学龄儿童青少年杏仁核形态发育规律及焦虑关联研究
文献类型：学位论文
| 作者 | 周荃 |
| 答辩日期 | 2021-12 |
| 文献子类 | 博士 |
| 授予单位 | 中国科学院心理研究所 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 左西年 |
| 关键词 | 杏仁核 体积 形态 焦虑 生长曲线 |
| 学位名称 | 理学博士 |
| 学位专业 | 认知神经科学 |
| 其他题名 | The morphological development of the amygdala across childhood and adolescence and their association with anxiety |
| 中文摘要 | Childhood and adolescence are generally considered to be a critical period for brain development and a sensitive period for the development of emotional functions. Amygdala plays an important role in affective and cognitive processes, especially in fear and threat processing. Its structure has been proved abnormal in many neurodevelopmental abnormalities. Anxiety is the most common mental illness in children and adolescents. In addition, the development of the structure morphology of amygdale throughout childhood and adolescence has been inconsistently reported in previous neuroimaging studies. Given the relatively small size of the amygdala on full brain MRI scans, discrepancies may be partly due to methodological differences in amygdalar segmentation. This study used an accelerated cohort longitudinal design (1-3 time points, 6-20 years old), characterized developmental changes of the volume and morphology of amygdala, measured the accuracy of three automatic segmentation methods and examined how different tracing methods lead to trajectory differences in amygdala development across school age. In addition, we examined longitudinal associations between amygdala structure and anxiety during childhood and adolescence. Study one used the manual tracing method, which we used as the’gold standard'，to extract the structure of the amygdala. The hierarchical linear mixed model was used to measure the intra-rater and inter-rater reliability of manual segmentation to confirm whether the manual segmentation results in this study can be used as the `gold standard' for subsequent analysis. The present study then compared FreeSurfer, FSL and volBrain segmentation measurements with those obtained by manual tracing to investigate the impact of volume extraction methods on amygdala volume. The manual tracing exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic (FreeSurfer and volBrain) and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae, and volBrain produced smaller amygdalae while FSL demonstrated a mixed pattern. The tracing bias was not uniform, but higher for smaller amygdalae. These suggest that for children and adolescents, it is very important to use manual tracing to extract the amygdala structure. Methodological improvements are warranted for current automatic tools to achieve more accurate tracing of the amygdala at school age, calling for next generation tools. Study two modeled amygdalar volume and morphology growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project. Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Compared to the manually traced amygdala trajectories, the shapes of developmental curves were similar when using the volBrain derived volumes. FreeSurfer derived trajectories had more nonlinearities and appeared flatter. FSL derived trajectories demonstrated an inverted U shape and were significantly different from those derived from manual tracing method. Surface unit-level analysis detected the linear growth trends overlay the medial nucleus of the bilateral amygdala and the lateral nucleus of the right amygdala in children and adolescents. These regions had the greatest area expansion of up to 40%. We also observed clearly non-linear trajectories of volume change for the lateral nucleus of the left amygdala with increasing in childhood and followed by a phase of relative volume stability during the teens. Area change maps also revealed the ventral regions of the basolateral nucleus contracted with the highest contraction ratio reached about一10%. Our findings revealed steady growth of the human amygdala and the robust