Causal Roles of Intrinsic Coupling Modes: an Integrated Multiscale Framework for Cognitive Network Dynamics

Functional coupling is a hallmark of brain networks, and there is a wealth of studies that have observed a relation between functional connectivity and cognition or sensorimotor processing. However, the vast majority of studies on this topic are correlative in nature, and causal evidence for the role of functional coupling is almost completely lacking. This project aims to fill this gap. Most of the coupling is intrinsically generated and occurs at multiple spatial and temporal scales. We will focus on two different types of such intrinsic coupling modes (ICMs): phase ICMs, arising from phase coupling of oscillatory signals, and envelope ICMs, resulting from coupled fluctuations of signal envelopes. The central hypothesis of this project is that both types of ICMs have causal relevance for cognitive processing and behavior. We will systematically manipulate, analyze and model the different types of ICMs to establish an integrated view on their functions and interrelations which currently is still lacking. Specifically, we aim to obtain the missing causal evidence on functional roles of ICMs, to unravel how phase and envelope ICMs differ in their relation to cognition and behavior, to reveal differences in the underlying mechanisms, and to unravel potential interactions between both types of ICMs. We will apply a translational approach which combines MEG recordings and tACS in humans with invasive electrophysiology and optogenetics in ferrets. We will use targeted multi-site interventions to dissect ICMs, independently manipulate phase and envelope coupling, and test the impact on cognitive processing and behavior. The experiments will be complemented by information-theoretic analyses and computational modeling of ICMs. This cutting-edge research program will yield an integrated multiscale framework for ICMs that is likely to have far-reaching implications for a better understanding of the mechanisms underlying cognition and the complexity of the human mind.