Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.
01 Jun 2000-Environmental Health Perspectives (National Institute of Environmental Health Science)-Vol. 108, pp 511-533
TL;DR: Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function, and the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.
Abstract: Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.
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TL;DR: Two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation.
1,649 citations
TL;DR: A review of fundamental brain development processes that occur in both rodents and humans to delineate a comparable time course of postnatal brain development across species offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development.
1,473 citations
TL;DR: To control the pandemic of developmental neurotoxicity, a global prevention strategy is proposed and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicants is proposed.
Abstract: Neurodevelopmental disabilities, including autism, attention-defi cit hyperactivity disorder, dyslexia, and other cognitive impairments, aff ect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identifi ed fi ve industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants—manganese, fl uoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these eff orts and to accelerate translation of science into prevention, we propose the urgent formation of a new international clearinghouse.
1,303 citations
TL;DR: Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics in this cohort, but these data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute toLD.
Abstract: Background
Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. We studied association between anesthetic exposure prior to age 4 and the development of reading, written language and math learning disabilities (LD).
1,235 citations
TL;DR: Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders.
1,201 citations
References
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Journal Article•
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TL;DR: A randomized controlled experiment is designed to test whether access to affordable day care (in the form of subsidies, for example) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired.
Abstract: This pilot aims to better understand the market for childcare in Saudi Arabia – both the supply and demand sides – and to design a randomized controlled experiment to test whether access to affordable day care (in the form of subsidies, for example) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired. In addition, the study seeks to understand the degree to which employment early on in one’s life impacts employment in later stages. The pilot will provide information on the groups of women the experiment should target, appropriate levels for the childcare subsidy, and the quality and current geographic locations of daycare sites. Expected Impact Determine the effects of facilitating childcare access on Saudi women’s employment. PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Peck
9,609 citations
"Critical periods of vulnerability f..." refers background in this paper
...There has also been some research on the development of play behavior in young children (211-214), including the correlation between play and language development (215) and coping behavior (216)....
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Book•
21 Jan 1954
TL;DR: In this paper, the authors make a distinction between simple temporal displacements in extension due to the repetition of primitive processes on the occasion of new problems analogous to old ones, and the temporal displacement in comprehension due to a transition from one plane of activity to another; that is, from the plane of action to that of representation.
Abstract: class does not exist either, precisely since the relation between the two shadows compared is not a relation of simple comparison and common appurtenance to the same totality, but of substantial participation. The shadow perceived on the table is therefore no more an isolable object than is, on the sensorimotor plane, the watch which disappears under one cushion and which the child expects to see appear under another. But if there is thus an apparent return to the past it is for an opposite reason to that which obstructs objectification in sensorimotor intelligence; in the latter case the object is difficult to form in proportion as the child has difficulty in intercoordinating perceptual images, whereas on the plane of conceptual thought the object, already elaborated, again loses its identity to the extent that it is coordinated with other objects to construct a class or a relation. In conclusion, in the case of the object as in that of space, from the very beginnings of verbal reflection there is a return of the difficulties already overcome on the plane of action, and there is repetition, with temporal displacements, of the stages and process of adaptation defined by the transition from egocentrism to objectivity. And in both cases the phenomenon is due to the difficulties experienced by the child, after he has reached the social plane, in inserting his sensorimotor acquisitions in a framework of relationships of logical classes and deductive structures admitting of true generalisation, that is, taking into account the point of view of others and all possible points of view as well as his own. § 4. From Sensori-Motor Universe to Representation of the Child’s World II. Causality and Time The development of causality from the first months of life to the eleventh or twelfth year reveals the same graphic curve as that of space or object. The acquisition of causality seems to