Cognitive development following early brain injury: evidence for neural adaptation

Over the past few decades a large body of work from developmental neurobiology has shown that mammalian brain development is the product of dynamic and adaptive processes operating within highly constrained, but continually changing, biological and environmental contexts. The recent study of children with prenatal focal brain injury supports this dynamic view of development for humans. Children's injuries often affect substantial portions of one cerebral hemisphere, resulting in damage that would compromise cognitive ability in adults. However, longitudinal behavioral studies of this population have revealed only mild deficits. It is suggested here that children's capacity for adaptation reflects normal developmental processes operating against a backdrop of serious neural perturbation. Data from three behavioral domains--linguistics, spatial cognition and affective development--illustrate this complex profile of change.     

Inflammation, glutamate, and glia in depression: a literature review

Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-alpha treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.     

Development and the epigenome: the ‘synapse’ of gene–environment interplay

This paper argues that there is a revolution afoot in the developmental science of gene–environment interplay. We summarize, for an audience of developmental researchers and clinicians, how epigenetic processes – chromatin structural modifications that regulate gene expression without changing DNA sequences – may offer a strong, parsimonious account for the convergence of genetic and contextual variation in the genesis of adaptive and maladaptive development. Epigenetic processes may play a plausible explanatory role in understanding: divergent trajectories and sexual dimorphisms in brain development; statistical interactions between genes and environments; the biological embedding of early psychosocial adversities; the linkages of such adversities to disorders of mental health; the striking individual variation in the strength of those linkages; the molecular origins of critical and sensitive periods; and the transgenerational inheritance of risk and protection. Taken together, these arguments converge in a claim that epigenetic processes constitute a promising and illuminating point of connection – a ‘synapse’ – between genes and environments.     

The Basics of Brain Development

Over the past several decades, significant advances have been made in our understanding of the basic stages and mechanisms of mammalian brain development. Studies elucidating the neurobiology of brain development span the levels of neural organization from the macroanatomic, to the cellular, to the molecular. Together this large body of work provides a picture of brain development as the product of a complex series of dynamic and adaptive processes operating within a highly constrained, genetically organized but constantly changing context. The view of brain development that has emerged from the developmental neurobiology literature presents both challenges and opportunities to psychologists seeking to understand the fundamental processes that underlie social and cognitive development, and the neural systems that mediate them. This chapter is intended to provide an overview of some very basic principles of brain development, drawn from contemporary developmental neurobiology, that may be of use to investigators from a wide range of disciplines.     

从炎症在心力衰竭进展中的作用谈心力衰竭治疗策略的制订

心力衰竭是一个以免疫激活和低程度的慢性炎症为特点的疾病。一些炎症因子能通过促进心肌细胞肥厚、恶化心肌收缩功能以及诱导凋亡,在心衰的发展过程中具有重要作用。炎症因子能成为心衰治疗的重要目标。但炎症因子还有心脏代偿和保护作用。制订新的心衰治疗策略时需要进一步了解心衰中炎症反应激活的机制。     

Les études des relations sociales précoces : sommes-nous trop « sécure » avec l'attachement ou trop « attaché » à la sécurité ?

During the past thirty years, empirical research has amply demonstrated the central role of early mother-child relations for subsequent social, cognitive and affective development. However, this confirmation of the vital role of primary attachment for later personal development has been accompanied by a relative neglect of the contribution of other social partners to the emerging competence of the young child. A critical review of the attachment literature underscores the need to replace the monotropic model of primary attachment by a more systemic model of development within the polyadic context of the family. For both theoretical and empirical reasons, a social ecological approach to early development permits overcoming the prosocial, positivistic biases of a single dimension, dyadic model of early socialization. The formulation of more systemic, multi-dimensional models of early family relations promises to advance our understanding of the complex adaptive processes that serve as developmental foundations for children’s emerging interpersonal competence.     

Developmental Pragmatics in Normal and Abnormal Children

We propose a critical review of current theories of developmental pragmatics. The underlying assumption is that such a theory ought to account for both normal and abnormal development. From a clinical point of view, we are concerned with the effects of brain damage on the emergence of pragmatic competence. In particular, the paper deals with direct speech acts, indirect speech acts, irony, and deceit in children with head injury, closed head injury, hydrocephalus, focal brain damage, and autism. Since no single theory covers systematically the emergence of pragmatic capacity in normal children, it is not surprising that we have not found a systematic account of deficits in the communicative performance of brain injured children. In our view, the challenge for a pragmatic theory is the determination of the normal developmental pattern within which different pragmatic phenomena may find a precise role. Such a framework of normal behavior would then permit the systematic study of abnormal pragmatic development.     

