心理科学进展, 2018, 26(10): 1857-1868 doi: 10.3724/SP.J.1042.2018.01857

研究前沿

体育锻炼促进认知功能的脑机制

夏海硕1, 丁晴雯2, 庄岩3, 陈安涛,1

1 西南大学心理学部, 重庆 400715

2 华中师范大学心理学院, 武汉 430079

3 西南大学体育学院, 重庆 400715

The brain mechanisms of the physical exercise enhancing cognitive function

XIA Haishuo1, DING Qingwen2, ZHUANG Yan3, CHEN Antao,1

1 School of Psychology, Southwest University, Chongqing 400715, China

2 Department of Psychology, Central China Normal University, Wuhan 430079, China

3 Department of Physical Education, Southwest University, Chongqing 400715, China

通讯作者: 陈安涛, E-mail: xscat@swu.edu.cn

收稿日期: 2017-10-16   网络出版日期: 2018-10-15

Received: 2017-10-16   Online: 2018-10-15

摘要

不同类型的体育锻炼对各种群体的多种认知功能均具有促进作用, 而相关的生理机制也在不同水平得到研究。在微观水平, 体育锻炼有利于脑细胞的营养供给和能量代谢, 并且能促进神经元的存活和突触生成。在宏观水平, 体育锻炼不仅能够提升海马和小脑等脑结构的体积, 还影响脑区激活水平和脑区间功能连接。值得注意的是, 体育锻炼对认知的促进效应受到诸多因素的影响, 比如个体差异、时间, 以及体育锻炼和认知刺激的相互作用等, 这些影响因素也为在两个水平上系统地阐明体育锻炼促进认知的脑机制提供了新的视角。

关键词: 体育锻炼 ; 认知增强 ; 脑成像 ; 脑源性营养因子 ; 突触生成

Abstract

It has been identified that physical exercise is able to enhance cognitive functions, attracting attention to the underlying brain mechanisms. The literature shows that the enhancing effects rely basically on two distinct mechanisms, on the microscale and macroscale levels, respectively. At the microscale level, physical exercise favored synaptogenesis and the survival of neurons through better nutrient supply and metabolism. At the macroscale level, physical exercise could enhance cognition through enlarging the volume of white and grey matter, and changing the brain activity and functional connectivity. Notably, multiple factors could influence the enhancing effects of physical exercise on cognition, such as individual differences, time, and the interaction between physical exercise and cognitive stimulations. These factors provide new directions to conduct deep and systematic investigations on the brain mechanisms of enhancing effects on the two levels.

Keywords: physical exercise ; cognitive enhancement ; brain imaging ; brain derived neurotrophic factor ; synaptogenesis

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本文引用格式

夏海硕, 丁晴雯, 庄岩, 陈安涛. (2018). 体育锻炼促进认知功能的脑机制. 心理科学进展, 26(10), 1857-1868

XIA Haishuo, DING Qingwen, ZHUANG Yan, CHEN Antao. (2018). The brain mechanisms of the physical exercise enhancing cognitive function. Advances in Psychological Science, 26(10), 1857-1868

体育锻炼(如, 跑步和游泳等)涉及肌肉对骨骼的拉伸和能量的消耗, 是一种旨在促进健康、提升运动技能, 且具有计划性和重复性的身体活动(Kylasov & Gavrov, 2011; Louis, Erickson, & Liu-Ambrose, 2013)。研究表明, 体育锻炼是保证身心健康的重要手段, 能够减少身体疾病(如, 心血管疾病和肥胖等)和心理疾病(如, 抑郁和焦虑等)的发病率(Huxley et al., 2014; Vankim & Nelson, 2013)。此外, 行为学研究也表明体育锻炼能够促进认知能力(Etnier et al., 1997)。从锻炼群体的角度讲, 体育锻炼能够促进包括未成年(Etnier, Labban, Piepmeier, Davis, & Henning, 2014)、成年人(Cox et al., 2016)以及老年人(Wong, 2017)等各类群体的认知功能。从锻炼特征的角度讲, 不同类型(如, 耐力训练、协调训练和拉伸训练)、强度以及持续时间的体育运动均能够促进认知能力(Etnier et al., 1997; Piepmeier, 2015)。从训练效果角度来讲, 体育锻炼也能提升不同类型的认知功能(如, 视觉记忆、听觉记忆、问题解决能力和认知控制能力等), 且促进效果能够在锻炼结束后维持一段时间(Chang, Labban, Gapin, & Etnier, 2012; Piepmeier, 2015)。

在行为层面, 研究包含的被试群体、锻炼类型和认知能力种类繁多, 因此需要元分析对结果进行统合(Hindin & Zelinski, 2012; Piepmeier, 2015)。一项元分析在纳入了近200项研究后发现体育锻炼能够正向预测认知能力。其中, 认知测验的类型和被试群体等因素能够对训练效果起到调节作用(Etnier et al., 1997)。进一步的, Chang等(2012)的元分析探究了运动特征对认知功能的影响, 并发现当体育运动的强度非常剧烈, 且运动时间在11分钟以上时, 体育锻炼对认知功能的促进效果最强。

除了行为学和元分析的研究外, 也有研究借助生化学和影像学等技术, 从不同层面考察体育锻炼促进认知功能的脑机制。微观层面的研究多以实验动物为主, 不仅考察了体育锻炼对脑细胞内环境稳态(如, 营养摄入和能量代谢)和生化反应的影响, 也探究了体育锻炼对神经胶质细胞生成、神经元存活和突触发生(synaptogenesis)的影响(Leckie et al., 2014; Thomas, Dennis, Bandettini, & Johansen-Berg, 2012)。宏观层面的研究则多利用形态解剖和无创脑成像技术, 探究体育锻炼对脑结构(如, 灰质和白质体积等)和脑功能(如, 脑区激活水平和功能连接)的影响(Cotman, Berchtold, & Christie, 2007; Voss, Vivar, Kramer, & van Praag, 2013)。本文将在简介行为学研究的基础上, 重点介绍体育锻炼对认知功能影响的微观和宏观机制。

1 体育锻炼促进认知功能的微观机制

在微观层面上, 营养的获得和能量的利用是神经元进行生命活动的必要前提(Bedi et al., 2003; Bélanger, Allaman, & Magistretti, 2011)。在充分营养供给和能量稳定代谢的基础上, 细胞将高效地完成各类生化反应, 合成维持神经元存活、突触建立所必须的神经递质和蛋白质等其他物质(Thomas et al., 2012)。体育锻炼能够影响上述的细胞活动过程, 例如脑源性神经营养因子的研究表明体育锻炼能够对细胞内的生化反应产生影响(Piepmeier, 2015)、而血管促进和脑疾病相关的研究则表明体育锻炼能够对细胞的营养供给和能量代谢产生影响(Caruso et al., 2015; Thomas et al., 2012)。

1.1 脑源性神经营养因子

脑源性营养因子(Brain Derived Neurotrophic Factor, BDNF)在体育锻炼促进认知能力的过程中起到促进作用。研究表明, BDNF大量存在于海马和大脑皮层等负责高级认知功能(如, 学习和记忆)的脑区(Hyman et al., 1991), 能够通过如下两条途径促进认知功能。首先, BDNF能通过影响神经胶质细胞促进神经元的功能。例如, Xiong等(2015)的研究发现, BDNF能够提升小神经胶质细胞的健康水平。由于小神经胶质细胞在稳定神经元的物理网络结构方面具有重要的作用(Streit, 2002)。因此, BDNF可能通过稳定和重塑神经元的物理结构提升认知能力。其次, 在维持已有神经元存活的同时促进突触再塑。具体来讲, BDNF能够通过影响包括钙调素激酶II (calcium-calmodulin kinase II)和丝裂原活化蛋白激酶(mitogen activating protein kinase)在内的细胞内信号转导系统促进环磷腺苷反应元件结合蛋白(cAMP responsive element-binding protein, CREB)的合成(Vaynman, Ying, Wu, & Gomez- Pinilla, 2006)。由于CREB在维持神经元存活以及突触可塑性(synaptic plasticity)的过程中至关重要(Dhar et al., 2014; Landeira et al., 2016), 因此BDNF能够通过促进CREB的合成促进认知功能。

作为一种与脑可塑性密切相关的高分子蛋白, BDNF的合成过程受到体育锻炼的影响(Piepmeier, 2015)。基因层面的研究表明, 体育锻炼能够通过影响能量代谢相关的神经调控因子PGC-1a调节鸢尾素基因FNDC5的表达, 最终促进BDNF的合成(Wrann et al., 2013)。而动物实验的结果表明, 长期跑步训练能够诱发大鼠BDNF的合成, 并通过提升神经胶质细胞的健康水平促进大鼠的空间记忆能力(Xiong et al., 2015)。最后, 来自人类的研究发现, 剧烈的体育锻炼或长期的散步均能够通过促进BDNF的合成提升中央执行功能、记忆和学习能力, 而且年龄起到正向调节作用(Leckie et al., 2014; Piepmeier, 2015)。因此, 无论是对于实验动物还是人类, 多种类型的体育锻炼均能够促进BDNF的合成, 在对神经胶质细胞和神经元产生积极影响的同时提升认知功能。

1.2 血管促进

体育锻炼能够促进血管健康并增加脑血流量, 在为大脑带来充足营养和能量的同时提升脑可塑性(Thomas et al., 2012)。以动物为对象的形态解剖学研究发现, 相对于非运动组小鼠, 运动组小鼠的脑皮层血管更加丰富(van der Borght et al., 2009), 结果表明体育锻炼能够促进大脑血管生成。而影像学的研究也证明体育锻炼能够提升单位时间内流经大脑的血液总量(Gligoroska & Manchevska, 2012)。充足的血液供给不仅提供了细胞代谢所需的能量, 还带来了丰富的营养物质。由于丰富的营养物质是某些脑再塑相关神经递质(如, 去甲肾上腺素、肾上腺素和5-羟色胺等)合成的必要前体物质(Brudzynski & Gibson, 1997; Girard & Garland, 2002; Meeusen et al., 1997)。因此体育锻炼能够通过改善细胞的血流环境, 使神经元高效地进行生化反应, 并最终促进神经元的存活和突触连接的建立。

体育锻炼能够促进脑血管生成, 改善脑细胞的营养供给和能量代谢过程, 并最终提升脑可塑性。但值得注意的是, 血管生成并不能完全解释体育锻炼促进认知功能的全部机制。Colcombe等(2004)的研究表明, 虽然耐力训练能够直接提升血管的健康水平, 但拉伸训练、协调能力训练等几乎不会影响血管生成的低强度运动同样能够促进认知功能。因此, Hötting和Röder (2013)指出在讨论体育锻炼促进认知功能的机制时, 应考虑除了血管促进外的其它因素, 并作出综合解释。

