Investigating resting-state BOLD fMRI in the human spinal cord as a means to improve imaging methods and understanding of spinal cord physiology

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Regulation of the excitability of spinal cord neurons by higher structures in the brainstem has been studied extensively and is an important component of sensory and pain perception. It is also important for quantitative MRI methods because this regulation may produce an unknown source of signal variance in time, even in the absence of a stimulus. Moreover, this descending regulation, and whether it is active and continuous, or entirely reactive to sensory or proprioceptive input, is important to our understanding of normal spinal cord function. Resting-state functional magnetic resonance imaging (fMRI) studies in the brain have proven to be extremely valuable for our understanding of cortical function, and there is now evidence for resting-state blood oxygenation-level dependent (BOLD) fluctuations in the cord and brainstem as well. The proposed research is part of a larger research program, and aims to answer two key questions: Are the apparent resting-state BOLD fluctuations in the spinal cord related to physiological motion, or natural fluctuations in blood gases during the respiratory cycle? Do the resting-state fluctuations change during sensory, motor, or cognitive stimulation? The answers to these questions will confirm whether or not there are continual natural variations in neural activity in the spinal cord, thereby improving our understanding of spinal cord function. Determining the contributions (if any) from physiological motion and variations during respiration will help to improve the sensitivity of quantitative MRI methods in the spinal cord.****  The proposed research builds upon my years of work to develop functional MRI methods for the brainstem and spinal cord. This work includes developing optimal imaging methods, writing dedicated analysis software, and characterizing sources of noise (i.e. unidentified or unpredictable signal variance) and artifacts in MR images of the spinal cord. Because of this prior work and experience, I am in a unique position to carry out the proposed research. The innovative approach I will take is to isolate the various contributions to MRI signal variance based on their origins and temporal properties as determined in previous studies, and identify the BOLD contribution. How the BOLD contribution varies with MR data acquisition parameters, and with motor, sensory, and cognitive functions, will demonstrate its origin(s).****  The proposed research presents valuable training opportunities for graduate students and research assistants, and continues my long record of training highly successful students. The skills and experience gained will contribute to a deep understanding of fMRI methods and the underlying theory, as well as understanding of spinal cord and brainstem neurophysiology. More importantly, it will provide valuable broader experience of multi-disciplinary research that can be carried into a wide range of future career paths.******