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PubMed1985

Temporal evolution of hypoxic-ischaemic brain lesions in asphyxiated full-term newborns as assessed by computerized tomography.

Hypoxic-ischaemic brain lesions may be detected as low density (LD) areas by means of computerized tomography (CT), but the clinical significance of such LD areas has been controversial. Since timing might be a critical factor, we studied the temporal evolution of LD areas in 9 asphyxiated term babies who had had two or more CT, and compared the changes to the neurodevelopmental outcome. Scans were classified according to the elapsed time after asphyxia as early (day 1-7, n = 6), intermediate (week 2-4, n = 7; week 4-7, n = 3) and late CT (3 months or more, n = 7). In early scans, no, or only ill defined, LD areas were seen in the periventricular region. In intermediate CT's, LD-zones were further diminished in those babies who later were normal. Sharply accentuated LD areas, however, appeared in those who later suffered from neurodevelopmental disorders. These LD areas, probably representing hypoxic-ischaemic lesions, were located periventricularly, extending into the subcortical white matter and the cortex, and usually involved both hemispheres symmetrically. They began to disappear at 4 to 7 weeks in some regions, possibly because of glial proliferation. LD persisting more than 4-7 weeks tended to transform into cyst-like lesions, or marked atrophy. We conclude (1) that hypoxic-ischaemic lesions appear as zones of low density on CT scans performed after the first week and (2) that the extent of such lesions can best be assessed between 9 to 23 days after asphyxia.

Asphyxia Neonatorum↗
PubMed2002

Molecular pathways to obesity.

Obesity results from a chronic imbalance between energy intake and energy expenditure. Environmental factors, such as the increased availability of high caloric food or the decreased need for physical activity, contribute to its development and their influence is amplified by genetic predisposition. In recent years remarkable progress has been made in the understanding of the pathophysiology of obesity. Although most of the insights into the regulation of energy balance have been obtained in rodent models, the rare clinical cases of monogenic obesity provided evidence for the importance of several of these mechanisms in humans. The identification of leptin as a factor originating from adipose tissue and informing the brain about the status of energy reserves firmly established the concept of long-term regulation of body fat stores. The disappointing therapeutic results with leptin in obese patients could be explained by the fact that during evolution this hormone developed rather as a starvation signal than as an adiposity signal. It is conceivable that the pharmacological interference with mechanisms downstream of leptin, for example with the melanocortin pathway, might be therapeutically more promising. The discovery of new molecular mechanisms involved in the regulation of the differentiation and proliferation of adipocytes and the elucidation of their paracrine and endocrine functions have changed the traditional view of adipose tissue as an inert depot for triglycerides. The identification of new uncoupling proteins could modify the current concepts of the regulation of thermogenesis in humans. The remarkable progress in the identification of novel targets involved in the regualtion of energy balance should have a positive impact on the search for new antiobesity agents.

Animals↗
PubMed1984

[New visual area on the inferior wall of the cruciate sulcus of the cat brain].

Properties of 187 neurons were studied in the lower bank of that part of cruciate sulcus where electrical stimulation evoked conjugate unidirectional oculomotor saccades. 172 neurons responded to visual stimulation. Neurons in the superficial cortical layers responded to conventional stimuli: light and dark spots or slits stationary or moving with the speed up to 30 degrees/s. These neurons had no orientational selectivity but sometimes showed directional selectivity. In the intermediate layers maximal responses were obtained when a flittering bird was presented to the cat; no responses were observed to conventional stimulation. Main feature of many neurons in the deep layers was selectivity to the motion in the depth in some parts of the visual field. This selectivity was invariant to the direction of contrast between stimulus and background. Visual responses in all layers were seen only in the state of arousal (during desynchronization in EEG) and were absent in the state of quiet wakefulness. All studied neurons showed no responses to acoustic or somatic stimulation. Neurons in the medial wall of the brain under the cruciate sulcus did not respond to visual stimulation but responded in correlation with definite eye movements. It is suggested that in this part of the brain two retinotopically organized areas are present one of which is connected with visual function and another with eye movements.