1.3 疾病干预

运动能够通过干预破坏内稳态的疾病起到保护脑可塑性和认知功能的作用(Hötting & Röder, 2013)。由于与新陈代谢相关的能量供给和与血液循环相关的营养供给是细胞进行生化反应的生理基础(Cotman et al., 2007), 因此代谢类疾病和循环系统疾病能够阻碍神经元的存活和突触的建立, 并进一步引发认知功能障碍(Stranahan & Mattson, 2012; Zochodne, 2014)。一项大样本的研究发现, 高血压、心血管疾病、心脏病以及其他类型的循环系统类疾病能够强烈预测认知功能的衰退; 而糖尿病这种代谢类疾病不仅能够导致认知功能的衰退, 还能提升阿尔兹海默症的患病风险(Haring et al., 2013)。

体育锻炼能够有效减少慢性炎症反应, 通过降低糖尿病和心血管疾病的发病风险保护认知功能(Espeland et al., 2017; Pedersen, 2017), 起到“防患于未然”的作用。相反, 减少体育锻炼不仅会提高罹患心血管疾病的风险, 还会进一步导致认知功能的衰退(Alosco et al., 2014)。另外, 对于已经罹患相关疾病的个体, 体育锻炼也能够起到“亡羊补牢”的作用。同样均患有二型糖尿病的个体, 经常运动的一组在认知测试中不仅拥有更好的成绩(Colberg, Somma, & Sechrist, 2008), 而且认知衰退的速度更慢(Caruso et al., 2015)。对于心血管病患者而言, 疾病对认知功能的影响也受到有氧运动的调节(Hayes, Alosco, & Forman, 2014)。相对于控制组, 进行了两周有氧运动的实验组患者表现出了更高水平的注意和中央执行功能(Tanne et al., 2005)。因此, 运动能够对认知能力起到“防患于未然”和“亡羊补牢”的双重保护作用。

2 体育锻炼促进认知功能的宏观机制

生化学研究从基因的翻译和转录、脑营养的供给和神经递质的合成等微观层面解释体育锻炼促进认知功能的生理机制(Leckie et al., 2014; Piepmeier & Aaron, 2015), 而形态解剖学和脑成像技术则能够从更宏观的层面描绘大脑特征。利用解剖学手段, 能够直接观察突触密度和皮层厚度等解剖学特征(Voss et al., 2013)。而利用影像学技术, 不仅能够对脑结构和脑激活模式进行无创观测(Friston, Frith, Liddle, & Frackowiak, 1993), 还能够利用大尺度脑网络分析等方法对全脑活动模式进行分析(Wang, Kang, Kemmer, & Guo, 2016)。

2.1 脑结构

体育锻炼对实验动物和人类的脑结构均有影响(Voss et al., 2013)。来自啮齿动物的研究表明, 体育锻炼不仅能够提升海马齿状回中神经元树突棘的密度(Stranahan, Khalil, & Gould, 2007), 还能提升运动皮层的厚度(Anderson, Eckburg, & Relucio, 2002)及其血管总量(Swain et al., 2003)。对于人类而言, 难以使用形态解剖学手段对人脑进行观测, 但无创脑成像技术(如, 基于体素的形态学分析和弥散成像技术)提供了探索脑结构特征的有效途径(Ashburner & Friston, 2000; Pierpaoli, Jezzard, Basser, Barnett, & Di Chiro, 1996)。

影像学的研究表明, 体育锻炼能够对人类运动相关脑区的结构产生影响。最初的研究表明, 仅仅是规律性的散步就能提升辅助运动区(supplementary motor area)的脑体积(Colcombe et al., 2006)。后来, 研究开始关注体育锻炼、脑结构变化和运动相关认知能力的关系。例如, Ji等(2017)的研究发现, 6周的有氧运动能够提升老年人手部运动皮层、纹状体和小脑的灰质体积。由于纹状体可能和体育运动过程中的中央执行功能(如, 注意和加工运动相关的信息)相关(Ji et al., 2017), 且小脑和运动中的动作习得和精确化相关(Schonewille et al., 2011), 因此可以推测体育锻炼能够通过改变大脑结构促进个体运动相关的认知能力。

除了运动相关的脑区, 体育锻炼也能够对海马和新皮层等脑区的结构产生影响(Fabel et al., 2003; Hötting, Schauenburg, & Röder, 2012; Klempin et al., 2013; Köbe et al., 2016)。一些研究利用弥散张量成像(diffusion tensor imaging, DTI)技术, 对脑白质纤维束的体积进行估计, 结果发现有氧训练能够使海马体积提升2%~16% (Erickson et al., 2011; Pajonk et al., 2010)。此外, 一些研究利用体素形态学分析法(voxel-based morphometry, VBM), 在全脑水平对体素类型做判断, 结果发现6个月的有氧训练和拉伸训练均能提升老年人大脑灰质和白质的体积(Colcombe et al., 2006), 降低背侧前扣带皮层、背外侧前额叶皮层、左侧颞叶(Voss et al., 2013; Ziegler et al., 2012)和顶叶(Ho et al., 2011)区域脑组织的流失速率。因此, 基于多方法的影像学研究均表明, 体育锻炼能够通过改变大脑结构促进认知功能。

2.2 脑活动模式

脑活动模式的改变是大脑发生重塑的重要指标之一, 意味着潜在的脑结构变化和认知能力的改变(Hohenfeld et al., 2016; Hötting & Röder, 2013)。通过功能性磁共振技术(functional magnetic resonance imaging, fMRI), 不仅能够探测特定脑区在执行认知任务时的血氧依赖水平(blood oxygenation level dependent, BOLD), 还能探测多个脑区BOLD信号时间序列的相关水平, 即脑功能连接模式(Friston et al., 1993; Greicius, Krasnow, Reiss, & Menon, 2003)。

2.2.1 脑激活水平的改变

体育锻炼能够对运动相关脑区的激活水平产生影响。一项利用低频震荡技术(amplitude of low- frequency oscillation function, ALFF)的研究表明, 相对于锻炼前, 体育锻炼后被试脑岛、小脑和纹状体的活动水平显著提升(Ji et al., 2017)。由于脑岛、小脑和纹状体在运动控制和运动学习的过程中发挥重要作用(Fink, Frackowiak, Pietrzyk, & Passingham, 1997; Schonewille et al., 2011), 因此可以推测体育锻炼能够通过改变运动相关脑区的活动模式, 提升运动相关的认知能力。

除了运动相关脑区, 体育锻炼也能够对高级认知功能相关脑区的激活水平产生影响(Prakash, Voss, Erickson, & Kramer, 2015)。首先, 有些研究发现体育锻炼能够降低一些脑区的激活水平。例如, 有氧运动能够降低老年人前扣带回和儿童前额叶的激活水平, 并提升中央执行功能(Chaddock- Heyman et al., 2013; Colcombe et al., 2004)。而背后的机制则可能是体育锻炼能够通过提升突触连接效率(An, Zagaar, & Alkadhi, 2015; Christie et al., 2008), 使这些脑区在完成同样强度认知任务的同时消耗更少的能量, 并表现出较低的激活水平。其次, 有些研究发现体育锻炼能够增强某些脑区的激活水平(Holzschneider, Wolbers, Röde, & Hötting, 2012)。例如, 有氧训练能够提高青少年双侧顶叶(Chen, Zhu, Yan, & Yin, 2016)和老年人左侧枕叶、右侧颞上回等脑区的激活水平(Hsu et al., 2018)。而背后的机制则可能是有氧运动能够通过提升血管健康和脑血液供给使皮层激活水平增强(Holzschneider et al., 2012)。值得注意的是, 对于同一脑区, 体育锻炼对激活水平影响的方向存在跨研究的一致性(Chaddock-Heyman et al., 2013; Ji et al., 2017)。但对于不同脑区, 激活方向将可能由于作用机制的不同而存在差异。

2.2.2 功能连接的改变

复杂的认知任务不仅需要某些特定脑区的参与, 也需要多脑区的协同配合(Burdette et al., 2010; Voss et al., 2010)。体育锻炼能够对运动相关脑区和高级认知功能相关脑区的功能连接产生影响(Chirles et al., 2017; Rajab et al., 2014; Voss et al., 2010)。

体育锻炼能够促进感觉运动相关脑区的功能连接, 并最终提升负责运动学习相关的认知能力(Rajab et al., 2014)。例如, Rajab等(2014)的研究表明, 体育锻炼不仅能够促进静息状态下次级躯体感觉皮层(secondary somatosensory cortex)的本土连接水平, 使个体表现出更好的触觉注意能力; 还能促进丘脑基底核本土连接的水平, 使个体更好地在运动学习过程中对奖赏做出反馈。

除了感觉运动相关的脑区, 体育锻炼还能促进高级认知功能相关脑区的功能连接。以中央执行功能为例, 相对于不进行运动的控制组, 运动组被试的纹状体和多个脑区(如, 丘脑、扣带回、颞叶、顶叶和枕区)的功能连接水平均有所提升, 其中纹状体和丘脑的功能连接程度能够正向预测运动组被试的中央执行功能(Ji et al., 2017)。此外, 体育锻炼也能对脑网络激活水平产生影响(Rajab et al., 2014)。例如, Voss等(2010)的研究表明体育锻炼能够改变默认脑网络(default mode network)和额叶执行网络(frontal executive network)的激活模式, 并使老年人表现出较高的中央执行功能。而Ji等(2017)的研究也表明, 体育锻炼能够提高听觉相关脑网络活动的同步性(Rajab et al., 2014)。

3 宏观和微观机制研究的不足

3.1 微观机制

目前来讲, 虽然有大量研究探究了体育锻炼促进认知功能的微观生理机制, 但仍存在需要解决的问题。首先, 体育锻炼促进认知功能的具体机制仍需深入探讨(Erickson, Hillman, & Kramer, 2015)。在血管促进方向, 虽然有研究发现体育锻炼能够通过促进血管生成提升认知功能(Kim, Jeong, Won, Ka, & Oh, 2014; Roelofs, Smithryan, Trexler, Hirsch, & Mock, 2016)。但充足的血液供给能够通过提供丰富的营养促进脑可塑性的观点仍停留在理论推测阶段。未来需要更多研究考察营养供给、神经递质合成在脑血管生成和脑可塑性间发挥的作用。此外, 在疾病干预方向, 虽然Espeland等(2017)Pedersen (2017)从流行病学和行为测量的角度明确了体育锻炼、疾病和认知衰退的关系, 且Anazodo、Shoemaker、Suskin和Lawrence (2013)也证明疾病对脑结构的损伤程度会因运动程度的不同而存在差异, 但运动在疾病和脑生化反应间的调节作用仍不明确。不同程度的运动如何调节患者大脑的营养供给和能量代谢过程, 并最终影响脑结构和脑功能, 需要在未来做进一步探究。

其次, 现有研究结果尚待进一步统合。例如, 虽然研究发现锻炼诱发的BDNF能够促进中央执行功能和记忆(Lee et al., 2014; Skriver et al., 2014), 但Tsai等(2014)的研究发现锻炼诱发的BDNF不能够影响中央认知功能。不一致的研究结果可能由锻炼时长、强度和种类的不同引发, 也有可能由被试群体和认知能力测量方式的不同所致, 未来需做进一步整合。

