Functional magnetic resonance imaging (fMRI) studies have produced much of our current knowledge about the functional organization of the human brain. fMRI studies make inferences about neural activity by measuring changes in local blood oxygenation, typically assuming a canonical hemodynamic response function (HRF) that evolves over several seconds. Due to these assumed slow hemodynamics, while fMRI has been a powerful tool for localizing brain activity, it has mostly been limited to mapping activity patterns at low temporal resolution. However, recent studies have demonstrated that the hemodynamics can react much more quickly than previously thought, and that fast fMRI can be used to directly image responses to oscillatory neural activity, suggesting new possibilities for applying fMRI to study fast brain activity. Many high-level cognitive processes, such as attention, language, and perceptual awareness, are associated with 0.1?1 Hz dynamics that cannot currently be precisely localized with noninvasive methods, and these could potentially be studied directly using fast fMRI approaches. An essential step towards using fast fMRI for neuroscience investigations is to identify the physiological properties of these fast BOLD responses: what mechanisms generate fast hemodynamic responses, and how fast and local can these responses be? This project aims to identify the neurovascular dynamics that enable fast fMRI responses, and advance the ultimate spatiotemporal resolution that can be achieved when using fast and ultra high field fMRI. We hypothesize that prolonged and rapidly varying neural activity causes a slow plateau in baseline vessel dilation, which allows fast fluctuations in blood flow to the stimulated brain region, and thus leads to fast and spatially localized responses. This `sustained dilation' hypothesis makes several specific predictions that we will test through advanced methods for human brain imaging of cerebral blood flow, cerebral blood volume, and blood oxygen level dependent (BOLD) fMRI, to identify the vascular dynamics underlying fast responses. We will then advance our acquisition and analysis approaches to explore the boundaries of the possible spatiotemporal resolution of fast BOLD fMRI. Using ultra high field imaging we will test whether oscillatory stimuli elicit more spatially precise hemodynamic responses, across the cortical surface and laminar depth, providing a new experimental paradigm that leads to more neuronally specific fMRI responses. We will also test whether this spatial information can be exploited to detect even faster (up to 1 Hz) responses by selectively analyzing voxels in the middle cortical depths.
These aims will identify the vascular dynamics underlying rapid fMRI responses, and will test the limits of the possible spatiotemporal resolution of neural activity at faster timescales. The ultimate goal is to provide a scientific and technical foundation enabling future fMRI studies to directly map 0.1-1 Hz neural dynamics throughout the human brain.

Public Health Relevance

Functional magnetic resonance imaging is the primary method used to study the organization of the human brain. However, it is typically limited to studying slow changes in brain activity. This study will investigate the biology of faster fMRI signals and will develop new imaging approaches to enable higher resolution measurements of human brain activity.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Biomedical Imaging Technology Study Section (BMIT)
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Babcock, Debra J
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Massachusetts General Hospital
United States
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