基于大尺度脑网络分析方法的脑可塑性研究
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摘要
脑可塑性是指大脑在外界环境和经验的作用下不断塑造自身的结构与功能从而适应环境需要的能力。在个体发展的整个过程中大脑都具有一定的可塑性。在刚出生时，婴儿大脑便拥有约两千万亿个神经元，但是此时的神经元之间的联结是相对冗余的、杂乱的。随着年龄的增长，在学习、训练以及多种经验等因素下，大脑神经元之间的联结开始逐渐精简和修饰。经常使用的联结得到强化并保留下来，逐渐形成适应外界环境的神经网络。因此，从神经元联结的角度上来说，学习是形成新联结的过程，而练习则是巩固已有联结的过程。以往的神经可塑性研究多从分子、突触水平到皮层功能区域水平的角度来研究，已取得了一定进展。虽然单个神经元或功能脑区都有自身不可忽略的作用，但是这些神经元或脑区构成的网络以及网络中不同部分之间的相互协调和相互作用才是个体表现出综合行为的根本原因。因此，从脑连接网络的角度考察个体发展、学习与训练引起的神经可塑性具有十分重要的理论和应用意义。
本文主要以脑功能磁共振成像（functional magnetic resonance imaging,fMRI）为载体，以大尺度脑功能连接网络分析方法为手段，辅以形态学分析，以及功能-功能（静息态-任务态）、功能-结构（静息态-结构像）的多模态融合，着重介绍和研究脑功能连接网络分析方法在神经可塑性研究中的应用。其中主要包括两部分的研究：
第一部分，高级认知专长的学习与训练引起的脑功能连接网络的可塑性变化。该部分主要以中国象棋大师为实验对象，以多模态脑网络分析方法为主线，探测学习与训练对特定的高级认知网络以及全脑大尺度网络的影响。
首先，研究中国象棋大师在执行与专业领域相关的高级认知任务时激活的四个认知网络（中央执行网络、背侧注意网络、突显性信息加工网络以及默认网络）与新手的差异，并基于任务激活图谱选取种子点，比较象棋大师与新手这四个网络的静息态功能连接差异。结果表明两组间任务态与静息态网络的差异都集中体现在默认网络上。
其次，针对象棋大师默认网络功能连接变化特征，我们融合了基于静息态功能磁共振成像的功能连接分析方法和基于结构磁共振成像的形态学测量方法，发现象棋大师纹状体的结构改变以及由此引起的纹状体-默认网络功能回路改变。
第三，针对象棋大师的全局行为特征，我们在全脑大尺度网络层面上，利用功能连接网络分析以及图论方法，探测高级认知专长的学习与训练对全脑功能网络拓扑属性的影响。我们发现象棋大师的全脑功能连接网络具有更高的网络聚类系数和“小世界”属性，表明长期高强度的高级认知训练增强了全脑网络的功能整合，提高了信息交换效率。
最后，利用功能连接密度分析方法来定量刻画大脑内部的短程和长程功能连接密度，寻找长期高强度专业象棋训练引起的更为精细的脑网络功能连接密度变化，拓展我们对大尺度脑功能连接网络可塑性的理解。
第二部分，大脑自然发育过程中与学习记忆相关的高级认知脑功能连接网络的可塑性变化。该部分主要集中在学习与记忆最关键的脑区——内侧颞叶系统的功能网络组织模式以及该网络由大脑发育引起的可塑性改变。
首先，利用基于静息态功能磁共振的大尺度功能连接分析方法全面研究内侧颞叶系统中7个子区域各自的功能连接回路以及这些回路对长时记忆的贡献作用，从而更好地理解学习与记忆的神经机制。
其次，选取24名7-9岁的正常发育儿童、19名13-17岁正常发育的青少年以及24名18-22岁的年轻人作为研究对象，利用静息态功能连接分析方法，探测儿童与成年人的内侧颞叶系统功能连接回路的异同，从而揭示内侧颞叶系统功能回路在正常发展过程中产生的可塑性变化。
Brain plasticity refers to the capacity of the nervous system to change its structure and function over a lifetime, in reaction to environmental diversity. At birth, the human brain consists of approximately10billion neurons, with rough and redundancy synaptic connections. A decrease in synapses is seen after a period of development, learning and training:synapses that are frequently used have strong connections while rarely used synapses are eliminated. In terms of neuroscience, learning is the process of forming new synaptic connections, and practice is the process of consolidating and strengthening the existing connections. Excaming the brain plasticity changes after learning and training is a major trend of the current neuroplasticity studies. Previous researches demonstrated that neuroplasitcity occurs on a variety of levels, ranging from neurons, columes, functional areas, and even, the large-scale functional networks. On macro scale, dispite the fact that, specific brain regions mediate specific functions, the networks consisted by those regions as well as their interaction and intercoordinations are the basis of the overall human behavior. Therefore, it has extremely important theoretic and application significance to explore the neuroplasticiy changes induced by brain development, learning and trainning, on the level of large-scale functional connectivity brain networks.
