7. Project Summary/Abstract (No more than 30 lines) The origin of the low frequencies (below 0.05Hz) resting state cerebral hemodynamic fluctuations (CHF) in default mode network (DMN) and other resting state networks (RSNs) remains unknown. We hypothesized that CHF at low frequencies correlated with fluctuations in resting systemic metabolism obtained from respiratory gas exchange measurements (O2 uptake, CO2 release and their ratio) in spontaneous breathing. We introduced a new brain-body interaction showing a strong correlation between CHF and breath-by-breath O2-CO2 exchange ratio (bER) which is a ratio of O2 uptake to CO2 release. With transcranial Doppler sonography and functional magnetic resonance imaging, bER was shown to be better than O2 uptake which in turn was far better than CO2 release in correlation with CHF. The superiority of O2 uptake over that of CO2 release indicates that O2 uptake and CO2 release are not redundant in their correlation with CHF. The coherence of bER with CHF was shown to be significant at the frequency range between 0.03Hz and 0.008Hz with the coherence getting stronger and stronger at lower and lower frequencies. Brain regions with strong bER-CHF coupling overlapped many areas of the default mode network (DMN), suggesting a potential association between oscillations of resting systemic metabolism characterized by bER and the rhythm of background brain activities characterized by DMN. We propose to study 60 normal individuals to increase our neuroimaging data base to improve our understanding on the role of bER-CHF coupling, a brain-body interaction between systemic metabolism and resting state brain activities, especially those at DMN. Such a data base will not only support more research on the basic mechanism of DMN and other cerebral resting state oscillations but also provide opportunities for future clinical research which images brain markers for conditions that modulate respiratory gas exchange for diagnostic as well as therapeutic purposes.