Functional MRI investigation of spinal cord resting-state networks and their physiological relevance

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Functional magnetic resonance imaging (fMRI) studies of the resting-state have provided a wealth of information about cortical function, and research in my lab has extended this capability to the brainstem (BS) and spinal cord (SC). Resting-state fMRI studies refer to coordinated blood oxygenation-level dependent (BOLD) responses that occur when no task or stimulus is applied, and therefore the neural activity corresponds with internally-directed cognition. My lab has obtained evidence that coordinated signaling in the SC, in the resting-state, is likely related to descending regulation of SC excitability, via the BS. The concept of resting-state coordination thus extends to the entire central nervous system, and to functions other than cognition. Research in my lab to date has demonstrated the primary sources of physiological noise in fMRI data, their relative contributions, and how to reduce/remove them. This enabled us to confirm that there is extensive coordination within and across BS and SC regions in the resting-state, and to begin to investigate how this coordination is altered by cognitive processes. The proposed research has the goals of 1) furthering our understanding of human SC neurophysiology and how function is regulated on a continuous basis, and 2) developing analysis tools for identifying and studying this regulation. The specific objectives are: Objective 1: Characterize the consistent networks of coordinated signaling in the resting-state across the BS and SC, in terms of regions and connections, rates of occurrence, and connection strengths. Objective 2: Identify variations in rs-networks across healthy people, and the relationships between resting-state connectivity and various functions (based on prior research), including; 1) pain sensitivity, 2) motor activity related to cardiac and respiratory function, 3) autonomic regulation. Objective 3: Develop and validate software tools for analysis and visualization of results for resting-state analyses in the BS and SC. The proposed research will provide a wealth of training opportunities for approximately 6 graduate students, as well as undergraduate thesis projects, and will contribute to our overall understanding of BS and SC function in healthy humans. It will also improve the tools we have available to do this research. It is expected that an understanding of these networks/systems and their continuous regulation will support future research into better understanding the effects of a wide variety of diseases and effects of injuries. Continuous resting-state function may be central to maintaining homeostasis of a number of systems and therefore may be a very important feature of our physiology. The proposed research thus has the potential for significant impact on our understanding of all functions that involve the brainstem and spinal cord.