最后, 以人类为被试的基因学和生化学研究数量较少, 且测量方式也不够直接。例如, 虽然Heyman等(2012)的研究通过检测血浆中内源性大麻酚(endocannabinoids)的含量间接推测了人脑中BDNF的含量, 但并未对BDNF的含量进行直接测量。因此, 未来的研究应在伦理道德许可的条件下, 设计更加巧妙的实验, 对这一问题做深入的探讨。

3.2 宏观机制

宏观机制的研究也存在一些不足。首先, 体育锻炼为什么对不同脑区激活程度的影响存在方向性差异, 目前尚无定论。虽然研究发现体育锻炼可能以提升突触连接效率、减少神经元能耗的方式降低前额叶和前扣带回等脑区的激活水平(Chaddock-Heyman et al., 2013; Christie et al., 2008; Colcombe et al., 2004), 也可能以促进脑血管生成的方式提升枕叶和颞叶等脑区的激活水平(Hsu et al., 2018; Holzschneider et al., 2012)。但并没有研究关注为什么在不同的脑区, 体育锻炼对脑激活水平的影响遵循了不同的机制。未来, 需要综合脑血管生成、突触连接生成和神经元能量消耗等因素, 对该问题做进一步探讨。

其次, 不同特征的体育锻炼对脑结构和脑功能的影响仍不明确。行为学的研究提示, 体育锻炼的特征会对认知功能的促进效果产生影响。相对于每次锻炼20分钟, 每次40分钟的锻炼对认知能力的促进效果更强(Davis et al., 2011)。对于老年人而言, 相对于每周锻炼一次, 只有每周锻炼一次以上才对认知功能有促进效果(Liu-Ambrose, Nagamatsu, Voss, Khan, & Handy, 2012)。虽然Voelcker-Rehage和Niemann (2013)的梳理了不同类型体育锻炼对脑结构和脑功能的影响, 但较少研究考察体育锻炼其他特征的作用。未来应结合形态解剖学和无创脑成像技术考察体育锻炼的频率、持续时间和强度对大脑的影响。

最后, 体育锻炼对脑功能连接影响的研究仍处在起步的阶段(Hötting & Röder, 2013)。从被试群体的角度讲, 大多数脑网络的研究样本仅局限于非健康个体(如, 多发性硬化症和癫痫患者等)和老年人(Flodin et al., 2015; Ji et al., 2017; Koirala, Lee, Eom, Kim, & Kim, 2017), 较少有研究以健康成年人和未成年人为被试。从功能连接类型的角度讲, 目前关注的脑网络种类也较为单一, 虽然Voss等(2010)的研究表明体育锻炼能够对默认脑网络和中央执行脑网路产生影响, 但较少研究关注体育锻炼对全脑网络的功能整合和信息交换效率的影响。因此, 未来的研究不仅应纳入更多类型的群体, 还应结合大尺度脑网络分析等方法深入探讨体育锻炼对脑功能连接的影响。

4 总结与展望

4.1 总结

该部分旨在对体育锻炼促进认知功能的机制做出梳理。具体来讲, 体育锻炼对认知功能的机制研究分为微观和宏观两个部分(图1)。在微观层面上, 体育锻炼对认知功能影响的生理机制涉及到内环境稳态、生化反应、神经元的存活和突触连接的建立(Prakash et al., 2015)。首先, 体育锻炼能够改善神经元生存的环境(Caruso et al., 2015; Thomas et al., 2012)。血管促进和疾病干预的研究均认为, 体育锻炼能够通过促进血管生成以及降低干扰内环境稳态的疾病, 使神经元的营养供给和能量代谢处于稳定状态。其次, 在稳定内环境的基础上, 体育锻炼将促进细胞的内生化反应(Piepmeier, 2015)。脑源性神经营养因子的研究表明, 体育锻炼能够通过调节细胞内能量利用和基因转录等过程, 促进BDFN、CREB等与脑再塑过程相关物质的合成。最后, 在保证高效且稳定进行生化反应的基础上, 体育锻炼将促进神经元的存活和突触的建立(Gligoroska & Manchevska, 2012; Xiong et al., 2015)。

图1

图1   体育锻炼促进认知功能的作用模式


在宏观层面上, 体育锻炼引发的细胞和突触的变化将带来大脑宏观尺度的变化(Hötting & Röder, 2013)。首先, 体育锻炼将引发脑结构的变化(Brown et al., 2003; Fabel et al., 2003; Köbe et al., 2016)。形态解剖和脑成像的研究均表明, 体育锻炼能够减少灰质和白质这些脑组织的流失速率, 并提升海马和小脑等脑区的体积。其次, 脑结构的变化也将带来脑活动模式和认知功能的变化(Chaddock-Heyman et al., 2013; Chirles et al., 2017)。例如, 体育锻炼不仅能够改变前扣带回、额叶等脑区的激活水平, 也能够改变额叶执行网络、默认脑网络等多脑区间的功能连接水平, 并最终提升中央执行功能等认知能力。

4.2 展望

4.2.1 影响锻炼效果的个体因素

体育锻炼能够提升各类群体的认知能力, 但促进效果和作用机制可能因为锻炼群体(如, 年龄、性别和健康水平等)的不同而不同(Etnier et al., 1997)。以年龄为例, 相对于发育成熟且功能稳定的大脑, 正在发育和衰老的脑更容易因为训练而发生改变(Blumen, Gopher, Steinerman, & Stern, 2010; De Luca & Leventer, 2008)。研究发现, 体育锻炼能够降低儿童执行注意控制任务中前额叶的激活水平(Chaddock-Heyman et al., 2013), 提升青少年顶叶和左侧海马(Chen et al., 2016)以及老年人左侧枕叶、右侧颞上回等脑区的激活水平(Hsu et al., 2018), 但无法促进成年人的中央执行功能(Hötting, Reich, et al., 2012)、语言记忆以及注意力(Stroth, Hille, Spitzer, & Reinhardt, 2009)。虽然有研究发现体育锻炼能够提升60岁以下中年人的记忆力(Hötting, Reich, et al., 2012), 但进一步的元分析表明, 相对于成年人(18~60岁), 体育锻炼对未成年人(18岁以下)以及老年人(61~90岁)的促进作用更强(Etnier et al., 1997)。

关于个体因素在体育锻炼和认知能力间的调节作用, 仍是未来需要深入探讨的问题。首先, 虽然充分的研究表明体育锻炼能够对未成年人和老年人的大脑产生积极影响(Blumen et al., 2010), 但目前依然缺乏体育锻炼对健康成年人大脑影响的影像学依据。此外, 虽然行为学的研究表明性别、对运动的反应程度和健康水平等因素能够调节体育锻炼促进认知功能的效果(Etnier et al., 1997; Hötting & Röder, 2013), 但同样缺乏相关影像学证据。未来也应考虑体育锻炼对大脑的影响是否会因为以上个体因素的不同而不同。

4.2.2 影响锻炼效果的时间因素

丰富且确凿的证据表明, 体育锻炼能够促进认知功能(Gligoroska & Manchevska, 2012; Hötting & Röder, 2013)。但体育训练结束后, 运动带来的认知功能提升是否能够继续保持、能够保持多久的问题同样值得关注。Rhyu等(2010)的研究发现, 两个月的体育锻炼能够提升猴子大脑皮层的血管总量和学习能力, 但当体育锻炼停止3个月后, 皮层血管总量又会恢复至运动前水平。来自人类的研究结果与之类似, 体育锻炼量降低到健康标准以下长达一年时, 个体发生认知衰退的风险将会明显提升(Alosco et al., 2014)。因此, 身体锻炼对认知功能的促进作用虽然是长期的, 但促进效果会随时间的流逝变小甚至消失。

关于体育锻炼对认知能力影响的长期效果, 仍存在需要解决的问题。首先, 虽然行为学的研究表明体育锻炼对认知能力的提升是长效的, 但该后效的持续时间和伴随时间的衰减速率仍不明确。未来应纳入锻炼类型、个体特征等变量, 考察不同特征的锻炼对于不同群体认知功能的长效作用。其次, 在训练停止较长一段时间后, 个体的脑结构和脑活动模式是否恢复至原有水平, 哪些类型的运动能够为大脑带来更持久的变化等问题仍不明确, 未来应结合生化和脑成像技术做深入探究。

4.2.3 认知刺激对锻炼效果的影响

行为学的研究表明, 认知刺激在体育锻炼促进认知功能的过程中起到了“锦上添花”的作用。相对于单独的认知训练或体育锻炼, 联合训练对认知能力的提升作用更强, 其效果也能在训练结束后保持更长的时间(Bhere et al., 2017; Heisz et al., 2017; Shatil, 2013)。Rahe等(2015)的研究表明, 单独的认知训练和联合训练都能够提升老年人的记忆, 但联合训练的效应量更高。在训练结束一年后, 联合训练对记忆力的提升效果仍然存在, 而认知训练组被试的记忆成绩和前测已无显著差异。类似的, Heisz等人(2017)也发现, 相对于单独的体育锻炼或认知训练, 联合训练能够更有效地促进健康成年人的记忆力。

在微观层面上, 认知刺激促进锻炼效果的脑神经机制已被初步探讨。研究表明, 体育锻炼能够使海马前部齿状回亚颗粒区的前体细胞快速增殖(Kempermann et al., 2010), 但却不能维持新增细胞的存活和整合进已有的功能网络(Kronenberg et al., 2006)。而相对于体育锻炼, 认知训练并不能促进前体细胞的激增, 但却能够防止新增细胞的凋亡(Kronenberg et al., 2006), 并促进新突触的生成和连接(Choo et al., 2017)。因此, 联合训练能够通过提供丰富的认知刺激使体育锻炼诱发的新生细胞功能化, 并最终促进认知功能的提升效果。

伴随了认知刺激的体育锻炼能够更好地促进认知功能, 但相应的脑神经机制仍需进一步探讨。首先, 现有微观机制的研究仅仅局限于海马脑区, 额叶和扣带回等其它脑区是否遵循相同的机制, 目前仍不明晰。其次, 宏观机制的研究存在明显不足。虽然 Holzschneider等(2012)的研究发现体育锻炼和空间记忆训练的联合训练能够提升海马等脑区的激活水平。但其他类型的联合训练对脑结构、脑区激活水平和脑区间功能连接模式的影响仍不明晰, 未来需要结合影像学手段做进一步探讨。

5 结论

总结来说, 体育锻炼对认知功能影响的研究目前取得了丰硕的成果。来自行为学和元分析的研究表明, 体育锻炼不仅能够提升身体健康水平, 还能够促进记忆、中央执行功能等认知能力(Etnier et al., 1997; Piepmeier, 2015)。除了行为层面的研究, 生化学和基因学的研究从微观层面入手, 讨论了体育锻炼对脑细胞生成、存活和突触连接建立的影响(Prakash et al., 2015)。最后, 影像学和形态解剖学的研究也提供了体育锻炼对大脑结构和功能影响的宏观证据(Hötting & Röder, 2013)。未来, 不仅应进一步探讨相关生理机制的不明晰之处, 还应重点考察个体特征、时间以及认知刺激等因素在体育锻炼、脑神经活动以及认知功能间的调节作用。

The authors have declared that no competing interests exist.
作者已声明无竞争性利益关系。

参考文献

Alosco M. L., Spitznagel M. B., Cohen R., Raz N., Sweet L. H., Josephson R., .. Gunstad J . ( 2014).

