Cortico-Hippocampal phase-amplitude coupling is a signature of learned audiovisual associations in humans

Abstract

Phase-amplitude coupling (PAC) has been proposed as a neural mechanism for representing sequential information in memory, binding memories, coordinating activity across distributed brain regions, and parsing complex sensory inputs. Importantly, the frequencies contributing to PAC can vary flexibly across brain regions and cognitive states. Here, we asked whether the pattern of coupling across these dynamically varying frequencies can carry information about learned representations. To address this question, we used human intracranial recordings acquired before, during, and after an audiovisual associative learning task. We first identified the emergence of task-related theta- and gamma-band activity within cortico-hippocampal networks during learning and showed that theta-gamma PAC strength within these networks increased following learning. Importantly, PAC comodulograms contained association-specific information: learned associations could be decoded across hippocampal, temporal, and frontal networks during and after learning, with significantly greater decoding accuracy than that obtained from cue-only PAC before learning and from models trained on theta and gamma magnitude alone. This dissociation suggests that the associative information encoded in PAC comodulograms was not reducible to cue-evoked activity or to either of its constituent frequency bands taken independently. Finally, decoding accuracy of models trained on PAC post-learning was positively correlated with behavioral performance. Together, these findings suggest that PAC contains content-specific information in the human brain and identify it as an endogenous neural signature of audiovisual associative learning.