Animals↗
PubMed1998

Changes in brain organic osmolytes in experimental cerebral ischemia.

The cell volume is regulated not only by inorganic ions, but also by organic osmolytes, such as amino acids, methylamines, and polyhydric alcohols (polyols). Using proton nuclear magnetic resonance spectroscopy (1H-NMR), we measured the tissue concentrations of amino acids (alanine, aspartate, gamma-aminobutyric acid (GABA), glutamate, glutamine, N-acetyl-aspartate (NAA), taurine), methylamines (glycerophosphorylcholine (GPC), creatine+phosphocreatine (total creatine, tCr)), and polyols (myo-inositol) in the rat brain after middle cerebral artery occlusion (incomplete focal ischemia) or after decapitation (complete global ischemia). The total osmolytes expressed as a sum of total amino acids, total methylamines, and total polyols were significantly decreased at 24 h of focal ischemia (58.7% of control value, P=0.0025) whereas they were not changed following decapitation. The water content was increased from control value of 77.9%-84.1% after focal ischemia (P<0.0001) but not after decapitation. These results suggest that the brain organic osmolytes are involved in the process of edema formation following focal cerebral ischemia. Further elucidation of the cellular mechanisms regulating these organic osmolytes in cerebral ischemia may promote greater understanding of the pathophysiology involved in the evolution of brain edema.

Alanine↗
PubMed2000

[Mortality in a pediatric hospital. Six-year retrospective study].

AIMS: To define the characteristics of patients dying in a pediatric hospital, including causes and modes of death. PATIENTS AND METHODS: This retrospective, descriptive, epidemiologic study was performed between 1 January 1990 and 31 December 1995. All patients who died in the hospital between these dates were included. Patients already dead on arrival (sudden infant death syndrome, children deceased during their transport), and those whose hospital records could not be found, were excluded. RESULTS: A total of 375 children were studied, including 195 neonates. The sex ratio was 1.3. Ninety-one percent of deaths took place in three departments: intensive care, neurosurgery-neurology and oncology. Median duration of hospitalization was three days. The most common causes of deaths were accidents, neurologic diseases (particularly among neonates) and tumours. Analysis of modes of death revealed that 41.1% occurred following unsuccessful resuscitation, 38.8% were the result of withdrawal of life-support or a 'do not resuscitate' order and 21.6% resulted from brain death. Evolution of modes of death over the six years showed a reduction of cases with unsuccessful resuscitation, an increase in decisions of 'do not resuscitate' orders and withdrawal of life-support and no change in rates of brain death. Organs were made available for transplantation from 12 of the 81 children with brain death (14.8%). CONCLUSION: Accidents were the most common cause of death. The distribution of deaths showed a clear increase in withdrawal or withholding of life-support care, relying on ethical decisions, which are more frequent than some years ago.

Adolescent↗
PubMed1983

Miniaturization and its effects on cranial morphology in plethodontid salamanders, genus Thorius (Amphibia, Plethodontidae): II. The fate of the brain and sense organs and their role in skull morphogenesis and evolution.

Relative size and arrangement of the brain and paired sense organs are examined in three species of Thorius, a genus of minute, terrestrial salamanders that are among the smallest extant tailed tetrapods. Analogous measurements of representative species of three related genera of larger tropical (Pseudoeurycea, Chiropterotriton) and temperate (Plethodon) salamanders are used to identify changes in gross morphology of the brain and sense organs that have accompanied the evolution of decreased head size in Thorius and their relation to associated changes in skull morphology. In adult Thorius, relative size (area measured in frontal plane, and length) of the eyes, otic capsules, and brain each is greater than in adults of all of the larger genera; relative size of the nasal capsules is unchanged or slightly smaller. Interspecific scaling phenomena--negative allometry of otic capsule, eye and brain size, isometry or slight positive allometry of nasal capsule size, all with respect to skull length--also are characteristic of intraspecific (ontogenetic) comparisons in both T. narisovalis and Pseudoeurycea goebeli. Predominance of the brain and eyes in Thorius results in greater contact and overlap among these structures and the nasal capsules in the anterior portion of the head. This is associated with anterior displacement of both the eyes and nasal capsules, which now protrude anterior to the skull proper; a change in eye shape; and medial deformation of anterior braincase walls. Posteriorly, predominance of the otic capsules has effected a reorientation of the jaw suspensorium to a fully vertical position that is correlated with the novel presence of a posteriorly directed squamosal process and shift in origin of the quadropectoralis muscle. Many of these changes in cranial morphology may be explained simply as results of mechanical (physical) interactions among the skeletal, nervous, and sensory components during head development at reduced size. This provides further evidence of the role of nervous, sensory, and other "soft" tissues in cranial skeletal morphogenesis, and reinforces the need to consider these tissues in analyses of skull evolution.

