统计学习的认知机制及其神经基础

本文主要探讨了人类统计学习研究的起源和发展、影响统计学习的因素及统计学习的脑神经基础.人类统计学习的研究起源于20世纪90年代关于婴儿听觉语音流切分的实验,之后,大量研究又考察了对听觉非语言信息及视觉图形的统计学习.这些研究表明,统计学习是一种具有一般性的、涉及发现和提取规则的学习类型,但是不同范畴的统计学习又受到与特定范畴有关因素的制约.例如,语言统计学习受到语言因素的制约,而非语言统计学习与呈现刺激的特征以及呈现的通道有关.近些年,研究者开始采用事件相关电位(event-related potentials,ERPs)技术考察统计学习的时间进程,以及采用功能核磁共振成像(functional magnetic resonance imaging,fMRI)技术考察统计学习的脑激活模式.ERPs研究较一致地发现400 ms左右产生的负波与统计信息的提取有关,而脑成像研究结果表明,与统计学习相关的脑区有大脑左侧颞上回(superiortemporal gyrus)、右侧纹状体(right striatum)和右侧颞叶内侧记忆系统(right medial temporal memory system).     

自闭症患者大脑语言功能的异常偏侧化研究进展

自闭症谱系障碍(autismspectrumdisorders,ASD)是一种广泛发展障碍,以社会交往障碍、言语和非言语交流缺陷、兴趣狭窄和行为刻板等为主要临床特征.本文简述了自闭症的核心症状——语言障碍,回顾了自1986年以来,对自闭症语言障碍神经机制的研究,从其大脑结构、功能不对称性及相关利手因素的影响三个方面,综述了自闭症语言功能的异常偏侧化领域的研究成果和进展,期望为自闭症语言障碍的鉴别与治疗提供帮助,并促进汉语背景下自闭症患者的语言功能偏侧化研究.     

昆虫脑神经髓结构图谱构建方法综述

脑控制和调节所有动物的行为,昆虫也不例外,构建脑神经髓结构图谱有利于阐明其对行为调控的神经机制。目前,除一些模式昆虫的脑图谱被构建外,大多数昆虫仅针对少数易识别的神经髓(如视叶、触角叶和蕈形体等)进行了三维重建,而对脑内大部分区域还未描述,这与其结构的复杂性有关。随着共聚焦显微成像和计算机三维重建技术的发展,人们有机会获取全脑的结构信息,并构建出三维可视化的图谱,这为研究全脑神经髓的功能提供了重要平台。特别是果蝇全脑神经髓的系统命名法的建立,极大的推动了昆虫脑神经髓结构的研究进展。本文对昆虫脑的结构组成、免疫染色方法、标准脑构建及脑神经髓命名等方面进行综述,提出在构建脑神经髓图谱过程中需要注意的问题及解决办法,这将为推动国内昆虫脑神经髓图谱的构建提供参考。     

精神药理影像遗传学研究进展及其临床应用前景

精神疾病危害严重,其发病机制复杂难解,临床治疗效果不一,且存在明显的个体差异.近期精准医学研究发现精神药物作用于脑神经的生化过程受到遗传多态性的影响.本文从五羟色胺能、去甲肾上腺素能和多巴胺能三大系统入手,系统综述精神药理影像遗传学的相关研究进展,深入探讨精神药理的神经作用机制以及药物-基因-脑之间的交互作用.我们发现:SLC6A4、BDNF、FKBP5、COMT和多巴胺相关受体等基因多态性与多种精神疾病的发生发展及其治疗效果具有一定的相关性,可能成为相关精神疾病诊断的候选基因.杏仁核、海马、眶额叶、扣带回和前额叶等皮层与皮层下脑结构可能是不同神经递质相关的基因多态性影响精神药物生化作用过程的关键靶点脑区.在建立精神药物-基因-脑影像-行为的因果链中,仍然存在很多相互矛盾的结果和一定的局限性.因此,开展同质性强的临床试验、研究表观遗传作用等可以作为未来的研究发展趋势.     

