Quadratic dose-response relationship between caffeine (1,3,7-trimethylxanthine) and EEG correlation dimension

Abstract

Many studies have failed to determine a systematic dose-response relationship across different cognitive tasks between caffeine and EEG power spectra. However, a nonlinear approach to EEG analysis, which reconstructs a multi-dimensional state space from each electrode recording, can be used to compute the number of active degrees of freedom in the signal (the correlation dimension, D₂), and can be interpreted as a measure of signal complexity. This study attempted to determine a consistent dose-response relationship between caffeine and EEG D₂, across six oral caffeine doses (100–600 mg), with each subject acting as their own control, to create a probabilistic bias against finding any consistent linear or nonlinear dose-response relationship across different cognitive tasks. The experiment (n = 10) was conducted with three within-subjects explanatory variables, 2 (experimental, placebo) × 8 (caffeine level) × 4 (type of cognitive task performed), with EEG D₂ as the response variable, measured from Fz, F3, F4 and Cz. A significant three-way interaction was found [F(21,245.3) = 3.65, P = 0.001]. Regression analyses revealed a linear trend for the response variable across trials for the placebo condition (average R ² = 0.54), whereas linear+quadratic trends explained an average 30% of the variance for the experimental condition, compared to 0.01% for the linear fit, indicating a robust quadratic dose-response relationship between caffeine and EEG D₂. Three conditions had positive quadratic co-efficients, and one condition had a negative quadratic co-efficient. These results are discussed in terms of the implications for brain dynamics, and with respect to recent criticisms of the computation of D₂ from EEG.