Inferring the direction of rhythmic neural transmission via inter-regional phase-amplitude coupling (ir-PAC)

Abstract

Phase-amplitude coupling (PAC) estimates the statistical dependence between the phase of a low-frequency and the amplitude of a high-frequency component of local field potentials (LFP). Characterizing the relationship between nested oscillations in LFPs, PAC has become a powerful tool for understanding neural dynamics in both animals and humans. In this work, we introduce a new application for this measure to two LFPs to infer the direction and strength of rhythmic neural transmission between distinct networks. Based on recently accumulating evidence that transmembrane currents related to action potentials contribute a broad-band component to LFP in the highgamma band, we hypothesized that PAC calculated between high-gamma in one LFP and low-frequencyoscillations in another would relate the output (spiking) of one area to the input (soma/dendritic postsynaptic potentials) of the other. We tested this hypothesis on theta-band long range communications between hippocampus and prefrontal cortex (PFC) and theta-band short range communications between different regions within the hippocampus. The results were interpreted within the known anatomical connections predicting hippocampus→PFC and DG→CA3→CA1, i.e., theta transmission is unidirectional in both cases: from hippocampus to PFC and along the tri-synaptic pathway within hippocampus. We found that (1) hippocampal highgamma amplitude was significantly coupled to theta phase in PFC, but not vice versa; (2) similarly, high-gamma amplitude in DG was significantly coupled to CA1 theta phase, but not vice versa, and (3) the DG high-gamma-CA1 theta PAC was significantly correlated with DG→CA1 Granger causality, a well-established analytical measure of directional neural transmission. These results support the hypothesis that inter-regional PAC (ir-PAC) can be used to relate the output of a "driver" network (i.e., high gamma) to the input of a "receiver" network (i.e., theta) and thereby establish the direction and strength of rhythmic neural transmission.

The generation and propagation of the human alpha rhythm

“…S8 and S9 didn't substantially change the results; Materials and Methods). If a given structure is generating alpha oscillations (and if local HGP reflects neural firing), its HGP should be synchronous with its alpha-band LFPg and exhibit phase-amplitude coupling (PAC) (28). PAC was assessed by using 2 methods: Tort's Modulation Index (MI) (29) and the coherence between the time-domain LFPg and HGP (30) (Fig.…”

Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats

“…Unlike theta rhythm, primarily generated in HC and conveyed to PFC 24 , producing strong PFC-HC coherence, the origin of the RRO coherence between these structures is less certain. RRO is generated outside of these structures, and from the OB it is faithfully transmitted to the PFC but much less reliably to the HC (Fig.…”

“…Oscillatory coupling between PFC and HC was reported in different states in freely moving rats and under Urethane anesthesia both in delta and theta frequency bands 16,21,22 maintained by various mono-and polysynaptic connections between the two structures. Theta peaks were dominant in PFC-HC coherence spectra during theta states (AW, REM sleep, urethane-theta) in this study, as well.…”

“…Communication and collaboration between HC and PFC and its impairment in psychiatric diseases has been the primary focus of extensive research to date [18][19][20][21] . HC theta driven PFC synchronization and its role in spatial working memory is relatively well-studied [25][26][27][28][29][30] .…”

Lack of redundancy between electrophysiological measures of long-range neuronal communication

“…Particularly, local phaseamplitude coupling (PAC)-the statistical relationship between the phase of a low-frequency and the amplitude of a high-frequency component-plays an important role in memory processing in the hippocampus of rats [37,38] and humans [39]. However, cross-regional PAC between the hippocampus and prefrontal cortex has also been used and was associated with directed information flow and cognitive functions [22][23][24]40]. Since high-frequency brain oscillations mainly reflect local aspects of information processing and low-frequency brain rhythms are relevant for inter-regional communication, CFC might represent a mechanism of transferring information from large-scale neuronal networks to local processes [36,41].…”