Connectionist models of development

How have connectionist models informed the study of development? This paper considers three contributions from specific models. First, connectionist models have proven useful for exploring nonlinear dynamics and emergent properties, and their role in nonlinear developmental trajectories, critical periods and developmental disorders. Second, connectionist models have informed the study of the representations that lead to behavioral dissociations. Third, connectionist models have provided insight into neural mechanisms, and why different brain regions are specialized for different functions. Connectionist and dynamic systems approaches to development have differed, with connectionist approaches focused on learning processes and representations in cognitive tasks, and dynamic systems approaches focused on mathematical characterizations of physical elements of the system and their interactions with the environment. The two approaches also share much in common, such as their emphasis on continuous, nonlinear processes and their broad application to a range of behaviors.     

Dual systems Competence ←-→ Procedural processing: A relational developmental systems approach to reasoning

Many current psychological models of reasoning minimize the role of deductive processes in human thought. In the present paper, we argue that deduction is an important part of ordinary cognition and we propose that a dual systems Competence ←-→ Procedural processing model conceptualized within relational developmental systems theory offers the most coherent and productive framework for integrating and explaining the sometimes conflicting findings on the development of deductive reasoning across the lifespan. This model invokes a distinction that is quite similar to, though not identical with, the system 2–system 1 dichotomy employed in other dual systems models. In addition, the Competence ←-→ Procedural processing model maintains the more specific distinction between algorithmic and reflective subsystems of system 2. In this account, the algorithmic system is represented as a kind of mental logic while the reflective system is the seat of practical and epistemic self-regulation, including emergent epistemic and metalogical norms. While the proposed systems of mind often appear as split-off component features in other dual systems models, relational developmental systems theory conceives of them as the highly complex and relationally integrated outcome of a self-organizing and self-regulating adaptive developmental process.     

Timing of human cortical functions during cognition: role of MEG

Understanding of sensory and cognitive brain processes requires information about activation timing within and between different brain sites. Such data can be obtained by magnetoencephalography (MEG) that tracks cortical activation sequences with a millisecond temporal accuracy. MEG is gaining a well-established role in human neuroscience, complementing with its excellent temporal resolution the spatially more focused brain imaging methods. As examples of MEG's role in cognitive neuroscience, we discuss time windows related to cortical processing of sensory and multisensory stimuli, effects of the subject's own voice on the activity of their auditory cortex, timing of brain activation in reading, and cortical dynamics of the human mirror-neuron system activated when the subject views another person's movements.     

Astrocytes and developmental white matter disorders

There is an increasing awareness that the astrocytes in the immature periventricular white matter are vulnerable to ischemia and respond to inflammation. Here we provide a synopsis of the articles that have evaluated the causes and consequences of developmental brain injuries to white matter astrocytes as well as the consequences of several genetic mutations that result in abnormal astrocyte development. Emerging data suggest that the astrocytes are not simply responding to the injury but are likely victims as well as culprits. Given the important roles that astrocytes play in maintaining ionic, neurotransmitter, and metabolic homeostasis in the brain, a more thorough understanding of the mechanisms that lead to their incapacitation, demise, or reactions as well as a better understanding of the stimuli that regulate their neuroprotective and regenerative properties will enable these cells to be manipulated to preserve the integrity of white matter and to potentially provide therapeutics to enhance neonatal regeneration and recovery from brain injury.     

Psychoneuroimmunology: A bio‐psycho‐social approach to health and disease

Since the early 1980s, the interdisciplinary field of psychoneuroimmunology has explored the complex bi‐directional interactions between brain, behavior, and the immune system. Taken together, this research has expanded the limits of the questions we can ask about the organism by challenging the biomedical paradigm of the immune system as predominantly “autonomous”. Psychoneuroimmunology has played a key role in establishing a biological basis for the ancient idea that the mind can play a role in health and disease. This article describes the development of psychoneuroimmunology and reviews a number of key findings concerning psychological phenomena of potential relevance to understanding brain‐behavior‐immune interactions, including learning, emotions, stress, and the role of sensory processes.     

