This project will develop, analyze and evaluate methods that enable the efficient use of functional Magnetic Resonance Imaging (MRI) using blood oxygenation level dependent (BOLD) contrast in regions of the brain that are proximal to tissue interfaces with air or bone. This project is motivated by the large signal voids and image distortions caused by magnetic susceptibility differences between tissue and air or bone. These artifacts are ubiquitous in fMRI for many inferior brain structures, for example, orbito-frontal cortex, inferior and medial temporal lobes, brain stem structures and the frontal pole. This project is further motivated by a trend in fh4RI towards using higher magnetic field systems, which improves sensitivity in many parts of the brain, but also exacerbates the artifacts. Many current techniques to remove these distortions have a large cost in terms of temporal resolution or sensitivity for detection of activation. As part of the research plan, methods will be developed that reduce the susceptibility-induced artifact but preserve the speed, robustness to motion and physiological noise, and contrast sensitivity of standard single- shot fMRI techniques. Unlike many other approaches, we will address both in-plane and through-plane sources of artifact. The methods under investigation include three-dimensional tailored excitation pulses and asymmetric spin-echo acquisitions for reduction of signal voids, and iterative image reconstruction methods and parallel receiver coil imaging for reduction of imaging distortions. These methods will be evaluated with respect to effectiveness in reducing susceptibility-induced artifact, reliability of activation in visual and motor areas, sensitivity to activation in the amygdala structure near the paranasal sinus, and temporal accuracy. Success in this project will lead to valuable new fMRI methods capable of probing all major brain structures in a manner that is sensitive to functional activation and robust to artifacts. The methods will be fast and sensitive to BOLD contrast, allowing common fMRI techniques, like event-related studies, to be used over the entire brain. In addition, they will dramatically aid in the study of brain regions implicated in a wide variety of neurological, psychiatric, and behavioral disorders, including pain disorders, affective disorders, schizophrenia, and alcohol and drug abuse.