Dai Twain, Seewoo Bhedita J, Hennessy Lauren A, Bolland Samuel J, Rosenow Tim, Rodger Jennifer
School of Biological Sciences, University of Western Australia, Perth, WA, Australia.
Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, WA, Australia.
Front Neurosci. 2023 May 22;17:1151525. doi: 10.3389/fnins.2023.1151525. eCollection 2023.
Resting-state functional MRI (rs-fMRI) in rodent models have the potential to bridge invasive experiments and observational human studies, increasing our understanding of functional alterations in the brains of patients with depression. A major limitation in current rodent rs-fMRI studies is that there has been no consensus on healthy baseline resting-state networks (RSNs) that are reproducible in rodents. Therefore, the present study aimed to construct reproducible RSNs in a large dataset of healthy rats and then evaluate functional connectivity changes within and between these RSNs following a chronic restraint stress (CRS) model within the same animals.
A combined MRI dataset of 109 Sprague Dawley rats at baseline and after two weeks of CRS, collected during four separate experiments conducted by our lab in 2019 and 2020, was re-analysed. The mICA and gRAICAR toolbox were first applied to detect optimal and reproducible ICA components and then a hierarchical clustering algorithm (FSLNets) was applied to construct reproducible RSNs. Ridge-regularized partial correlation (FSLNets) was used to evaluate the changes in the direct connection between and within identified networks in the same animals following CRS.
Four large-scale networks in anesthetised rats were identified: the DMN-like, spatial attention-limbic, corpus striatum, and autonomic network, which are homologous across species. CRS decreased the anticorrelation between DMN-like and autonomic network. CRS decreased the correlation between amygdala and a functional complex (nucleus accumbens and ventral pallidum) in the right hemisphere within the corpus striatum network. However, a high individual variability in the functional connectivity before and after CRS within RSNs was observed.
The functional connectivity changes detected in rodents following CRS differ from reported functional connectivity alterations in patients with depression. A simple interpretation of this difference is that the rodent response to CRS does not reflect the complexity of depression as it is experienced by humans. Nonetheless, the high inter-subject variability of functional connectivity within networks suggests that rats demonstrate different neural phenotypes, like humans. Therefore, future efforts in classifying neural phenotypes in rodents might improve the sensitivity and translational impact of models used to address aetiology and treatment of psychiatric conditions including depression.
啮齿动物模型中的静息态功能磁共振成像（rs-fMRI）有潜力在侵入性实验和人类观察性研究之间架起桥梁，增进我们对抑郁症患者大脑功能改变的理解。当前啮齿动物rs-fMRI研究的一个主要局限在于，对于在啮齿动物中可重复的健康基线静息态网络（RSN）尚无共识。因此，本研究旨在在一个大型健康大鼠数据集中构建可重复的RSN，然后评估在同一动物中采用慢性束缚应激（CRS）模型后这些RSN内部以及之间的功能连接变化。
对我们实验室在2019年和2020年进行的四项独立实验中收集的109只Sprague Dawley大鼠在基线和CRS两周后的联合MRI数据集进行重新分析。首先应用mICA和gRAICAR工具箱来检测最优且可重复的ICA成分，然后应用层次聚类算法（FSLNets）来构建可重复的RSN。采用岭正则化偏相关（FSLNets）来评估在CRS后同一动物中已识别网络之间以及内部直接连接的变化。
在麻醉大鼠中识别出四个大规模网络：类默认模式网络（DMN-like）、空间注意力-边缘系统、纹状体和自主神经系统，这些在不同物种间具有同源性。CRS降低了类DMN网络和自主神经系统之间的负相关。CRS降低了纹状体网络中右侧半球杏仁核与一个功能复合体（伏隔核和腹侧苍白球）之间的相关性。然而，观察到RSN内CRS前后功能连接存在较高的个体变异性。
在啮齿动物中CRS后检测到的功能连接变化与报道的抑郁症患者功能连接改变不同。对此差异的一个简单解释是，啮齿动物对CRS的反应并未反映出人类所经历的抑郁症的复杂性。尽管如此，网络内功能连接的高个体间变异性表明，大鼠与人类一样表现出不同的神经表型。因此，未来在啮齿动物中对神经表型进行分类的努力可能会提高用于解决包括抑郁症在内的精神疾病病因和治疗的模型的敏感性及转化影响力。
