Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity

Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections. Reduced brain size should favor long-distance connectivity; brain overgrowth should favor short-distance connectivity; and inconsistent deviations from the normal growth trajectory - as occurs in autism - should result in potentially disruptive changes to established patterns of functional and physical connectivity during development. To explore this hypothesis, neural networks which modeled inter-hemispheric interaction were grown at the rate of either typically developing children or children with autism. The influence of the length of the inter-hemispheric connections was analyzed at multiple developmental time-points. The networks that modeled autistic growth were less affected by removal of the inter-hemispheric connections than those that modeled normal growth - indicating a reduced reliance on long-distance connections - for short response times, and this difference increased substantially at approximately 24 simulated months of age. The performance of the networks showed a corresponding decline during development. And direct analysis of the connection weights showed a parallel reduction in connectivity. These modeling results support the hypothesis that the deviant growth trajectory in autism spectrum disorders may lead to a disruption of established patterns of functional connectivity during development, with potentially negative behavioral consequences, and a subsequent reduction in physical connectivity. The results are discussed in relation to the growing body of evidence of reduced functional and structural connectivity in autism, and in relation to the behavioral phenotype, particularly the developmental aspects.     

网络游戏成瘾与海洛因成瘾存在相同的神经机制吗?——基于MRI的证据

网游成瘾与海洛因成瘾具有许多相似的临床表现,但其神经机制是否相同还不得而知。综合近5年来的MRI研究发现,两类成瘾存在部分相同区域的脑结构和功能损害,且在成瘾线索诱发下二者的4个成瘾相关环路(认知控制环路、奖赏环路、动机环路和记忆-学习环路)均出现了广泛而增强的脑区激活反应。但海洛因成瘾的脑损害区域偏向更高级的认知控制环路和奖赏环路,损害范围也更广(4个环路的功能连通性均降低),而网游成瘾的脑损害主要发生在相对低级的记忆-学习环路和动机环路,损害范围也较窄(功能连通性降低只发生在认知控制和记忆-学习环路之间)。这些结果说明,两类成瘾行为的神经机制既有相同点,又有差异性。     

Neural reuse: a fundamental organizational principle of the brain

An emerging class of theories concerning the functional structure of the brain takes the reuse of neural circuitry for various cognitive purposes to be a central organizational principle. According to these theories, it is quite common for neural circuits established for one purpose to be exapted (exploited, recycled, redeployed) during evolution or normal development, and be put to different uses, often without losing their original functions. Neural reuse theories thus differ from the usual understanding of the role of neural plasticity (which is, after all, a kind of reuse) in brain organization along the following lines: According to neural reuse, circuits can continue to acquire new uses after an initial or original function is established; the acquisition of new uses need not involve unusual circumstances such as injury or loss of established function; and the acquisition of a new use need not involve (much) local change to circuit structure (e.g., it might involve only the establishment of functional connections to new neural partners). Thus, neural reuse theories offer a distinct perspective on several topics of general interest, such as: the evolution and development of the brain, including (for instance) the evolutionary-developmental pathway supporting primate tool use and human language; the degree of modularity in brain organization; the degree of localization of cognitive function; and the cortical parcellation problem and the prospects (and proper methods to employ) for function to structure mapping. The idea also has some practical implications in the areas of rehabilitative medicine and machine interface design.     

Transplantation of fetal brain tissue

Fetal brain tissue transplanted to the brain of an adult mammalian host is known to develop within this environment. The grafted tissue also forms connections with the host brain and can produce recovery from behavioral deficits associated with destruction of parts of the host brain. The ability of grafts of fetal brain tissue to both develop in and form electrophysiologically viable connections with brains previously exposed to neurotoxins is discussed in this review. Restoration of neurotoxin-induced behavioral dysfunction by fetal brain grafts is also discussed. Finally, several uses for neural transplantation in neurotoxicological research are suggested. These uses include restoration of behavioral function, identification of the particular structures responsible for observed behavioral deficits, from among several structures damaged by an environmental neurotoxin, and identification of mechanisms underlying neurotoxicity.     

