Essa S. Yacoub, Ph.D. - US grants

DESCRIPTION (provided by applicant): Functional magnetic resonance imaging (fMRI) has the ability to monitor the vascular response to neuronal activity. The vascular response, changes in local blood flow, blood volume and oxygen consumption, is measured by the corresponding changes in oxygenation levels The paramagnetic nature of deoxygenated hemoglobin serves as a contrast agent for monitoring hemodynamic changes accompanying neural activity. Blood oxygen level dependent (BOLD) contrast has been widely utilized and the method of choice for non-invasive imaging of brain function, specifically in humans. With the application of BOLD fMRl to high spatial resolution mapping of brain function, it is becoming increasingly important to understand the specificity limitations of the vascular response and how to exploit these limits of specificity when using BOLD fMRI. BOLD fMRI may be performed using either T2 or T2' weighted images, both of which have sensitivity, although different, to BOLD effects. Our long-range goal is to realize the limitations of BOLD signals for the purpose of increasing the accuracy of mapping high resolution functional structures in the human brain. The central hypothesis of the proposed research is that T2 weighted BOLD fMRl can be efficiently implemented for high spatial resolution applications in humans and at high magnetic fields maximizes the specificity of the BOLD response. This hypothesis has been formdated from a substantial amount of preliminary data, which suggest feasibility of high resolution T2 weighted BOLD fMRl in humans, and theoretical considerations which predict advantages in specificity and sensitivity for T2 weighted BOLD signals at high magnetic fields. The central hypothesis will be tested and the objective of the application will be accomplished by pursuing three specific aims: 1) Develop a high-resolution T2 weighted imaging sequence for use in the human brain, 2) assess the vascular nature of the T2 response as it changes with fields strength, and 3) to determine whether or not T2 weighted BOLD fMRl is more suited, than conventional T2' weighted BOLD fMRl, for high spatial resolution applicants in humans. The rationale for the proposed research is: T2 weighted BOLD fMRl can provide more detailed and more specific information on microvascufar and hemodynamic changes associated with functional brain activation. As an advanced MR center, we are uniquely positioned to undertake the proposed research. Our laboratory has well-established expertise in functional imaging, advanced hardware and software development, and specialized RF coil design. The proposed research is innovative as high resolution T2 weighted BOLD fMRl in the human brain at submillimeter resolutions has not been feasible to date. We expect that T2 weighted BOLD fMRI will be the imaging method of choice for high spatial resolution applications. This is significant because of the increasing demands to reliably map high resolution functional structures in the human brain. It will advance the field of non-invasive brain mapping to unmatched levels of specificity and sensitivity to neuronal activity.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During the past 4 years, we have challenged the limits of BOLD fMRI to the level of sub-millimeter structures (i.e. cortical columns) in humans and laminar specificity in the animal model. We have established that SE BOLD technique at high fields is more suitable for mapping columnar structures. Our strategy of employing high-field SE BOLD contrast has allowed us to explore, in addition to ODCs, orientation columns in the human brain, which were previously unmapped. Here, we will develop new capabilities for larger volume coverage for high-resolution fMRI acquisitions in humans as well as continued application and development of a high resolution animal fMRI model.

Abstract Not Provided.

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DESCRIPTION (provided by applicant): Currently, the vast majority of magnetic resonance imaging and functional imaging studies are conducted at relatively low magnetic fields of 1.5 or 3.0 Tesla. However, theoretical considerations as well as experimental evidence have suggested that there is a fundamental dependence of image signal to noise ratios, functional imaging contrast and spatial specificity on the magnetic field strength. More recently, it has been suggested that even routine anatomic imaging has potential advantages at high magnetic fields. Thus far, in humans, functional imaging studies have only been done at fields as high as 7 Tesla. Much of the experimental data suggesting advantages for higher field studies have been acquired using animal models. While animal studies provide us with data that can elucidate the biophysics of MRI/fMRI in certain cases, they are not necessarily fully applicable to the human brain. Furthermore, almost all of the studies in humans or animals at high magnetic fields have been done using limited field of views and / or a single or few slices. Shorter T2*s, increased susceptibility effects, increased physiological noise, increased SAR, and inhomogeneous B1 fields can all hinder the advantages offered by high magnetic fields. To alleviate some of the problems associated with these issues and thereby making high field imaging more attractive for general applications of the whole brain, technical development is required. With the recent growth and development of parallel imaging and parallel imaging techniques, including transmit and receive coil arrays, many of these problems commonly observed at high magnetic fields can be addressed. In addition, sequence modification and new sequence design can also help to significantly reduce the technical problems associated with high field studies. The general aim of this proposal is development of fMRI and MRI techniques for whole brain acquisitions at high magnetic fields (7 T &9.4 T). In achieving this aim, fMRI/MRI studies will be conducted at the ultra-high magnetic field of 9.4 Tesla for the first time in humans. Furthermore, we will systematically compare the advantages of higher field systems with lower field systems (3 T) for general applications.

