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

Abstract

Communication between brain areas has been implicated in a wide range of cognitive and emotive functions and is impaired in numerous mental disorders. In rodent models, various functional connectivity metrics have been used to quantify inter-regional neuronal communication. However, in individual studies, typically only very few measures of coupling are reported and, hence, redundancy across such indicators is implicitly assumed. In order to test this assumption, we here comparatively assessed a broad range of directional and non-directional metrics like coherence, weighted Phase-Lag-Index (wPLI), Granger causality (GC), spike-phase coupling (SPC), cross-regional phase-amplitude coupling, amplitude cross-correlations, and others. We applied these analyses to simultaneous field recordings from the prefrontal cortex and the ventral and dorsal hippocampus in the schizophrenia-related Gria1-knockout mouse model which displays a robust novelty-induced hyperconnectivity phenotype. We find that across such measures there is a considerable lack of functional redundancy. While coherence and GC yielded similar results, other measures, especially wPLI and SPC, often produced deviating conclusions. Bivariate correlations within animals revealed that virtually none of the metrics consistently co-varied with any of the other measures across the three connections and two genotypes analysed. Parametric GC showed the qualitatively highest degree of redundancy with other metrics and would be most suitable for connectivity analysis. We conclude that analysis of multiple metrics is necessary to characterise functional connectivity.