Music as neuromodulation: A systematic review with insights from human intracranial electrophysiology

Music engages a wide range of cognitive and affective processes; however, the precise mechanisms by which music shapes brain activity remain incompletely understood. Human intracranial electrophysiology (iEEG) provides a unique opportunity to answer this question through direct recordings of neural activity with high spatial and temporal resolution. Here, we systematically review the intracranial literature on music perception and its cell- and circuit-level neural effects, identifying common principles extending across experimental paradigms and brain regions. Following PRISMA guidelines, three databases were queried for published literature describing quantitative modulations of neural activity in response to music exposure. We performed a narrative synthesis of study characteristics, main interventions and outcomes, and study quality. Integrating all studies, we outline a conceptual framework in which music is processed in an anatomically distributed fashion across multiple levels of abstraction. Within auditory cortex, iEEG studies demonstrate robust evidence for the encoding of basic acoustic features, while moderate evidence supports the predictive processing of musical expectations. In contrast, evidence remains sparse for the generation of emotional, mnemonic, and action-related representations of music in more distant cortical and subcortical regions. Studies of electrical stimulation mapping and single-unit neural activity also represent key areas for future research. Altogether, we propose that music can be understood as a neuromodulator that dynamically coordinates neural activity across sensory, association, limbic, and motor systems. We position music as a powerful model system for investigating sensory perception and integration in a complex, real-world context, while spotlighting iEEG as a valuable tool in this ongoing exploration.