Normal development of brain circuits.
TL;DR: To contextualize the developmental origins of a wide array of neuropsychiatric illnesses, this review describes the development and maturation of neural circuits from the first synapse through critical periods of vulnerability and opportunity to the emergent capacity for cognitive and behavioral regulation, and finally the dynamic interplay across levels of circuit organization and developmental epochs.
About: This article is published in Neuropsychopharmacology.The article was published on 2010-01-01 and is currently open access. It has received 1035 citations till now.
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TL;DR: The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or her own research.
Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or
7,563 citations
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02 Jan 2009TL;DR: Pending the prevention and cure of diabetes or the development of methods that provide glucose-regulated insulin replacement or secretion, the authors need to learn to replace insulin in a much more physiological fashion, to prevent, correct, or compensate for compromised glucose counterregulation, or both if they are to achieve near-euglycemia safely in most people with diabetes.
Abstract: Iatrogenic hypoglycemia causes recurrent morbidity in most people with type 1 diabetes and many with type 2 diabetes, and it is sometimes fatal. The barrier of hypoglycemia generally precludes maintenance of euglycemia over a lifetime of diabetes and thus precludes full realization of euglycemia’s long-term benefits. While the clinical presentation is often characteristic, particularly for the experienced individual with diabetes, the neurogenic and neuroglycopenic symptoms of hypoglycemia are nonspecific and relatively insensitive; therefore, many episodes are not recognized. Hypoglycemia can result from exogenous or endogenous insulin excess alone. However, iatrogenic hypoglycemia is typically the result of the interplay of absolute or relative insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine stand high in the hierarchy of redundant glucose counterregulatory factors that normally prevent or rapidly correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation. Reduced sympathoadrenal responses cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. Thus, short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in most affected patients. The clinical approach to minimizing hypoglycemia while improving glycemic control includes 1 ) addressing the issue, 2 ) applying the principles of aggressive glycemic therapy, including flexible and individualized drug regimens, and 3 ) considering the risk factors for iatrogenic hypoglycemia. The latter include factors that result in absolute or relative insulin excess: drug dose, timing, and type; patterns of food ingestion and exercise; interactions with alcohol and other drugs; and altered sensitivity to or clearance of insulin. They also include factors that are clinical surrogates of compromised glucose counterregulation: endogenous insulin deficiency; history of severe hypoglycemia, hypoglycemia unawareness, or both; and aggressive glycemic therapy per se, as evidenced by lower HbA 1c levels, lower glycemic goals, or both. In a patient with hypoglycemia unawareness (which implies recurrent hypoglycemia) a 2- to 3-week period of scrupulous avoidance of hypoglycemia is advisable. Pending the prevention and cure of diabetes or the development of methods that provide glucose-regulated insulin replacement or secretion, we need to learn to replace insulin in a much more physiological fashion, to prevent, correct, or compensate for compromised glucose counterregulation, or both if we are to achieve near-euglycemia safely in most people with diabetes.
1,167 citations
TL;DR: The evidence for the existence of sensitive periods for the adverse effects of early life stress in humans is reviewed and the potential importance of identifying sensitive time periods of opportunity for early interventions that might prevent or reverse the detrimental outcomes ofEarly life stress and its transmission across generations is discussed.
843 citations
TL;DR: The study of environmental factors in schizophrenia may have important implications for the identification of causes and prevention of this disorder, and offers the potential to complement, and refine, existing efforts on explanatory neurodevelopmental models.
569 citations
TL;DR: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children, higher but nonetheless within the range of levels measured in the general U.S. population.
Abstract: Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely impact children’s cognitive development.
Objective: To examine associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children.
Methods: We conducted a birth-cohort study (CHAMACOS) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at age 6 months and 1, 2, 3½ and 5 years. We administered the Wechsler Intelligence Scale for Children-IV to 329 seven-year old children. Analyses were adjusted for maternal education and intelligence, HOME score, and language of cognitive assessment.
Results: Urinary DAP concentrations measured during the 1st and 2nd half of pregnancy had similar relations to cognitive scores, thus we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full Scale IQ. Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ-points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores.
Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher, but nonetheless within the range of levels measured in the general U.S. population.
545 citations
Cites background from "Normal development of brain circuit..."
