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Induced and spontaneous seizures in man produce increases in regional brain lipid detected by in vivo proton magnetic resonance spectroscopy.

Elevations of brain concentrations of arachidonic acid and other free fatty acids (FFAs) by seizures induced in animals were demonstrated some years ago. Similarly, large shifts of potassium (K+) from intra- to extracellular space during seizure activity have been documented in numerous studies. More recent studies of cell membrane function demonstrated a direct effect of FFAs on membrane K+ conductance, suggesting that FFAs may play a primary role in seizure evolution in brain tissue. Using electroconvulsive therapy (ECT), in which generalized seizures are induced in patients by passage of electrical current, as a controlled human model of seizures, we studied the in vivo biochemical effects of single generalized seizures with localized proton magnetic resonance spectroscopy (1H MRS). We found that ECT reliably induces an elevation in the lipid signal that resonates at approximately 1.2 ppm. We observed a similar increase in brain lipids in a patient with temporal lobe epilepsy temporarily off medication; the signal disappeared after re-medication. Similar observations were noted for a subject with focal gliosis bordering a resected brain tumor. Finally, acute alcohol effects seem also to induce observable lipid changes. The 1H MRS technique does not yet permit direct identification of the specific lipids involved but analysis of cerebrospinal fluid obtained by lumbar puncture before and immediately after ECT may permit more precise characterization of the observed lipid increases. Theoretical and clinical implications of these results for the study of brain FFAs and epilepsy will be discussed.

Brain↗

What comparative studies of neocortex tell us about the human brain.

There are several ways in which comparative studies of brain organization and function can be informative in attempts to understand the human brain. Often investigators study a favorable and sometimes specialized species in order to reveal features that may reflect general or widespread principles. The example used here is that the cortical representation of the unique and highly specialized receptor sheet of the nose of the star-nosed mole provides further evidence that the receptor sheet instructs the development of cortex. Comparative studies are also used to reconstruct the evolution of brain systems. As an example, comparative studies suggest that the visual area MT in the upper temporal lobe of primates evolved from a visual area along the border of V2. A third and very important use of comparative studies is to provide another level of evaluation of theories developed from a particular species. Since the brains of different mammals are modifications of an ancestral plan, conclusions about brain organization in any given species should be consistent with those for other species, within the framework of evolutionary change. When current proposals for how visual cortex is organized in rats and humans are considered from a comparative point of view, key concepts are clearly challenged.

Anatomy, Comparative↗

Neurosteroids and the songbird model system.

The brain is now widely recognized as having the capacity to make steroids, neurosteroidogenesis. Although many functions are known for steroids that might be made in the brain, the evolution of and natural biological functions for these neurosteroids are not fully understood. In songbirds, neurosteroids may function in the development of neural circuits controlling song and may also participate in the activation of some steroid-dependent behaviors during the non-breeding season. In addition to neuroanatomical and behavioral evidence, we have physiological, molecular, and biochemical evidence for the expression and activity of steroidogenic enzymes in the brains of developing and adult songbirds. We review the evidence published so far for songbird neurosteroidogenesis and discuss why we believe songbird species are excellent models for the study of brain steroid synthesis and action.

3-Hydroxysteroid Dehydrogenases↗

Nonlinear analysis of cerebral hemodynamic and intracranial pressure signals for characterization of autoregulation.

The objective of this study was to determine whether or not the underlying physiological systems that generates spontaneous arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), and intracranial pressure signals could be adequately approximated as a linear stochastic process. Furthermore, a new measure (C) capable of capturing the degree of nonlinear dependency between two ABP and CBFV signals (including a time-varying situation) was proposed for quantifying the degree of cerebral blood flow autoregulation. A surrogate data test of fifteen ABP, CBFV, and intracranial pressure (ICP) segments was conducted for detecting whether there exists a statistically significant deviation from the null hypothesis of linear signals. The extension of the established block computation method of C measure to an adaptive one was achieved. This new algorithm was then applied to study the C evolution using brain injury patients data from a hyperventilation study and two propofol studies. Nonlinearity has not been detected for all the fifteen recordings, neither has nonlinear dependency between CBFV and ABP. However, their presences in some of the signal segments justified the adoption of a nonlinear measure of dependency capable of characterizing both linear and nonlinear correlations for inferring autoregulation status. C measure started to decrease with the introduction of hypocapnia state indicating that hyperventilation may reduce the dependency of CBFV on ABP fluctuations. On the other hand, complex patterns of C measure evolution were observed among 14 cases of propofol data indicating a nontrivial effect of propofol on the dependency of CBFV on ABP.

