A Comprehensive Meta-Analytic Review of the Neurophysiological Properties of the Heartbeat Evoked Potential in Health and Disease

BACKGROUND: The heartbeat evoked potential (HEP) is an electrophysiological indicator of cortical processing of cardiac signals and a putative neural index of cardiac interoception. Various clinical conditions are associated with disrupted heart-brain communication, raising the possibility that the HEP could serve as a valid biomarker of disrupted cardiac interoception. However, there is limited understanding of how the HEP signal and its various parameters are associated with different health conditions. METHODS: We synthesized the current evidence for HEP amplitude as a biomarker across all available clinical subpopulations using a random-effects multilevel meta-analysis. Secondly, we systematically characterized and quantitatively evaluated key HEP parameters, such as latency windows, reference electrodes, and scalp topographies, across HEP studies. RESULTS: Subgroup analyses for each condition showed no difference in HEP amplitude between clinical conditions relative to healthy comparisons; however, large negative effect estimates were found in neurological and cardiovascular diseases, although these were based on a small number of studies and should be interpreted with caution. In subsequent multivariate analysis, clinical category partially explained the global variability in HEP parameters. CONCLUSIONS: Based on these results, no firm conclusions can be drawn regarding the utility of HEP amplitude as a clinical biomarker. Substantial heterogeneity and widespread methodological inconsistencies across studies preclude definitive interpretations, and rigorous standardized research is needed before the clinical value of HEP can be established.