Christoffel Kelsey, De Asis-Cruz Josepheen, Govindan Rathinaswamy B, Kim Jung Hoon, Cook Kevin Michael, Kapse Kushal, Andescavage Nickie, Basu Sudeepta, Spoehr Emma, Limperopoulos Catherine, du Plessis Adre
Developing Brain Institute, Children's National Hospital, Washington, District of Columbia, USA,
Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia, USA,
Dev Neurosci. 2024;46(6):373-385. doi: 10.1159/000536513. Epub 2024 Feb 6.
The Central Autonomic Network (CAN) is a hierarchy of brain structures that collectively influence cardiac autonomic input, mediating the majority of brain-heart interactions, but has never been studied in premature neonates. In this study, we use heart rate variability (HRV), which has been described as the "primary output" of the CAN, and resting-state functional MRI (rsfMRI) to characterize brain-heart relationships in premature neonates.
We studied premature neonates who underwent rsfMRI at term (37-week postmenstrual age or above) and had HRV data recorded during the same week of their MRI. HRV was derived from continuous electrocardiogram data during the week of the rsfMRI scan. For rsfMRI, a seed-based approach was used to define regions of interest (ROIs) pertinent to the CAN, and blood oxygen level-dependent signal was correlated between each ROI as a measure of functional connectivity. HRV was correlated with CAN connectivity (CANconn) for each region, and subgroup analysis was performed based on sex and clinical comorbidities.
Forty-seven premature neonates were included in this study, with a mean gestational age at birth of 28.1 +/- 2.6 weeks. Term CANconn was found to be significantly correlated with HRV in approximately one-fifth of CAN connections. Two distinct patterns emerged among these HRV-CANconn relationships. In the first, increased HRV was associated with stronger CANconn of limbic regions. In the second pattern, stronger CANconn at the precuneus was associated with impaired HRV maturation. These patterns were especially pronounced in male premature neonates.
We report for the first time evidence of brain-heart relationships in premature neonates and an emerging CAN, most striking in male neonates, suggesting that the brain-heart axis may be more vulnerable in male premature neonates. Signatures in the heart rate may eventually become an important noninvasive tool to identify premature males at highest risk for neurodevelopmental impairment.
中枢自主神经系统（CAN）是一个由脑结构组成的层级体系，共同影响心脏自主神经输入，介导大部分脑-心相互作用，但从未在早产新生儿中进行过研究。在本研究中，我们使用心率变异性（HRV）（其被描述为CAN的“主要输出”）和静息态功能磁共振成像（rsfMRI）来表征早产新生儿的脑-心关系。
我们研究了在足月时（孕龄37周或以上）接受rsfMRI检查且在MRI检查同一周记录了HRV数据的早产新生儿。HRV来自rsfMRI扫描周期间的连续心电图数据。对于rsfMRI，采用基于种子的方法来定义与CAN相关的感兴趣区域（ROI），并将每个ROI之间的血氧水平依赖信号作为功能连接性的度量进行相关性分析。将每个区域的HRV与CAN连接性（CANconn）进行相关性分析，并根据性别和临床合并症进行亚组分析。
本研究纳入了47名早产新生儿，出生时的平均孕龄为28.1±2.6周。在大约五分之一的CAN连接中，发现足月时的CANconn与HRV显著相关。在这些HRV-CANconn关系中出现了两种不同的模式。第一种模式中，HRV增加与边缘区域更强的CANconn相关。在第二种模式中，楔前叶更强的CANconn与HRV成熟受损相关。这些模式在男性早产新生儿中尤为明显。
我们首次报告了早产新生儿脑-心关系以及一个新兴的CAN的证据，在男性新生儿中最为显著，这表明脑-心轴在男性早产新生儿中可能更易受损。心率特征最终可能成为识别神经发育障碍风险最高的早产男性的重要非侵入性工具。
