DEVELOPMENT OF fMRI COMPATIBLE REVERSIBLE DEACTIVATION

描述(申请人提供)：功能磁共振成像(FMRI)的发展极大地扩展了我们在受试者执行各种知觉、认知或运动任务时检查神经处理的能力。功能磁共振成像允许同时检查许多不同大脑区域的功能活动，并提供对多个区域如何协同工作以产生特定行为的更好理解。在这种方法的演变中，下一个必要的步骤是在受试者被扫描时停用大脑中的一个特定区域，以确定这个区域对其功能网络活动的贡献--通过检查没有这个区域的其他网络组件的活动。为了实现这一目标，我们建议开发一种与功能磁共振成像兼容的可逆失活方法。这项技术的开发将基于一项成熟的冷冻技术，即在行为正常的动物体内长期植入冷却装置。我们提出了四个阶段的发展计划。在第一阶段(开发)，我们将开发一种非金属冷却装置，能够使大脑皮层的特定区域失活。在第二阶段(测试)，我们将在表现良好的猫身上通过冷却初级视觉皮质(V1)区域来测试该设备，同时动物执行视觉定向任务。一旦我们确定了设备的可靠性，并可能产生行为缺陷，我们将麻醉猫，并在功能磁共振成像中检查设备的功能，以确认兼容性。在第三阶段(实施)，我们将长期将该装置植入非人类灵长类动物的V1区域，这些灵长类动物已经接受了视觉引导的眼跳训练。如果V1被成功停用，对暗点内目标的扫视应该被取消。这些猴子将在磁铁中执行任务时进行测试，并将在冷却停用之前、期间和之后收集图像。我们还将研究远距离失活对MTN5区和上丘的影响，同时猴子在注视过程中看到视觉流动的扩张和收缩。最后，在第四阶段(评估)，我们将在冷却过程中应用放射性标记的2-脱氧葡萄糖，以便我们可以将放射自显影与在磁体中收集的失活图像进行比较。总而言之，我们希望完全开发和测试一种设备，在磁铁中的行为测试期间，可以可逆地使大脑中的各个部位失活。这样的发展应该会有广泛的吸引力，并将极大地提高我们用功能磁共振技术剖析功能电路的能力。

DESCRIPTION (provided by applicant): The development of functional magnetic resonance imaging (fMRI) has greatly expanded our ability to examine neural processing while subjects perform a variety of perceptual, cognitive, or motor tasks. fMRI permits the simultaneous examination of functional activity in many different brain regions and provides a better understanding of how multiple regions work in concert to produce particular behaviors. The next necessary step in the evolution of this approach is to deactivate a specific region in the brain, while a subject is being scanned, to determine the contribution of this site to the activity of its functional network -- by examining the activity of other network components in the absence of this region. To accomplish this goal, we propose to develop a reversible deactivation approach that is fMRI-compatible. The development of this technique will be based on a well-established cryoloop technique in which a cooling device is chronically implanted in behaving animals. We propose a four-phase development program. In phase 1 (development), we will develop a non-metallic cooling device capable of deactivating specific regions of the cerebral cortex. In phase 2 (testing), we will test the device in the behaving cat by cooling regions of primary visual cortex (V1) while the animal performs a visual orienting task. Once we establish device reliability, and can produce behavioral deficits, we will anesthetize the cats and examine the function of the device in the fMRI to confirm compatibility. In phase 3 (implementation), we will chronically implant the device over a region of V1 in non-human primates that have been trained to make visually guided saccades. If V1 is successfully deactivated, saccades to targets within the scotoma should be abolished. The monkeys will be tested while performing the task in the magnet and images will be collected before, during, and after cooling deactivation. We will also examine the distant deactivation consequences on area MTN5 and the superior colliculus while the monkeys view expanding and contracting visual flow during fixation. Finally, in phase 4 (evaluation), we will administer radiolabelled 2-deoxyglucose during cooling so that we may compare the autoradiograms with the deactivation images collected in the magnet. In summary, we expect to fully develop and test a device to reversibly deactivate sites in the brain during behavioral testing in the magnet. Such a development should have wide appeal and will greatly advance our ability to dissect functional circuits with fMRI.