DEVELOPMENT OF fMRI COMPATIBLE REVERSIBLE DEACTIVATION

描述（由申请人提供）：功能性磁共振成像（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，并更好地了解多个区域如何协同工作以产生特定行为。这种方法发展的下一个必要步骤是，当受试者被扫描时，停用大脑中的特定区域，以确定该区域对其功能网络活动的贡献——通过检查该区域缺失时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fmri兼容的可逆失活方法。这项技术的发展将基于一种成熟的冷冻循环技术，在这种技术中，一种冷却装置长期植入行为正常的动物体内。我们建议分四个阶段发展。在第一阶段（开发），我们将开发一种能够使大脑皮层特定区域失活的非金属冷却装置。在第二阶段（测试）中，我们将在行为猫执行视觉定向任务时，通过冷却初级视觉皮层（V1）区域来测试该设备。一旦我们确定了设备的可靠性，并且可以产生行为缺陷，我们将对猫进行麻醉，并在fMRI中检查设备的功能以确认兼容性。在第3阶段（实施），我们将在非人类灵长类动物的V1区域长期植入该设备，这些灵长类动物已经接受了视觉引导的扫视训练。如果V1被成功地去激活，对暗斑内目标的扫视应该被取消。研究人员将对猴子在磁铁中执行任务时进行测试，并在冷却停止活动之前、期间和之后收集图像。我们还将研究当猴子在注视过程中视觉流扩张和收缩时，MTN5区域和上丘的远端失活后果。最后，在第4阶段（评估），我们将在冷却期间给予放射性标记的2-脱氧葡萄糖，以便我们可以将自放射成像与磁铁中收集的失活图像进行比较。总而言之，我们期望充分开发和测试一种设备，在磁铁的行为测试中可逆地使大脑中的某些部位失活。这样的发展应该有广泛的吸引力，并将大大提高我们的能力解剖功能电路与功能磁共振成像。

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.