Principal Investigators(Last, first, middle):KLEINFELD, DAVID and ROSEN, BRUCE R. Functional magnetic resonant imaging (fMRI) is the only means to infer neuronal activity within the entire volume of the human brain. A powerful aspect of fMRI concerns coordinated fluctuations in the amplitude of blood oxygen level dependent (BOLD) signals across distant regions of the brain, which are interpreted as resting-state functional connections. Here we address the underlying biophysical mechanism that underlies resting-state functional connectivity. Our hypothesis is that the natural ultra-low frequency oscillations in the smooth muscle of arteriole walls, termed vasomotion, acts as an intermediate oscillator that links oscillations in neuronal activity with the blood oxygenation and thus fMRI signals. Rodent models permit us to test this hypothesis through detailed two-photon imaging, advanced fMRI measurements, and manipulations of cortical vascular dynamics and blood oxygenation under controlled conditions. We then advance the spatial resolution of ultra high field MR imaging in humans to image single intracortical vessels, with 100 micrometer or better resolution, to test whether vasomotion may be a unifying mechanism for resting and task-driven fMRI signals. The results of these studies have two consequences. One is to provide the underpinnings for interpreting resting state connectivity relative to neuronal projections. The second is a new model of mapping functional connections via changes in arteriole volume. In particular, the strong homologies between the physiology of rodents and primates suggest that these methods can be extended to map resting- state functional connections in the human brain with higher resolution and greater precision than previously achieved. This new mechanistic insight will advance our use of fMRI to study cognition and a variety of neuropsychiatric disorders.

Public Health Relevance

Program Director (Last, first, middle): Kleinfeld, David and Rosen, Bruce R. Functional magnetic resonant imaging (fMRI) is a unique tool that permits a detailed inference of neuronal activity within the entire volume of the human brain during task stated. A particularly powerful aspect of fMRI concerns measurements of coordinated brain activity at extremely low frequencies, corresponding to periods of ten seconds, but the neurobiological meaning of these correlations remains unclear. Here we explore a hypothesis that directly links these fMRI-derived ?resting state? signals with real neuronal connections, providing a mechanistic understanding of the link between local and long range electrophysiological signaling and functional MR signals.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Special Emphasis Panel (ZMH1)
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Bennett, Yvonne
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University of California, San Diego
La Jolla
United States
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Polimeni, Jonathan R; Uluda?, Kâmil (2018) Neuroimaging with ultra-high field MRI: Present and future. Neuroimage 168:1-6
Polimeni, Jonathan R; Wald, Lawrence L (2018) Magnetic Resonance Imaging technology-bridging the gap between noninvasive human imaging and optical microscopy. Curr Opin Neurobiol 50:250-260
Papadopoulos, Lia; Blinder, Pablo; Ronellenfitsch, Henrik et al. (2018) Comparing two classes of biological distribution systems using network analysis. PLoS Comput Biol 14:e1006428
He, Yi; Wang, Maosen; Chen, Xuming et al. (2018) Ultra-Slow Single-Vessel BOLD and CBV-Based fMRI Spatiotemporal Dynamics and Their Correlation with Neuronal Intracellular Calcium Signals. Neuron 97:925-939.e5
Polimeni, Jonathan R; Renvall, Ville; Zaretskaya, Natalia et al. (2018) Analysis strategies for high-resolution UHF-fMRI data. Neuroimage 168:296-320
Mateo, Celine; Knutsen, Per M; Tsai, Philbert S et al. (2017) Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent ""Resting-State"" Connectivity. Neuron 96:936-948.e3
Báez-Yánez, Mario Gilberto; Ehses, Philipp; Mirkes, Christian et al. (2017) The impact of vessel size, orientation and intravascular contribution on the neurovascular fingerprint of BOLD bSSFP fMRI. Neuroimage 163:13-23