Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
Neuroimage. 2012 Mar;60(1):436-46. doi: 10.1016/j.neuroimage.2011.12.026. Epub 2011 Dec 22.
Correlative low frequency fluctuations in functional MRI (fMRI) signals across brain regions at rest have been taken as a measure of functional connectivity to map large-scale neural networks; however, the neural origin is still not clear. Receptor-targeted pharmacological manipulation could elucidate the role of neuroreceptor systems in resting-state functional connectivity to provide another perspective on the mechanism. In this study, the dose-dependent effects of an α(2)-adrenergic receptor agonist, medetomidine, on brain activation and functional connectivity were investigated. Forepaw stimulation-induced activation and resting-state fluctuation in the rat somatosensory cortices and caudate putamen were measured using the blood oxygenation level dependent (BOLD) fMRI. The results showed significant dose-dependent suppression of inter-hemispheric correlation but not the amplitude in the somatosensory areas, while the stimulation-induced activation in the same areas remained unchanged. To clarify the potential change in the hemodynamic response caused by the vasoconstrictive effect of medetomidine, the resting perfusion fluctuation was studied by arterial spin labeling and showed similar results as the BOLD. This suggests that the oxygen metabolic rate and hence the neural activity may not be affected by medetomidine but only the synchrony between brain regions was suppressed. Furthermore, no change in functional connectivity with medetomidine dosages was seen in the caudate putamen, a region with much lower α(2)-receptor density. These results indicate that resting-state signal correlation may reflect underlying neuroreceptor activity and a potential role of the adrenergic system in the functional connectivity.
静息状态下大脑区域间功能磁共振成像（fMRI）信号的相关低频波动被用作测量功能连接以绘制大尺度神经网络图谱的指标；然而，其神经起源仍不清楚。受体靶向的药物处理可以阐明神经受体系统在静息状态功能连接中的作用，为其机制提供另一种视角。在这项研究中，研究了 α（2）-肾上腺素能受体激动剂，美托咪定，对大脑激活和功能连接的剂量依赖性影响。使用血氧水平依赖（BOLD）fMRI 测量了前爪刺激诱导的大鼠躯体感觉皮质和尾状核的激活和静息状态波动。结果显示，在躯体感觉区，美托咪定的剂量依赖性抑制了半球间的相关性，但没有抑制振幅，而同一区域的刺激诱导的激活保持不变。为了阐明美托咪定的血管收缩作用引起的血流动力学反应的潜在变化，通过动脉自旋标记研究了静息灌注波动，结果与 BOLD 相似。这表明，氧代谢率，从而神经活动可能不受美托咪定影响，而只是被抑制了脑区之间的同步性。此外，在尾状核（α（2）-受体密度较低的区域）中，美托咪定剂量没有改变功能连接。这些结果表明，静息状态信号相关性可能反映了潜在的神经受体活性以及肾上腺素能系统在功能连接中的潜在作用。
