PROJECT SUMMARY Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) is widely used as a non-invasive technique to study brain function. It operates based on the premise that cerebral blood flow renews the supply of energetic substrates to brain regions with increased neuronal activity in a process known as neurovascular coupling.
Project Summary/Abstract The electroencephalogram (EEG) and magnetoencephalogram (MEG) are directly and instantaneously coupled to the currents across cortical neuronal membranes which mediate information processing. They are widely used for both clinical diagnosis and for investigating the neural mechanisms of cognition with excellent temporal resolution. The goal of this application is to advance our understanding of the relationships between brain imaging signals at the macroscopic levels – EEG and MEG - and the underlying circuits and cellular activity at the fine-grained scales.
The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use noninvasive technologies. This is in contrast to animal models where a rich, detailed view on the cellular level brain function has become available due to recent advances in microscopic optical imaging and genetics.
Project Description Functional MRI (fMRI) based on the blood oxygenation level dependent (BOLD) contrast has become a powerful neuroimaging modality and has gained a prominent position in neuroscience for imaging brain activation at working state and functional connectivity at rest. However, most of fMRI research focus on functional mapping of brain activity at the system level with macroscopic scale. Recently, high-resolution fMRI at ultrahigh field has shown the feasibility of mapping the functional activity of elementary computational units from ocular dominance to orientation column.
PROJECT SUMMARY Our knowledge of signal processing in various parts of the human brain has been heavily influenced by non- invasive functional magnetic resonance imaging (fMRI) experiments. FMRI infers the location and selectivity of neural activity from vascular signals. However, brain circuits are much more complex than regional differences in neuronal selectivity. Specifically, the largest part of the brain (neocortex) accounts for up to 80% of the brain volume and is divided into six distinct layers. Specific computations, e.g., local processing vs. feedforward inputs vs. vs.
The blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) fluctuations used to map functional connectivity contain a wealth of information about neural activity and physiological processes in the brain. Most functional connectivity studies wish to detect time-varying activity related to cognition and information processing, and view the presence of other contributors to the spontaneous BOLD fluctuations as a complication.
Project Summary / Abstract A major obstacle in the study of human brain function is that we currently have limited understanding of how the measurements made by different instruments, such as fMRI and EEG, relate to one another and to the underlying neuronal circuitry. Significant efforts have led to development of models within various specialist fields, but fragmentation has held us back from advancing our interpretation of the spatiotemporal characteristics of non-invasive imaging signals.
PROJECT SUMMARY/ABSTRACT All fMRI signals have a vascular origin, and this has been believed to be a major limitation to precise spatiotemporal localization of neuronal activation when using hemodynamic functional contrast such as BOLD. However, significant recent discoveries made using powerful ultrahigh-resolution optical imaging techniques have challenged this belief. Unfortunately these measures require invasive procedures and therefore cannot be performed in humans.
Project Summary This RFA is aimed at bringing together interdisciplinary teams to focus on novel, transformative and integrative efforts that will revolutionize our understanding of the biological and bioinformatics content of the data collected from non-invasive human functional brain imaging techniques. Our proposal does exactly this. We are a multidisciplinary team of scientists with combined expertise in optogenetics, two photon Ca2+ imaging, biomedical engineering, molecular biology, animal and human fMRI, network theory, data analysis and modeling.
Neuronal Substrates of Hemodynamic Signals in the Prefrontal Cortex PIs: Dr. John P. O'Doherty and Dr. Doris Tsao Institution: California Institute of Technology PROJECT SUMMARY fMRI is the dominant technique for probing human prefrontal cortex functions in cognition, learning and decision-making. This work is predicated on the assumption that fMRI activation relates in a principled manner to the underlying neuronal activity in a given area of prefrontal cortex.