Connecting the Dots: A Review of Resting Connectivity MRI Studies in Attention-Deficit/Hyperactivity Disorder

Psychopathology is increasingly viewed from a circuit perspective in which a disorder stems not from circumscribed anomalies in discrete brain regions, but rather from impairments in distributed neural networks. This focus on neural circuitry has rendered resting state functional connectivity MRI (rs-fcMRI) an increasingly important role in the elucidation of pathophysiology including attention-deficit/hyperactivity disorder (ADHD). Unlike many other MRI techniques that focus on the properties of discrete brain regions, rs-fcMRI measures the coherence of neural activity across anatomically disparate brain regions, examining the connectivity and organization of neural circuits. In this review, we explore the methods available to investigators using rs-fcMRI techniques, including a discussion of their relative merits and limitations. We then review findings from extant rs-fcMRI studies of ADHD focusing on neural circuits implicated in the disorder, especially the default mode network, cognitive control network, and cortico-striato-thalamo-cortical loops. We conclude by suggesting future directions that may help advance subsequent rs-fcMRI research in ADHD.     

Synaptic plasticity and the organization of behaviour after early and late brain injury.

Hebb proposed that synaptic change underlies behavioural and cognitive plasticity. When applied to recovery from brain injury, the general hypothesis is that if there is recovery following brain injury, then there ought to be a correlated synaptic change, which is presumed to be responsible for recovery. In contrast, if recovery fails to occur, or expected recovery is blocked in some manner, then the synaptic change will likely not be present. Systematic study of functional recovery and synaptic change following brain injury at different ages supports these predictions. Good recovery is always correlated with enhanced connectivity whereas poor recovery is always correlated with an absence of reorganized connectivity. Furthermore, factors that stimulate recovery, such as neurotrophins or experience, stimulate synaptic change and functional recovery. Factors that retard recovery, such as depletion of neuromodulators, also block synaptic change. These results thus support Hebb's general idea that synaptic plasticity is related to behavioural change.     

Large-scale brain systems in ADHD: beyond the prefrontal-striatal model

Attention-deficit/hyperactivity disorder (ADHD) has long been thought to reflect dysfunction of prefrontal-striatal circuitry, with involvement of other circuits largely ignored. Recent advances in systems neuroscience-based approaches to brain dysfunction have facilitated the development of models of ADHD pathophysiology that encompass a number of different large-scale resting-state networks. Here we review progress in delineating large-scale neural systems and illustrate their relevance to ADHD. We relate frontoparietal, dorsal attentional, motor, visual and default networks to the ADHD functional and structural literature. Insights emerging from mapping intrinsic brain connectivity networks provide a potentially mechanistic framework for an understanding of aspects of ADHD such as neuropsychological and behavioral inconsistency, and the possible role of primary visual cortex in attentional dysfunction in the disorder.     

Cognitive functions, bodily sensibility and the brain

Body representations traverse the whole of the brain. They provide vital sources of information for every facet of an animal’s behavior, and such direct neural connectivity of visceral input throughout the nervous system demonstrates just how strongly cognitive systems are linked to bodily representations. At each level of the neural axis there are visceral appraisal systems that are integral in the organization of action. Cognition is not one side of a divide and viscera the other, with action merely a reflexive outcome. There is no divide between cognition and bodily functions once the brain is involved. Cognitive mechanisms that permeate neural function are a cardinal piece of biological function and adaptation.     

