Wang Xiaopeng, Yang Haoxun, Cheng Yueyang, Liu Shujia, Jin Guangyuan, Qiao Zichen, Qi Lei, Wang Siyi, Ge Junliang, Hu Dongmei, Tang Hai, Gao Runshi, Xu Cuiping, Zhang Xiaohua, Wang Di, Xue Xiangyu, Dai Anqi, Zhao Wenbo, Yu Tao, Wang Yuping, Si Bailu, Zhao Guoguang, Ren Liankun
Department of Neurology, Xuanwu Hospital, Clinical Center for Epilepsy, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
Clinical Research Center of Epilepsy, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Cardiovasc Res. 2025 Jul 31;121(8):1228-1239. doi: 10.1093/cvr/cvaf099.
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.
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 pre-frontal 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 via SEEG.
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.
心脏与大脑之间的相互作用几个世纪以来一直是人们感兴趣的课题，因为这种相互作用的功能障碍与各种心血管疾病和神经疾病有关。尽管有了这一进展，但目前对于人类大脑与心律之间通信的机制了解有限。在此，我们旨在描述人类大脑对心律的处理过程，并将人类大脑地形图与心律进行映射。
我们在一组54名耐药性癫痫患者中研究了人类大脑如何处理心律，这些患者在术前评估期间同时记录了心电图和立体脑电图（SEEG）。通过对连续静息状态SEEG时段中心跳R波时间锁定的大脑反应进行平均得出的颅内心跳诱发电位（HEP），根据其形态以及在大脑中的时空分布进行了表征。分析揭示了心律的复杂大脑地形图，包括预期的双侧丘脑、岛叶、杏仁核和前扣带回皮质，同时还延伸到背外侧前额叶皮质、缘上回和颞上回。采用特征微状态方法，我们在R波峰后100至400毫秒的时间窗口中解开了HEP网络的两个突出成分，反映了早期（100 - 250毫秒）和延迟（250 - 400毫秒）的处理途径。此外，我们将人类大脑神经递质受体特征映射到HEP地形图上，首次证明血清素受体5HT2a在皮质水平上是该组织的主要特征。此外，表现出更强HEP的脑区在通过SEEG进行直接电刺激后显示出更明显的心率变化。
我们生成了跨皮质和皮质下区域的HEP时空动态图。我们对HEP的表征揭示了各种主要成分，并在其地形组织与神经递质受体分布之间建立了直接关联。这项研究为理解大脑对心脏信号的处理提供了一个基础框架，并为新型治疗干预和心血管疾病铺平了道路。
