Hsu Li-Ming, Shih Yen-Yu Ian
Center for Animal Magnetic Resonance Imaging, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Magn Reson Imaging. 2025 Apr;61(4):1597-1617. doi: 10.1002/jmri.29575. Epub 2024 Sep 15.
The integration of functional magnetic resonance imaging (fMRI) with advanced neuroscience technologies in experimental small animal models offers a unique path to interrogate the causal relationships between regional brain activity and brain-wide network measures-a goal challenging to accomplish in human subjects. This review traces the historical development of the neuromodulation techniques commonly used in rodents, such as electrical deep brain stimulation, optogenetics, and chemogenetics, and focuses on their application with fMRI. We discuss their advantageousness roles in uncovering the signaling architecture within the brain and the methodological considerations necessary when conducting these experiments. By presenting several rodent-based case studies, we aim to demonstrate the potential of the multimodal neuromodulation approach in shedding light on neurovascular coupling, the neural basis of brain network functions, and their connections to behaviors. Key findings highlight the cell-type and circuit-specific modulation of brain-wide activity patterns and their behavioral correlates. We also discuss several future directions and feature the use of mediation and moderation analytical models beyond the intuitive evoked response mapping, to better leverage the rich information available in fMRI data with neuromodulation. Using fMRI alongside neuromodulation techniques provide insights into the mesoscopic (relating to the intermediate scale between single neurons and large-scale brain networks) and macroscopic fMRI measures that correlate with specific neuronal events. This integration bridges the gap between different scales of neuroscience research, facilitating the exploration and testing of novel therapeutic strategies aimed at altering network-mediated behaviors. In conclusion, the combination of fMRI with neuromodulation techniques provides crucial insights into mesoscopic and macroscopic brain dynamics, advancing our understanding of brain function in health and disease. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
在实验性小动物模型中将功能磁共振成像（fMRI）与先进的神经科学技术相结合，为探究局部脑活动与全脑网络指标之间的因果关系提供了一条独特途径，而这一目标在人类受试者中很难实现。本综述追溯了啮齿动物中常用的神经调节技术的历史发展，如深部脑电刺激、光遗传学和化学遗传学，并重点介绍了它们在fMRI中的应用。我们讨论了它们在揭示脑内信号结构方面的优势作用，以及进行这些实验时所需的方法学考虑因素。通过展示几个基于啮齿动物的案例研究，我们旨在证明多模态神经调节方法在阐明神经血管耦合、脑网络功能的神经基础及其与行为的联系方面的潜力。主要发现突出了全脑活动模式的细胞类型和回路特异性调节及其行为相关性。我们还讨论了几个未来的方向，并介绍了除直观的诱发反应映射之外的中介和调节分析模型的使用，以便更好地利用fMRI数据与神经调节中的丰富信息。将fMRI与神经调节技术一起使用，可深入了解与特定神经元事件相关的介观（与单个神经元和大规模脑网络之间的中间尺度有关）和宏观fMRI测量。这种整合弥合了神经科学研究不同尺度之间的差距，有助于探索和测试旨在改变网络介导行为的新型治疗策略。总之，fMRI与神经调节技术的结合为介观和宏观脑动力学提供了关键见解，推动了我们对健康和疾病状态下脑功能的理解。证据水平：1 技术疗效：1期。
