Resting State Connectivity in Primate Spinal Cord

 描述(申请人提供)：这项建议旨在检测和描述脊髓(SC)内功能磁共振(FMRI)信号静息状态波动的区域间相关性，并验证其神经元和解剖学基础作为功能连通性的衡量标准。我们在人类和猴子的脊髓灰质不同角之间的MRI信号同步变化的发现表明，这些模式描绘了具有功能意义的神经回路。此外，损伤后它们的变化表明它们可能提供实用的功能完整性的成像生物标记物。我们在人类受试者身上的早期研究刺激了这个使用非人类灵长类动物(NHP)进行研究的平行计划。我们将使用非常高分辨率的高场成像(9.4T)来研究麻醉猴子脊椎灰质中的网络，扩展我们之前对初级体感皮质功能组织的研究。虽然已经有几千项研究报告使用静息状态功能磁共振来检测和表征大脑中的功能连接，但到目前为止，只有少数几项关于任务诱导激活的研究，而且以前没有可靠的结果表明静息状态在SC的灰质中波动。我们在人类和NHP上的初步研究援引了强有力的证据，表明静息状态变化是可靠的可测量、可重复性的，并产生描述脊柱节段内和跨脊髓节段的不同神经回路的模式。然而，尽管大脑中静息状态的相关性已经被广泛利用，但它们的准确解释仍然不清楚，它们作为功能连接指标的生物物理基础也没有得到证实。脊椎的情况更是如此，我们对详细的血管生理学或特定功能神经回路的组织知之甚少。因此，我们建议[1]表征NHP脊髓中亚毫米分辨率的静息状态fMRI信号的空间连通性模式；[2]通过与定量电生理学和组织学的比较来验证静息状态fMRI信号的连通性测量；以及[3]通过药物操作和脊髓损伤前后的比较来验证静息状态fMRI信号的连通性测量的解释。我们将获取静息状态的fMRI数据，进行电生理测量，评估猴子在单侧脊柱横断损伤前后以及传入信息药物调节后的死后组织学行为和连接。总体而言，这项研究将对SC的功能结构建立新的见解，并为研究SC在正常和病理条件下的功能提供新的机会。为应用静息状态MRI评价脊柱损伤后的功能完整性和功能恢复提供了坚实的基础。

 DESCRIPTION (provided by applicant): This proposal aims to detect and characterize inter-regional correlations in resting-state fluctuations of functional magnetic resonance (fMRI) signals within the spinal cord (SC), and to validate their neuronal and anatomical bases as measures of functional connectivity. Our discovery of synchronized variations of MRI signals between the various horns of spinal cord grey matter in humans and monkeys suggest these patterns depict neural circuits of functional significance. Moreover, their changes post-injury suggest they may provide practical imaging biomarkers of functional integrity. Our earlier studies in human subjects have stimulated this parallel program of research using non-human primates (NHPs). We will use very high-resolution imaging at high field (9.4T) to study networks in the grey matter of the spines of anesthetized monkeys, extending our previous studies of the functional organization of primary somatosensory cortex. Although there have been several 1000s of studies reported that have used resting state fMRI to detect and characterize functional connectivity in the brain, to date there have been only a handful of studies of task-induced activation, and no previous reliable findings of resting state fluctuations, in the grey matter of the SC. Our preliminary studies in humans and NHPs have adduced strong evidence that resting state variations are reliably measurable, reproducible, and produce patterns depicting distinct neural circuits within and across spinal segments. However, although resting state correlations in brain are already being widely exploited, their precise interpretation remain unclear, and their biophysical basis as indicators of functional connectivity is unsubstantiated. This is even more the case in the spine, where we have much less knowledge of the detailed vascular physiology or organization of specific functional neural circuits. We therefore propose [1] to characterize the spatial connectivity patterns of resting state fMRI signals at sub-millimetr resolution in the spinal cords of NHPs; [2] validate the connectivity measures from resting state fMRI signals by comparisons with quantitative electrophysiology and histology; and [3] validate the interpretation of connectivity measures from resting state MRI signals by comparisons before and after pharmacological manipulations and spinal cord injury. We will acquire resting state fMRI data, perform electrophysiological measurements, evaluate behavior and quantify connectivity from post-mortem histology in monkeys before and after unilateral transectional injuries to the spine, and after pharmacological modulation of afferent inputs. Overall, this research would establish new insights into the functional architecture of the SC and provide new opportunities to investigate SC function in normal and pathological conditions. It would provide a firm foundation for the application of resting state MRI to assess the functional integrity and recovery post-injury of the spine in patients suffering a variety of disorders of the SC.