Temporal misalignment of brain-heart coupling accounts for multilevel interoceptive dysfunction in schizophrenia.

Schizophrenia involves profound disturbances in the sense of a bodily self. These disturbances increasingly appear to arise from disrupted interoception, the perception of internal physiological signals. However, dominant models that emphasize either intrinsic neural timescales or interoceptive inference tend to treat cardiac signals merely as passive sensory inputs. Here, we propose that cardiac rhythm dynamics may provide a phase-based temporal reference for large-scale neural coordination, potentially synchronizing neural activity across otherwise disparate temporal scales. This scaffolding function is mediated by mechanically transduced pulsatile signals that may influence cortical excitability across distributed networks. Within this framework, interoceptive dysregulation in schizophrenia is reconceptualized as a decoupling of hierarchical cortical oscillations from peripheral cardiac phases. Reduced variability in cardiac rhythms may weaken the stability of temporal references available to higher-order networks. This, in turn, may drive a compensatory increase in the prior precision assigned to ambiguous visceral inputs, thereby blurring the distinction between internally generated and externally driven signals. Such processes may contribute to hallucinations, delusions, and motivational deficits. Emerging therapeutic strategies, therefore, aim to restore temporal alignment across the heart-brain axis. Translating the phenomenology of interoception into quantifiable metrics of neuro-visceral misalignment holds promise as a potential bridge between neurobiology and targeted psychiatric intervention.