新发二型糖尿病患者工作记忆相关脑区的超激活现象 ——来自功能磁共振研究的证据

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	新发二型糖尿病患者工作记忆相关脑区的超激活现象 ——来自功能磁共振研究的证据
其他题名	Hyperactivation of working memory-related brain circuits in newly diagnosed type II diabetics: A functional magnetic resonance imaging study
	何晓松
	2015-06
摘要	一、新发二型糖尿病患者工作记忆相关脑区的超激活现象二型糖尿病会造成大脑器质性病变及多种认知功能损伤。而现有研究仍主要关注于老年或长期患病的患者群体。相对年轻的中年患者处于二型糖尿病发病初期时，其大脑功能是否受到影响，仍有待研究。我们招募了12 名新诊断的中年患者以及12 名匹配的正常对照。我们使用功能磁共振测量了所有被试执行工作记忆任务——数字N-back 任务（0-，1-，2-back）时脑功能激活状况，并比较了患者与对照的差异。患者执行N-back 任务的正确率与对照相比并无显著性差别。然而，我们在右侧背外侧前额叶，左侧额中/下回以及左侧顶叶发现了显著的任务负载与分组之间的交互作用，即患者的脑功能激活在执行2-back（最高负载）时要显著性高于对照，而在执行0-back 或1-back（较低负载）时与对照无差异。我们进一步以实时血糖浓度作为协变量，分析了糖化血红蛋白浓度与脑功能激活的相关。我们仅在患者组发现，在前扣带回和双侧背外侧前额叶等脑区，有着更高的糖化血红蛋白浓度（更严重的慢性高血糖程度）的患者存在有更高的脑功能激活。综上所述，在二型糖尿病发病的早期，患者大脑存在代偿性超激活，并且更严重的慢性高血糖可能会带来更高的超激活。二、甲状腺功能减退症患者静息态功能网络连接的初步研究结果我们之前的研究（He et al., 2011）显示，在执行工作记忆任务时，甲状腺功能减退症患者存在包括内侧前额叶，后扣带回/楔前叶以及双侧角回的“默认网络”脑区的功能改变，然而在静息状态下，“默认网络”这些脑区的功能连接是否受到影响，仍有待探索。因此我们对14 名成年女性甲状腺功能减退症患者在接受左旋甲状腺激素替代治疗前后各进行一次静息态功能磁共振的扫描，并在相同阶段对15 名匹配的正常对照进行了两次扫描。对于所有受试者我们在扫描前均测量了他们的血清甲状腺激素水平，以及焦虑、抑郁和记忆水平。结果发现，治疗前的甲状腺功能减退症患者存在更低的甲状腺激素水平，更高的焦虑、抑郁水平，以及更低的记忆功能。治疗后，患者激素水平恢复正常，焦虑、抑郁水平显著下降，记忆功能也得到显著改善。然而与对照组相比，治疗后患者组的记忆功能仍显著性偏低。对于静息态脑功能连接数据，本研究拟通过三种常用的方法进行分析：（1）基于种子的相关分析；（2）独立成分分析；（3）基于图论的小世界网络分析。目前刚刚完成了基于种子的相关分析，因此在本报告中先报告这部分的结果。为了探索甲状腺功能减退症患者“默认网络”内部脑区之间功能连接是否存在改变，我们以默认网络的核心枢纽后扣带回/楔前叶作为种子，分析了其它默认网络脑区（双侧颞叶，双侧海马，双侧丘脑，双侧额上回，双侧角回及内侧前额叶）与种子区功能连接强度的差异。我们通过重复方差检验发现有且仅有双侧丘脑存在显著的被试类型×治疗前后的交互作用，在这两个脑区，对照组的功能连接强度在两次扫描间没有显著性差异，而患者组在治疗后却出现了显著性下降。目前的相关分析没有发现双侧丘脑治疗后脑功能连接下降与治疗后患者的临床、情绪和认知改善程度之间的显著相关。这种静息态功能连接的改变在生理和心理上的意义还有待进一步分析摸索。
其他摘要	Part I: Hyperactivation of working memory related brain circuits in newly-diagnosed middle-aged type 2 diabetics Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which lead to multidimensional cognitive deficits and wildly-spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly-diagnosed middle-aged T2DM patients with no previous diabetic treatment history and twelve matched controls were recruited. Brain activations during a working memory task, the digit n-back paradigm (0-, 1- and 2-back), were obtained with functional magnetic resonance imaging (fMRI) and tested by repeated measures ANOVA. Whereas patients performed the n-back task comparably well as controls, significant load-by-group interactions of brain activation were found in the right dorsolateral prefrontal cortex (DLPFC), left middle/inferior frontal gyrus, and left parietal cortex, where patients exhibited hyperactivation in the 2-back but not the 0-back or 1-back condition compared to controls. Furthermore, the severity of chronic hyperglycemia, estimated by glycosylated hemoglobin (HbA1c) level, was entered into partial correlational analyses with task-related brain activations, while controlling for the real-time influence of glucose, estimated by instant plasma glucose level measured before scanning. Significant positive correlations were found between HbA1c and brain activations in the anterior cingulate cortex and bilateral DLPFC only in patients. Taken together, these findings