Caffeine dose effect on activation-induced BOLD and CBF responses

Caffeine is a popular psychostimulant, typically found in beverages. While low to intermediate doses of caffeine are associated with positive feelings and increased mental performance and alertness, high doses induce negative feelings such as insomnia, anxiety and nervousness. We investigate if this nonlinear dose-response is present for caffeine's effects on functional activation. Twenty-seven healthy subjects were assigned randomly to four different groups: saline, 1 mg/kg, 2.5 mg/kg and 5 mg/kg doses of caffeine. Simultaneous ASL/BOLD timeseries were collected both before and after an intravenous infusion of saline or caffeine and the task-induced CBF and BOLD percent changes were compared. The maximum increase in BOLD response was associated with the intermediate caffeine dose of 2.5 mg/kg, which increased BOLD response by 32.2% and 32.5% in motor and visual areas respectively. The maximum increase in CBF response was associated with the highest caffeine dose of 5 mg/kg. This difference could be related to a different density of A1 and A2A adenosine receptors in the brain.