Effects of Reversible Lesions on Resting fMRI in Awake Macaques

描述（由申请人提供）：该项目研究了一个新的，但了解甚少的发现，从功能磁共振成像（fMRI），是提供新的见解，基本的大脑结构。功能成像研究表明，类似的非连续大脑区域在广泛的任务中被共同激活。值得注意的是，当受试者休息时，这些共激活中的许多被重演。因此，静息态fMRI（rs-fMRI）被认为反映了任务相关的功能网络。了解维持这些内在共激活的原理是非常有意义的。大多数功能连接研究都集中在皮层上。包括丘脑在内的大脑深层结构与这些网络有关，但关于它们究竟扮演什么角色却知之甚少。大多数输入到大脑皮层的信号都经过丘脑，包括许多感觉信号、小脑和基底神经节的输入。因此，丘脑处于调节或维持功能连接的理想解剖位置。 局灶性病变可以揭示许多关于功能连接的结构和维持。该领域的进展集中在自然发生的病变上。在非人类灵长类动物中的实验性损伤可以精确地放置，并重复以获得其效果的统计学置信度。最近，rs-fMRI 在非人类灵长类动物中发现的大脑皮层网络与在人类中观察到的相似。蝇蕈醇是一种GABAA激动剂，可以注射到组织中以抑制局部活性，并且可以精确监测失活部位。我们建议在猕猴中使用可逆失活来研究丘脑和皮质在维持静息状态网络功能连接中的作用，并使用新的图论方法来表征失活对网络的影响。这项工作将揭示皮层连接的神经元基础，更普遍地说，可能会为创伤性脑损伤和其他疾病的康复方法提供信息。

DESCRIPTION (provided by applicant): This project examines a new but poorly understood finding from functional magnetic resonance imaging (fMRI) that is providing new insights into fundamental brain architecture. Functional imaging studies show that similar sets of non-contiguous brain regions are co-activated across a wide range of tasks. Remarkably, many of these co-activations are recapitulated when subjects are at rest. Thus, resting state fMRI (rs-fMRI) is thought to reflect task-related functional networks. It is of great interest to know what principles are responsible for the maintenance of these intrinsic co-activations. Most functional connectivity studies have focused on the cortex. Deep brain structures, including the thalamus, have been implicated in these networks, but little is known regarding exactly what role they might play. Most input to the cerebral cortex passes through the thalamus, including many sensory signals, cerebelar and basal ganglia inputs. As a result, the thalamus is in an ideal anatomical position to regulate or maintain functional connectivity. Focal lesions can reveal much about the structure and maintenance of functional connectivity. Progress in this area has focused on naturally occurring lesions. Experimental lesions in non-human primates can be precisely placed, and repeated to obtain statistical confidence in their effects. Recently, rs-fMRI in non-human primates has revealed cortical networks similar to those observed in humans. Muscimol, a GABAA agonist, can be injected into tissue to inhibit local activity, and the sites of inactivation can be precisely monitored. We propose to use reversible inactivation in the macaque monkey to examine the roles of the thalamus and cortex in maintaining resting state network functional connectivity, and to characterize the effects of inactivation on the networks using novel graph theoretic approaches. This work will shed light on the neuronal underpinnings of cortical connectivity and more generally, may inform rehabilitation approaches for traumatic brain injury and other disorders.