Adaptation, Physiological↗

Use of 31P magnetic resonance spectroscopy to characterize evolving brain damage after perinatal asphyxia.

We investigated postasphyxial brain damage with 31P magnetic resonance spectroscopy (MRS) and correlated it with neurologic assessment and standard laboratory evaluation during the first 10 months of life in 1 infant, baby G. We compared these observations to 31P MRS data from 7 healthy term newborns, 1 normal infant examined serially over the first 8.5 months of life, and 5 other term infants following perinatal asphyxia. MRS noninvasively provides biochemical correlates of the evolution of brain damage following perinatal asphyxia and suggests that pH derived from the inorganic phosphate peak may serve as a marker for brain injury.

Asphyxia Neonatorum↗

[Brain of the cod (Gadus morhua morhua, Linné 1758) (Pisces, Paracanthopterygii). Qualitative and quantitative analysis of major subdivisions].

The Cod, Gadus morhua, is a North Atlantic fish of the family Gadidae which occurs at depths of 80 to 600 m (usually 150 to 200 m). It often occurs in shoals and tends to be migratory. It has a typical teleost brain except for the gadid feature of long olfactory tracts. Gadid fishes have a low level of encephalization (RIDET, 1982). The index of encephalization of the Cod is near the mean for the family. This index changes with season due to the change in body weight; it is lowest during the spawning season (which takes place in spring). Five subspecies of Gadus morhua are recognized. A comparison was made of the index of encephalization of the subspecies which is restricted to the White Sea, Gadus morhua maris albi, Derjugin 1920 and Gadus m. morhua, Linné 1758. The index of the White Sea form was significantly higher, thus supporting its recognition as subspecies. A volumetric analysis was made of the subdivisions of the Cod brain. It was found to have a large cerebellum, large medulla oblongata and a tendency to macrosmy, but a small telencephalon and tectum opticum (tendency to micropty). This is what would be expected from the environment and habits of this fish.

Animals↗

Of coiled oysters and big brains: how to rescue the terminology of heterochrony, now gone astray.

During the past decade, the terminology of heterochrony, heretofore consistent and workable, has become internally illogical and incoherent as the unfortunate result of an extension of terms, properly devised to describe shifts in developmental timing of shapes and features, to the rates and timings that cause these shifts. All the resulting, and extensive, confusion in the literature arises as a pure consequence of this error in logic and nomenclature, and not at all from disagreement about the important empirical questions described by this central concept and phenomenon in the integration of evolution and development. In particular, the claim that the same feature in human evolution (the paedomorphic shape of the human cranium) expresses either neoteny or the apparently opposite phenomenon of hypermorphosis only records the terminological error, and not any factual disagreement-for this neotenic feature has probably arisen by a prolongation of juvenile growth patterns inappropriately designated as "hypermorphosis of rate." I show that a prominent and unchallenged case of neoteny in fossil oysters arises by exactly the same evolutionary mode. When we restore the terminology of heterochrony by the "paedomorphic" intellectual event of dropping these inadaptive terminal accretions (the illogical extension of shape categories to describe rates), then the concept of heterochrony will again make proper distinctions by designating a clearly meaningful category of evolutionary changes originating by shifts in timing for features already present in ancestors. "It's not all het- erochrony"-and this particular statement of "less is more" represents heterochrony's strength as an interesting subset with definite meaning, rather than an illogical hodge-podge apparently applicable to all phenomena, and therefore explaining nothing.

Animals↗

Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging.