Decreased physical activity predicts cognitive dysfunction and reduced cerebral blood flow in heart failure

Journal of the Neurological Sciences, 339( 1-2), 169-175.

URL     [本文引用: 2]

An T. D., Zagaar M. A., & Alkadhi K. A . ( 2015).

Moderate treadmill exercise protects synaptic plasticity of the dentate gyrus and related signaling cascade in a rat model of Alzheimer’s disease

Molecular Neurobiology, 52( 3), 1067-1067.

URL     [本文引用: 1]

Anazodo U. C., Shoemaker J. K., Suskin N ., & Lawrence, K. S. S. ( 2013).

An investigation of changes in regional gray matter volume in cardiovascular disease patients, pre and post cardiovascular rehabilitation

NeuroImage: Clinical, 3, 388-395.

URL     [本文引用: 1]

Anderson B. J., Eckburg P. B., & Relucio K. I . ( 2002).

Alterations in the thickness of motor cortical subregions after motor-skill learning and exercise

Learning & Memory, 9( 1), 1-9.

[本文引用: 1]

Ashburner J., & Friston, K. J . ( 2000).

Voxel-based morphometry-the methods

NeuroImage, 11( 6), 805-821.

URL     [本文引用: 1]

Bedi, K. S . ( 2003).

Review

Nutritional Neuroscience, 6( 3), 141-152.

URL     [本文引用: 1]

Bélanger M., Allaman I., & Magistretti P. J . ( 2011).

Brain energy metabolism: Focus on astrocyte-neuron metabolic cooperation

Cell Metabolism, 14( 6), 724-738.

URL     PMID:22152301      [本文引用: 1]

Abstract The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes. Copyright 2011 Elsevier Inc. All rights reserved.

Bherer L., Lussier M., Desjardins L., Fraser S., Li K. Z., Berryman N., .. Vu T . ( 2017).

Effects of physical exercise, cognitive training, and combined intervention on executive functions

Innovation in Aging, 1( 1), 1365.

[本文引用: 1]

Blumen H. M., Gopher D., Steinerman J. R., & Stern Y . ( 2010).

Training cognitive control in older adults with the space fortress game: The role of training instructions and basic motor ability

Frontiers in Aging Neuroscience, 2, 145.

[本文引用: 2]

Brown J., Cooper-Kuhn C. M., Kempermann G., van Praag H., Winkler J., & Gage F. H . ( 2003).

Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis

European Journal of Neuroscience, 17( 10), 2042-2046.

URL     [本文引用: 1]

Brudzynski S. M., & Gibson, C. J . ( 1997).

Release of dopamine in the nucleus accumbens caused by stimulation of the subiculum in freely moving rats

Brain Research Bulletin, 42( 4), 303-308.

URL     [本文引用: 1]

Burdette J. H., Laurienti P. J., Espeland M. A., Morgan A., Telesford Q., Vechlekar C. D., .. Rejeski W. J . ( 2010).

Using network science to evaluate exercise-associated brain changes in older adults

Frontiers in Aging Neuroscience, 2, 2.

URL     PMID:2893375      [本文引用: 1]

Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise.

Caruso R., Santucci A., Caruso M. P., Pittella F., Dellafiore F., Corbetta S., & Mosconi E . ( 2015).

Physical activity, dietary habits and cognitive decline in over 65 years Italian outpatients with type 2 diabetes: a cross-sectional pilot study

International Diabetes Nursing, 12( 2), 69-73.

URL     [本文引用: 3]

Chaddock-Heyman L., Erickson K. I., Voss M. W., Knecht A. M., Pontifex M. B., Castelli D. M., .. Kramer A. F . ( 2013).

The effects of physical activity on functional MRI activation associated with cognitive control in children: A randomized controlled intervention

Frontiers in Human Neuroscience, 7, 72.

[本文引用: 5]

Chang Y. K., Labban J. D., Gapin J. I., & Etnier J. L . ( 2012).

The effects of acute exercise on cognitive performance: A meta-analysis

Brain Research, 1453, 87-101.

[本文引用: 2]

Chen A. G., Zhu L. N., Yan J., & Yin H. C . ( 2016).

Neural basis of working memory enhancement after acute aerobic exercise: fMRI study of preadolescent children

Frontiers in Psychology, 7, 1804.

[本文引用: 2]

Chirles T. J., Reiter K., Weiss L. R., Alfini A. J., Nielson K. A., & Smith J. C . ( 2017).

Exercise training and functional connectivity changes in mild cognitive impairment and healthy elders

Journal of Alzheimer’s Disease, 57( 3), 845-856.

URL     [本文引用: 2]

Choo M., Miyazaki T., Yamazaki M., Kawamura M., Nakazawa T., Zhang J. L., .. Kano M . ( 2017).

Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum

Nature Communications, 8, 195.

URL     PMID:5543168      [本文引用: 1]

Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). A single CF is strengthened whereas the other CFs are eliminated in each PC dependent on postsynaptic activity in PC, but the underlying mechanisms are largely unknown. Here, we report that brain-derived neurotrophic factor (BDNF) from PC facilitates CF synapse elimination. By PC-specific deletion of BDNF combined with knockdown of BDNF receptors in CF, we show that BDNF acts retrogradely on TrkB in CFs, and facilitates elimination of CF synapses from PC somata during the third postnatal week. We also show that BDNF shares signaling pathway with metabotropic glutamate receptor 1, a key molecule that triggers a canonical pathway for CF synapse elimination. These results indicate that unlike other synapses, BDNF mediates punishment signal for synapse elimination in the developing cerebellum. During development, synapses are selectively strengthened or eliminated by activity-dependent competition. Here, the authors show that BDNF-TrkB retrograde signaling is a unishment signal that leads to elimination of climbing fiber-onto-Purkinje cell synapses in the developing cerebellum.

Christie B. R., Eadie B. D., Kannangara T. S., Robillard J. M., Shin J., & Titterness A. K . ( 2008).

Exercising our brains: How physical activity impacts synaptic plasticity in the dentate gyrus

Neuromolecular Medicine, 10( 2), 47-58.

URL     PMID:18535925      [本文引用: 2]

Exercise that engages the cardiovascular system has a myriad of effects on the body; however, we usually do not give much consideration to the benefits it may have for our minds. An increasing body of evidence suggests that exercise can have some remarkable effects on the brain. In this article, we will introduce how exercise can impact the capacity for neurons in the brain to communicate with one another. To properly convey this information, we will first briefly introduce the field of synaptic plasticity and then examine how the introduction of exercise to the experimental setting can actually alter the basic properties of synaptic plasticity in the brain. Next, we will examine some of the candidate physiological processes that might underlay these alterations. Finally, we will close by noting that, taken together, this data points toward our brains being dynamic systems that are in a continual state of flux and that physical exercise may help us to maximize the performance of both our body and our minds.

Colberg S. R., Somma C. T., & Sechrist S. R . ( 2008).

Physical activity participation may offset some of the negative impact of diabetes on cognitive function

Journal of the American Medical Directors Association, 9( 6), 434-438.

URL     [本文引用: 1]

Colcombe S. J., Erickson K. I., Scalf P. E., Kim J. S., Prakash R., Mcauley E., .. Kramer A. F . ( 2006).

Aerobic exercise training increases brain volume in aging humans

The Journals of Gerontology: Series A, 61( 11), 1166-1170.

URL     PMID:17167157      [本文引用: 2]

BACKGROUND: The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition. METHODS: Fifty-nine healthy but sedentary community-dwelling volunteers, aged 60-79 years, participated in the 6-month randomized clinical trial. Half of the older adults served in the aerobic training group, the other half of the older adults participated in the toning and stretching control group. Twenty young adults served as controls for the magnetic resonance imaging (MRI), and did not participate in the exercise intervention. High spatial resolution estimates of gray and white matter volume, derived from 3D spoiled gradient recalled acquisition MRI images, were collected before and after the 6-month fitness intervention. Estimates of maximal oxygen uptake (VO2) were also obtained. RESULTS: Significant increases in brain volume, in both gray and white matter regions, were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning (nonaerobic) control group. As predicted, no significant changes in either gray or white matter volume were detected for our younger participants. CONCLUSIONS: These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans. Furthermore, these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults.

Colcombe S. J., Kramer A. F., Erickson K. I., Scalf P., McAuley E., Cohen N. J., .. Elavsky S . ( 2004).

Cardiovascular fitness, cortical plasticity, and aging

Proceedings of the National Academy of Sciences of the United States of America, 101( 9), 3316-3321.

URL     PMID:14978288      [本文引用: 3]

Abstract Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.

Cotman C. W., Berchtold N. C., & Christie L. A . ( 2007).

Exercise builds brain health: Key roles of growth factor cascades and inflammation

Trends in Neurosciences, 30( 9), 464-472.

URL     [本文引用: 2]

Cox E. P., O'Dwyer N., Cook R., Vetter M., Cheng H. L., Rooney K., & O'Connor H . ( 2016).

Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review

Journal of Science and Medicine in Sport, 19( 8), 616-628.

URL     [本文引用: 1]

Davis C. L., Tomporowski P. D., McDowell J. E., Austin B. P., Miller P. H., Yanasak N. E., .. Naglieri J. A . ( 2011).

Exercise improves executive function and achievement and alters brain activation in overweight children: A randomized, controlled trial

Health Psychology, 30( 1), 91-98.

URL     [本文引用: 1]

De Luca, C. R., & Leventer, R. J . ( 2008).

Developmental trajectories of executive functions across the lifespan

In V. Anderson, R. Jacobs, P. J. Anderson,( Eds.), Executive functions and the frontal lobes: A lifespan perspective

URL     [本文引用: 1]

react-text: 411 To study the association between performance on psychological tests of executive function and performance on lower extremity tasks with different attentional demands in a large sample of nondemented, older adults. Cross-sectional study. Community-based. Nine hundred twenty-six persons aged 65 and older, without dementia, stroke, parkinsonism, visual impairment, or current treatment with... /react-text react-text: 412 /react-text [Show full abstract]

Dhar M., Zhu M., Impey S., Lambert T. J., Bland T., Karatsoreos I. N., .. Wayman G. A . ( 2014).

Leptin induces hippocampal synaptogenesis via CREB-regulated microRNA-132 suppression of p250GAP

Molecular Endocrinology, 28( 7), 1073-1082.

URL     [本文引用: 1]

Erickson K. I., Hillman C. H., & Kramer A. F . ( 2015).

Physical activity, brain, and cognition

Current Opinion in Behavioral Sciences, 4, 27-32.

