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

长期生理压力对发育中的婴儿大脑的影响早已被发育科学家记录下来。经历过慢性生理压力的婴儿，正如从母体生理压力中所阐明的那样，已经发现偏离了“典型的”发育大脑的轨迹（Troller-Renfree，2020）。这些改变通常由低频EEG功率过多和高频功率相对缺乏组成，已被归因于称为“成熟滞后”的发育延迟，其已被假定为描述中枢神经系统发育的延迟，特别是皮质发育的延迟（Corning，Steffy，安德森& Bowers，1986）。我过去的研究已经扩展了这些发现，研究慢性照顾者压力介导的婴儿EEG功率增长曲线之间的差异及其对皮质发育的影响。使用功能性脑成像技术进行的研究并不多，以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，以及比较婴儿与有和没有慢性压力的照顾者，而我的研究目标是成为第一批这样做的研究。功能近红外光谱（fNIRS）是一种相对新颖的方法，科学家可以通过这种方法阐明大脑中发生的血液动力学变化的数据。虽然功能磁共振成像是研究这些变化最常用的技术，但其庞大和静态的性质使其难以用于婴儿。fNIRS是一种体积相对较小、便于携带的方法，更适合婴儿期的研究。这种方法通过检查神经元之间的连接/同步值来推断大脑的细胞结构，因为它们在大脑中相互通信。这些研究中的许多都是使用fMRI进行的，但最近，科学家们开始使用fNIRS来研究婴儿的功能连接。这些研究大多是在心理和神经病理学的情况下进行的，但也存在非病理学的文献。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，并找到更多的信息来证实或挑战成熟滞后假说，我建议进行差异功能连接研究，比较照顾者有慢性压力的婴儿和照顾者没有慢性压力的婴儿。照顾者的压力会影响婴儿的功能连接发展吗？这项研究非常符合剑桥婴儿实验室目前正在进行的PIPKIN项目，该项目包括出生后1/2周、5个月和9个月时的fNIRS扫描。照顾者的压力将通过头发皮质醇确定。已经发现毛发皮质醇是慢性压力水平的可靠量度（Ursache等人，2017），并允许我们对我们研究的婴儿所经历的压力进行推断，而无需使用侵入性措施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功能连接，但现在我指出Gao等人使用的方法，2014年，在fcMRI中确定了9个功能网络，并能够通过3个定量指标推断它们的相对成熟度：网络内连接，网络外连接和与成人参考的整体相似性。在收集每个婴儿的休息数据和从看护者那里收集头发样本后，我将进行统计分析，比较各组（高头发皮质醇和低头发皮质醇），以确定它们之间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，以确定电位差的大小和头发皮质醇水平的差异之间是否存在相关性。

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.