The work presented here uses combined blood oxygenation level-dependent (BOLD) and arterial spin tagging (AST) approaches to study the effect of indomethacin on cerebral blood flow (CBF) and oxygen consumption (CMRO 2 ) increases during motor activation. While indomethacin reduced the CBF increase during activation, it did not significantly affect the CMRO 2 increase during activation. The ratio of the activationinduced CBF increase in the presence and absence of indomethacin was 0.54 ؎ 0.08 (؎SEM, n ؍ 8, P < 0.001), while the ratio of the CMRO 2 increase in the presence and absence of the drug was 1.02 ؎ 0.08 (؎SEM, N ؍ 8, ns There is increasing interest in using functional magnetic resonance imaging (fMRI) to investigate drug effects on regional brain activity. One approach has been to study the effects of drugs on the amplitude of the MR signal, which has been called pharmacological MRI (phMRI) (1). phMRI effects have been studied with the use of cocaine (2), metamphetamine (3), diazepam (3), nicotine (4), and indomethacin (5). Another approach has been to study the effects of drugs on the focal blood oxygenation level-dependent (BOLD) signal observed during activation protocols. Studies have examined the effects of cocaine, alcohol, indomethacin, and caffeine on BOLD signals observed during visual stimulation (5-8); the effect of alcohol on BOLD signals observed during auditory stimulation (9); the effects of caffeine and methylphenidate on BOLD signals observed during motor stimulations (8,10); and the effects of amphetamine, physostigmine, lorazepam, and scopolamine on cognitive tasks (11-13). The work presented here focuses on the second approach, i.e., the effect of drugs on BOLD signals observed during activation.BOLD signals are a function of changes in the cerebral metabolic rate of oxygen (CMRO 2 ) and cerebral blood flow (CBF) during activation (14). Drugs that affect BOLD signals can do so by altering the CMRO 2 or CBF changes, or both. The main problem in interpreting drug-induced changes in BOLD signals is to separate the metabolic effects of the drug from the vascular effects. One way to accomplish this is to use the approach proposed by Davis et al. (15), Hoge et al. (16), and Kim et al. (17). They used a simple model to interpret combined arterial spin tagging (AST)/BOLD data in terms of CMRO 2 and CBF changes during activation. In the current study we extended this approach to separate the effects of indomethacin on CMRO 2 changes during motor activation from the effects of indomethacin on CBF changes during motor activation. Indomethacin, which has previously been shown to affect BOLD signals observed during visual activation (5), was chosen for these initial studies because its vascular effects are rapid (5), which enables control and drug experiments to be performed in the same exam, and long-lasting (18), which allows sufficient time to average the AST data.