be completed with the formation of sensorimotor intelligence; in the measure that objectification and spatialisation of relations of cause and effect succeed the magico-phenomenalistic egocentrism of the primitive connections, a whole evolution resumes with the advent of speech and representative thought which seems to reproduce the preceding evolution before really extending it. But among the displacements to which this history of the concept of cause gives rise, distinction must again be made between the simple temporal displacements in extension due to the repetition of primitive processes on the occasion of new problems analogous to old ones, and the temporal displacements in comprehension due to the transition from one plane of activity to another; that is, from the plane of action to that of representation. It seems useless to us to emphasise the former. Nothing is more natural than the fact that belief in the efficacy of personal activity, a belief encouraged by chance comparisons through immediate or phenomenalistic experience, is again found throughout childhood in those moments of anxiety or of desire which characterise infantile magic. The second type of temporal displacements, however, raises questions which it is useful to mention here. During the first months of life the child does not dissociate the external world from his own activity. Perceptual images, not yet consolidated into objects or coordinated in a coherent space, seem to him to be governed by his desires and efforts, though these are not attributed to a self which is separate from the universe. Then gradually, as progress is made in the intelligence which elaborates objects and space by spinning a tight web of relations among these images, the child attributes an autonomous causality to things and persons and conceives of the existence of causal relations independent of himself, his own body becoming a source among other sources of effects integrated in this total system. What will happen when, through speech and representative thought, the subject succeeds not only in foreseeing the development of phenomena and in acting upon them but in evoking them apart from any action in order to try to explain them? It is here that the paradox of displacement in comprehension appears. By virtue of the "why" obsessing the child’s mind, as soon as his representation of the world can be detached without too much risk of error, one perceives that this universe, centred on the self, which seemed abolished because it was eliminated from practical action relating to the immediate environment, reappears on the plane of thought and impresses itself on the little child as the sole understandable conception of totality. Undoubtedly the child no longer behaves, as did the baby, as though he commanded everything and everybody. He knows that adults have their own will, that the rain, wind, clouds, stars, and all things are characterised by movements and effects he undergoes but cannot control. In short, on the practical plane, the objectification and spatialisation of causality remain acquired. But this does not at all prevent the child from representing the universe to himself as a large machine, organised exactly by whom he does not know, but organised with the help of adults and for the sake of the well-being of men and particularly of children. Just as in a house everything is arranged according to a plan, despite imperfections and partial failures, so also the raison d’être for everything in the physical universe is the function of a sort of order in the world, an order both material and moral, of which the child is the center. Adults are there "to take care of us," animals to do us service, the stars to warm us and give us light, plants to nourish us, rain to make the gardens grow, clouds to "make night," mountains to climb on, and lakes for boats, etc. Furthermore, to this more or less explicit and coherent artificialism there corresponds a latent animism which endows everything with the will to play its role and with just the force and awareness needed to act with regularity. Thus the causal egocentrism, which on the sensorimotor plane disappears gradually under the influence of spatialisation and objectification, reappears from the time of the beginnings of thought in almost as radical a form. Doubtless the child no longer attributes personal causality to others or to things, but while endowing objects with specific activities he centers all these activities on man and above all on himself. It seems clear that in this sense we may speak of temporal displacement from one plane to another and that the phenomenon is thus comparable to the phenomena which characterise the evolution of space and object. But it is in a still deeper sense that the primitive schemata of causality are again transposed in the child’s first reflective representations. If it is true that from the second year of life the child attributes causality to others and to objects instead of reserving a monopoly on them for his own activity, we have still to discover how he represents to himself the mechanism of these causal relations. We have just recalled that corresponding to the egocentric artificialism which makes the universe gravitate around man and child is an animism capable of explaining the activity of creatures and things in this sort of world. This example is precisely of a kind to help us understand the second kind of temporal displacement of which we now speak: if the child renounces considering his actions as the cause of every event, he nevertheless is unable to represent to himself the action of bodies except by means of schemata drawn from his own activity. An object animated by a "natural" movement