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In a seminal paper by von Stein and Sarnthein (2000), it was hypothesized that "bottom-up" information processing of "content" elicits local, high frequency (beta-gamma) oscillations, whereas "top-down" processing is "contextual", characterized by large scale integration spanning distant cortical regions, and implemented by slower frequency (theta-alpha) oscillations. This corresponds to a mechanism of cortical information transactions, where synchronization of beta-gamma oscillations between distant cortical regions is mediated by widespread theta-alpha oscillations. It is the aim of this paper to express this hypothesis quantitatively, in terms of a model that will allow testing this type of information transaction mechanism. The basic methodology used here corresponds to statistical mediation analysis, originally developed by (Baron and Kenny 1986). We generalize the classical mediator model to the case of multivariate complex-valued data, consisting of the discrete Fourier transform coefficients of signals of electric neuronal activity, at different frequencies, and at different cortical locations. The "mediation effect" is quantified here in a novel way, as the product of "dual frequency RV-coupling coefficients", that were introduced in (Pascual-Marqui et al 2016, http://arxiv.org/abs/1603.05343). Relevant statistical procedures are presented for testing the cross-frequency mediation mechanism in general, and in particular for testing the von Stein & Sarnthein hypothesis., Comment: https://doi.org/10.1101/119362 licensed as CC-BY-NC-ND 4.0 International license: http://creativecommons.org/licenses/by-nc-nd/4.0/

Identifying dynamic transactions between brain regions has become increasingly important. Measurements within and across brain structures, demonstrating the occurrence of bursts of beta/gamma oscillations only during one specific phase of each theta/alpha cycle, have motivated the need to advance beyond linear and stationary time series models. Here we offer a novel measure, namely, the "dual frequency RV-coupling coefficient", for assessing different types of frequency-frequency interactions that subserve information flow in the brain. This is a measure of coherence between two complex-valued vectors, consisting of the set of Fourier coefficients for two different frequency bands, within or across two brain regions. RV-coupling is expressed in terms of instantaneous and lagged components. Furthermore, by using normalized Fourier coefficients (unit modulus), phase-type couplings can also be measured. The dual frequency RV-coupling coefficient is based on previous work: the second order bispectrum, i.e. the dual-frequency coherence (Thomson 1982; Haykin & Thomson 1998); the RV-coefficient (Escoufier 1973); Gorrostieta et al (2012); and Pascual-Marqui et al (2011). This paper presents the new measure, and outlines relevant statistical tests. The novel aspects of the "dual frequency RV-coupling coefficient" are: (1) it can be applied to two multivariate time series; (2) the method is not limited to single discrete frequencies, and in addition, the frequency bands are treated by means of appropriate multivariate statistical methodology; (3) the method makes use of a novel generalization of the RV-coefficient for complex-valued multivariate data; (4) real and imaginary covariance contributions to the RV-coherence are obtained, allowing the definition of a "lagged-coupling" measure that is minimally affected by the low spatial resolution of estimated cortical electric neuronal activity., Comment: technical report, pre-print, 2016-03-16