The appearance and evolution of brain infarcts over 3 days following proximal occlusion of the left middle cerebral artery (MCA) in SHR rats were measured non-invasively by magnetic resonance imaging (MRI). Infarcts were clearly visible in coronal, T2 weighted brain sections, 24, 48 and 72 h after MCA occlusion in the left hemisphere, as areas of increased NMR signals. The infarcts were quantified by pixel counting in each section, the sum of 4 sections representing an accurate estimate of the total infarct size. The location and extent of infarction, determined by MRI, were found to be highly reproducible and correlated well with post-mortem histological and biochemical data. A neurological score, made every 24 h, paralleled the evolution of the infarct size, which culminated after 48 h. Pre- or post-treatment of MCA occluded rats with the dihydropyridine calcium antagonist PN 200-110 resulted in a substantial reduction of infarct size, determined by MRI 24, 48 and 72 h after infarction, compared to vehicle treated controls. These findings were corroborated by corresponding improvements of the neurological scores as well as histological and biochemical data. Post-treatment with nimodipine showed qualitatively similar effects. These results support the notion that calcium antagonists, through vascular and/or metabolic mechanisms, are effective in treating acute stroke. Since they were obtained in a chronic, relevant model of stroke with a method directly applicable also to humans, they should encourage further clinical studies with calcium antagonists.

Animals↗

Adaptations, exaptations, and spandrels.

Adaptation and natural selection are central concepts in the emerging science of evolutionary psychology. Natural selection is the only known causal process capable of producing complex functional organic mechanisms. These adaptations, along with their incidental by-products and a residue of noise, comprise all forms of life. Recently, S. J. Gould (1991) proposed that exaptations and spandrels may be more important than adaptations for evolutionary psychology. These refer to features that did not originally arise for their current use but rather were co-opted for new purposes. He suggested that many important phenomena--such as art, language, commerce, and war--although evolutionary in origin, are incidental spandrels of the large human brain. The authors outline the conceptual and evidentiary standards that apply to adaptations, exaptations, and spandrels and discuss the relative utility of these concepts for psychological science.

Adaptation, Physiological↗

Noradrenergic neurons in the locus coeruleus of birds express TrkA, transport NGF, and respond to NGF.

The chicken locus coeruleus contains a population of noradrenergic neurons which express the neurotrophin receptor p75 (von Bartheld and Bothwell, 1992). To determine which neurotrophin may regulate the development of noradrenergic neurons in the chicken locus coeruleus, expression of trk receptors, retrograde transport of neurotrophins, and responses to NGF were examined. P75-expressing noradrenergic neurons were found to project to the basal forebrain. They transport radio-iodinated NGF after injections into this target. The retrograde transport of NGF is specific to the noradrenergic neuronal population as evidenced by double labeling with antibodies against dopamine-beta-hydroxylase. The same neuronal population expresses trkA receptor mRNA. The size of noradrenergic neurons in the locus coeruleus proper, but not in the nucleus subcoeruleus, is significantly increased after injections of NGF into the telencephalon, consistent with the hypothesis that target-derived NGF provides trophic support. Noradrenergic coeruleus neurons are rescued from toxic effects of 6-hydroxydopamine injected into the telencephalon when NGF is injected into the midbrain. NGF has no rescue effect when it is coinjected with 6-hydroxy-dopamine into the telencephalon. In explant or dissociated cultures, noradrenergic coeruleus neurons do not respond to elevated levels of NGF with increased neurite outgrowth. Taken together, these results suggest that NGF plays a role in the development and maintenance of noradrenergic coeruleus neurons in the chick brain. The data also support our previous conclusion that major species differences exist between birds (chicken) and mammals with regard to trophic regulation of presumptive homologous neuronal populations.

Animals↗

Human immunodeficiency virus type 1 genetic diversity in the nervous system: evolutionary epiphenomenon or disease determinant?