Animals↗
PubMed2006

The evolutionary psychology of left and right: costs and benefits of lateralization.

Why do the left and right sides of the vertebrate brain play different functions? Having a lateralized brain, in which each hemisphere carries out different functions, is ubiquitous among vertebrates. The different specialization of the left and right side of the brain may increase brain efficiency--and some evidence for that is reported here. However, lateral biases due to brain lateralization (such as preferences in the use of a limb or, in animals with laterally placed eyes, of a visual hemifield) usually occur at the population level, with most individuals showing similar direction of bias. Individual brain efficiency does not require the alignment of lateralization in the population. Why then are not left--and right-type individuals equally common? Not only humans, but most vertebrates show a similar pattern. For instance, in the paper I report evidence that most toads, chickens, and fish react faster when a predator approaches from the left. I argue that invoking individual brain efficiency (lateralization may increase fitness), evolutionary chance or direct genetic mechanisms cannot explain this widespread pattern. Instead, using concepts from mathematical theory of games, I show that alignment of lateralization at the population level may arise as an "evolutionarily stable strategy" when individually asymmetrical organisms must coordinate their behavior with that of other asymmetrical organisms. Thus, the population structure of lateralization may result from genes specifying the direction of asymmetries which have been selected under "social" pressures.

Animals↗
PubMed2006

The percipient observations of Constantin von Economo on encephalitis lethargica and sleep disruption and their lasting impact on contemporary sleep research.

The study, and the preceding companion article, reviews the pioneering contributions of Constantin von Economo (1876-1931) to Neuroscience in a modern context. The neurological studies of von Economo include the discovery of a new nosological entity, encephalitis lethargica, with which his name is forever linked ('von Economo disease'). Based on a percipient analysis of pathoanatomical material from patients with encephalitis lethargica who manifested with either insomnia or somnolence, von Economo deduced the existence of distinct centres in the brain for the regulation of sleep and wakefulness. He presented a synthesis of his ideas in a series of lectures in New York in 1929 and at the First International Neurological Congress held in Berne in 1931. Constantin von Economo was nominated three times for the Nobel Prize in Physiology or Medicine for the discovery of encephalitis lethargica. As those studies have exerted and continue to exert the highest impact among von Economo's publications, the present article examines the spectrum of his observations on encephalitis lethargica and the cerebral control of sleep, documented in 63 published works--including post-humous translations into French and English of original German texts; complete bibliographic information is given. His remaining 76 works of an annotated total of 139 scientific publications deal with brain structure, evolution and intelligence, as well as general works on nervous and mental pathology and form the focus of the preceding article.

Biomedical Research↗
PubMed2004

The processing of verbs and nouns in neural networks: insights from synthetic brain imaging.

The paper presents a computational model of language in which linguistic abilities evolve in organisms that interact with an environment. Each individual's behavior is controlled by a neural network and we study the consequences in the network's internal functional organization of learning to process different classes of words. Agents are selected for reproduction according to their ability to manipulate objects and to understand nouns (objects' names) and verbs (manipulation tasks). The weights of the agents' neural networks are evolved using a genetic algorithm. Synthetic brain imaging techniques are then used to examine the functional organization of the neural networks. Results show that nouns produce more integrated neural activity in the sensory-processing hidden layer, while verbs produce more integrated synaptic activity in the layer where sensory information is integrated with proprioceptive input. Such findings are qualitatively compared with human brain imaging data that indicate that nouns activate more the posterior areas of the brain related to sensory and associative processing, while verbs activate more the anterior motor areas.

