鼠模型的表型提供了机会。小鼠 rs-fMRI 通常在麻醉下进行，这会导致大脑活动的区域抑制和大尺度神经网络的破坏。以前使用啮齿动物进行的各种药物对长程功能连接 (FC) 影响的比较研究报告了特定于药物的 FC 模式，但是，区域抑制的影响很少被探索。在这里，我们使用小鼠 rs-fMRI 检查了六种不同麻醉条件下的区域连接变化，目的是细化局部麻醉下大脑激活的理解框架。局部一致性 (ReHo) 用于绘制大脑局部同步性的图谱，然后根据 ReHo 图谱分析几个脑区。结果显示大多数脑区具有较高的局部一致性。初级体感皮层和尾状核-壳核显示出特定于药物的特性。在右美托咪定麻醉下，扣带皮层的局部一致性较低，特别是与右美托咪定和异氟烷联合使用时相比。丘脑与麻醉水平和多个核之间的局部一致性相关。这些结果表明，通过不同的分子靶点诱导的麻醉通过不同的分子靶点促进了特定于药物的区域连接。此外，ReHo 是一种数据驱动的方法，用户交互最少，易于使用且计算速度快。鉴于在人类 rs-fMRI 研究中广泛应用对大脑进行局部检查，因此我们的结果表明，它可以提取有关在与小鼠功能成像相关的六种不同方案下变化的神经元活动的信息。因此，这些结果将为未来的小鼠 rs-fMRI 研究和所使用的麻醉剂类型提供信息，并有助于在这一新兴研究领域和跨分析尺度的人类研究之间架起桥梁。