Over the past decade there has been a revolution in the understanding and care of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-associated disease. Much of this progress stems from a broader recognition of the importance of differences in viral types, including receptor preference(s), replication properties, and reservoirs, as contributing factors to immunosuppresion and disease progression. In contrast, there is limited conceptualizatin of viral diversity and turnover in the brain and circulation in relation to neurocognitive impairments. Herein, the authors review current concepts regarding viral molecular diversity and phenotypes together with features of HIV-1 neuroinvasion, neurotropism, neurovirulence and neurosusceptiblity. Viral genetic and antigenic diversity is reduced within the brain compared to blood or other systemic organs within individuals. Conversely, viral molecular heterogeneity is greater in patients with HIV-associated dementia compared to nondemented patients, depending on the viral gene examined. Individual viral proteins exert multiple neuropathogenic effects, although the neurological consequences of different viral polymorphisms remain uncertain. Nonetheless, host genetic polymorphisms clearly influence neurological disease outcomes and likely dictate both acquired and innate immune responses, which in turn shape viral evolution within the host. Emerging issues include widespread antiretroviral therapy resistance and increasing awareness of viral superinfections together with viral recombination, all of which are likely to impact on both HIV genetic variation and neuropathogenesis. With the persisting prevalence of HIV-induced neurocognitive disabilities, despite marked improvements in managing immunosuppression, it remains imperative to fully define and understand the mechanisms by which viral dynamics and diversity contribute to neurological disease, permitting the development of new therapeutic strategies.

AIDS Dementia Complex↗

cDNA sequence, genomic organization, and evolutionary conservation of a novel gene from the WAGR region.

A new gene (239FB) with predominant and differential expression in fetal brain has recently been isolated from a chromosome 11p13-p14 boundary area near FSHB. The corresponding mRNA has an open reading frame of 294 amino acids, a 3' untranslated region of 1247 nucleotides, and a highly GC-rich 5' untranslated region. The coding and 3' UT sequence is specified by 6 exons within nearly 87 kb of isolated genomic locus. The 5' end region of the transcript maps adjacent to the only genomically defined CpG island in a chromosomal subregion that may be associated with part of the mental retardation of some WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome patients. In addition to nucleotide and amino acid similarity to an EST from a normalized infant brain cDNA library, the predicted protein has extensive similarity to two Caenorhabditis elegans polypeptides of, as yet, unknown function. The 239FB locus is, therefore, likely part of a family of genes with two members expressed in human brain. The extensive conservation of the predicted protein suggests a fundamental function of the gene product and will enable evaluation of the role of the 239FB gene in neurogenesis in model organisms.

Amino Acid Sequence↗

Early brain growth in Homo erectus and implications for cognitive ability.

Humans differ from other primates in their significantly lengthened growth period. The persistence of a fetal pattern of brain growth after birth is another important feature of human development. Here we present the results of an analysis of the 1.8-million-year-old Mojokerto child (Perning 1, Java), the only well preserved skull of a Homo erectus infant, by computed tomography. Comparison with a large series of extant humans and chimpanzees indicates that this individual was about 1 yr (0-1.5 yr) old at death and had an endocranial capacity at 72-84% of an average adult H. erectus. This pattern of relative brain growth resembles that of living apes, but differs from that seen in extant humans. It implies that major differences in the development of cognitive capabilities existed between H. erectus and anatomically modern humans.

Aging↗

[Pathology of cerebral edema. II. Experimental models and modifying agents].

Current experimental models of brain edema are described and evaluated for their contribution to the knowledge of basic processes involved in its production as well their contribution to the understanding of different clinical forms. The participation of each main pathogenic mechanism in a given experimental model is analyzed and proves to vary with each particular model and site studied. The importance of various experimental models in the evaluation of different therapeutic procedures directed to control the genesis and evolution of brain edema is stressed.

Animals↗

Frog brain and liver show evolutionary conservation of tissue-specific differences among insulin receptors.

The insulin receptors of frog brain and liver show features typical of other insulin receptors with regard to affinity and specificity of binding to insulins and proinsulin, solubility in Triton X-100, binding to and elution from wheat germ agglutinin, and insulin-sensitive tyrosine kinase activity. Likewise, the brain and liver receptors differ from one another in electrophoretic mobility and susceptibility to treatment with neuraminidase, analogous to brain and liver receptors of reptiles, birds, and mammals; while the functional implications of these differences are unknown, their evolutionary conservation for 400-500 million years suggests the possibility that they might have importance.

