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. Modern neuroimaging such as fMRI and PET has opened up enormously exciting frontiers for studying brain function and human behavior. Understanding the relation between the imaging signals and the underlying brain physiology has become increasingly important and urgent. Although tremendous insights about neurovascular coupling have been gained, it is still elusive of the quantitative relation between brain metabolic energy and neuronal activity (i.e., neurometabolic coupling). Particularly important and intensely debated question is how much increases of cerebral metabolic rate of oxygen (CMRO2) are needed, or can be provided by brain for supporting task-evoked neuronal activity. The major challenge in this regard is the lack of a fast, noninvasive and quantitative method able to directly image absolute CMRO2 at both basal and activated brain states. The high-field 17O MRS imaging (MRSI) approach for imaging CMRO2 which has been successfully developed by us over the first funding cycle could overcome this hurdle. This innovative and unique approach offers a golden opportunity for studying the neurometabolic coupling and its impact on brain function. A large body of our preliminary results has not only demonstrated the feasibility, reliability and applicability of this 17O-based CMRO2 imaging approach, but also provided crucial evidence showing the importance and possible mechanism of cerebral oxidative metabolism for supporting brain energy at rest and during activation. These findings lead us to hypothesize that cerebral oxidative metabolism should be the major energy source for both resting and activated brain due to the tight neurometabolic coupling;however, its capacity might be limited which in large is used for intrinsic brain activity at rest;thus, there exist a strong correlation between task-evoked CMRO2 change and baseline CMRO2, and an energy compensation mechanism for utilizing brain energy during brain activation with optimal efficacy. This central hypothesis will be examined in the cat brain through four testable hypotheses and four specific aims by using 17O-based CMRO2 imaging approach combined with other established approaches including electrophysiology recording. This research will (i) highlight the importance of cerebral oxidative metabolism at both baseline and activated brain states;(ii) elucidate the mechanism of cerebral bioenergetics associated with neuronal activity and brain function;and (iii) provide the neurophysiology basis for modern neuroimaging techniques. Relevance to public health: This research could provide new insights about crucial impact of cerebral oxidative metabolism on the brain disorders and dysfunctions associated with oxidative metabolism abnormality. The success in developing the 17O-based CMRO2 imaging modality will further enhance the ability of MR technology in neuroscience discovery and potentially in diagnosis of brain diseases.
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