Caregiver Cumulative Cortisol Mediates Deviations in Functional Connectivity in Infants: A Novel fNIRS Study

发育科学家很早就记录了慢性生理压力对发育中的婴儿大脑的影响。根据母体生理应激的解释，经历过慢性生理应激的婴儿被发现偏离了“典型的”大脑发育轨迹(特罗尔-伦弗里特，2020)。这些变化通常包括过多的低频脑电功率和相对较少的高频功率，已被归因于一种名为“成熟滞后”的发育延迟，该延迟被假设为描述中枢神经系统，特别是皮质发育的延迟(Corning，Steffy，Anderson&Bowers，1986)。我过去的研究扩展了这些发现，研究了由慢性照顾者压力调节的婴儿脑电功率增长曲线之间的差异及其对皮质发育的影响。使用脑功能成像技术来确定这些电生理和结构变化是否也标志着血液动力学反应的变化，当比较婴儿与有和没有慢性应激的照顾者时，还没有做过很多研究，我提议的研究旨在成为这样做的第一个研究。功能近红外光谱(FNIRS)是一种相对新颖的方法，科学家可以用它来阐明发生在大脑中的血液动力学变化的数据。虽然fMRI是研究这些变化最常用的技术，但其笨重和静态的性质使其很难在婴儿身上使用。FNIRS相对更小、更便携，更适合婴儿时期的研究。这种方法通过检查神经元之间的连接性/同步性的值来推断大脑的细胞结构，因为它们在大脑中相互通信。其中许多研究都是使用功能磁共振成像完成的，但最近，科学家们开始使用功能近红外光谱来研究婴儿的功能连接。这项研究的大部分都是在心理和神经病理学的情况下进行的，但也存在非病理文献。为了获得更多关于婴儿大脑在受到慢性压力影响时发生的变化的信息，并找到更多信息来证实或挑战成熟滞后假说，我建议进行一项差异功能连接性研究，比较有慢性压力的照顾者和没有照顾者的婴儿。照顾者压力是否会影响婴儿的功能连通性发育？这项研究非常符合剑桥婴儿实验室目前正在进行的管道项目，该项目包括在出生后一周/两周、5个月和9个月时进行fNIR扫描。照顾者的压力将通过头发皮质醇来确定。头发皮质醇已被发现是衡量慢性应激水平的可靠指标(Ursache等人，2017)，并允许我们对我们研究的婴儿经历的应激做出推断，而不使用侵入性测量来确定他们的皮质醇水平。必须确定一个适当的管道来描述fNIRS功能连通性，但现在我指出Gao等人在2014年使用的方法，该方法确定了fcMRI中的9个功能网络，并能够通过3个定量指标对它们的相对成熟度做出推断：网络内连通性、网络外连通性和与成人参考文献的总体相似性。在收集了每个婴儿的休息数据，并从照顾者那里收集了头发样本后，我将对两组(高发皮质醇和低发皮质醇)进行统计分析，以确定他们在每个功能网络中是否存在任何显著差异，并进行功率分析，以确定潜在差异的大小与头发皮质醇水平的差异是否存在相关性。

The effects of chronic physiological stress on the developing infant brain have long been recorded by developmental scientists. Infants who have experienced chronic physiological stress, as elucidated from maternal physiological stress, have been found to have deviations from the "typical" developing brain's trajectories (Troller-Renfree, 2020). These alterations, usually consisting of an overabundance of low frequency EEG power and a relative paucity of high-frequency power, have been attributed to a developmental delay entitled the "maturational lag" which has been postulated to describe a delay in the development of central nervous system, and in particular, cortical development (Corning, Steffy, Anderson & Bowers, 1986). My past research has extended these findings, looking into the differentiations between EEG power growth curves of infants mediated by chronic caregiver stress and its implications on cortical development. Not much research has been done using functional brain imaging techniques to determine whether these electrophysiological and structural changes are also marked by changes in hemodynamic responses as well when comparing infants with caregivers with and without chronic stress, and my proposed research aims to be some of the first research to do so.Functional near infrared spectroscopy (fNIRS) is a relatively novel method in which scientists can elucidate data about the hemodynamic changes happening in the brain. Though fMRI is the most commonly used technique to study these changes, its bulky and static nature makes it difficult to use on infants. fNIRS is comparatively smaller and portable, and much more suited to research in infancy.This method makes inferences about the brain's cytoarchitecture by examining values of connectivity/synchrony between neurons as they communicate with each other across the brain. Many of these studies have been done using fMRI, but more recently, scientists have begun to use fNIRS to study functional connectivity in infants. Much of this research has been done in cases of psycho- and neuropathology, but non-pathological literature also exists.To gain more information about the changes that occur to the infant brain when impacted by chronic stress, and to find more information either confirming or challenging the maturational lag hypothesis, I propose that a differential functional connectivity study be carried out, comparing infants with caregivers with chronic stress with those with infants with caregivers without. Will caregiver stress influence functional connectivity development in infants? This study fits very well into the PIPKIN project that is currently ongoing within the Cambridge Baby Lab, which includes fNIRS scanning at one/two weeks post-birth, at 5 months and at 9 months. Caregiver stress will be determined via hair cortisol. Hair cortisol has been found to be a reliable measure of chronic stress levels (Ursache et al., 2017) and allows us to make inferences about the stress that the infants we study experience, without using an invasive measure to determine their cortisol levels. An appropriate pipeline must be determined for the description of fNIRS functional connectivity but for now I point to the methods used in Gao et al., 2014, which identified 9 functional networks in fcMRI and was able to make inferences about their relative maturation via 3 quantitative measures: within-network connectivity, outside-network connectivity and overall similarity to adult references. After collection of resting data from each infant, and collecting hair samples from the caregiver, I will conduct a statistical analysis comparing the groups (high hair cortisol against low hair cortisol) to determine whether any significant differences arise between them in each functional network as well as carry out power analyses to determine whether correlations occur between magnitude of potential difference and difference in hair cortisol levels.