URL     [本文引用: 1]

In this brief review we summarize the promising effects of physical activity and fitness on brain and cognition in children and older adults. Research in children finds that higher fit and more active preadolescent children show greater hippocampal and basal ganglia volume, greater white matter integrity, elevated and more efficient patterns of brain activity, and superior cognitive performance and scholastic achievement. Higher fit and more physically active older adults show greater hippocampal, prefrontal cortex, and basal ganglia volume, greater functional brain connectivity, greater white matter integrity, more efficient brain activity, and superior executive and memory function. Despite these promising results, more randomized trials are needed to understand heterogeneity in response to physical activity, mechanisms, and translation to public policy.

Erickson K. I., Voss M. W., Prakash R. S., Basak C., Szabo A., Chaddock L., .. Kramer A. F . ( 2011).

Exercise training increases size of hippocampus and improves memory

Proceedings of the National Academy of Sciences of the United States of America, 108( 7), 3017-3022.

URL     PMID:21282661      [本文引用: 1]

Title: Exercise training increases size of hippocampus and improves memory The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.

Espeland M. A., Lipska K., Miller M. E., Rushing J., Cohen R. A., Verghese J ., .. for the LIFE Study Investigators.( 2017).

Effects of physical activity intervention on physical and cognitive function in sedentary adults with and without diabetes

The Journals of Gerontology: Series A, 72( 6), 861-866.

[本文引用: 2]

Etnier J.L., Labban J. D., Piepmeier A., Davis M. E., & Henning D. A . ( 2014).

Effects of an acute bout of exercise on memory in 6 th grade children

Pediatric Exercise Science, 26( 3), 250-258.

URL     [本文引用: 1]

Etnier J. L., Salazar W., Landers D. M., Petruzzello S. J., Han M., & Nowell P . ( 1997).

The influence of physical fitness and exercise upon cognitive functioning: A meta-analysis

Journal of Sport and Exercise Psychology, 19( 3), 249-277.

URL     [本文引用: 7]

ABSTRACT Nearly 200 studies have examined the impact that either acute or long-term exercise has upon cognition. Subsets of these studies have been reviewed using the traditional narrative method, and the common conclusion has been that the results are mixed. Therefore, a more comprehensive review is needed that includes all available studies and that provides a more objective and reproducible review process. Thus, a meta-analytic review was conducted that included all relevant studies with sufficient information for the calculation of effect size (W = 134). The overall effect size was 0.25, suggesting that exercise has a small positive effect on cognition. Examination of the moderator variables indicated that characteristics related to the exercise paradigm, the participants, the cognitive tests, and the quality of the study influence effect size. However, the most important finding was that as experimental rigor decreased, effect size increased. Therefore, more studies need to be conducted that emphasize experimental rigor.

Fabel K., Fabel K., Tam B., Kaufer D., Baiker A., Simmons N., .. Palmer T. D . ( 2003).

VEGF is necessary for exercise-induced adult hippocampal neurogenesis

European Journal of Neuroscience, 18( 10), 2803-2812.

URL     PMID:14656329      [本文引用: 2]

Abstract Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic–pituitary–adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced neurogenesis but had no detectable effect on baseline neurogenesis in non-running animals. These data suggest that VEGF is an important element of a ‘somatic regulator’ of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.

Fink G. R., Frackowiak R. S., Pietrzyk U., & Passingham R. E . ( 1997).

Multiple nonprimary motor areas in the human cortex

Journal of Neurophysiology, 77( 4), 2164-2174.

URL     PMID:9114263      [本文引用: 1]

Abstract We measured the distribution of regional cerebral blood flow with positron emission tomography while three subjects moved their hand, shoulder, or leg. The images were coregistered with each individual's anatomic magnetic resonance scans. The data were analyzed for each individual to avoid intersubject averaging and so to preserve individual gyral anatomy. Instead of inspecting all pixels, we prospectively restricted the data analysis to particular areas of interest. These were defined on basis of the anatomic and physiological literature on nonhuman primates. By examining only a subset of areas, we strengthened the power of the statistical analysis and thereby increased the confidence in reporting single subject data. On the lateral convexity, motor related activity was found for all three subjects in the primary motor cortex, lateral premotor cortex, and an opercular area within the premotor cortex. In addition, there was activation of somatosensory cortex (SI), the supplementary somatosensory area (SII) in the Sylvian fissure, and parietal association areas (Brodmann areas 5 and 40). There was also activation in the insula. We suggest that the activation in the dorsal premotor cortex may correspond with dorsal premotor area (PMd) as described in the macaque brain. We propose three hypotheses as to the probable location of vental premotor area (PMv) in the human brain. On the medial surface, motor-related activity was found for all three subjects in the leg areas of the primary motor cortex and somatosensory cortex and also activity for the hand, shoulder, and leg in the supplementary motor area (SMA) on the dorsal medial convexity and in three areas in the cingulate sulcus. We suggest that the three cingulate areas may correspond with rostral cingulate premotor area, dorsal cingulate motor area (CMAd), and ventral cingulate motor area (CMAv) as identified in the macaque brain. Somatotopic mapping was demonstrated in the primary motor and primary somatosensory cortex. In all three subjects, the arm region lay anterior to the leg region in parietal area 5. Also in all three subjects, the arm region lay anterior to the leg region in the supplementary motor cortex.

Flodin P., Martinsen S., Mannerkorpi K., Löfgren M., Bileviciute-Ljungar I., Kosek E., & Fransson P . ( 2015).

Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy

NeuroImage: Clinical, 9, 134-139.

URL     [本文引用: 1]

Friston K. J., Frith C. D., Liddle P. F ., & Frackowiak, R. S. J. ( 1993).

Functional connectivity: The principal-component analysis of large (pet) data sets

Journal of Cerebral Blood Flow & Metabolism, 13( 1), 5-14.

URL     PMID:8417010      [本文引用: 2]

Abstract The distributed brain systems associated with performance of a verbal fluency task were identified in a nondirected correlational analysis of neurophysiological data obtained with positron tomography. This analysis used a recursive principal-component analysis developed specifically for large data sets. This analysis is interpreted in terms of functional connectivity, defined as the temporal correlation of a neurophysiological index measured in different brain areas. The results suggest that the variance in neurophysiological measurements, introduced experimentally, was accounted for by two independent principal components. The first, and considerably larger, highlighted an intentional brain system seen in previous studies of verbal fluency. The second identified a distributed brain system including the anterior cingulate and Wernicke's area that reflected monotonic time effects. We propose that this system has an attentional bias.

Girard I., & Garland, T. J . ( 2002).

Plasma corticosterone response to acute and chronic voluntary exercise in female house mice

Journal of Applied Physiology, 92( 4), 1553-1561.

URL     PMID:11896022      [本文引用: 1]

Abstract Plasma levels of corticosterone (B) respond acutely to exercise in all mammals that have been studied, but the literature contains conflicting reports regarding how chronic activity alters this response. We measured acute and chronic effects of voluntary activity on B in a novel animal model, mice selectively bred for high voluntary wheel running. Female mice were housed with or without wheels for 8 wk beginning at 26 days of age. Wheel-access selection mice had significantly higher B at night 8, day 15, and night 29, compared with wheel-access controls. Elevation of B was an acute effect of voluntary exercise. When adjusted for running in the previous 20 min, no difference between wheel-access selection and control animals remained. No training effect on B response was observed. These results are among the strongest evidence that, in some animals, the acute B response is unaffected by chronic voluntary exercise. In mice without wheels, selection mice had significantly higher B than controls at day 15, night 29, and night 50, suggesting that selection resulted in a modulation of the hypothalamic-pituitary-adrenal axis. Growth over the first 4 wk of treatment was significantly and inversely related to average night B levels within each of the four treatment groups.

Gligoroska J. P., & Manchevska, S. ( 2012).

The effect of physical activity on cognition -physiological mechanisms

Materia Socio-Medica, 24( 3), 198-202.

URL     [本文引用: 3]

The presumption that physical activity, i.e. exercise, as an independent and separated factor influences different aspects of cognitive mechanisms is substantially supported by the literature. The investigations of the influence of physical activity on cognitive functioning have offered several mechanisms which could explain this relationship. Physiological mechanisms including increased cerebral blood flow, changes in neurotransmitter release, structural changes in central nervous system and altered arousal levels are based on physical changes that occur in the body as a consequence of the physical activity. There is evidence that physical training selectively increases angiogenesis, synaptogenesis and neurogenesis. The role of central (BDNF) and peripheral (estrogens, corticosteroids, growth hormone, IGF-1) factors in mediation of the effects of physical exercise on brain functions, has been promoted. Also, there is convergent data on molecular and cellular level, as well as on behavioral and systemic level which support the presumption that physical activity is beneficial to cognition. These data emphasizes the importance of promotion of physical activity during the life span for the prevention of contemporary (obesity, diabetes and cardiovascular) diseases and cognitive decline in humans.

Greicius M. D., Krasnow B., Reiss A. L., & Menon V . ( 2003).

Functional connectivity in the resting brain: A network analysis of the default mode hypothesis

Proceedings of the National Academy of Sciences of the United States of America, 100( 1), 253-258.

URL     PMID:12506194      [本文引用: 1]

Abstract Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.

Haring B., Leng X., Robinson J., Johnson K. C., Jackson R. D., Beyth R., .. Wassertheil‐Smoller S . ( 2013).

Cardiovascular disease and cognitive decline in postmenopausal women: Results from the women's health initiative memory study

Journal of the American Heart Association, 2( 6), e000369.

[本文引用: 1]

Hayes S. M., Alosco M. L., & Forman D. E . ( 2014).

The effects of aerobic exercise on cognitive and neural decline in aging and cardiovascular disease

Current Geriatrics Reports, 3( 4), 282-290.

URL     [本文引用: 1]

Heisz J. J., Clark I. B., Bonin K., Paolucci E. M., Michalski B., Becker S., & Fahnestock M . ( 2017).

The effects of physical exercise and cognitive training on memory and neurotrophic factors

Journal of Cognitive Neuroscience, 29( 11), 1895-1907.

URL     PMID:28699808      [本文引用: 2]

Abstract Accepted for publication on March 24, 2017 This study examined the combined effect of physical exercise and cognitive training on memory and neurotrophic factors in young adults. Ninety-five participants completed six weeks of exercise training, combined exercise and cognitive training, or no training (control). Both the exercise and combined training groups improved performance on a high-interference memory task, whereas the control group did not. In contrast, neither training group improved on general recognition performance, suggesting that exercise training selectively increases high-interference memory that may be linked to hippocampal function. Individuals that experienced greater fitness improvements from the exercise training (i.e., high responders to exercise) also had greater increases in the serum neurotrophic factors brain-derived neurotrophic factor (BDNF) and insulin like growth factor-1 (IGF-1). This was accompanied by better high-interference memory performance as a result of the combined exercise and cognitive training compared to exercise alone, suggesting that potential synergistic effects may depend on the availability of neurotrophic factors. These findings are especially important, as memory benefits accrued from a relatively short intervention in high functioning young adults.

