Resting State Connectivity in Primate Spinal Cord

摘要/摘要 这项建议旨在继续我们的研究，以确定和表征静息状态的功能磁共振 脊髓灰质内的信号，并验证静息状态功能的解释 脊椎中的连接性(RsFC)网络似乎反映了特定的、与行为相关的功能。在 目前的资金期我们发现CORD内的休眠状态网络呈现出更复杂的连接性 比以前报告的更多，无论是在部门内还是跨部门，包括与 与自主神经功能和左右协调有关的中间区和灰色连合。 重要的是，通过在非人类灵长类动物身上实施颈椎背柱损伤，我们已经 已确认这些网络内的连接优势通常与功能相关 性能，网络中的变化对应于例如熟练的手使用中的行为变化。 我们的下一个目标是全面描述rsFC的子组件，并将它们与更具体的功能联系起来。我们 将在高场(9.4T)下采集松鼠猴子的亚毫米、多参数磁共振图像，并对 三个主要目标。(1)我们将使用选择性损伤来识别和区分脊髓内的rsFC网络。 以及药物干预，以确定哪些组件和网络连接性受 特定的正常感觉或运动通路的中断。我们将隔离受(A)可逆影响的电路 用药剂阻断运动或感觉输入；(B)永久消融运动的驱动 来自腹角初级运动皮质的神经元；以及(C)干扰背角神经元的感觉信号。 切开脊神经后根。我们将使用CEST和DTI跟踪每个损伤的演变 测量损伤的程度和严重程度，DTI和QMT以验证损伤严重程度并量化变化 在轴突完整性和髓鞘形成方面。(2)我们将通过与MRI的比较来验证来自MRI的rsFC测量 电生理学、微刺激和轨迹追踪组织学。我们将(A)直接刺激特定节点 同时使用电生理和功能磁共振监测下游活动；(B)进行纵向功能磁共振和 微阵列记录每只接受特定干预的猴子的电连贯性(目标1)； (C)确定通过功能磁共振成像似乎在功能上相连的区域是否也显示出强大的解剖学 通过注射示踪剂和在死后进行组织学评估来建立联系。(3)我们会决定 RsFC的功能和行为相关性，通过中断每个电路，识别相应的变化 并将这些变化与熟练的手感觉运动行为的表现联系起来。到完工时 在这项研究中，我们将验证rsFC测量作为脊髓功能的指标，并建立精细的- 脊椎内回路的粒状内在结构。这些研究将提供有关神经的新信息。 脊髓的组织，验证对连接性的大胆测量的解释，并提供 使用功能磁共振成像研究人类脊髓功能的路线图。

ABSTRACT / SUMMARY This proposal aims to continue our research to identify and characterize resting state functional MRI signals within the grey matter of the spinal cord, and to validate the interpretation of resting state functional connectivity (rsFC) networks in the spine that appear to reflect specific, behaviorally-relevant functions. In the current funding period we have found resting state networks within the cord exhibit more complex connectivity than previously reported, both within and across segments, including significant correlations with the intermediate region and grey commissure that are relevant for autonomic functions and left-right coordination. Importantly, by implementing a dorsal column injury to the cervical spine in a non-human primate, we have confirmed that the strengths of connectivity within these networks are in general related to functional performance, and changes in the networks correspond to behavioral changes in, for example, skilled hand use. We next aim to fully characterize the sub-components of rsFC and relate them to more specific functions. We will acquire sub-millimeter, multi-parametric MR images at high field (9.4T) in squirrel monkeys and address three main aims. (1) We will identify and differentiate rsFC networks within spinal cord using selective lesions and pharmacological interventions to determine which components and network connectivities are affected by specific disruptions of normal sensory or motor pathways. We will isolate circuits affected by (a) reversible block of motor or sensory inputs with pharmacological agents; (b) permanently ablating the drive of motor neurons from primary motor cortex in ventral horn; and (c) disrupting sensory signals to dorsal horn neurons by sectioning dorsal spinal nerve roots. We will follow the evolution of each injury using CEST and DTI to measure the extent and severity of the injury, and DTI and qMT to validate injury severity and quantify changes in axonal integrity and myelination. (2) We will validate the rsFC measures from MRI by comparisons with electrophysiology, micro-stimulation and tract-tracing histology. We will (a) directly stimulate specific nodes while monitoring down-stream activity with electrophysiology and fMRI; (b) perform longitudinal fMRI and microarray recordings of electrical coherences in each monkey subjected to specific interventions (Aim 1); and (c) determine whether regions which appear to be functionally connected by fMRI also show strong anatomical connections by injecting tracers and performing histological assessments post mortem. (3) We will determine the functional and behavioral relevance of rsFC by disrupting each circuit, identifying corresponding changes in rsFC, and relating these changes to performance of skilled hand sensorimotor behavior. By the completion of the study, we will validate rsFC measurements as indicators of spinal cord functions, and establish the fine- grained intrinsic architecture of intra-spinal circuits. These studies will provide new information on the neural organization of the spinal cord, validate the interpretation of BOLD measurements of connectivity, and provide a roadmap for the use of fMRI for studying human spinal cord functions.