Effects of Reversible Lesions on Resting fMRI in Awake Macaques

描述(由申请人提供)：这个项目研究了功能磁共振成像(FMRI)的一个新发现，但人们对此知之甚少，它为基本大脑结构提供了新的见解。功能成像研究表明，在广泛的任务中，相似的非连续脑区被共同激活。值得注意的是，当受试者休息时，这些共同激活中的许多都会被重述。因此，静息状态fMRI被认为反映了任务相关的功能网络。人们非常有兴趣知道是什么原则负责维持这些内在的共同激活。大多数功能连接研究都集中在大脑皮层。包括丘脑在内的大脑深层结构与这些网络有关，但人们对它们可能扮演的角色知之甚少。大脑皮层的大部分输入都通过丘脑，包括许多感觉信号、小脑和基底节输入。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通性的结构和维持。这一领域的进展主要集中在自然发生的损害上。非人灵长类动物的实验损伤可以精确放置，并重复进行，以获得对其影响的统计信心。最近，RS-fmri 在非人类灵长类动物中发现了类似于在人类中观察到的皮质网络。可以将GABAA激动剂Muscimol注射到组织中以抑制局部活动，并可以精确地监测失活部位。我们建议使用猕猴的可逆失活来研究丘脑和皮质在维持静息状态网络功能连通性中的作用，并利用新的图论方法来表征失活对网络的影响。这项工作将阐明皮层连接的神经元基础，更广泛地说，可能为创伤性脑损伤和其他疾病的康复方法提供参考。

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.