老化认知神经科学:研究现状与未来展望

人口老龄化已经成为我国乃至全球面临的一个严峻的社会问题.开展老化认知神经科学研究,从认知、脑结构和脑功能层面揭示脑老化的机制和规律,进而探索并开发出延缓认知下降的方法和工具,对保持老年脑健康及提升生活质量具有重要意义.本文从脑结构老化、脑功能老化以及脑血流量与脑老化等方面概述了认知老化的神经机制.前人从补偿和去分化角度构建了多个认知老化理论和假说,然而,这些理论和假说较少考虑到脑结构老化、静息态研究及脑血流量的研究发现.坚持规律的运动、多做一些认知参与的活动、保持健康的生活方式和饮食模式,有助于老年人保持认知功能并延缓认知与脑老化.在老化认知神经科学未来发展方向上,从认知老化理论的发展以及成人毕生发展视角,对脑老化的脑功能网络研究、脑老化与可塑性以及基因对脑老化的影响等方面进行了展望.最后,本文从建立中国成人毕生发展行为-基因-脑数据库、使用和研发新技术研究认知老化、深入探索有效的脑功能改善方法、开展农村老年人研究及临床老年群体研究等方面,对国内老化认知神经科学的发展趋势进行了展望.     

拖延的脑机制:基于大尺度脑网络的分析

拖延是指个体明知有害却仍自愿推迟执行任务的一种不理智行为.拖延不仅会对人们的情绪、学业表现以及社会成就等产生不利的影响,而且会降低人们的主观幸福感,更有甚者会损害人们的身心健康.关于拖延的神经基础,目前研究只探索了拖延和脑区局部活动及简单的功能连接的关系.然而,拖延行为涉及任务价值表征、认知控制、趋近与回避动机等复杂的心理过程,以单变量和局部的脑活动来对拖延的神经基础进行描述会存在可见的局限.因此本研究采用图论拓扑分析的方法从大尺度脑网络连接角度考察拖延的神经基础.首先,定义Power等人的全脑264个感兴趣区(regions of interest, ROIs)为网络的节点,进一步采用图论分析的方法重构了全脑10个固有大尺度脑网络,结果发现构建的脑网络具有较好的网络拓扑属性(如较高的局部效率和全局效率).其次,采用皮尔逊相关的方法计算了10个脑网络内以及网络间的功能连接的强度.最后,考察了脑网络连接的强度与拖延行为之间的关系.结果发现,拖延与扣带执行网络的内部连接存在显著的负相关,而与皮层下网络的内部连接存在显著的正相关;进一步的网络间的功能连接发现,突显网络与皮层下网络间的功能连接与拖延存在显著的正相关.这些结果表明,皮层下网络和扣带执行网络内的连接以及突显网络对皮层下网络的调节可能是特质性拖延的神经基础.本研究的结果证明了认知控制与冲动性价值表征等认知能力在拖延行为中的重要作用.     

自闭症的预防和治疗方法

自闭症(孤独症)是一种以外在表现命名的、发现于幼儿期的中枢神经系统发育迟缓症.其莫名的攻击性行为、特异的生活模式符合潜意识的特征.自闭症的三要素是语言和沟通障碍、社会性和人际关系障碍、行为的同一性.1943年堪那提出了自闭症的五个症状:极端的孤独,缺乏和别人情感的接触;对环境事物有要求同一性(sameness)的强烈欲望;时某些物品有特殊的偏好,且以极好的精细动作操弄这些物品;没有语言,或者虽有语言但其语言似乎不能用于人际沟通;保留智能,呈沉思外貌,并具有良好的认知潜能.自闭症患儿的意识层面有符合潜意识特征的想法,有时在清醒状态也会表现出心理紊乱的特征.自闭症患儿由于睡眠障碍,较长时间处于心理紊乱状态.基于对现状的分析和对相关心理理论的研究,提出自闭症的预防和治疗应从四个方面入手:一是纠正心理紊乱,即克服睡眠障碍、补充睡眠时间;二是促进其神经系统发育;三是减轻病理因素的影响;四是加强学习训练,纠正意识层面具有潜意识特征的想法.充足的睡眠还可以促进中枢神经系统的发育,在根本上治疗自闭症.由于中药治本、西药治标的特点,在用药上,应交替服用促进发育、调理睡眠的中药,而禁服西药.     