Heyman E., Gamelin F. X., Goekint M., Piscitelli F., Roelands B., Leclair E., .. Meeusen R . ( 2012).

Intense exercise increases circulating endocannabinoid and BDNF levels in humans-possible implications for reward and depression

Psychoneuroendocrinology, 37( 6), 844-854.

URL     [本文引用: 1]

Hindin S. B., & Zelinski, E. M . ( 2012).

Extended practice and aerobic exercise interventions benefit untrained cognitive outcomes in older adults: A meta-analysis

Journal of the American Geriatrics Society, 60( 1), 136-141.

URL     [本文引用: 1]

Ho A. J., Raji C. A., Becker J. T., Lopez O. L., Kuller L. H., Xue H., .. Thompson P. M . ( 2011).

The effects of physical activity, education, and body mass index on the aging brain

Human Brain Mapping, 32( 9), 1371-1382.

URL     PMID:3184838      [本文引用: 1]

Abstract Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 ± 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical activity, higher educational levels were associated with 652–3% greater tissue volumes, on average, in the temporal lobe gray matter. After controlling for age, sex, and education, greater physical activity was associated with 652–2.5% greater average tissue volumes in the white matter of the corona radiata extending into the parietal-occipital junction. Body mass index (BMI) was highly correlated with both education and physical activity, so we examined BMI as a contributing factor by including physical activity, education, and BMI in the same model; only BMI effects remained significant. This is one of the largest MRI studies of factors influencing structural brain aging, and BMI may be a key factor explaining the observed relationship between education, physical activity, and brain structure. Independent contributions to brain structure could not be teased apart as all these factors were highly correlated with one another. Hum Brain Mapp, 2010. 08 2010 Wiley-Liss, Inc.

Hohenfeld C., Nellessen N., Dogan I., Kuhn H., Müller C., Papa F., .. Reetz K . ( 2016).

EP 131. Real-time fMRI neurofeedback training in elderly leads to cognitive improvement and changes in cerebral connectivity

Clinical Neurophysiology, 127( 9), e295-e296.

[本文引用: 1]

Hötting K., Reich B., Holzschneider K., Kauschke K., Schmidt T., Reer R., .. Röder B . ( 2012).

Differential cognitive effects of cycling versus stretching/coordination training in middle-aged adults

Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association, 31( 2), 145-155.

URL     [本文引用: 2]

Hötting K., & Röder, B. ( 2013).

Beneficial effects of physical exercise on neuroplasticity and cognition

Neuroscience & Biobehavioral Reviews, 37( 9), 2243-2257.

URL     PMID:23623982      [本文引用: 8]

Abstract The human brain adapts to changing demands by altering its functional and structural properties ("neuroplasticity") which results in learning and acquiring skills. Convergent evidence from both human and animal studies suggests that physical activity facilitates neuroplasticity of certain brain structures and as a result cognitive functions. Animal studies have identified an enhancement of neurogenesis, synaptogenesis, angiogenesis and the release of neurotrophins as neural mechanisms mediating beneficial cognitive effects of physical exercise. This review summarizes behavioral consequences and neural correlates at the system level following physical exercise interventions in humans of different ages. The results suggest that physical exercise may trigger processes facilitating neuroplasticity and, thereby, enhances an individual's capacity to respond to new demands with behavioral adaptations. Indeed, some recent studies have suggested that combining physical and cognitive training might result in a mutual enhancement of both interventions. Moreover, new data suggest that to maintain the neuro-cognitive benefits induced by physical exercise, an increase in the cardiovascular fitness level must be maintained. Copyright 2013 Elsevier Ltd. All rights reserved.

Hötting K., Schauenburg G., & Röder B . ( 2012).

Long- term effects of physical exercise on verbal learning and memory in middle-aged adults: Results of a one-year follow-up study

Brain Sciences, 2( 3), 332-346.

URL     [本文引用: 1]

Holzschneider K., Wolbers T., Röder B., & Hötting K . ( 2012).

Cardiovascular fitness modulates brain activation associated with spatial learning

NeuroImage, 59( 3), 3003-3014.

URL     PMID:22027496      [本文引用: 4]

Aerobic exercise has beneficial effects on cognitive functioning in aging humans, especially on executive functions associated with frontal brain regions. In rodents, exercise has been shown to induce structural and neurophysiological changes especially in the hippocampus and to improve spatial learning. The present study investigated the relationship between cardiovascular fitness, spatial learning and associated patterns of brain activation cross-sectionally and longitudinally in a sample of middle-aged men and women (40 55 years) that took part in a six-month exercise intervention and an additional spatial training. Spatial learning capacities before and after the interventions were measured with a virtual maze task. During this task, participants were repeatedly moved through a virtual town and were instructed to infer the spatial layout of the environment. Brain activations during encoding of the virtual town were assessed with functional magnetic resonance imaging ( f MRI). The f MRI data revealed that brain activations during successful spatial learning were modulated by the individual fitness level in a neural network, comprising the hippocampus, retrosplenial cortex, cuneus, precuneus, parahippocampal gyrus, caudate nucleus, insula, putamen, and further frontal, temporal, occipital and cingulate regions. Moreover, physical exercising induced changes in cardiovascular fitness that correlated positively with changes in brain activations in the medial frontal gyrus and the cuneus. However, overall spatial learning performance did not vary with cardiovascular fitness. These data suggest that cardiovascular fitness has an impact on brain regions associated with spatial learning in humans and hence, could be a potent intervention to prevent age-related cognitive decline.

Hsu C. L., Best J. R., Davis J. C., Nagamatsu L. S., Wang S., Boyd L. A., .. Liu-Ambrose T . ( 2018).

Aerobic exercise promotes executive functions and impacts functional neural activity among older adults with vascular cognitive impairment

British Journal of Sports Medicine, 52( 3), 184-191.

URL     [本文引用: 3]

Huxley R. R., Misialek J. R., Agarwal S. K., Loehr L. R., Soliman E. Z., Chen L. Y., & Alonso A . ( 2014).

Physical activity, obesity, weight change, and risk of atrial fibrillation: The atherosclerosis risk in communities study

Circulation: Arrhythmia and Electrophysiology, 7( 4), 620-625.

URL     [本文引用: 1]

Hyman C., Hofer M., Barde Y. A., Juhasz M., Yancopoulos G. D., Squinto S. P., & Lindsay R. M . ( 1991).

BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra

Nature, 350( 6315), 230-232.

URL     PMID:2005978      [本文引用: 1]

Abstract Brain-derived neurotrophic factor (BDNF), present in minute amounts in the adult central nervous system, is a member of the nerve growth factor (NGF) family, which includes neurotrophin-3 (NT-3). NGF, BDNF and NT-3 all support survival of subpopulations of neural crest-derived sensory neurons; most sympathetic neurons are responsive to NGF, but not to BDNF; NT-3 and BDNF, but not NGF, promote survival of sensory neurons of the nodose ganglion. BDNF, but not NGF, supports the survival of cultured retinal ganglion cells but both NGF and BDNF promote the survival of septal cholinergic neurons in vitro. However, knowledge of their precise physiological role in development and maintenance of the nervous system neurons is still limited. The BDNF gene is expressed in many regions of the adult CNS, including the striatum. A protein partially purified from bovine striatum, a target of nigral dopaminergic neurons, with characteristics apparently similar to those of BDNF, can enhance the survival of dopaminergic neurons in mesencephalic cultures. BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease. Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra.

Ji L., Zhang H., Potter G. G., Zang Y. F., Steffens D. C., Guo H., & Wang L . ( 2017).

Multiple neuroimaging measures for examining exercise-induced neuroplasticity in older adults: A quasi-experimental study

Frontiers in Aging Neuroscience, 9, 102.

URL     [本文引用: 6]

Kempermann G., Fabel K., Ehninger D., Babu H., Leal- Galicia P., Garthe A., & Wolf S. A . ( 2010).

Why and how physical activity promotes experience-induced brain plasticity

Frontiers in Neuroscience, 4, 189.

URL     PMID:3000002      [本文引用: 1]

Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses) are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, increasing the likelihood of cognitive challenges. In the wild (other than in front of a TV), no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading “an active life” but an evolutionarily fundamental aspect of “activity,” which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback.

Kim J. I., Jeong H. C., Won J. Y., Ka S. S., & Oh B. S . ( 2014).

Effects of aerobic exercise on middle-aged male smokers' blood vessel health

Journal of Digital Convergence, 12( 4), 349-356.

URL     [本文引用: 1]

This research is aimed to prove if harmful effects of smoking, as the main reason for recently elevated blood vessel disease, could be reduced by aerobic exercise, and identify the positive effects of the aerobic exercise on smokers` blood vessel health(blood pressure, pulse pressure, and blood vessel elasticity. Experiments were performed on 40 male smokers aged between 40 and 55, which was equally divided into two groups of Aerobic Exercise Group (AEG) and Non Exercise Group (NEG). After measuring each group`s blood pressure, pulse pressure, and blood vessel elasticity, AEG practiced aerobic exercise program for 50 minutes for each trial, three times a week, sustaining 12 weeks while NEG continued daily-life patterns without any special treatment. In 12 weeks, blood pressure, pulse pressure, and blood vessel elasticity of both groups were measured as the same way. As a result, the difference of systolic blood pressure between the two groups was not significant, while that of diastolic blood pressure was meaningful. The difference of pulse pressure between the two groups was meaningful, and that of blood vessel elasticity was also meaningful in all measuring points including left hand, right hand, left foot and right foot. As a consequent, it was found that aerobic exercise had positive effects on middle aged male smokers` blood vessel health.

Klempin F., Beis D., Mosienko V., Kempermann G., Bader M., & Alenina N . ( 2013).

Serotonin is required for exercise-induced adult hippocampal neurogenesis

Journal of Neuroscience, 33( 19), 8270-8275.

URL     PMID:23658167      [本文引用: 1]

Voluntary wheel running has long been known to induce precursor in adult hippocampal in . However, mechanisms that couple activity with the promitotic effect are not yet fully understood. Using tryptophan hydroxylase () 2 deficient (-deficient) that lack brain , we explored the relationship between signaling and exercise-induced . Surprisingly, -deficient exhibit normal baseline hippocampal but impaired activity-induced proliferation. Our data demonstrate that the proproliferative effect of running requires the release of central in young-adult and aged . Lack of brain further results in alterations at the stage of -positive precursor cells, suggesting physiological adaptations to changes in supply to maintain in the neurogenic niche. We conclude that plays a direct and acute regulatory role in activity-dependent hippocampal . The understanding of exercise-induced might offer preventive but also therapeutic opportunities in and .

Köbe T., Witte A. V., Schnelle A., Lesemann A., Fabian S., Tesky V. A., .. Flöel A . ( 2016).

Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment

NeuroImage, 131, 226-235.

URL     [本文引用: 2]

Koirala G. R., Lee D., Eom S., Kim N. Y., & Kim H. D . ( 2017).