...…nervous systems may be more vulnerable to in utero exposure to OP pesticides due to the many unique processes occurring during this stage of development: e.g., cell division, migration, differentiation, formation of synapses, pruning of synapses, apoptosis, and myelination (Tau and Peterson 2010)....
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...Briefly, pregnant women were recruited in 6 community clinics serving primarily farmworker families, between October 1999 and 2000....
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References
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TL;DR: This method is used to examine receptive fields of a more complex type and to make additional observations on binocular interaction and this approach is necessary in order to understand the behaviour of individual cells, but it fails to deal with the problem of the relationship of one cell to its neighbours.
Abstract: What chiefly distinguishes cerebral cortex from other parts of the central nervous system is the great diversity of its cell types and interconnexions. It would be astonishing if such a structure did not profoundly modify the response patterns of fibres coming into it. In the cat's visual cortex, the receptive field arrangements of single cells suggest that there is indeed a degree of complexity far exceeding anything yet seen at lower levels in the visual system. In a previous paper we described receptive fields of single cortical cells, observing responses to spots of light shone on one or both retinas (Hubel & Wiesel, 1959). In the present work this method is used to examine receptive fields of a more complex type (Part I) and to make additional observations on binocular interaction (Part II). This approach is necessary in order to understand the behaviour of individual cells, but it fails to deal with the problem of the relationship of one cell to its neighbours. In the past, the technique of recording evoked slow waves has been used with great success in studies of functional anatomy. It was employed by Talbot & Marshall (1941) and by Thompson, Woolsey & Talbot (1950) for mapping out the visual cortex in the rabbit, cat, and monkey. Daniel & Whitteiidge (1959) have recently extended this work in the primate. Most of our present knowledge of retinotopic projections, binocular overlap, and the second visual area is based on these investigations. Yet the method of evoked potentials is valuable mainly for detecting behaviour common to large populations of neighbouring cells; it cannot differentiate functionally between areas of cortex smaller than about 1 mm2. To overcome this difficulty a method has in recent years been developed for studying cells separately or in small groups during long micro-electrode penetrations through nervous tissue. Responses are correlated with cell location by reconstructing the electrode tracks from histological material. These techniques have been applied to
12,923 citations
TL;DR: Evidence for partially segregated networks of brain areas that carry out different attentional functions is reviewed, finding that one system is involved in preparing and applying goal-directed selection for stimuli and responses, and the other is specialized for the detection of behaviourally relevant stimuli.
Abstract: We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.
10,985 citations
TL;DR: A baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF is identified, suggesting the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
Abstract: A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
10,708 citations
"Normal development of brain circuit..." refers background in this paper
...Sets of regions that share temporally correlated activity at rest are believed to constitute functional networks (Beckmann et al, 2005; Damoiseaux et al, 2006; Deluca et al, 2006; Fox et al, 2005, 2006; Fox and Raichle, 2007; Greicius et al, 2003; Kelly et al, 2008; Raichle et al, 2001)....
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TL;DR: This chapter demonstrates the functional importance of dopamine to working memory function in several ways and demonstrates that a network of brain regions, including the prefrontal cortex, is critical for the active maintenance of internal representations.
Abstract: Publisher Summary This chapter focuses on the modern notion of short-term memory, called working memory. Working memory refers to the temporary maintenance of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be maintained for longer periods of time through active rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behavior. Working memory is a system that is critically important in cognition and seems necessary in the course of performing many other cognitive functions, such as reasoning, language comprehension, planning, and spatial processing. This chapter demonstrates the functional importance of dopamine to working memory function in several ways. Elucidation of the cognitive and neural mechanisms underlying human working memory is an important focus of cognitive neuroscience and neurology for much of the past decade. One conclusion that arises from research is that working memory, a faculty that enables temporary storage and manipulation of information in the service of behavioral goals, can be viewed as neither a unitary, nor a dedicated system. Data from numerous neuropsychological and neurophysiological studies in animals and humans demonstrates that a network of brain regions, including the prefrontal cortex, is critical for the active maintenance of internal representations.
10,081 citations
Book•
01 Jun 1981
TL;DR: The principles of neural science as mentioned in this paper have been used in neural networks for the purpose of neural network engineering and neural networks have been applied in the field of neural networks, such as:
Abstract: Principles of neural science , Principles of neural science , کتابخانه دانشگاه علوم پزشکی و خدمات بهداشتی درمانی کرمان
8,872 citations