Algorithms↗
PubMed1998

An area specialized for spatial working memory in human frontal cortex.

Working memory is the process of maintaining an active representation of information so that it is available for use. In monkeys, a prefrontal cortical region important for spatial working memory lies in and around the principal sulcus, but in humans the location, and even the existence, of a region for spatial working memory is in dispute. By using functional magnetic resonance imaging in humans, an area in the superior frontal sulcus was identified that is specialized for spatial working memory. This area is located more superiorly and posteriorly in the human than in the monkey brain, which may explain why it was not recognized previously.

Animals↗
PubMed2001

Radiosurgery for re-irradiation of brain metastasis: results in 54 patients.

PURPOSE: To evaluate in terms of probabilities of local-regional control and survival, as well as of treatment-related toxicity, results of radiosurgery for brain metastasis arising in previously irradiated territory. PATIENTS AND METHODS: Between January 1994 and March 2000, 54 consecutive patients presenting with 97 metastases relapsing after whole brain radiotherapy (WBRT) were treated with stereotactic radiotherapy. Median interval between the end of WBRT and radiosurgery was 9 months (range 2-70). Median age was 53 years (24-80), and median Karnofski performance status (KPS) 70 (60-100). Forty-seven patients had one radiosurgery, five had two and two had three. Median metastasis diameter and volume were 21 mm (6-59) and 1.2 cc (0.1-95.2), respectively. A Leksell stereotactic head frame (Leksell Model G, Elektra, Instrument, Tucker, GA) was applied under local anesthesia. Irradiation was delivered by a gantry mounted linear accelerator (linacs) (Saturne, General Electric). Median minimal dose delivered to the gross disease was 16.2 Gy (11.8-23), and median maximal dose 21.2 Gy (14- 42). RESULTS: Median follow-up was 9 months (1-57). Five metastases recurred. One- and 2-year metastasis local control rates were 91.3 and 84% and 1- and 2-year brain control rates were 65 and 57%, respectively. Six patients died of brain metastasis evolution, and three of leptomeningeal carcinomatosis. One- and 2-year overall survival rates were 31 and 28%, respectively. According to univariate analysis, KPS, RPA class, SIR score and interval between WBRT and radiosurgery were prognostic factors of overall survival and brain free-disease survival. According to multivariate analysis, RPA was an independent factor of overall survival and brain free-disease survival, and the interval between WBRT and radiosurgery longer than 14 months was associated with longer brain free-disease survival. Side effects were minimal, with only two cases of headaches and two of grade 2 alopecia. CONCLUSION: Salvage radiosurgery of metastasis recurring after whole brain irradiation is an effective and accurate treatment which could be proposed to patients with a KPS>70 and a primary tumour controlled or indolent. We recommend that a dose not exceeding 14 Gy should be delivered to an isodose representing 70% of the maximal dose since local control observed rate was similar to that previously published in literature with upper dose and side effects were minimal.

Adult↗
PubMed2004

Plasticity of the adult avian song control system.

There is extensive plasticity of the song behavior of birds and the neuroendocrine circuit that regulates this behavior in adulthood. One of the most pronounced examples of plasticity, found in every species of seasonally breeding bird examined, is the occurrence of large seasonal changes in the size of song control nuclei and in their cellular attributes. This seasonal plasticity of the song circuits is primarily regulated by changes in the secretion and metabolism of gonadal testosterone (T). Both androgenic and estrogenic sex steroids contribute to seasonal growth of the song system. These steroids act directly on the forebrain song nucleus HVC, which then stimulates growth of its efferent target nuclei transsynaptically. Seasonal growth and regression of the song circuits occur rapidly and sequentially following changes in circulating T and its metabolites. As the neural song circuits change across seasons, there are changes in different aspects of song behavior, including the structural stereotypy of songs, their duration, and the rate of production. The burden of evidence supports a model in which changes in song behavior are a consequence rather than a cause of the changes in the song circuits of the brain. Seasonal plasticity of the song system may have evolved as an adaptation to reduce the energetic demands imposed by these regions of the brain outside the breeding season, when the use of song for mate attraction and territorial defense is reduced or absent. The synaptic plasticity that accompanies seasonal changes in the song system may have acted as a preadaptation that enabled the evolution of adult song learning in some species of birds.