spatial gradient of morphological changes, mirroring its functional development across the school age. Study three used morphological measurement analysis in shape modeling to represent the deformation of amygdala structure, combined semi-parametric mixed effect spline model to fit the relationship between amygdala structure (volume and deformation) and anxiety, and explored the location and degree of amygdala change related to anxiety. Secondly, combined with the time-varying effect model, the age-related changes of the relationship between amygdala morphology and anxiety were explored. The results showed that although the amygdala volume is not significantly correlated with anxiety during the whole school age, the time-varying effect model analysis reported that the amygdala volume is significantly positively correlated with anxiety at the stage of 8-10 years old, and significantly negatively correlated with anxiety at the stage of 11 .5-13.5 years old. In addition, GAMM analysis showed that there was no significant correlation between amygdala surface deformation and anxiety during the whole school age, while the analysis of time-varying effect model showed that the central nucleus and part of the medial nucleus regions of bilateral amygdala was more likely to show a significant positive correlation with anxiety in mid childhood, part of the regions of accessory basal nucleus may show a significant negative correlation with anxiety in early adolescence. The results of this study revealed that the relationships between anxiety and the amygdala volume were inconsistent across different periods. It also revealed that the changes in the amygdale volume associated with anxiety do not necessarily reflect the same defects in the entire structure but reflect regional specificity and time一specificity. |
| 英文摘要 | 儿童青少年时期被普遍认为是大脑发育的关键时期，也是情绪功能发展的敏感时期。杏仁核在情感和认知过程中发挥着重要的作用，是负责恐惧等情绪管理的核心，该阶段杏仁核结构异常与多种神经发育异常有关。其中焦虑症是儿童青少年群体最常见的心理障碍之一，焦虑也成为对儿童青少年发展产生负面影响的消极情绪。然而，学界对儿童青少年时期杏仁核结构大小和形状的发育，及其与焦虑发展的关系尚待明确，需要对其深入研究。在之前的神经影像学研究中，有关儿童青少年时期杏仁核体积随龄变化的研究结果存在争议。鉴于杏仁核很小且结构复杂，这些差异可能部分是由于杏仁核的提取和建模方法不同造成。因此本研究采用“彩巢计划一成长在中国”采集的6-19岁纵向追踪多模态脑成像数据，利用手动追踪方法获得杏仁核结构，探索儿童青少年杏仁核的形态(体积和表面形状)生长发育曲线。通过检验各种自动分割方法的准确性，对比自动分割和手动追踪得到的杏仁核生长发育曲线之间的异同，检验分割方法的不同是否会影响对应杏仁核生长发育建模，并据此探索儿童青少年杏仁核体积、表面形态的发育与焦虑发展的关联规律。包括以下三个研究: 研究一:采用作为领域“金标准”的手动追踪方法来提取杏仁核结构，并通过分层线性混合模型测量手动追踪杏仁核的评估者内和评估者间信度，来确认本研究中的手动分割结果是否能够作为金标准应用于后续研究分析。为了进一步验证在儿童青少年群体中使用手动分割杏仁核的必要性，本研究对比了手动分割和三种自动分割方法(FreeSurfer, FSL和volBrain的性能表现。结果表明:两个评估者的手动追踪均获得了几乎完美的评估者内和评估者间信度，追踪结果可作为金标准评估自动分割准确性和进行后续的分析。与手动追踪相比，FreeSurfer高估了杏仁核体积，而volBrain则低估了杏仁核体积，FSL则表现出更复杂的高低混合模式，并且三种自动方法的分割准确性依赖于杏仁核大小均在分割较小杏仁核时出现更高的分割偏差。上述研究结果提示了对于儿童青少年研究，使用手动追踪准确描述人类杏仁核是至关重要的，三种自动方法在分割性能方面都与手动结果存在系统性差异，现在的自动工具有待进一步改进谨慎使用自动分割绘制生长曲线，建议尽可能使用手动追踪方法提取杳仁核。 研究二:对手动提取的杏仁核结构，采用加速队列纵向设计(1-3个时间点，6-19岁)样本，检验杏仁核体积、表面形态的变化，建模其生长曲线。为验证杏仁核分割提取方法的不同是否影响杏仁核生长曲线建模，本研究对比了自动分割同手动追踪得到的杏仁核发育曲线之间的相似性和差异性。结果表明: 学龄期女孩和男孩的杏仁核均表现出线性生长模式，虽然男孩的杏仁核显著大于女孩，但其生长发育模式是平行的。进一步的杏仁核生长曲线建模揭示volBrain分割所得发育曲线近乎线性，而FreeSurfer所得发育曲线表现出更多非线性，FSL则给出显著倒U形的发育曲线，与手动追踪方法导出的线性生长发育曲线显著不同。形态分析揭示了:双侧杏仁核的部分内侧核和右侧杏仁核的部分侧核区域呈现线性扩张的生长模式，在学龄儿童青少年中发生了最高程度达到40%的扩张;左侧杏仁核的部分侧核区域在学龄儿童期表现出线性增长，而到了青春期则进入生长的减速阶段并达到平台期;杏仁核的腹侧区域发生了收缩，最高收缩比例近10%。上述研究结果揭示了学龄儿童青少年杏仁核学龄儿 童青少年杏仁核体积的稳定生长和表面形态变化的强烈空间梯度，反映了其在整个学龄期的功能发展，这为将来研究提供了一个生长标准。 研究三:采集学龄期焦虑数据，基于三维表面的形态测量分析技术，利用形状建模的方法来重构杏仁核结构的表面，构建半参数混合效应样条模型，拟合杏仁核体积与焦虑的关系，探索学龄期发展中与焦虑相关的杏仁核区域;最后结合时变效应模型，揭示杏仁核体积、表面形态与焦虑关联的发展规律。结果表明:全学龄段整体上未检测到杳仁核体积与焦虑相关，但时变效应模型分析显示杏仁核与焦虑的关联随时间而变化，在8-10岁阶段杏仁核体积与焦虑显著正相关，在11.5-13.5岁阶段这一关系则为显著负相关;类似地，杏仁核表面形态与焦虑的相关在全学龄段也不显著，时变效应分析表明在儿童中期杏仁核中央核和小部分内侧核的扩张与高焦虑有关，在青春期早期杏仁核体积缩小、杏仁核腹侧和背侧交界处的部分副基底核区域的收缩则与高焦虑有关。上述研究结果揭示了学龄期焦虑与杏仁核形态发育之间的动态关联规律和机制，即不同年龄阶段的关联不同，不同杏仁核区域与焦虑之间的关联不同，体现了空间特异和时间特异的脑智关联规律。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/41172]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 周荃. 学龄儿童青少年杏仁核形态发育规律及焦虑关联研究[D]. 中国科学院心理研究所. 中国科学院心理研究所. 2021. |
入库方式： OAI收割
来源：心理研究所
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