Animals↗

Towards an artificial brain.

Three components of a brain model operating on neuromolecular computing principles are described. The first component comprises neurons whose input-output behavior is controlled by significant internal dynamics. Models of discrete enzymatic neurons, reaction-diffusion neurons operating on the basis of the cyclic nucleotide cascade, and neurons controlled by cytoskeletal dynamics are described. The second component of the model is an evolutionary learning algorithm which is used to mold the behavior of enzyme-driven neurons or small networks of these neurons for specific function, usually pattern recognition or target seeking tasks. The evolutionary learning algorithm may be interpreted either as representing the mechanism of variation and natural selection acting on a phylogenetic time scale, or as a conceivable ontogenetic adaptation mechanism. The third component of the model is a memory manipulation scheme, called the reference neuron scheme. In principle it is capable of orchestrating a repertoire of enzyme-driven neurons for coherent function. The existing implementations, however, utilize simple neurons without internal dynamics. Spatial navigation and simple game playing (using tic-tac-toe) provide the task environments that have been used to study the properties of the reference neuron model. A memory-based evolutionary learning algorithm has been developed that can assign credit to the individual neurons in a network. It has been run on standard benchmark tasks, and appears to be quite effective both for conventional neural nets and for networks of discrete enzymatic neurons. The models have the character of artificial worlds in that they map the hierarchy of processes in the brain (at the molecular, neuronal, and network levels), provide a task environment, and use this relatively self-contained setup to develop and evaluate learning and adaptation algorithms.

Artificial Intelligence↗

Engineers have more sons, nurses have more daughters: an evolutionary psychological extension of Baron-Cohen's extreme male brain theory of autism.

In his extreme male brain theory of autism, Baron-Cohen postulates that having a typically male brain was adaptive for ancestral men and having a typically female brain was adaptive for ancestral women. He also suggests that brain types are substantially heritable. These postulates, combined with the insight from the Trivers-Willard hypothesis regarding parental ability to vary offspring sex ratio, lead to the prediction that people who have strong male brains should have more sons than daughters, and people who have strong female brains should have more daughters than sons. The analysis of the 1994 US General Social Survey data provides support for this prediction. Our results suggest potentially fruitful extensions of both Baron-Cohen's theory and the Trivers-Willard hypothesis.

Adaptation, Physiological↗

Oculomotor and sensory mesencephalic trigeminal neurons in lungfishes: phylogenetic implications.

The location and number of neurons in the brainstem with projections to the eye muscles were investigated by means of fluorescent tracers in the African lungfish Protopterus dolloi. The oculomotor nucleus (M III) projects bilaterally with a ratio of 3:1 (70 ipsilateral, 20 contralateral neurons). Three subdivisions of this nucleus can be differentiated: one projects exclusively ipsilaterally, another projects exclusively contralaterally, and a third component projects bilaterally. The trochlear nucleus (M IV) is located caudally, distinct from M III, and projects predominantly to contralateral eye muscles with a ratio of 6:1 (18:3 neurons). The abducens nucleus (M VI) contains about 30 neurons with ipsilateral projections only. There is no evidence for an accessory abducens nucleus in Protopterus. Intraocular injections of tracers do not reveal any retinopetal projections in Protopterus. The mesencephalic trigeminal nucleus (Mes V) of Protopterus and Neoceratodus contains about 540-590 neurons on each side. In juvenile Protopterus, up to 75 Mes V neurons are located caudally in a ventral projection of the tectum above the velum medullare anterius. Fifty-five Mes V neurons (10% of the total number) have processes that exit the brain with the trochlear nerve. The relatively large number of Mes V neurons in lungfishes correlates with the well developed jaw musculature. The present study provides the first conclusive evidence for the location of oculomotor subdivisions in the brain of a lepidosirenid lungfish. The organization of the oculomotor nucleus is consistent with the observation that lungfishes possess the pattern of eye-muscle innervation seen in elasmobranchs and supports the unconventional view that lungfishes may be the sistergroup of elasmobranchs.

Abducens Nerve↗