We have recently developed a non-invasive method for mapping the rate of cerebral metabolic oxygen consumption (CMRO2) in the human brain. The method calibrates the blood oxygenation level dependent (BOLD) FMRI signal, using mild and well-tolerated respiratory challenges (hyperoxia and hypercapnia), to measure the fraction of oxygen extracted (OEF) from blood on its passage through the brain. Given the reliance of the brain’s energy supply on oxidative metabolism, CMRO2 offers a good marker of brain activity levels. Until now its measurement has only been possible through the use of radioactive tracers in positron emission tomography (PET). The present project aims to develop our MRI-based CMRO2 mapping technique to speed it up, maximizing the efficiency of data collection, and to demonstrate the proof-of-concept for its use as a tool to map pharmacologically-induced alterations in cerebral metabolism. This proof-of-concept study will be performed using oral caffeine in healthy volunteers. Caffeine is safe, commonly ingested in the population and well known to have a vasoconstrictive effect and thus alters substantially OEF, the measurement of which lies at the core of our method. Success in this project will promote the use of our method in research investigations and clinical trials of neurological and psychiatric disease and their pharmacological treatments.