The purpose of this study was to identify the mechanisms underlying effects of coffee on cognition in the context of brain networks. Here we investigated functional connectivity before and after drinking coffee using graph-theoretic analysis of electroencephalography (EEG). Twenty-one healthy adults voluntarily participated in this study. The resting-state EEG data and results of neuropsychological tests were consecutively acquired before and 30 min after coffee consumption. Graph analyses were performed and compared before and after coffee consumption. Correlation analyses were conducted to assess the relationship between changes in graph measures and those in cognitive function tests. Functional connectivity (FC) was reorganized toward more efficient network properties after coffee consumption. Performance in Digit Span tests and Trail Making Test Part B improved after coffee consumption, and the improved performance in executive function was correlated with changes in graph measures, reflecting a shift toward efficient network properties. The beneficial effects of coffee on cognitive function might be attributed to the reorganization of FC toward more efficient network properties. Based on our findings, the patterns of network reorganization could be used as quantitative markers to elucidate the mechanisms underlying the beneficial effects of coffee on cognition, especially executive function.

Significance: Clustering of phosphatidylinositol 4,5-bisphosphate (PIP₂) with proteins into what are known as “PIP₂rafts” is a critical component of intracellular signaling, yet little is known about PIP₂clusters at the atomic level. Using molecular dynamics simulations and network theory, this paper shows that Ca²⁺generates large clusters by linking PIP₂dimers already formed by doubly charged P4/P5 phosphates, while monovalent cations form smaller and less-stable clusters by adding PIP₂monomers preferentially via weaker interactions with P4/P5 (for Na⁺) or with glycerol P1 (for K⁺). Synergy arises between K⁺and Ca²⁺because each ion forms linkages with different phosphates, thereby giving clusters more ways to grow. This explains why Ca²⁺is pumped into cells by ion channels to form PIP₂rafts.