Visual category-selectivity for faces, places and objects emerges along different developmental trajectories

The organization of category-selective regions in ventral visual cortex is well characterized in human adults. We investigated a crucial, previously unaddressed, question about how this organization emerges developmentally. We contrasted the developmental trajectories for face-, object-, and place-selective activation in the ventral visual cortex in children, adolescents, and adults. Although children demonstrated adult-like organization in object- and place-related cortex, as a group they failed to show consistent face-selective activation in classical face regions. The lack of a consistent neural signature for faces was attributable to (1) reduced face-selectivity and extent of activation within the regions that will become the FFA, OFA, and STS in adults, and (2) smaller volumes and considerable variability in the locus of face-selective activation in individual children. In contrast, adolescents showed an adult-like pattern of face-selective activation, although it was more right-lateralized. These findings reveal critical age-related differences in the emergence of category-specific functional organization in the visual cortex and support a model of brain development in which specialization emerges from interactions between experience-dependent learning and the maturing brain.     

Changes in frontal and posterior cortical activity underlie the early emergence of executive function

Executive function (EF) is a key cognitive process that emerges in early childhood and facilitates children's ability to control their own behavior. Individual differences in EF skills early in life are predictive of quality‐of‐life outcomes 30 years later (Moffitt et al., 2011). What changes in the brain give rise to this critical cognitive ability? Traditionally, frontal cortex growth is thought to underlie changes in cognitive control (Bunge & Zelazo, 2006; Moriguchi & Hiraki, 2009). However, more recent data highlight the importance of long‐range cortical interactions between frontal and posterior brain regions. Here, we test the hypothesis that developmental changes in EF skills reflect changes in how posterior and frontal brain regions work together. Results show that children who fail a “hard” version of an EF task and who are thought to have an immature frontal cortex, show robust frontal activity in an “easy” version of the task. We show how this effect can arise via posterior brain regions that provide on‐the‐job training for the frontal cortex, effectively teaching the frontal cortex adaptive patterns of brain activity on “easy” EF tasks. In this case, frontal cortex activation can be seen as both the cause and the consequence of rule switching. Results also show that older children have differential posterior cortical activation on “easy” and “hard” tasks that reflects continued refinement of brain networks even in skilled children. These data set the stage for new training programs to foster the development of EF skills in at‐risk children.     

Ontogenetic changes in the neural mechanisms of eyeblink conditioning

The rodent eyeblink conditioning paradigm is an ideal model system for examining the relationship between neural maturation and the ontogeny of associative learning. Elucidation of the neural mechanisms underlying the ontogeny of learning is tractable using eyeblink conditioning because the necessary neural circuitry (cerebellum and interconnected brainstem nuclei) underlying the acquisition and retention of the conditioned response (CR) has been identified in adult organisms. Moreover, the cerebellum exhibits substantial postnatal anatomical and physiological maturation in rats. The eyeblink CR emerges developmentally between postnatal day (PND) 17 and 24 in rats. A series of experiments found that the ontogenetic emergence of eyeblink conditioning is related to the development of associative learning and not related to changes in performance. More recent studies have examined the relationship between the development of eyeblink conditioning and the physiological maturation of the cerebellum, a brain structure that is necessary for eyeblink conditioning in adult organisms. Disrupting cerebellar development with lesions or antimitotic treatments impairs the ontogeny of eyeblink conditioning. Studies of the development of physiological processes within the cerebellum have revealed striking ontogenetic changes in stimulus-elicited and learning-related neuronal activity. Neurons in the interpositus nucleus and Purkinje cells in the cortex exhibit developmental increases in neuronal discharges following the unconditioned stimulus (US) and in neuronal discharges that model the amplitude and time-course of the eyeblink CR. The developmental changes in CR-related neuronal activity in the cerebellum suggest that the ontogeny of eyeblink conditioning depends on the development of mechanisms that estavlish cerebellar plasticity. Learning and the induction of neural plasticity depend on the magnitude of the US input to the cerebellum. The role of developmental changes in the efficacy of the US pathway has been investigated by monitoring neuronal activity in the inferior olive and with stimulation techniques. The results of these experiments indicate that the development of the conditioned eyeblink response may depend on dynamic interactions between multiple developmental processes within the eyeblink neural circuitry.     

