Fractional changes in BOLD, CBF and CMRO2 relative to either the pre-caffeine baseline (a–c) or relative to the baseline immediately preceding the stimulus (d–f). Blue time courses are pre-caffeine. Red time courses are post-caffeine. Black bars indicate stimulus on period of 20 s. Error bars indicate ± s.e.m. At baseline, error is considered relative to 0. Evoked response s.e.m. is considered relative to mean baseline shown. Percent changes from the pre-caffeine baseline: a, The BOLD baseline was shifted post-caffeine (change of −6.27±1.1%, p<0.001), while the BOLD response to the visual stimulus was not significantly different (change of −3.64±7.3%, p=0.63). b, There was a large overall decrease in the baseline CBF (−26.9±3.5%, p<0.001) and in the fractional δCBF response post-caffeine (−20.3±8.2%, p=0.036). c, In contrast to the baseline CBF decrease, there was a trend for increased baseline CMRO2 (+21.8±8.4%, p=0.030), and the δCMRO2 response to the visual stimulus was dramatically increased (60.7±9.5%, p<0.001) post-caffeine. Conventional analysis showing percent changes relative to the baseline preceding the stimulus: d, Baseline shifts are no longer apparent, and the BOLD response to the visual stimulus remained unchanged (pre=1.20±0.09 versus post=1.23±0.07, p=0.67). e, When considered relative to the baseline preceding the stimulus, the fractional δCBF response increased slightly relative to the pre-caffeine response (9.28±10.2%, p=0.38). f, Similarly, the fractional δCMRO2 response also increased (34.0±10.7%, p=0.01) but less so than when considered relative to the pre-caffeine baseline.