语言发展认知神经科学研究:重要进展、趋势与规划建议

语言是人类独特的脑高级功能.语言发展和脑发育是发展认知神经科学研究的核心领域之一.深入理解语言发展和脑发育的复杂联系,不仅对破解人脑奥秘意义重大,同时可为理解和促进人类脑智发育提供重要依据.本文概述了语言获得和发展的脑机制、阅读发展与脑发育、二语学习年龄效应及脑机制、语言发展的遗传因素等方面的重要研究进展,并基于当前该领域的主要发展趋势,为我国布局该领域研究提出了建议.当前语言发展认知神经科学研究呈现如下主要趋势:通过方法创新,深化语言不同成分发展的脑机制研究,从而推进语言作为整体系统的研究;将语言发展脑机制的研究向认知、情感、社会行为相互联系的脑机制研究推进,以破解人类脑智发育奥秘;通过整合基因-环境-脑和行为,探索语言脑发育的生物-社会-心理机制;重视基础数据收集和积累,特别重视开展大样本长期追踪的语言脑发育队列研究.基于国际进展、趋势和我国现实需要,建议我国在此领域研究规划中重视研制、推广应用语言发展评估标准化工具,加强先进仪器设备的方法学训练;围绕汉语发展的脑机制,尽快开展脑与语言发展的大规模前瞻性队列研究,强化我国相关研究的优势和特色;重视面向满足国家促进亿万儿童语言发展的重大需求,结合政策、教育与医疗应用的具体需求,在语言发展促进,特别是阅读能力提升和障碍防治等领域,尽快开展有针对性的转化应用研究.此外,为推进语言认知神经科学基础与转化应用研究,还需要大力提倡合作与开放,推动本领域原始和集成创新.     

大鼠老化过程大脑皮层及小脑神经元染色质构象分析

 本文在前文~[2]的基础上进一步以MCN和DNaseⅠ为探针研究大鼠脑神经元终末分化后不同生理时期染色质构象,结果表明:MCN酶解DNA产物PAGE显示脑老化过程大脑皮层及小脑神经元染色质核小体单体DNA分别保持在176bp和215bp水平,核小体连接DNA长度存在组织差异,但不受老化影响;<2>DNaseⅠ酶解DNA产物PAGE显示各年龄组大脑皮层及小脑神经元染色质DNA存在10bp间隔重复结构和相同的泳动区带分布特征,提示脑老化中染色质具有稳定的B型双螺旋结构和一致的螺线管卷曲形式。染色质DNaseⅠ降解率随年龄增加而降低,提示老化导致活性染色质区域减少,老化过程脑神经元染色质构象改变成为其转录功能减退的结构基础。     

发展性阅读障碍的产生机制——从行为到遗传研究

发展性阅读障碍(developmental dyslexia,DD)是一种特殊的学习障碍,探索DD的产生机制有助于寻求DD儿童的鉴别和治疗方法.目前拼音文宁国家对DD的产生机制研究很多,结果也很丰富,但是很多观点还不一致.汉语DD研究起步较晚,各方面还不够深入和完善.简述了DD在认知、脑神经和基因方面的研究进展,对拼音文字DD与汉语DD的研究结果进行了对比,以揭示不同语言文字系统下DD者的认知神经差异.研究认为,应该大力加强对汉语DD的探究,这样不但为中国DD儿童的诊治提供理论基础,也可以为DD的语种特异性问题提供科学依据.     

Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm

Background

Altered brain development is evident in children born very preterm (24–32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age.

Methods

42 right-handed children born very preterm (24–32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling.

Results

After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes.

Conclusions

In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.     

Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology

The principle omega-3 fatty acid in brain, docosahexaenoic acid (DHA), accumulates in the brain during perinatal cortical expansion and maturation. Animal studies have demonstrated that reductions in perinatal brain DHA accrual are associated with deficits in neuronal arborization, multiple indices of synaptic pathology including deficits in serotonin and mesocorticolimbic dopamine neurotransmission, neurocognitive deficits, and elevated behavioral indices of anxiety, aggression, and depression. In primates and humans, preterm delivery is associated with deficits in fetal cortical DHA accrual, and children/adolescents born preterm exhibit deficits in cortical gray matter maturation, neurocognitive deficits particularly in the realm of attention, and increased risk for attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. Individuals diagnosed with ADHD or schizophrenia exhibit deficits in cortical gray matter maturation, and medications found to be efficacious in the treatment of these disorders increase cortical and striatal dopamine neurotransmission. These associations in conjunction with intervention trials showing enhanced cortical visual acuity and cognitive outcomes in preterm and term infants fed DHA, suggest that perinatal deficits in brain DHA accrual may represent a preventable neurodevelopmental risk factor for the subsequent emergence of psychopathology.     

Cortical thickness and behavior abnormalities in children born preterm

Aim

To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities.

Methods

We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL).

Results

We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas.

Interpretation

The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems.     

Assessment of Structural Connectivity in the Preterm Brain at Term Equivalent Age Using Diffusion MRI and T2 Relaxometry: A Network-Based Analysis

Preterm birth is associated with a high prevalence of adverse neurodevelopmental outcome. Non-invasive techniques which can probe the neural correlates underpinning these deficits are required. This can be achieved by measuring the structural network of connections within the preterm infant''s brain using diffusion MRI and tractography. We used diffusion MRI and T₂ relaxometry to identify connections with altered white matter properties in preterm infants compared to term infants. Diffusion and T₂ data were obtained from 9 term neonates and 18 preterm-born infants (born <32 weeks gestational age) at term equivalent age. Probabilistic tractography incorporating multiple fibre orientations was used in combination with the Johns Hopkins neonatal brain atlas to calculate the structural network of connections. Connections of altered diffusivity or T₂, as well as their relationship with gestational age at birth and postmenstrual age at the time of MRI, were identified using the network based statistic framework. A total of 433 connections were assessed. FA was significantly reduced in 17, and T₂ significantly increased in 18 connections in preterm infants, following correction for multiple comparisons. Cortical networks associated with affected connections mainly involved left frontal and temporal cortical areas: regions which are associated with working memory, verbal comprehension and higher cognitive function – deficits which are often observed later in children and adults born preterm. Gestational age at birth correlated with T₂, but not diffusion in several connections. We found no association between diffusion or T₂ and postmenstrual age at the time of MRI in preterm infants. This study demonstrates that alterations in the structural network of connections can be identified in preterm infants at term equivalent age, and that incorporation of non-diffusion measures such as T₂ in the connectome framework provides complementary information for the assessment of brain development.     

Cognitive abilities and language comprehension in preschool children with perinatal brain lesion

