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

Summary Phase–Amplitude Coupling (PAC) has been proposed as an elegant neural mechanism for representing sequential items in memory, coordinating distant brain regions, and parsing complex sensory inputs. Yet, whether PAC carries content-specific, behaviorally meaningful information has not been demonstrated to date. Here, using human intracranial recordings before, during and after an audio–visual associative learning task, we show that PAC is an information-coding mechanism. PAC strength in cortico–hippocampal networks increased linearly during learning and remained significantly stronger post vs. pre-learning. More importantly, PAC comodulograms carried stimulus- and association-specific information: auditory items were decodable in auditory cortex before learning based on PAC features, while learned associations were classified across hippocampo–temporo–frontal networks during and after learning. Post-learning brain decoding confusion matrices closely mirrored behavioral confusion matrices, and PAC patterns were independent of low-level stimulus features. These findings suggest that PAC is an endogenously generated marker that supports perception and associative learning in the human brain. One-sentence summary We demonstrate that phase-amplitude coupling (PAC) in cortico-hippocampal networks serves as a specific, endogenously generated, and behaviorally meaningful neurophysiological mechanism for perceiving, learning, and maintaining audio-visual associations.