suggest there might be a compensatory mechanism due to brain inefficiency related to chronic hyperglycemia at the initial onset stage of T2DM. PartII: Preliminaryfindings of a resting-state functional connectivity study in patients with hypothyroidism before and after treatment Our previous study (He et al, 2011) showed that during performing a working memory task, patients with hypothyroidism presented abnormally reduced deactivation within several brain regions, including the medial prefrontal cortex, posterior cingulate cortex/precuneus, and angle gyrus, which are key components of a well defined brain network, the “default mode” network (DMN). However, the functional connectivity between components of the DMN under resting state in hypothyroid patients has not been investigated yet. Accordingly, we scanned 14 female hypothyroid patients using resting-state functional MRI before and after their levothyroxinetreatment. We also scanned 15 matched controls twice during the same period to provide baseline comparison. Serum hormone levels, anxiety, depression and memory function were tested at the time they were scanned. Our preliminary results showed that priori of their treatment, patients showed abnormally reduced thyroid hormone levels, increased anxiety and depression, and declined memory function. After treatment, the patients’ thyroid hormone levels were restored and their anxiety and depression were reduced. Their memory was also improved but still lower than controls. We planed to exploring the resting-state functional connectivity data in three common ways: (1) seed-based correlational analysis; (2) independent component analysis; (3) Graph theory based “small-world” analysis. Since it is an ongoing project, I only reported the preliminary data from the seed-based correlational analysis in this report. In this method, we took the hub region of the DMN, the posterior cingulate cortex/precuneus as seed, and components, including bilateral superior frontal gyri, temporal lobes, hippocampus, thalamus and angle gyri, as well as medial frontal cortex. Repeated measures ANOVAs revealed a significant subject type (patients, controls) by scan time (pre-, post-treatment) interaction in the bilateral thalamus. Post-hoc tests showed that in these two regions, the functional connectivity remained the same level in controls between the two scans while reduced in patients after the treatment, indicating a treatment specific change in functional connectivity in these patients. However, we did not find any correlation between such alteration in functional connectivity and the hormone and psychological improvement, hence the underlying physiological and psychological implication of such functional connectivity change remained to be explored in our further analysis.
学科领域	认知心理学
学位类型	博士
语种	中文
学位专业	心理学
学位授予单位	中国科学院研究生院
学位授予地点	北京
文献类型	学位论文
条目标识符	http://ir.psych.ac.cn/handle/311026/19530
专题	认知与发展心理学研究室
作者单位	中国科学院心理研究所
推荐引用方式 GB/T 7714	何晓松. 新发二型糖尿病患者工作记忆相关脑区的超激活现象 ——来自功能磁共振研究的证据[D]. 北京. 中国科学院研究生院,2015.

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