Perinatal brain lesion is a risk factor for development, making parents of such children particularly worried about consequences it may have on the child's cognitive and language development. Although literature findings on the outcome of perinatal brain lesion are inconsistent, most of the studies have found a positive general outcome, but also subtle deficits that affect the child's academic success. Since language comprehension and cognitive abilities influence learning abilities at school, we wanted to know how six-year olds who were selected based on pathological ultrasonographical findings (ischemic or hemorrhagic brain lesion) would perform on subtests of Wechsler battery (WISC) and language comprehension measures (Reynell Developmental Language Scale and Peabody Picture Vocabulary Test), compared with controls. The second issue we investigated was whether in children who suffered a perinatal brain lesion cognitive abilities predicted the level of language comprehension in the same way as in children without perinatal brain lesion. The relation between cognitive and linguistic abilities is still a controversial one, and a different relation would mean that these two groups of children have different structure of abilities probably due to perinatal brain lesion. Forty children who suffered a perinatal brain lesion and forty age-matched children without perinatal risk factors were examined. Our results showed that the groups differed more in linguistic than in cognitive variables. Also, the two groups showed different relation patterns between cognitive abilities and language comprehension. Cognitive abilities were statistically significantly associated with language comprehension in children who suffered a perinatal brain lesion, while this association was not statistically significant within the control group. Since a number of participants with perinatal brain lesion had language difficulties, it is presumed that they rely on cognitive abilities in order to overcome and compensate for language shortcomings.     

A Multivariate Surface-Based Analysis of the Putamen in Premature Newborns: Regional Differences within the Ventral Striatum

Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus) between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity disorder and attention-related learning disabilities in preterm neonates.     

Complement inhibition and statins prevent fetal brain cortical abnormalities in a mouse model of preterm birth

Premature babies are particularly vulnerable to brain injury. In this study we focus on cortical brain damage associated with long-term cognitive, behavioral, attentional or socialization deficits in children born preterm. Using a mouse model of preterm birth (PTB), we demonstrated that complement component C5a contributes to fetal cortical brain injury. Disruption of cortical dendritic and axonal cytoarchitecture was observed in PTB-mice. Fetuses deficient in C5aR (−/−) did not show cortical brain damage. Treatment with antibody anti-C5, that prevents generation of C5a, also prevented cortical fetal brain injury in PTB-mice. C5a also showed a detrimental effect on fetal cortical neuron development and survival in vitro. Increased glutamate release was observed in cortical neurons in culture exposed to C5a. Blockade of C5aR prevented glutamate increase and restored neurons dendritic and axonal growth and survival. Similarly, increased glutamate levels – measured by ¹HMRS – were observed in vivo in PTB-fetuses compared to age-matched controls. The blockade of glutamate receptors prevented C5a-induced abnormal growth and increased cell death in isolated fetal cortical neurons. Simvastatin and pravastatin prevented cortical fetal brain developmental and metabolic abnormalities -in vivo and in vitro. Neuroprotective effects of statins were mediated by Akt/PKB signaling pathways. This study shows that complement activation plays a crucial role in cortical fetal brain injury in PTL and suggests that complement inhibitors and statins might be good therapeutic options to improve neonatal outcomes in preterm birth.     

Topological Organization of Functional Brain Networks in Healthy Children: Differences in Relation to Age,Sex, and Intelligence

Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence.     

183例早产儿围产期高危因素及并发症分析

目的:探讨早产儿发生的围产期高危因素及并发症方法:收集我院2006.1-2009.12出生的早产儿183例的临床资料,总结其早产的相关围产期高危因素及并发症结果:胎膜早破、多胎妊娠、妊娠高血压综合征是早产发生的主要原因;早产儿的主要并发症为肺炎和颅内出血等。结论:加强围生期保健,早期干预各种围产期高危因素,积极防治早产儿各种并发症,是提高早产儿存活率降低致残率的关键     

183例早产儿围产期高危因素及并发症分析

目的：探讨早产儿发生的围产期高危因素及并发症。方法：收集我院2006．1—2009．12出生的早产儿183例的临床资料,总结其早产的相关围产期高危因素及并发症。结果：胎膜早破、多胎妊娠、妊娠高血压综合征是早产发生的主要原因;早产儿的主要并发症为肺炎和颅内出血等。结论：加强围生期保健,早期干预各种围产期高危因素,积极防治早产儿各种并发症,是提高早产儿存活率降低致残率的关键。