The current work dedicated to investigating the brain plasticity changes on the large-scale brain network level, by means of functional magnetic resonance imaging (fMRI), as well as a newly introduced functional-funcitonal (task-rest), and functional-strutural(rest-VBM) multi-modal fusion methods. Two aspects of this dissertation have been put forword:
The first part investigated the brain plasticity changes on the level of large-scale brain network after long-term and intensive learning and trainning of high level cognitive expertise. In this part, we studied the brain network differences between world-level Chinese chess grandmaters and noices.
First, we excamined the influence of cognitive expertise on four networks associated with cognitive task performance:the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network), both during task and rest. We found that, in those four networks, the chess grandmasters and noives only showed significant differences in the DMN.
Secondly, according to the changed functional connectivity in the DMN, we combined the structural and fucntioanl MRI, and found the structural changes of the striatum as well as striatum-DMN connectivity in chess grandmaters.
Thirdly, by means of the functional connectivity analysis and graph theoretical analysis, we investigated the whole-brain functional connectivity network and its topological properties of chess grandmaster. Increased small-world topology and clustering coefficient were found in chess grandmasters, which indicated that long-term cognitive skill learning leaded to a more efficient organization of the brain networks.
Finally, we used functional connectivity density mapping analysis to quantificationally depict the short-range and long-range functional connectivity density. We aimed to explore more delicate alteration in the brain of chess grandmasters after long-term training on high-level cognitive expertise.
In the second part of this dissertation, we investigated the plasticity changes in the learning-and memory-related networks induced by brain natural development. In this part, we focused on the functional organization of the medial temporal lobe (MTL) network and differences in this network between children and adults.
First, we provided a comprehensive intrinsic functional connectivity analysis of seven distinct subdivisions of the human MTL to delineate the functional circuitry of the MTL for better understanding the contributions of its subregions to learning and memory.
Secondly, we investigated developmental changes in functional connectivity of the MTL system in twenty-four7-to9-year-old typically developing children, nineteen13-to17-year-old adolescents, and twenty-four19-to22-year-old health adults. Adults showed significantly stronger intrinsic connectivity analysis of the hippocampus with widely-distributed cortical and subcortical areas, demonstrating the functional integration of the MTL system after brain development.
本文主要以脑功能磁共振成像（functional magnetic resonance imaging,fMRI）为载体，以大尺度脑功能连接网络分析方法为手段，辅以形态学分析，以及功能-功能（静息态-任务态）、功能-结构（静息态-结构像）的多模态融合，着重介绍和研究脑功能连接网络分析方法在神经可塑性研究中的应用。其中主要包括两部分的研究：
第一部分，高级认知专长的学习与训练引起的脑功能连接网络的可塑性变化。该部分主要以中国象棋大师为实验对象，以多模态脑网络分析方法为主线，探测学习与训练对特定的高级认知网络以及全脑大尺度网络的影响。
首先，研究中国象棋大师在执行与专业领域相关的高级认知任务时激活的四个认知网络（中央执行网络、背侧注意网络、突显性信息加工网络以及默认网络）与新手的差异，并基于任务激活图谱选取种子点，比较象棋大师与新手这四个网络的静息态功能连接差异。结果表明两组间任务态与静息态网络的差异都集中体现在默认网络上。
其次，针对象棋大师默认网络功能连接变化特征，我们融合了基于静息态功能磁共振成像的功能连接分析方法和基于结构磁共振成像的形态学测量方法，发现象棋大师纹状体的结构改变以及由此引起的纹状体-默认网络功能回路改变。
第三，针对象棋大师的全局行为特征，我们在全脑大尺度网络层面上，利用功能连接网络分析以及图论方法，探测高级认知专长的学习与训练对全脑功能网络拓扑属性的影响。我们发现象棋大师的全脑功能连接网络具有更高的网络聚类系数和“小世界”属性，表明长期高强度的高级认知训练增强了全脑网络的功能整合，提高了信息交换效率。
最后，利用功能连接密度分析方法来定量刻画大脑内部的短程和长程功能连接密度，寻找长期高强度专业象棋训练引起的更为精细的脑网络功能连接密度变化，拓展我们对大尺度脑功能连接网络可塑性的理解。
第二部分，大脑自然发育过程中与学习记忆相关的高级认知脑功能连接网络的可塑性变化。该部分主要集中在学习与记忆最关键的脑区——内侧颞叶系统的功能网络组织模式以及该网络由大脑发育引起的可塑性改变。
首先，利用基于静息态功能磁共振的大尺度功能连接分析方法全面研究内侧颞叶系统中7个子区域各自的功能连接回路以及这些回路对长时记忆的贡献作用，从而更好地理解学习与记忆的神经机制。
其次，选取24名7-9岁的正常发育儿童、19名13-17岁正常发育的青少年以及24名18-22岁的年轻人作为研究对象，利用静息态功能连接分析方法，探测儿童与成年人的内侧颞叶系统功能连接回路的异同，从而揭示内侧颞叶系统功能回路在正常发展过程中产生的可塑性变化。
