Caffeine's effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism

Abstract

The blood-oxygenation-level-dependent (BOLD) signal is dependent on multiple physiological factors such as cerebral blood flow (CBF), local oxygen metabolism (CMRO(2)) and cerebral blood volume (CBV). Since caffeine affects both CBF and neural activity, its effects on BOLD remain controversial. The calibrated BOLD approach is an excellent tool to study caffeine because it combines CBF and BOLD measures to estimate changes in CMRO(2). The present study used the calibrated BOLD approach with 5% CO(2) to determine if a 2.5 mg/kg intravenous injection of caffeine changes the coupling between CBF and CMRO(2) during motor and visual tasks. The results show that caffeine decreases n, the CBF:CMRO(2) coupling ratio, from 2.58 to 2.33 in motor (p=0.006) and from 2.45 to 2.23 in visual (p=0.002) areas respectively. The current study also demonstrated that caffeine does not alter cerebrovascular reactivity to CO(2). These results highlight the importance of the calibrated BOLD approach in improving interpretation of the BOLD signal in the presence of substances like caffeine.

Figures

Figure 1

Experimental design. Each study was divided into two identical sessions by a 10 minute injection of 2.5mg/kg caffeine diluted in a 50ml saline solution. Each of the sessions consisted of two functional scans and two hypercapnia scans. During the functional scans, subjects performed auditory-cued bilateral finger tapping and viewed a grayscale flashing checkerboard simultaneously. Two levels of stimulation frequency were used for the functional scans to ensure a good fit for the coupling ratio, n. 5% CO2 was used for all resting –state hypercapnia scans. Functional paradigms for the functional and hypercapnia scans are also shown.

Figure 2

a) Disposable mouthpiece and nose clip used for delivery of CO2. b) A 100L nondiffusable bag used for storage of CO2 gas mixture. White arrow marks the valve used to switch between gas mixture in bag and room air. c) Red rectangle marks the position of the slices acquired in the functional and hypercapnia scans.

Figure 3

CBF and BOLD timecourses collected during the hypercapnia scans, averaged over the two scans in each session for all 14 subjects. Thick red line marks the time during which CO2 was administered. Notice the pre- and post-caffeine CBF timecourses appear identical, whereas the BOLD amplitude increased after caffeine.

Figure 4

Average M values calculated by fitting Equation [1] to the hypercapnia data from all subjects. Error bars denote standard deviation. In both motor and visual cortices, caffeine increased M, signifying a change in resting state physiology.

Figure 5

%ΔCMRO2 vs. %ΔCBF plots for motor and visual tasks measured pre- (blue) and post-caffeine (pink). In both cortices, caffeine increases the slope of the fitted line, signifying a larger increase in ΔCMRO2 per unit increase in ΔCBF during activations.

Figure 6

Average CBF:CMRO2 coupling ratios for motor and visual cortices pre- and post-caffeine administration. Notice caffeine decreases the coupling ratio in both cortices.