Development of brain functional connectivity and its relation to infant sustained attention in the first year of life

The study of brain functional connectivity is crucial to understanding the neural mechanisms underlying the improved behavioral performance and amplified ERP responses observed during infant sustained attention. Previous investigations on the development of functional brain connectivity during infancy are primarily confined to the use of functional and structural MRI techniques. The current study examined the relation between infant sustained attention and brain functional connectivity and their development during infancy with high‐density EEG recordings. Fifty‐nine infants were tested at 6 (N = 15), 8 (N =14), 10 (N = 17), and 12 (N = 13) months. Infant sustained attention was defined by measuring infant heart rate changes during infants’ looking. Functional connectivity was estimated from the electrodes on the scalp and with reconstructed cortical source activities in brain regions. It was found that infant sustained attention was accompanied by attenuated functional connectivity in the dorsal attention and default mode networks in the alpha band. Graph theory analyses showed that there was an increase in path length and a decrease in clustering coefficient during infant sustained attention. The functional connectivity within the visual, somatosensory, dorsal attention, and ventral attention networks and graph theory measures of path length and clustering coefficient were found to increase with age. These findings suggest that infant sustained attention is accompanied by distinct patterns of brain functional connectivity. The current findings also suggest the rapid development of functional connectivity in brain networks during infancy.     

主观记忆减退老年人情节记忆的行为表现及其脑机制

情节记忆是个体对特定时间,特定地点所经历的特定事件的记忆.主观报告情节记忆下降是主观记忆减退老年人最典型的表现.与健康对照组老年人相比, 主观记忆减退老年人情节记忆下降的速率更快, 罹患老年性痴呆的风险更高, 但其情节记忆加工的脑机制尚不明确.前人研究提示, 主观记忆减退老年人在外在记忆行为尚未出现损伤的情况下, 其大脑情节记忆相关脑区的神经活动已经出现异常.探究主观记忆减退的记忆神经环路关键节点和路径的异常, 揭示神经环路在老年痴呆发生发展中的变化规律, 对深入理解老年痴呆的发病机制有重要的科学意义.同时, 主观记忆减退老年人作为特殊的记忆损伤群体, 对其神经环路的深入探究, 也必将为揭示人类记忆的神经机制做出独特的贡献.     

The psychopath magnetized: insights from brain imaging

Psychopaths commit a disproportionate amount of violent crime, and this places a substantial economic and emotional burden on society. Elucidation of the neural correlates of psychopathy may lead to improved management and treatment of the condition. Although some methodological issues remain, the neuroimaging literature is generally converging on a set of brain regions and circuits that are consistently implicated in the condition: the orbitofrontal cortex, amygdala, and the anterior and posterior cingulate and adjacent (para)limbic structures. We discuss these findings in the context of extant theories of psychopathy and highlight the potential legal and policy implications of this body of work.     

抑郁症的脑功能异常:来自静息态功能磁共振成像的证据

静息态功能磁共振成像是指在静息状态下测量的BOLD信号,即受试者安静地躺在扫描仪中,不给受试者任何特定的任务,受试者也不用做任何反应,此时受试者的大脑活动处于自发状态。通过使用该技术可以为抑郁症发作的临床现象提供神经影像学依据,以期为将来抑郁症的治疗提供生物标记。因此,本文综述了大量抑郁症患者在静息态脑功能方面的差异研究,发现了单、双相抑郁症,首、复发抑郁症,早发性、晚发性抑郁症,难治、非难治性抑郁症等不同类型的抑郁症在包括局部一致性(Re Ho)和低频振幅(ALFF)在内的功能分化以及包括功能连接密度(FCD)、功能同伦(VMHC)、复杂网络(Complex Network)和ROI功能连接在内的功能整合两大指标的改变。     

发展性阅读障碍的脑区连接异常

过去几十年中, 研究者基于脑区功能定位的思想对发展性阅读障碍的神经机制进行了大量的研究, 揭示出阅读障碍者在特定脑区的异常。近些年, 考虑到阅读加工过程的复杂性以及需要多脑区协同参与的特点, 越来越多的研究者从脑区连接的角度探讨阅读障碍的神经机制。结果发现阅读障碍者在阅读相关脑区间的白质结构连接和功能连接上均表现出异常, 这说明阅读技能受损和脑区连接异常之间存在着密切的联系。未来的研究还需进一步探讨脑区连接异常和特定脑区异常之间的关系, 以及结合基因、脑、行为和环境等多个因素探寻阅读障碍的发生机制。     