Brain plasticity refers to the capacity of the nervous system to change its structure and function over a lifetime, in reaction to environmental diversity. At birth, the human brain consists of approximately10billion neurons, with rough and redundancy synaptic connections. A decrease in synapses is seen after a period of development, learning and training:synapses that are frequently used have strong connections while rarely used synapses are eliminated. In terms of neuroscience, learning is the process of forming new synaptic connections, and practice is the process of consolidating and strengthening the existing connections. Excaming the brain plasticity changes after learning and training is a major trend of the current neuroplasticity studies. Previous researches demonstrated that neuroplasitcity occurs on a variety of levels, ranging from neurons, columes, functional areas, and even, the large-scale functional networks. On macro scale, dispite the fact that, specific brain regions mediate specific functions, the networks consisted by those regions as well as their interaction and intercoordinations are the basis of the overall human behavior. Therefore, it has extremely important theoretic and application significance to explore the neuroplasticiy changes induced by brain development, learning and trainning, on the level of large-scale functional connectivity brain networks.
The current work dedicated to investigating the brain plasticity changes on the large-scale brain network level, by means of functional magnetic resonance imaging (fMRI), as well as a newly introduced functional-funcitonal (task-rest), and functional-strutural(rest-VBM) multi-modal fusion methods. Two aspects of this dissertation have been put forword:
The first part investigated the brain plasticity changes on the level of large-scale brain network after long-term and intensive learning and trainning of high level cognitive expertise. In this part, we studied the brain network differences between world-level Chinese chess grandmaters and noices.
First, we excamined the influence of cognitive expertise on four networks associated with cognitive task performance:the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network), both during task and rest. We found that, in those four networks, the chess grandmasters and noives only showed significant differences in the DMN.
Secondly, according to the changed functional connectivity in the DMN, we combined the structural and fucntioanl MRI, and found the structural changes of the striatum as well as striatum-DMN connectivity in chess grandmaters.
Thirdly, by means of the functional connectivity analysis and graph theoretical analysis, we investigated the whole-brain functional connectivity network and its topological properties of chess grandmaster. Increased small-world topology and clustering coefficient were found in chess grandmasters, which indicated that long-term cognitive skill learning leaded to a more efficient organization of the brain networks.
Finally, we used functional connectivity density mapping analysis to quantificationally depict the short-range and long-range functional connectivity density. We aimed to explore more delicate alteration in the brain of chess grandmasters after long-term training on high-level cognitive expertise.
In the second part of this dissertation, we investigated the plasticity changes in the learning-and memory-related networks induced by brain natural development. In this part, we focused on the functional organization of the medial temporal lobe (MTL) network and differences in this network between children and adults.
First, we provided a comprehensive intrinsic functional connectivity analysis of seven distinct subdivisions of the human MTL to delineate the functional circuitry of the MTL for better understanding the contributions of its subregions to learning and memory.
Secondly, we investigated developmental changes in functional connectivity of the MTL system in twenty-four7-to9-year-old typically developing children, nineteen13-to17-year-old adolescents, and twenty-four19-to22-year-old health adults. Adults showed significantly stronger intrinsic connectivity analysis of the hippocampus with widely-distributed cortical and subcortical areas, demonstrating the functional integration of the MTL system after brain development.
引文
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