Neurophysiology Imaging Facility Core: Functional and Structural MRI

人类功能磁共振成像的出现改变了现代神经科学的焦点，突出了人类大脑中的过程。这种对大脑功能的宏观描述对于解决大规模过程非常有用，并且将神经科学扩展到人类对于了解大脑功能以及向公众传播神经科学研究的重要性至关重要。 与此同时，能够将功能磁共振成像激活模式（通过血流变化介导）与处理感觉信息和产生行为的潜在神经电回路联系起来，这既令人满意，也很重要。 我们对灵长类动物大脑的大部分了解并不是来自对人类的研究，而是来自对动物（尤其是猴子）大脑中神经元活动的直接观察。因此，理解功能磁共振成像和神经反应之间的转换的关键是建立猴子的功能磁共振成像和神经信号之间的对应关系。 神经生理学成像设施（NIF）核心提供了一个完整的程序，通过该程序，三个赞助机构（NIMH，NINDS和NEI）的研究人员可以测试清醒行为的猴子大脑中的功能信号。 在其功能计划中，NIF专注于猴子的功能成像，这些猴子也参加了电生理学实验计划。 这需要大量的开发，需要MR兼容的椅子和约束设备，奖励交付和响应键。 这种方法的好处是，经过训练的动物可以很容易地在神经生理学或功能磁共振成像环境中隔日进行测试。 该设施的初步工作表明，这是富有成效的，因为三项研究即将完成，其中两项研究专门依赖于用这两种技术测试猴子。 结合技术的优点包括：（1）定位目标电极记录的活动，（2）在特定感觉或行为范例的背景下评估神经和功能磁共振成像信号的等效性，以及（3）基于受试者内差异而不是受试者之间的平均值来比较功能磁共振成像和电生理数据。 此外，还可以在扫描仪孔内同时进行微电极和fMRI记录。 这项技术被用于研究不同唤醒状态下活动的协变，这是一种用于推断猴子大脑功能连接原理的方法。 在猴子身上使用神经参照物提供了一个比人类更清晰、更有意义的信号，每个fMRI信号波动的元素都与潜在的神经事件有着特定的联系。 目前，人类功能连接的潜在神经基础在很大程度上是未知的，NIF的工作旨在更清楚地了解大规模大脑网络中的信息是如何整合的。 结构成像是NIF核心设施的另一个主要目标，在过去的一年里，我们已经扩大了我们的服务范围，以更大的NIH社区。 在该设施中，高分辨率扫描在其对比度方面进行了优化，以可视化感兴趣的解剖特征。 在清醒和完全麻醉的动物准备中进行解剖成像。 此外，该设施还为电生理学家提供了许多技术，以促进有针对性的微电极记录。 首先，无框架立体定位系统允许从任何角度对任何目标进行手术，从而允许对潜在的感兴趣轨迹以及要避免的结构进行完整评估。 这种方法经常被该设施的用户使用，并且有助于高度可靠地靶向深层皮质和皮质下结构。 在猴子中使用磁共振成像的一个很大的优势是能够将联合收割机MR测量与侵入性技术相结合。 一种特别有用的技术是在成像之前将MR可见或神经活性物质注射到大脑中。 在NIF设施中，我们提供了将多种物质注入大脑的能力，从造影剂（如钆）到解剖示踪剂（如氯化锰），再到神经递质类似物和阻滞剂。 注射通常通过先前植入的插管进行，动物处于麻醉或清醒状态。 局部注射的造影剂可用于可视化共同注射的药剂在神经元中的扩散。 解剖学示踪剂可用于识别从注射点发出的多突触神经束，其可能例如对应于功能激活区域。 神经递质类似物可用于局部激活或失活结构，然后可以通过监测整个大脑的fMRI时间序列来监测其效果。 除了满足NIH非人类灵长类动物成像社区的需求外，NIF还在不断升级和开发其尖端的4.7垂直猴子扫描仪。 过去一年的发展包括开发了大约十几个RF线圈，以适应不同的扫描挑战。 此外，还开发、发布了新的脉冲序列，并提供给MR成像界。 在未来的一年里，磁铁将得到升级，这将保持其在猴子成像领域的最前沿地位。 具体来说，8通道系统将取代1通道系统，从而大大提高成像质量，这将转化为有关大脑结构和活动的更精确的知识。 硬件开发、脉冲测序、其他技术里程碑和分析软件开发方面的所有创新都立即提供给整个NIH社区用于灵长类动物成像。

The advent of human fMRI has changed the focus of modern neuroscience, highlighting processes in the human brain. This macroscopic description of brain function is highly useful for addressing large-scale processes, and the extension of neuroscience to humans has been critical for learning about brain function, and disseminating the importance of neuroscientific research to the general public. At the same time it is both desirable and important to be able link patterns of fMRI activation, which are mediated through changes in blood flow, to the underlying electrical neural circuits that process sensory information and generate behavior. A large portion of our understanding of the primate brain has arisen not from studying humans, but from directly examining the activity of neurons in the brains of animals, and in particular monkeys. Critical for understanding the translation between fMRI and neural responses is therefore to establish correspondence between the fMRI and neural signals in monkeys. The Neurophysiology Imaging Facility (NIF) core offers a complete program by which investigators in each of the three sponsoring institutes (NIMH, NINDS, and NEI) may test awake behaving monkeys for functional signals in their brains. In its functional program, the NIF concentrates on functional imaging in monkeys that are also enrolled in an electrophysiology experimental program. This has required a large amount of development, requiring MR-compatible chairs and restraint devices, reward delivery, and response keys. The benefit of this approach is that trained animals can easily be tested on alternate days in either the neurophysiology or fMRI environment. Initial work in the facility has shown that this is fruitful, as three studies are nearing completion, with two of them specifically relying on testing monkeys with both techniques. The merits of combining techniques include (1) localizing activity for targeted electrode recordings, (2) evaluating the equivalence of neural and fMRI signals in the context of a particular sensory or behavioral paradigm, and (3) basing