Mapping human brain topography to heart rhythms: an SEEG study

Aims The interplay between the heart and brain has been a subject of interest for centuries, as dysfunction in this interaction is implicated in various cardiovascular diseases and neurological disorders. Despite this advancement, there is currently a limited understanding of the mechanisms that the human brain communicates with heart rhythms. Here, we aim to characterize the human brain processing of heart rhythms and map human brain topography to heart rhythms. Methods and Results We investigated how the human brain processes heart rhythms in a cohort of 54 drug-resistant epilepsy patients who simultaneously recorded electrocardiography and stereoelectroencephalography (SEEG) during pre-surgical evaluation. Intracranial heartbeat-evoked potentials (HEPs) derived from averaging brain responses time-locked to R peaks of heartbeats in consecutive resting-state SEEG epochs, were characterized in terms of their morphology and spatiotemporal distribution across the brain. The analysis revealed a complex brain topography to heart rhythms that includes the anticipated bilateral thalamus, insula, amygdala, and anterior cingulate cortex, while also extending to the dorsolateral prefrontal cortex, supramarginal gyrus, and superior temporal gyrus. Employing an eigen microstates approach, we disentangled two prominent components of the HEPs network in the time window from 100 to 400 ms post R-peak, reflecting early (100-250 ms) and delayed (250-400 ms) processing pathways. Furthermore, we mapped human brain neurotransmitter receptor signatures onto the HEPs topography, providing the first evidence that serotonin receptor 5HT2a serves as a dominant signature of this organization at the cortical level. Additionally, brain regions exhibiting stronger HEPs showed more pronounced heart rate changes following direct electrical stimulation (DES) via SEEG. Conclusions We generated a spatiotemporal dynamic map of HEPs across cortical and subcortical regions. Our characterization of HEPs revealed various dominant components and established a direct association between its topographic organization and distribution of neurotransmitter receptors. This study provides a foundational framework for understanding the brain processing of heart signals and paves the way for novel therapeutic interventions and cardiovascular diseases.