like the wind which pushes clouds, or the moon which advances, thus seems endowed with purposefulness and finality, for the child is unable to conceive of an action without a conscious goal. Through lack of awareness, every process involving a relation of energies, such as the rising of the water level in a glass in which a pebble has been dropped, seems due to forces copied from the model of personal activity; the pebble "weighs" on the bottom of the water, it "forces" the water to rise, and if one held the pebble on a string midway of the column of the water the level would not change. In short, even though there is objectivity on the practical plane, causality may remain egocentric from the representative point of view to the extent that the first causal conceptions are drawn from the completely subjective consciousness of the activity of the self. With regard to spatialisation of the causal connection the same temporal displacement between representation and action is observable. Thus the child can acknowledge in practice the necessity for a spatial contact between cause and effect, but that does not make causality geometric or mechanical. For example, the parts of a bicycle all seem necessary to the child long before he thinks of establishing irreversible causal series among them. However, subsequent to these primitive stages of representation during which one sees reappear on the plane of thought forms of causality relative to those of the first sensorimotor stages and which seem surpassed by the causal structures of the final stages of sensorimotor intelligence, one witnesses a truly reflective objectification and spatialisation, whose progress is parallel to that which we have described on the plane of action. Thus it is that subsequent to the animism and dynamism we have just mentioned, we see a gradual "mechanism" taking form, correlative to the principles of conservation described in § 3 and to the elaboration of a relative space. Causality, like the other categories, therefore evolves on the plane of thought from an initial egocentrism to a combined objectivity and relativity, thus reproducing, in surpassing, its earlier sensorimotor evolution. With regard to time, concerning which we have tried to describe on the purely practical plane of the first two years of life the transformation from
5,878 citations
"Critical periods of vulnerability f..." refers background in this paper
...Infants also progress through a series of stages of understanding that an object that is no longer in sight still exists (225), a Figure 11....
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TL;DR: On May 25, 1977, IEEE member, Virginia Edgerton, a senior information scientist employed by the City of New York, telephoned the chairman of CSIT's Working Group on Ethics and Employment Practices, having been referred to the committee by IEEE Headquarters.
Abstract: On May 25, 1977, IEEE member, Virginia Edgerton, a senior information scientist employed by the City of New York, telephoned the chairman of CSIT's Working Group on Ethics and Employment Practices, having been referred to the committee by IEEE Headquarters. She said that she had encountered a situation that might lead to the degradation of a data processing system (called SPRINT) used to dispatch police cars in response to emergency calls, and that her immediate superior, who disagreed with this assessment, refused to have the problem studied. Ms. Edgerton sought advice from the committee.
5,633 citations
"Critical periods of vulnerability f..." refers background in this paper
...Dyslexia is associated with neuronal ectopias and architectonic dysplasias in various areas of the cerebral cortex (331,332) as well as other structural abnormalities....
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TL;DR: The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory, but the role of this system is only temporary, as time passes after learning, memory stored in neoc cortex gradually becomes independent of medialporal lobe structures.
Abstract: Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures.
3,096 citations
TL;DR: The human frontal cortex helps mediate working memory, a system that is used for temporary storage and manipulation of information and that is involved in many higher cognitive functions.
Abstract: The human frontal cortex helps mediate working memory, a system that is used for temporary storage and manipulation of information and that is involved in many higher cognitive functions. Working memory includes two components: short-term storage (on the order of seconds) and executive processes that operate on the contents of storage. Recently, these two components have been investigated in functional neuroimaging studies. Studies of storage indicate that different frontal regions are activated for different kinds of information: storage for verbal materials activates Broca's area and left-hemisphere supplementary and premotor areas; storage of spatial information activates the right-hemisphere premotor cortex; and storage of object information activates other areas of the prefrontal cortex. Two of the fundamental executive processes are selective attention and task management. Both processes activate the anterior cingulate and dorsolateral prefrontal cortex.
2,820 citations
"Critical periods of vulnerability f..." refers background in this paper
...The PFC in primates is considered necessary for so-called executive functions (283,295,296), including organization of behavior in time and space, planning, inhibition of inappropriate actions (impulse control), ability to change strategy (set-shift), and emotional control....
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