? In this research, we will focus on spatial and temporal resolution of the autofluorescence signal induced by neural activity. Optical imaging of autofluorescence signal of mitochondrial endogenous flavoprotein can be used for monitoring spatial and temporal patterns of neural activity from a relatively large cortical area of the brain with high spatial and temporal resolution. Despite a long history of optical measurements of cellular autofluorescence and recent successful attempts of flavoprotein imaging in rodent cortex in vivo, application of this technique to phylogenetically higher animals and humans for functional brain mapping has been underestimated.
The specific aim of this proposed research is to investigate the feasibility of flavoprotein autofluorescence imaging for functional brain mapping in phylogenetically higher animals' visual cortex whose functions are relevant to the human brain. Our long-term goal is to elucidate the spatiotemporal correlation between neuronal activity and their metabolic responses induced by stimulation, and inherent spatial and temporal resolution of the metabolic-based functional brain imaging. The specific hypotheses to be tested are: 1) neural activity-dependant metabolic change detected by flavoprotein autofluorescence signal is highly confined to neural active sites, and 2) the flavin autofluorescence signal immediately emerges after the onset of stimulation. We base these hypotheses on general observations that i) a stimulus-induced increase in gluclose utilization is well localized to neural active sites and that ii) a stimulus- induced tissue oxygen tension change is tightly correlated with neural spiking activity. We will test these hypotheses on the model of orientation columns in the primary visual cortex. The orientation column is a functional structure related to stimulus orientation, in which neurons in response to the same orientation cluster together and form columns through pia to white mater, and it has been extensively investigated electrophysiologically, anatomically, and with hemodynamic-based optical imaging of intrinsic signals. The orientation maps obtained from flavoprotein signal will be quantitatively compared to the maps of the well- established hemodynamic-based intrinsic signals for its evaluation. We believe that the establishment of this technique will greatly improve the acuracy of mapping neural activity which will provide cruicial information for diagnosis and treatment of disease and human brain functions. ? ? ?

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZEB1-OSR-A (M1))
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Zhang, Yantian
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University of Pittsburgh
Schools of Medicine
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Fukuda, Mitsuhiro; Vazquez, Alberto L; Zong, Xiaopeng et al. (2013) Effects of the ??-adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex. Eur J Neurosci 37:80-95
Vazquez, Alberto L; Fukuda, Mitsuhiro; Kim, Seong-Gi (2012) Evolution of the dynamic changes in functional cerebral oxidative metabolism from tissue mitochondria to blood oxygen. J Cereb Blood Flow Metab 32:745-58