Altered brain functional connectivity induced by physical exercise may improve neuropsychological functions in patients with benign epilepsy

Epilepsy & Behavior, 76, 126-132.

[本文引用: 1]

Kronenberg G., Bick-Sander A., Bunk E., Wolf C., Ehninger D., & Kempermann G . ( 2006).

Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus

Neurobiology of Aging, 27( 10), 1505-1513.

URL     [本文引用: 2]

Kylasov A., & Gavrov, S. ( 2011).

Diversity of sport: Non-destructive evaluation (pp. 462-491). Paris: UNESCO: Encyclopedia of

Life Support Systems.

[本文引用: 1]

Landeira B. S., Santana T. T., Araújo J. A. M., Tabet E. I., Tannous B. A., Schroeder T., & Costa M. R . ( 2016).

Activity-independent effects of CREB on neuronal survival and differentiation during mouse cerebral cortex development

Cerebral Cortex, 28( 2), 538-548.

[本文引用: 1]

Lee J. K. W., Koh A. C. H., Koh S. X. T., Liu G. J. X., Nio A. Q. X ., & Fan, P. W. P. ( 2014).

Neck cooling and cognitive performance following exercise-induced hyperthermia

European Journal of Applied Physiology, 114( 2), 375-384.

URL     PMID:24318656      [本文引用: 1]

Abstract PURPOSE: To assess the efficacy of neck cooling on cognitive performance following exertional hyperthermia. METHODS: Twelve healthy men completed two experimental trials [control (CON) and neck cooling collar (NCC)] in a counter-balanced design. They ran on a treadmill at 70% VO2peak under warm and humid conditions (dry bulb temperature: 30.2 ± 0.3 °C, relative humidity: 71 ± 2 %) for 75 min or until volitional exhaustion. Gastrointestinal, neck and skin temperatures, heart rate and subjective ratings were assessed. Serum brain-derived neurotrophic factor (BDNF) levels were measured before and after each run. Cognitive performance comprising symbol digit matching, search and memory, digit span, choice reaction time and psychomotor vigilance test (PVT) were assessed before and after exercise. RESULTS: Mean gastrointestinal temperature was similar after exercise between trials (CON: 39.5 ± 0.4 °C vs. NCC: 39.6 ± 0.3 °C; p = 0.15). Mean neck temperature was lowered in NCC compared to CON after the run (36.4 ± 1.6 °C vs. NCC: 26.0 ± 0.3 °C; p < 0.001). Exercise-induced hyperthermia improved mean reaction time in the symbol digit matching test (-134 ± 154 ms; p < 0.05) and the PVT (-18 ± 30 ms; p < 0.05). Maximum span was increased in the digit span test (1 ± 2; p < 0.05). Application of NCC reduced the number of search errors made in level 3 of the search and memory test (p < 0.05). Mean serum BDNF levels were increased following exercise-induced hyperthermia in both trials (p < 0.05). CONCLUSION: Exercise-induced hyperthermia improves working memory and alertness. Neck cooling may only enhance performance in tasks of higher complexity.

Leckie R. L., Oberlin L. E., Voss M. W., Prakash R. S., Szabo-Reed A., Chaddock-Heyman L., .. Erickson K. I . ( 2014).

BDNF mediates improvements in executive function following a 1-year exercise intervention

Frontiers in Human Neuroscience, 8, 895.

URL     PMID:25566019      [本文引用: 3]

Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF), which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82). Participants were randomized to a stretching and toning control group or a moderate intensity walking intervention group. BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up. We found that age moderated the effect of intervention group on changes in BDNF levels, with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise (p= 0.036). The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy, but did so as a function of age, such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71. These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes, particularly in elderly populations.

Liu-Ambrose T., Nagamatsu L. S., Voss M. W., Khan K. M., & Handy T. C . ( 2012).

Resistance training and functional plasticity of the aging brain: A 12-month randomized controlled trial

Neurobiology of Aging, 33( 8), 1690-1698.

URL     [本文引用: 1]

Louis B., Erickson K. I., & Liu-Ambrose T . ( 2013).

A review of the effects of physical activity and exercise on cognitive and brain functions in older adults

Journal of Aging Research, 2013, 657508.

[本文引用: 1]

Meeusen R., Smolders I., Sarre S., de Meirleir K., Keizer H., Serneels M., .. Michotte Y . ( 1997).

Endurance training effects on neurotransmitter release in rat striatum: An in vivo microdialysis study

Acta Physiologica, 159( 4), 335-341.

[本文引用: 1]

Pajonk F. G., Wobrock T., Gruber O., Scherk H., Berner D., Kaizl I., .. Falkai P . ( 2010).

Hippocampal plasticity in response to exercise in schizophrenia

Archives of General Psychiatry, 67( 2), 133-143.

URL     [本文引用: 1]

Pedersen, B. K . ( 2017).

Anti-inflammatory effects of exercise: Role in diabetes and cardiovascular disease

European Journal of Clinical Investigation, 47( 8), 600-611.

URL     PMID:28722106      [本文引用: 2]

Abstract BACKGROUND: Persistent inflammation is involved in the pathogenesis of chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). AIMS: The aim of this review was to provide the reader with an update of the mechanisms whereby exercise-induced cytokines may impact cardiometabolic diseases. RESULTS: Evidence exists that interleukin (IL)-10205 is involved in pancreatic 0205-cell damage, whereas TNF-02± is a key molecule in peripheral insulin resistance. In addition, TNF-02± appears to be involved in the pathogenesis of atherosclerosis and heart failure. A marked increase in IL-6 and IL-10 is provoked by exercise and exerts direct anti-inflammatory effects by an inhibition of TNF-02± and by stimulating IL-1ra, thereby limiting IL-10205 signalling. Moreover, muscle-derived IL-6 appears to have direct anti-inflammatory effects and serves as a mechanism to improve glucose tolerance. In addition, indirect anti-inflammatory effects of long-term exercise are mediated via improvements in body composition. CONCLUSION: Physical activity represents a natural, strong anti-inflammatory strategy with minor side effects and should be integrated in the management of patients with cardiometabolic diseases. 0008 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Piepmeier, A. T . ( 2015).

A closer look at the role of BDNF as a causal link in the physical activity cognition relationship: A dose-response study (Unpublished doctorial dissertation)

The University of North Carolina at Greensboro (UNCG).

[本文引用: 9]

Pierpaoli C., Jezzard P., Basser P. J., Barnett A., & Di Chiro G . ( 1996).

Diffusion tensor MR imaging of the human brain

Radiology, 201( 3), 637-648.

URL     PMID:8939209      [本文引用: 1]

Abstract PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximately 2,100 x 10(-6) mm2/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, particularly in the centrum semiovale, diffusion anisotropy was low, and cylindrical symmetry was not observed. Maps of parameters derived from D were also used to segment tissues based on their diffusion properties. CONCLUSION: A quantitative characterization of water diffusion in anisotropic, heterogeneously oriented tissues is clinically feasible. This should improve the neuroradiologic assessment of a variety of gray and white matter disorders.

Prakash R. S., Voss M. W., Erickson K. I., & Kramer A. F . ( 2015).

Physical activity and cognitive vitality

Annual Review of Psychology, 66, 769-797.

URL     PMID:25251492      [本文引用: 3]

We examine evidence supporting the associations among physical activity (PA), cognitive vitality, neural functioning, and the moderation of these associations by genetic factors. Prospective epidemiological studies provide evidence for PA to be associated with a modest reduction in relative risk of cognitive decline. An evaluation of the PA-cognition link across the life span provides modest support for the effect of PA on preserving and even enhancing cognitive vitality and the associated neural circuitry in older adults, with the majority of benefits seen for tasks that are supported by the prefrontal cortex and the hippocampus. The literature on children and young adults, however, is in need of well-powered randomized controlled trials. Future directions include a more sophisticated understanding of the dose-response relationship, the integration of genetic and epigenetic approaches, inclusion of multimodal imaging of brain-behavior changes, and finally the design of multimodal interventions that may yield broader improvements in cognitive function.

Rahe J., Petrelli A., Kaesberg S., Fink G. R., Kessler J., & Kalbe E . ( 2015).

Effects of cognitive training with additional physical activity compared to pure cognitive training in healthy older adults

Clinical Interventions in Aging, 10, 297-310.

[本文引用: 1]

Rajab A. S., Crane D. E., Middleton L. E., Robertson A. D., Hampson M., & Macintosh B. J . ( 2014).

A single session of exercise increases connectivity in sensorimotor- related brain networks: A resting-state fMRI study in young healthy adults

Frontiers in Human Neuroscience, 8, 625.

[本文引用: 4]

Rhyu I. J., Bytheway J. A., Kohler S. J., Lange H., Lee K. J., Boklewski J., .. Cameron J. L . ( 2010).

Effects of aerobic exercise training on cognitive function and cortical vascularity in monkeys

Neuroscience, 167( 4), 1239-1248.

URL     PMID:3417752      [本文引用: 1]

Abstract This study examined whether regular exercise training, at a level that would be recommended for middle-aged people interested in improving fitness could lead to improved cognitive performance and increased blood flow to the brain in another primate species. Adult female cynomolgus monkeys were trained to run on treadmills for 1 h a day, 5 days a week, for a 5 month period (n=16; 1.9+/-0.4 miles/day). A sedentary control group sat daily on immobile treadmills (n=8). Half of the runners had an additional sedentary period for 3 months at the end of the exercise period (n=8). In all groups, half of the monkeys were middle-aged (10-12 years old) and half were more mature (15-17 years old). Starting the fifth week of exercise training, monkeys underwent cognitive testing using the Wisconsin General Testing Apparatus (WGTA). Regardless of age, the exercising group learned to use the WGTA significantly faster (4.6+/-3.4 days) compared to controls (8.3+/-4.8 days; P=0.05). At the end of 5 months of running monkeys showed increased fitness, and the vascular volume fraction in the motor cortex in mature adult running monkeys was increased significantly compared to controls (P=0.029). However, increased vascular volume did not remain apparent after a 3-month sedentary period. These findings indicate that the level of exercise associated with improved fitness in middle-aged humans is sufficient to increase both the rate of learning and blood flow to the cerebral cortex, at least during the period of regular exercise. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Roelofs E. J., Smith-Ryan A. E., Trexler E. T., Hirsch K. R., & Mock M. G . ( 2016).

Effects of pomegranate extract on blood flow and vessel diameter after high-intensity exercise in young, healthy adults

European Journal of Sport Science, 17( 3), 317-325.

[本文引用: 1]

Schonewille M., Gao Z., Boele H. J., Veloz M. F. V., Amerika W. E., Šimek A. A ., .. de Zeeuw, C. I.( 2011).

Reevaluating the role of ltd in cerebellar motor learning

Neuron, 70( 1), 43-50.

URL     PMID:21482355      [本文引用: 2]

Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or 伪CamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.

Shatil E., ( 2013).

Does combined cognitive training and physical activity training enhance cognitive abilities more than either alone? A four-condition randomized controlled trial among healthy older adults

Frontiers in Aging Neuroscience, 5, 8.

