Caffeine alters resting-state functional connectivity measured by blood oxygenation level-dependent MRI

This study aimed to investigate the pharmacological effect of caffeine on functional connectivity measured by resting-state blood oxygenation level-dependent (BOLD) MRI in the motor cortex, visual cortex and default mode network (DMN). The protocols and procedures of the study were reviewed and approved by the Institutional Review Board of our institution. On a 3-T clinical MR system, 20 healthy volunteers underwent imaging before and after oral ingestion of a 200-mg over-the-counter caffeine pill (data from three individuals were excluded from further analysis because of excessive motion). The demographics of the remaining participants were as follows: female/male, 8/9; age, 21–35 years; non-habitual caffeine consumers over the past 6 months. Functional connectivity was calculated using the general linear model, assessed in terms of connected area (voxels) and statistical significance (Student t-values), and correlated with changes in regional cerebral blood flow as measured by arterial spin labeling MRI. Per-subject data analysis showed that caffeine decreased functional connectivity in the motor/visual cortices, but its effects on DMN varied among subjects. Correlation analysis of the changes in functional connectivity and regional blood flow suggested that the effect of caffeine on BOLD functional connectivity was predominantly neural (motor/visual cortices) and partly vascular (DMN). Group analysis showed that, after caffeine ingestion, DMN involved more attentional networks, and more extrastriate areas were integrated into the functional connectivity of the visual cortex, which may be associated with the known pharmacological effect of caffeine in elevating alertness. Caffeine consumption should thus be considered in the experimental design and data interpretation of functional connectivity studies using resting-state BOLD MRI.