Adaptation, Physiological↗
PubMed1996

Common ground plans in early brain development in mice and flies.

Comparing expression patterns of orthologous genes between insects and vertebrates, we have recently proposed that the ventral nerve cord in insects may correspond to the dorsal nerve cord in vertebrates. Here we show that the early development of the insect and vertebrate brain anlagen is indeed very similar. Insect and vertebrate brains express similar sets of genes in comparable areas with similar functions in the adult. In addition, early axogenesis establishes surprisingly similar patterns of axonal connectivity in both groups. We therefore propose that insect and vertebrate brains are built according to a common ground plan, and that specific areas of the insect and vertebrate brains be considered as homologous, meaning that these areas already existed, with their specific functions, in their common ancestor.

Animals↗
PubMed2006

The signalling contributions of Constantin von Economo to basic, clinical and evolutionary neuroscience.

The study, and the companion article that follows, reviews the entire spectrum of the epoch-making contributions of Constantin von Economo (1876-1931) to basic, clinical and evolutionary Neuroscience. An astute observer and avid writer, von Economo left marks of brilliance on fundamental areas of brain research through an exuberant record of publications dating from 1899 to 1932. His ingenious medical career began with the histological study of the developing pigeon and chick hypophysis, and culminated with bold propositions about the neuroanatomy of talent and the future evolution of the human brain. On the way, he made the seminal discovery of encephalitis lethargica ('von Economo disease'), and produced, with Georg N. Koskinas (1885-1975), one of the masterpieces of brain science, the 1925 Cytoarchitectonics of the Adult Human Cerebral Cortex, defining 107 cortical areas on the basis of cytoarchitectonic criteria. His untimely death at age 55, barely 5.5 months after inaugurating his new Brain Research Institute in Vienna, deprived the Neuroscience world of one of its brightest protagonists during the 20th century. An annotated total of 139 scientific works by von Economo have been identified. The present study covers the 76 works on brain structure, evolution and intelligence, and general works on nervous and mental pathology, with the complete bibliographic information. The companion article covers the remaining 63 works on encephalitis lethargica and sleep regulation.

Biological Evolution↗
PubMed2006

Chimpanzee and felid diet composition is influenced by prey brain size.

Prey use a wide variety of anti-predator defence strategies, including morphological and chemical defences as well as behavioural traits (risk-modulated habitat use, changes in activity patterns, foraging decisions and group living). The critical test of how effective anti-predator strategies are is to relate them to relative indices of mortality across predators. Here, we compare biases in predator diet composition with prey characteristics and show that chimpanzee (Pan troglodytes) and felid show the strongest and the most consistent predator bias towards small-brained prey. We propose that large-brained prey are likely to be more effective at evading predators because they can effectively alter their behavioural responses to specific predator encounters. Thus, we provide evidence for the hypothesis that brain size evolution is potentially driven by selection for more sophisticated and behaviourally flexible anti-predator strategies.

Analysis of Variance↗
PubMed1985

Embryonic life and human life.

A new human life comes into being not when there is mere cellular life in a human embryo, but when the newly developing body organs and systems begin to function as a whole, the author argues. This is symmetrical with the dealth of an existing human life, which occurs when its organs and systems have permanently ceased to function as a whole. Thus a new human life cannot begin until the development of a functioning brain which has begun to co-ordinate and organise the activities of the body as a whole.

Abortion, Induced↗