Recent theories of the effects of ethanol on the brain have focused on its direct actions on neuronal membrane proteins. However, neuromolecular mechanisms whereby ethanol produces its CNS effects in low doses typically used by social drinkers (e.g., 2-3 drinks, 10-25 mM, 0.05-0.125 gm/dl) remain less well understood. We propose the hypothesis that ethanol may act by introducing a level of randomness or "noise" in brain electrical activity. We investigated the hypothesis by applying a battery of tests originally developed for nonlinear time series analysis and chaos theory to EEG data collected from 32 men who had participated in an ethanol/placebo challenge protocol. Because nonlinearity is a prerequisite for chaos and because we can detect nonlinearity more reliably than chaos, we concentrated on a series of measures that quantitated different aspects of nonlinearity. For each of these measures the method of surrogate data was used to assess the significance of evidence for nonlinear structure. Significant nonlinear structure was found in the EEG as evidenced by the measures of time asymmetry, determinism, and redundancy. In addition, the evidence for nonlinear structure in the placebo condition was found to be significantly greater than that for ethanol. Nonlinear measures, but not spectral measures, were found to correlate with a subject's overall feeling of intoxication. These findings are consistent with the notion that ethanol may act by introducing a level of randomness in neuronal processing as assessed by EEG nonlinear structure.

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How the neuromolecular actions of ethanol translate to its observed intoxicating effects remains poorly understood. Synchrony of phase (phase locking) of event-related oscillations (EROs) within and between different brain areas has been suggested to reflect communication exchange between neural networks and as such may be a sensitive and translational measure of ethanol’s effects. Using a similar auditory event-related potential paradigm in both rats and humans we investigated the phase variability of EROs collected from 38 young men who had participated in an ethanol/placebo challenge protocol, and 46 adult male rats given intraperitoneal injections of ethanol/saline. Phase locking was significantly higher in the delta frequencies in humans than in rats. Phase locking was also higher for the rare (target) tone than the frequent (non-target) tone in both species. Significant reductions in phase locking to the rare (target) tone in the delta, theta, alpha, beta and gamma frequencies, within and between brain sites, was found at one hour following ethanol as compared to placebo/saline administration in both rats and humans. Reductions in phase locking in the alpha frequencies in the parietal cortex were found to be correlated with blood ethanol concentrations. These findings are consistent with the hypothesis that ethanol’s intoxicating actions in the brain include reducing synchrony within and between neuronal networks, perhaps by increasing the level of noise in key neuromolecular interactions.

Skin-electrode impedance was measured for four different types of conventional electrocardiographic electrodes applied under different conditions. All types of contacts were frequency dependent; a decrease in impedance was found with increasing frequency. Occasionally, impedance values at a frequency range of 6 to 100 cycles per second were in the tens of thousands of ohms with all electrode types. Tracings obtained under working conditions were evaluated to determine the influence of skin-electrode impedance on the recorded data. Single channel electrocardiographs accurately recorded cardiac potentials; however, simultaneously recorded multiple channel data had considerable distortion in half of the subjects. Frank vectorcardiograms demonstrated significant amplitude loss in half of the patients, with the most prominent distortion occurring in the T wave as compared to QRS. The inclusion of a buffer amplifier between the skin-electrode contacts and the resistor network produced distortionfree tracings. The inclusion of such devices is suggested to obviate any potential error produced by the highest skin-electrode impedance contact values obtained under working conditions.