Caffeine dose effect on activation-induced BOLD and CBF responses

Abstract

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 A(1) and A(2A) adenosine receptors in the brain.

Figures

Figure 1

Measured plasma caffeine concentrations from collected blood samples, averaged over all subjects in each group. Error bars represent standard errors for each group. The baseline timepoint was calculated as the average of the two baseline blood samples.

Figure 2

CBF data collected during infusion, normalized as percent change from mean of first 60s. Each timepoint is the average signal of a whole brain gray matter region-of-interest. a) Saline (green) and 1mg (pink) data. b) 2.5mg (blue) and 5mg (red) data. Black arrow marks the onset of infusion. No change from baseline was observed for saline, but significant decrease was seen for the three caffeine doses after the initial 60s of baseline.

Figure 3

BOLD data collected during infusion, normalized as percent change from mean of first 60s. Each timepoint is the average signal of a whole brain gray matter region-of-interest. a) Saline (green) and 1mg (pink) data. b) 2.5mg (blue) and 5mg (red) data. Black arrow marks the onset of infusion. No change from baseline was observed for the lowest caffeine dose and saline, but significant decrease was seen for the two higher doses.

Figure 4

Event-related BOLD timecourses for saline (top row), 1mg/kg (middle row) and 5mg/kg (bottom row) for both motor (left) and visual (right) cortices, averaged over all trials and all subjects.

Figure 5

Graph of percent change in task-related BOLD and CBF activation post-infusion relative to pre-infusion for the four groups.