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 suggest these patterns depict neural circuits of functional significance. Moreover, their changes post-injury suggest they may provide practical imaging biomarkers of functional integrity. These preliminary 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 he SC. Our preliminary studies in humans and NHPs have adduced strong evidence that resting state variations are reliably measureable and produce patterns suggestive of distinct neural circuits within and across spinal segments. However, although resting state correlations in brain are already being widely exploited, their precise interpretation remains 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 th spatial connectivity patterns of resting state fMRI signals at sub-millimeter 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] evaluate 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 potentially establish new insights into the functional architecture of the SC and open a new field of investigation into 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.