Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) provides a critical tool to the medical and scientific communities. Despite the indispensable role of the BOLD fMRI technique in mapping human brain function, MRI cannot be readily used to map sub‑millimeter functional structures such as cortical columns due to its relatively broad point spread function, which extends beyond the neuronally active area. It has been proposed, however, that a BOLD signal decrease, which precedes the positive BOLD signal change, can be used to improve the spatial specificity of fMRI. This early negative BOLD signal (sometimes referred to as the """"""""dip"""""""") is presumably induced by an early localized increase in oxygen consumption rate without a commensurate localized cerebral blood flow (CBF) increase. Recently, by using the early negative BOLD signal, mapping of functional columns in the cat visual cortex has been successfully achieved in our laboratory. However, the existence of the dip in other species is highly controversial. Further, the negative BOLD signal change observed so far is small and transient, thus its utility to columnar resolution fMRI is limited. Therefore, to fully utilize the dip for functional imaging, it is imperative to understand the biophysical and physiological sources of the early negative BOLD signal change. In this application, we aim to elucidate the origin of the early negative BOLD signal and determine the spatial specificity of fMRI techniques. This will be accomplished by using a well‑established feline orientation column model at an ultra‑high field of 9.4 Tesla. The hypotheses to be tested are: 1.) The source of the early negative BOLD signal change is an early oxygen consumption increase followed by a delayed CBF increase. 2.) The magnitude and dynamics of the early negative BOLD signal are heavily influenced by changes in CBF during increased neural activity. 3.) Columnar structures can be mapped using the CBF response as well as the early negative BOLD signal. The long‑term goal is to improve the spatial resolution of fMRI, so that it will ultimately yield the capability of mapping columnar structures in both animals and humans non‑invasively. Further insight into functional columnar organization in animals and humans will greatly facilitate our basic understanding of the structure, development and plasticity of cortical maps.
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