[本文引用: 1]

Skriver K., Roig M., Lundbye-Jensen J., Pingel J., Helge J. W., Kiens B., & Nielsen J. B . ( 2014).

Acute exercise improves motor memory: Exploring potential biomarkers

Neurobiology of Learning and Memory, 116, 46-85.

URL     PMID:25128877      [本文引用: 1]

Abstract We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memory and skill acquisition. Thirty-two healthy young male subjects were randomly allocated into either an exercise or control group. Following either an intense bout of cycling or rest subjects practiced a visuomotor tracking task. Motor skill acquisition was assessed during practice and retention 1 h, 24 h and 7 days after practice. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epinephrine, norepinephrine, dopamine and lactate were analyzed at baseline, immediately after exercise or rest and during motor practice. The exercise group showed significantly better skill retention 24h and 7 days after acquisition. The concentration of all blood compounds increased significantly immediately after exercise and remained significantly elevated for 15 min following exercise except for BDNF and VEGF. Higher concentrations of norepinephrine and lactate immediately after exercise were associated with better acquisition. Higher concentrations of BDNF correlated with better retention 1 h and 7 days after practice. Similarly, higher concentrations of norepinephrine were associated with better retention 7 days after practice whereas lactate correlated with better retention 1h as well as 24 h and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory. Copyright 2014 Elsevier Inc. All rights reserved.

Stranahan A. M., Khalil D., & Gould E . ( 2007).

Running induces widespread structural alterations in the hippocampus and entorhinal cortex

Hippocampus, 17( 11), 1017-1022.

URL     [本文引用: 1]

Stranahan A. M., & Mattson, M. P . ( 2012).

Recruiting adaptive cellular stress responses for successful brain aging

Nature Reviews Neuroscience, 13( 3), 209-216.

URL     PMID:22251954      [本文引用: 1]

Successful ageing is determined in part by genetic background, but also by experiential factors associated with lifestyle and culture. Dietary, behavioural and pharmacological interventions have been identified as potential means to slow brain ageing and forestall neurodegenerative disease. Many of these interventions recruit adaptive cellular stress responses to strengthen neuronal networks and enhance plasticity. In this Science and Society article, we describe several determinants of healthy and pathological brain ageing, with insights into how these processes are accelerated or prevented. We also describe the mechanisms underlying the neuroprotective actions of exercise and nutritional interventions, with the goal of recruiting these molecular targets for the treatment and prevention of neurodegenerative disease.

Streit W. J. ( 2002).

Physiology and pathophysiology of microglial cell function

In: W. J. Streit (ed.), Microglia in the regenerating and degenerating central nervous system. New York: Springer.

URL     [本文引用: 1]

The primary objective of this first chapter is to provide a brief overview and synthesis of the subsequent chapters in this book and to elaborate on some favorite subjects, such as the role of microglia in the normal brain and their role in Alzheimer disease. Other pathological conditions where microglia are thought to play important roles, such as autoimmune CNS inflammatory disease, experimental allergic encephalomyelitis and multiple sclerosis, or infectious diseases such as HIV, will not be covered specifically in this book, but there are excellent reviews available on these topics (Gonzalez-Scarano and Baltuch (1999); Benveniste et al. (1997)).

Stroth S., Hille K., Spitzer M., & Reinhardt R . ( 2009).

Aerobic endurance exercise benefits memory and affect in young adults

Neuropsychological Rehabilitation, 19( 2), 223-243.

URL     PMID:18609015      [本文引用: 1]

Exercise seems a simple and widely practised behaviour that activates molecular and cellular signalling cascades involved in various central nervous system processes. Despite impressive results obtained in animal studies, fitness interventions have produced less reliable effects in humans, particularly in young adults. In the present study we tested the hypothesis that an individually adapted exercise training consisting of three running sessions of 30 minutes per week for 6 weeks, has the potential to improve visuospatial and verbal memory, concentration performance, and affect in young and healthy adults. Twenty-eight students participated and underwent a graded fitness test to assess individual fitness. The experimental group took part in an aerobic running programme, whereas the control group were asked not to vary their everyday activities. We found a significant increase in visuospatial memory performance and a significant increase in positive affect on a .05 alpha level of significance. However, we observed no effects of running training on concentration performance and verbal memory. We conclude that physical activity can possibly serve as a means to improve positively valenced aspects of affect and benefit visuospatial but not verbal memory in young adults.

Swain R. A., Harris A. B., Wiener E. C., Dutka M. V., Morris H. D., Theien B. E., .. Greenough W. T . ( 2003).

Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat

Neuroscience, 117( 4), 1037-1046.

URL     [本文引用: 1]

Tanne D., Freimark D., Poreh A., Merzeliak O., Bruck B., Schwammenthal Y., .. Adler Y . ( 2005).

Cognitive functions in severe congestive heart failure before and after an exercise training program

International Journal of Cardiology, 103( 2), 145-149.

URL     [本文引用: 1]

Thomas A. G., Dennis A., Bandettini P. A., & Johansen- Berg H . ( 2012).

The effects of aerobic activity on brain structure

Frontiers in Psychology, 3, 86.

URL     PMID:3311131      [本文引用: 5]

Abstract Aerobic activity is a powerful stimulus for improving mental health and for generating structural changes in the brain. We review the literature documenting these structural changes and explore exactly where in the brain these changes occur as well as the underlying substrates of the changes including neural, glial, and vasculature components. Aerobic activity has been shown to produce different types of changes in the brain. The presence of novel experiences or learning is an especially important component in how these changes are manifest. We also discuss the distinct time courses of structural brain changes with both aerobic activity and learning as well as how these effects might differ in diseased and elderly groups.

Tsai C. L., Chen F. C., Pan C. Y., Wang C. H., Huang T. H., & Chen T. C . ( 2014).

Impact of acute aerobic exercise and cardiorespiratory fitness on visuospatial attention performance and serum BDNF levels

Psychoneuroendocrinology, 41, 121-131.

URL     [本文引用: 1]

van der Borght K., Kóbor-Nyakas D. E., Klauke K., Eggen B. J. L., Nyakas C., van der Zee, E. A., & Meerlo P . ( 2009).

Physical exercise leads to rapid adaptations in hippocampal vasculature: Temporal dynamics and relationship to cell proliferation and neurogenesis

Hippocampus, 19( 10), 928-936.

URL     [本文引用: 1]

Vankim N. A., & Nelson, T. F . ( 2013).

Vigorous physical activity, mental health, perceived stress, and socializing among college students

American Journal of Health Promotion, 28( 1), 7-15.

URL     [本文引用: 1]

Vaynman S., Ying Z., Wu A., & Gomez-Pinilla F . ( 2006).

Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity

Neuroscience, 139( 4), 1221-1234.

URL     [本文引用: 1]

Voelcker-Rehage C., & Niemann, C. ( 2013).

Structural and functional brain changes related to different types of physical activity across the life span

Neuroscience & Biobehavioral Reviews, 37( 9), 2268-2295.

[本文引用: 1]

Voss M. W., Prakash R. S., Erickson K. I., Basak C., Chaddock L., Kim J. S., .. Kramer A. F . ( 2010).

Plasticity of brain networks in a randomized intervention trial of exercise training in older adults

Frontiers in Aging Neuroscience, 2, 32.

[本文引用: 3]

Voss M. W., Vivar C., Kramer A. F., & van Praag H . ( 2013).

Bridging animal and human models of exercise- induced brain plasticity

Trends in Cognitive Sciences, 17( 10), 525-544.

URL     PMID:4565723      [本文引用: 4]

Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity, neurotrophic factors, and vasculature. Areas of research focused more within species, such as hippocampal neurogenesis in rodents, also provide crucial insight into the protective role of physical activity. Overall, converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer's disease (AD) in humans.

Wang Y., Kang J., Kemmer P. B., & Guo Y . ( 2016).

An efficient and reliable statistical method for estimating functional connectivity in large scale brain networks using partial correlation

Frontiers in Neuroscience, 10, 123.

[本文引用: 1]

Wong, R. Y . ( 2017).

Physical exercise, cognition, and function in older people

Journal of the American Medical Directors Association, 18( 4), 282-283.

URL     PMID:28236611      [本文引用: 1]

react-text: 105 Rural health is an important priority in many jurisdictions as an example of social accountability. The choice to practice in a rural community can be influenced by personal factors, educational factors, and systemic factors. Medical education makes significant contribution to rural health by proactively and positively modifying the educational factors. The experience of the Faculty of... /react-text react-text: 106 /react-text [Show full abstract]

Wrann C. D., White J. P., Salogiannnis J., Laznik-Bogoslavski D., Wu J., Ma D., .. Spiegelman B. M . ( 2013).

Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway

Cell Metabolism, 18( 5), 649-659.

URL     PMID:3980968      [本文引用: 1]

61Exercise induces FNDC5 in the hippocampus61PGC-1α regulates neuronal Fndc5 gene expression in02vitro and in02vivo61FNDC5 positively regulates the expression of the important neurotrophin BDNF61Peripheral delivery of FNDC5 via adenoviral vectors induces Bdnf in the hippocampus

Xiong J. Y., Li S. C., Sun Y. X., Zhang X. S., Dong Z. Z., Zhong P., & Sun X. R . ( 2015).

Long-term treadmill exercise improves spatial memory of male appswe/ps1de9 mice by regulation of BDNF expression and microglia activation

Biology of Sport, 32( 4), 295-300.

URL     [本文引用: 2]

Ziegler G., Dahnke R., Jäncke L., Yotter R. A., May A., & Gaser C . ( 2012).

Brain structural trajectories over the adult lifespan

Human Brain Mapping, 33( 10), 2377-2389.

URL     PMID:21898677      [本文引用: 1]

The aim of this large-sample cross-sectional voxel-based morphometry (VBM) study of anatomical brain data was to investigate linear and nonlinear age-related trajectories of grey matter volume in the human brain during the adult lifespan. To date, there are only a few structural brain studies investigating local nonlinear aspects at the voxel level, i.e., without using anatomical ROIs as a priori hypothesis. Therefore, we analyzed 547 T1-weighted MR images of healthy adult brains with an age range of 19 to 86 years, including 161 scans of subjects with ages 60 and older. We found that the gray matter volume in some regions did not linearly decrease over time, but rather exhibited a delayed decline. Nonlinear age trajectories were observed in the medial temporal lobe regions, the basal ganglia, and parts of the cerebellum. Their trajectories indicated a preservation of grey matter volume during the early adult lifespan. Interestingly, we found nonlinear grey matter structural dynamics specifically in parts of the brain that have been extensively discussed in the context of learning and memory. We propose a hypothesis in relation to the functional role of these brain regions that may explain these results. Hum Brain Mapp 33:2377 2389, 2012. 2011 Wiley Periodicals, Inc.

Zochodne, D. W . ( 2014).

Mechanisms of diabetic neuron damage: Molecular pathways

Handbook of Clinical Neurology, 126, 379-399.

URL     [本文引用: 1]

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