反刍思维的脑功能网络机制

反刍思维是指个体在经历了消极生活事件后不由自主地反复思考该事件的产生原因、经过和结果, 表现出负性自我参照加工、消极情绪性以及持续性的特点。采用脑功能网络分析方法, 研究者发现反刍思维的上述三个特点分别与默认网络内部的异常活动模式、突显网络功能连接的改变以及注意相关网络之间的异常耦合有关。未来研究应进一步明确反刍思维与相关脑网络活动之间的因果关系, 探究反刍思维脑功能网络的结构基础, 同时也应关注反刍思维及其脑网络的老龄化特征, 并致力于探索有效干预反刍思维的神经调控技术。     

Intelligence and neural efficiency: Measures of brain activation versus measures of functional connectivity in the brain

The neural efficiency hypothesis of intelligence suggests a more efficient use of the cortex (or even the brain) in brighter as compared to less intelligent individuals. This has been shown in a series of studies employing different neurophysiological measurement methods and a broad range of different cognitive task demands. However, most of the studies dealing with the brain–IQ relationship used parameters of absolute or relative brain activation such as the event-related (de-)synchronization of EEG alpha activity, allowing for interpretations in terms of more or less brain activation when individuals are confronted with cognitively demanding tasks. In order to investigate the neural efficiency hypothesis more thoroughly, we also used measures that inform us about functional connectivity between different brain areas (or functional coupling, respectively) when engaged in cognitive task performance. Analyses reveal evidence that higher intelligence is associated with a lower brain activation (or a lower ERD, respectively) and a stronger phase locking between short-distant regions of the frontal cortex.     

自尊的认知神经机制

自尊是个体对自己总体的情感性评价。自尊有助于促进个体的心理健康,帮助个体应对威胁,具有重要的适应价值。近年来随着社会认知神经科学的兴起,关于自尊的认知神经机制的研究日益增多,主要涉及三个方面:1)自尊与大脑的结构(如海马体积、前扣带回等区域的灰质体积)和功能(静息态下的默认网络活动以及脑区之间的功能联结性)存在一定的关联;2)自尊调节大脑对威胁的反应,与高自尊个体相比,低自尊个体面对威胁时产生更强的防御性反应,自尊通过影响个体面对威胁时的大脑活动帮助个体更好地应对威胁;3)自我评价过程涉及大脑前额叶、眶额叶、扣带回等多个脑区,自尊调节个体在自我评价过程中的大脑活动。总之,自尊作为个体重要的人格特质,与大脑的结构、功能以及活动状态等都具有一定的关系;这些发现在一定程度上揭示了自尊的神经机制,加深了对自尊及其功能的理解。     

Brain Networks in Schizophrenia

Schizophrenia—a severe psychiatric condition characterized by hallucinations, delusions, loss of initiative and cognitive function—is hypothesized to result from abnormal anatomical neural connectivity and a consequent decoupling of the brain’s integrative thought processes. The rise of in vivo neuroimaging techniques has refueled the formulation of dysconnectivity hypotheses, linking schizophrenia to abnormal structural and functional connectivity in the brain at both microscopic and macroscopic levels. Over the past few years, advances in high-field structural and functional neuroimaging techniques have made it increasingly feasible to reconstruct comprehensive maps of the macroscopic neural wiring system of the human brain, know as the connectome. In parallel, advances in network science and graph theory have improved our ability to study the spatial and topological organizational layout of such neural connectivity maps in detail. Combined, the field of neural connectomics has created a novel platform that provides a deeper understanding of the overall organization of brain wiring, its relation to healthy brain function and human cognition, and conversely, how brain disorders such as schizophrenia arise from abnormal brain network wiring and dynamics. In this review we discuss recent findings of connectomic studies in schizophrenia that examine how the disorder relates to disruptions of brain connectivity.     

