Ordering Information in Working Memory and Modulation of Gamma by Theta Oscillations in Humans

Ordering information is a critical process underlying several cognitive functions, especially working memory. Theta phase-gamma amplitude coupling is regarded as a neurophysiological representation of ordering information during working memory performance. However, direct evidence has been lacking in humans. Seventy healthy subjects performed the N-back task, a working memory task that tests ordering information at 3 different levels of difficulties and with 3 different types of trials. Using electroencephalography (EEG) during N-back performance, theta-gamma coupling was assessed during response trials. Multivariate general linear model (GLM) and discriminant analysis were used to assess coupling and theta and gamma power across the N-back conditions and the trial types. During the N-back trials that required ordering of information, N-back condition had independent effects on coupling and on theta and gamma power, with equal contributions among these 3 variables. Theta-gamma coupling contribution declined significantly on the trials that did not require ordering and was intermediate on trials that favored but not necessarily required ordering. Our findings demonstrate for the first time the role of theta-gamma coupling as a mechanism that supports ordering information. They also highlight the potential of using theta-gamma coupling as a neurophysiological marker of brain function in health or disease states.