comparisons between fMRI and electrophysiology data upon within-subject differences rather than between-subject averages. In addition, it is possible to perform simultaneous microelectrode and fMRI recordings inside the scanner bore. This technique is being used in the facility to examine the covariation of activity in different states of arousal, a method used to infer principles of functional connectivity in the monkey brain. The use of a neural reference in the monkey provides a cleaner and potentially more meaningful signal than can be attained in humans, with each element of fMRI signal fluctuation tied specifically to underlying neural events. At present, the underlying neural basis of functional connectivity in humans is largely unknown, and work in the NIF aims to provide a clearer picture of how information in large-scale brain networks might be integrated. Structural imaging is another main goal of the NIF core facility, and in the last year we have expanded our sphere of service to the greater NIH community. In the facility, high resolution scans have been optimized in their contrast for visualizing anatomical features of interest. Anatomical imaging is carried out in both the awake and fully anesthetized animal preparation. In addition, the facility offers a number of techniques to electrophysiologists in order to facilitate targeted microelectrode recordings. First, a frameless stereotaxy system permits surgical approach to any target from any angle, allowing for a complete evaluation of potential trajectories of interest, as well as structures to be avoided. This approach is used regularly by users of the facility, and has contributed to the highly reliable targeting of deep cortical and subcortical structures. A great advantage of using magnetic resonance imaging in monkeys is the capacity to combine MR measurements with invasive techniques. One particularly useful technique is injection of either MR-visible or neuroactive substances into the brain prior to imaging. In the NIF facility, we offer the capacity to inject a number of substances into the brain, ranging from contrast agents such as Gadolinum, to anatomical tracers such as manganese chloride, to neurotransmitter analogs and blockers. Injections are typically performed through a previously implanted cannula with the animal either anesthetized or awake. Locally injected contrast agents can be used to visualize the spread of a co-injected agent in the neuropil. Anatomical tracers can be used to identify polysynaptic neural tracts emanating from the injection point, which might, for example, correspond to a region of functional activation. Neurotransmitter analogs can be used to locally activate or inactivate a structure, the effect of which can then be monitored by monitoring the fMRI time series over the entire brain. In addition to serving the needs of the NIH non-human primate imaging community, the NIF is continually upgrading and developing its cutting edge 4.7 Vertical monkey scanner. Development in the past year have included the development of roughly a dozen RF coils to accommodate different scanning challenges. New pulse sequences have additionally been developed, published, and offered to the MR-imaging community. In the coming year, the magnet will receive an upgrade, which maintain its position at the forefront of monkey imaging. Specifically an 8-channel system will replace the 1-channel system, leading to a great improvement in imaging quality, which translates to more refined knowledge about brain structure and activity. All innovations on the side of hardware development, pulse sequencing, other technical milestones, and the development of analysis software, are immediately made available to the entire NIH community for use in primate imaging.