The developmental cognitive neuroscience of functional connectivity

Developmental cognitive neuroscience is a rapidly growing field that examines the relationships between biological development and cognitive ability. In the past decade, there has been ongoing refinement of concepts and methodology related to the study of ‘functional connectivity’ among distributed brain regions believed to underlie cognition and behavioral control. Due to the recent availability of relatively easy-to-use tools for functional connectivity analysis, there has been a sharp upsurge of studies that seek to characterize normal and psychopathologically abnormal brain functional integration. However, relatively few studies have applied functional and effective connectivity analysis techniques to developmental cognitive neuroscience. Functional and effective connectivity analysis methods are ideally suited to advance our understanding of the neural substrates of cognitive development, particularly in understanding how and why changes in the functional ‘wiring’ of neural networks promotes optimal cognitive control throughout development. The purpose of this review is to summarize the central concepts, methods, and findings of functional integration neuroimaging research to discuss key questions in the field of developmental cognitive neuroscience. These ideas will be presented within a context that merges relevant concepts and proposals from different developmental theorists. The review will outline a few general predictions about likely relationships between typical ‘executive’ cognitive maturation and changes in brain network functional integration during adolescence. Although not exhaustive, this conceptual review also will showcase some of recent findings that have emerged to support these predictions.     

Cognitive rehabilitation: attention and neglect

Cognitive neuroscience can make a significant contribution towards the development of a scientific basis for the practice of brain rehabilitation. Though rehabilitation is a vast worldwide industry, there is little scientific basis for the training and therapy that are designed to help damaged brain circuits to recover. The systematic application of cognitive neuroscience models to rehabilitation can not only foster better, more theoretically grounded rehabilitation, but the models themselves can be tested and modified by data generated in rehabilitation-oriented research. The example of unilateral spatial neglect is used here to show how non-intuitive but clinically tractable methods can emerge out of systematic application of cognitive neuroscience to the problem of how to foster dynamic change and recovery in the damaged brain. Examples are given of recently developed rehabilitation methods for unilateral spatial neglect that are both derived from theoretical models of cognitive function, and that feed back into these models. These include dorsal–ventral stream interactions, perceptuo–motor interactions, interhemispheric inhibitory dynamics, and arousal–spatial attention interactions. It will be to the mutual benefit of basic cognitive neuroscience and rehabilitation if this type of research is expanded into other domains of cognitive function, in which similar theory–practice interactions exist.     

A smarter brain is associated with stronger neural interaction in healthy young females: A resting EEG coherence study

General intelligence, the g factor, is a major issue in psychology and neuroscience. However, the neural mechanism of the g factor is still not clear. It is suggested that the g factor should be non-modular (a property across the brain) and show good colinearity with various cognitive tests. This study examines the hypothesis that functional connectivity may be a good candidate for the g factor. We recorded resting state eyes-closed EEG signals in 184 healthy young females. Coherence values of 38 selected channel pairs across delta, theta, alpha, beta and gamma frequencies were correlated with six intelligence quotient (IQ) subtests, including symbol search, block design, object assembly, digit span, similarity and arithmetic. A three-stage analytic flow was constructed to delineate common (g factor) and unique neural components of intelligence. It is noticed that the coherence pattern demonstrates good correlation with five of the IQ subtests (except symbol search) and non-modularity in the brain. Our commonality analyses support connectivity strength in the brain as a good indicator of the g factor. For the digit span and arithmetic tests, the uniqueness analyses provide left-lateralized topography relevant to the operation of working memory. Performance on the arithmetic test is further correlated with strengths at left temporo-parietal and bilateral temporal connections. All the significant correlations are positive, indicating that the stronger the connectivity strengths, the higher the intelligence. Our analyses conclude that a smarter brain is associated with stronger interaction in the central nervous system. The implication and why the symbol search does not show parallel results are discussed.