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Architecture; Blood Vessels; Brain; CRISP; Cats; Cell Communication and Signaling; Cell Signaling; Cells; Cognitive; Column of Bertini; Common Rat Strains; Computer Retrieval of Information on Scientific Projects Database; Cortical Column; Data; Domestic Cats; Dominance, Ocular; Encephalon; Encephalons; Engineering / Architecture; Eye Dominance; Feline Species; Felis catus; Felis domestica; Felis domesticus; Felis sylvestris catus; Functional Magnetic Resonance Imaging; Funding; Grant; Hand; Human; Human, General; Institution; Intracellular Communication and Signaling; Investigators; Knowledge; MRI, Functional; Magnetic Resonance Imaging, Functional; Mammals, Cats; Mammals, Rats; Man (Taxonomy); Man, Modern; Maps; Method LOINC Axis 6; Methodology; Monkeys; NIH; National Institutes of Health; National Institutes of Health (U.S.); Neocortex; Nervous System, Brain; Ocular Dominance; Ocular dominance columns; Pattern; Physiologic; Physiological; Process; Property; Property, LOINC Axis 2; Rat; Rattus; Relative; Relative (related person); Renal Column of Bertini; Research; Research Personnel; Research Resources; Researchers; Resources; Signal Transduction; Signal Transduction Systems; Signaling; Source; Structure; System; System, LOINC Axis 4; United States National Institutes of Health; Visual Cortex; base; biological signal transduction; blood oxygen level dependent; day; experiment; experimental research; experimental study; fMRI; gray matter; homotypical cortex; human subject; isocortex; magnetic field; neopallium; research study; sensory cortex; substantia grisea; vascular; visual cortical

ABSTRACT Functional magnetic resonance imaging (fMRI) is undeniably the workhorse for neuroscientists who want localized measurements of neural correlates of human behavior. However, recent studies have presented fMRI results that conflict with traditional invasive (direct) electrophysiological measurements of neural population responses: attention strongly modulates the fMRI response in primary visual cortex (V1) but only weakly modulates neural firing rates; fMRI responses in V1 predict perceptual states while only subtle aspects of direct recordings of V1 neural responses correlate with perception. An important step toward reconciling the differences between fMRI data and invasive electrophysiology is to obtain fMRI data that can map out the details of the local neural population code on a scale that is closer to that sampled by electrodes. The proposed experiments will use 7 Tesla fMRI with sub-millimeter resolution ? a spatial scale comparable to that of the local field potential in electrophysiology ? to determine how the spatial details of the neural population response in V1 depend on visual stimulus properties as well as perceptual state. Because input, output and local connections are segregated according to depth, the primary focus of this research is to dissociate signals at different cortical depths. Several recent literature reports show that the fMRI response amplitude is different at different cortical depths. However, it is not yet established whether depth-dependent fMRI actually reflects local neural network changes at different cortical depths. The following aims seek to verify that fMRI has differential laminar sensitivity that corresponds meaningfully to neural activity. The first aim is to validate layer-specific fMRI against known properties of the intrinsic neural network. While fMRI and electrophysiological measurements of V1 response modulation due to behavioral or perceptual processes (putative feedback processes) disagree, there has been ample demonstration of the agreement between fMRI and electrophysiological measurements of intrinsic neural responses such as contrast sensitivity or orientation selectivity. Two sets of experiments will therefore quantify the depth-dependent fMRI response to simple visual stimuli, validating the fMRI laminar profile against laminar profiles predicted by electrophysiology. The second aim is to study modulation of neural responses in V1 by visual information that is extracted over a larger spatial scale. Enhancement of V1 neural responses by global scene structure (figure/ground segmentation) and suppression of V1 neural responses by uniform texture (orientation-dependent surround suppression) differ importantly in the role of awareness in regulating the modulation in V1. We will quantify fMRI laminar profiles under these two different kinds of contextual modulation. Because both visual feature grouping and iso-orientation suppression are affected by neurological disorders such as autism and schizophrenia, validating a technique for monitoring these mechanisms of visual contextual modulation has utility in the clinical setting.

The six layers of cortex form distinct computational units that together govern the information flow and processing required for complex behavior. Hence, unravelling the brain's computational strategies requires understanding the layer-specific organization of the neocortex. Until recently, layer-resolved recordings have been confined to animal models, ignoring specific properties of the human brain and limiting our ability to study uniquely human functions such as language. The unprecedented opportunity to combine laminar electrophysiology recordings in humans with High-field fMRI in the same human subjects could close this gap; however, inherent vascular artifacts prevent a straightforward depth-resolved interpretation of the BOLD signal. To disentangle vascular from neuronal processes, we propose to develop a neurovascular coupling model by combining the laminar electrophysiology data with laminar fMRI in the same human subjects. To this end, we will exploit a unique opportunity to record ground truth, layer-resolved neuronal activity in epilepsy patients. We hypothesize that such a model - validated using data from patients and controls and multiple tasks - will resolve layer-specific neuronal activation from fMRI responses and will be applicable to the general population, across tasks, and cortical areas ? without the need for additional electrophysiological data. 1