Applied developmental psychology as an implementation of a life-span view of human development

Application of knowledge about psychological development should, ideally, be theory based. As such, these applications represent “natural ontogenetic experiments”; the results of the evaluation of such interventions feed back to the theory, helping to support, falsify, or refine the ideas from the theory which led to the particular application. Such applied developmental intervention research is central within a currently popular perspective of life-span human development. Thus, applied developmental intervention research provides critical tests of such key concepts within this life-span perspective as: plasticity; multidirectionality; the synthesis of continuous and discontinuous processes across ontogeny; contextual embeddedness; and the role of individuals as agents in their own development. This paper elucidates some of the major features of the dynamic linkage between applied developmental psychology and this view of life-span human development. Key elements of this life-span perspective and the facts of developmental intervention, as seen from this perspective, are specified. Finally, the doctoral training program at the authors' institution is presented as one example of how this link may be institutionalized in the form of graduate education.     

晚期正成分的时间-空间迁移模式在情绪调节发展研究中的应用

近二十年,使用认知神经科学手段探讨情绪调节成为了研究的热点。晚期正成分(Late Positive Potential,LPP)是情绪调节脑电研究中的一个典型成分,在不同的时间窗中分析LPP的波幅的变化及其优势激活脑区的迁移能够反映情绪调节加工过程中个体由对情绪刺激的感知到相应的认知调控过程的转变。LPP的时间-空间迁移模式被应用于情绪调节的发展研究,揭示从童年到青少年再到成年期个体情绪的潜在神经机制。研究者关注幼儿期、童年期、青少期、成人期个体在情绪调节加工过程中LPP波幅的变化及其时间-空间迁移模式特征,把不同年龄段个体情绪调节的发展特点与其大脑关键脑区(主要是前额叶)发育状况进行联系,为儿童身体发育和心理发展的主题提供更多的证据支持。未来的研究应加强对LPP在异常发展研究中应用,关注大脑发育与激素变化对LPP变化的影响,并加强对LPP调节效应的个体差异等问题的探讨。     

Fetal Programming: Prenatal Origins of Health and Illness

ABSTRACT— Research on young animals and humans has demonstrated the critical importance of the fetal stage as a formative period in normal development. However, the significance of these findings has not always been incorporated into our thinking when trying to elucidate the origins of health and disease. It is not only that babies react to the state of the mother and to salient environmental events while still in the uterus. This stimulation and priming seems to be essential for guiding the optimal maturation of the nervous, endocrine, and immune systems. Experiences during prenatal life also program the regulatory set points that will govern physiology in adulthood. During this malleable maturational phase, these biological processes should be viewed as flexible "learning systems" that guide the developmental trajectory toward health or derail it toward pathology. Our studies on infant primates have shown that the competence of their immune responses and the structure and activity of certain brain regions, as well as many aspects of behavior and emotional reactivity, are strongly affected by the pregnancy conditions of their mothers.     

心理社会应激的免疫反应规律与机制

心理社会应激会引起免疫系统发生免疫防御、免疫自稳和免疫监视方面的功能变化, 并随着应激刺激的时间和强度的变化而发生着异常与正常之间的动态转变。其机制与遗传、神经内分泌、自由基代谢和肠道菌群变化等生物学因素相关, 且小胶质细胞可能在其中起着重要的中介作用。诸多的生物学因素与年龄、性别和经济地位等人口学因素共同决定着心理社会应激的免疫反应发生发展。在其干预中, 运动疗法中的体育锻炼是极为值得重视的一种手段。     

Developmental science and the media. Early brain development

Media coverage of early brain development not only has focused public attention on early childhood but also has contributed to misunderstanding of developmental neuroscience research. This article critically summarizes current research in developmental neuroscience that is pertinent to the central claims of media accounts of early brain development, including (a) scientific understanding of formative early experiences, (b) whether critical periods are typical for brain development, (c) brain development as a lifelong process, (d) biological hazards to early brain growth, and (e) strengths and limits of current technology in developmental brain research. Recommendations are offered for strengthening the constructive contributions of research scientists and their professional organizations to the accurate and timely coverage of scientific issues in the media.