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Axonal trees and cortical architecture.

In modern computer design considerable care is taken to arrange the components in such a way that wiring is kept to a minimum. Certain features of cortical structure--the mappings, stripes and blobs within areas, and areas themselves--are somewhat reminiscent of the layout of computer components, and suggest that the cortex may also be organized so as to economize on neuronal 'wiring'. One important difference between the brain and a computer is that the wiring in the brain takes the form of elaborate branched structures, namely axonal trees. In this article, it is argued that an assessment of the efficiency of cortical wiring must take account of the branching rules of these trees.

Animals↗

Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylazoxymethanol in utero.

Cortical disorganization represents one of the major clinical findings in many children with medically intractable epilepsy. To study the relationship between seizure propensity and abnormal cortical structure, we have begun to characterize an animal model exhibiting aberrant neuronal clusters (heterotopia) and disruption of cortical lamination. In this model, exposing rats in utero to the DNA methylating agent methylazoxymethanol acetate (MAM; embryonic day 15) disrupts the sequence of normal brain development. In MAM-exposed rats, cells in hippocampal heterotopia exhibit neuronal morphology and do not stain with immunohistochemical markers for glia. In hippocampal slices from MAM-exposed animals, extracellular field recordings within heterotopia suggest that these dysplastic cell clusters make synaptic connections locally (i.e. within the CA1 hippocampal subregion) and also make aberrant synaptic contact with neocortical cells. Slice perfusion with bicuculline or 4-aminopyridine leads to epileptiform activity in dysplastic cell clusters that can occur independent of input from CA3. Taken together, our findings suggest that neurons within regions of abnormal hippocampal organization are capable of independent epileptiform activity generation, and can project abnormal discharge to a broad area of neocortex, as well as hippocampus.

4-Aminopyridine↗

The development of a human auditory localization response: a U-shaped function.

Research during the past 10 years on the neonatal head-turn response to off-centred rattle sounds is reviewed, and various procedural and stimulus conditions that influence the probability of eliciting a correct response are identified. Also, the existence of a U-shaped developmental function is confirmed in a cross-sectional study of 104 infants between 3 days and 7 months of age. Neonates responded reliably, but slowly; the response decreased in frequency and magnitude between 1-3 months of age and increased again by 4-5 months of age. Speculation that this U-shaped function reflects a maturational shift in locus of control from subcortical to cortical structures was supported by the infants' responses to the presence effect (PE), which is thought to be cortically mediated. The PE was produced by playing the rattle sound through two loudspeakers with the output of one delayed by 5 ms, relative to the other; adults perceive only one sound at the leading loudspeaker. As predicted, neonates failed to respond to the PE, and the onset of correct PE responses corresponded closely to the upswing in the U-shaped function for SS responses. Other explanations for the temporary decline in orientation responses to sound are also discussed.

Attention↗

An estimation of the soluble tubulin content in Tetrahymena cells of normal and of size-altered phenotype.

The amount of soluble tubulin in a temperature-sensitive (ts) size mutant of the ciliate Tetrahymena was measured in a variety of physiological conditions. For this purpose a competitive ELISA assay for tubulin was set up. The assay is based on an antiserum against Tetrahymena axonemal tubulin. Characterization of the antiserum shows its mono-specificity towards tubulin as well as its potential to recognize tubulin from a wide variety of cellular sources and organisms. After fractionation of the cells into soluble material, cold-labile and cold-resistant structures, we found very little tubulin soluble (less than 20% of the total), while most of the tubulin is polymerized, especially into cortical structures. Prolonged starvation does not alter the tubulin content. During the culture growth cycle the percentage of the soluble tubulin increases. Growing the ts mutant at high temperature to a large cell size will also increase the pool of soluble tubulin to a large extent. Only under this condition is the amount of soluble tubulin about equal to that fixed in cilia. The tubulins in the three different compartments are polymorphic and have a different metabolism. This is indicated by the much higher specific activity of soluble tubulin compared with the structurally bound material. In agreement, the half-life of the soluble tubulin is shorter than that of the cortical tubulin.

Animals↗

State-modulation of cortico-cortical connections underlying normal EEG alpha variants.

Normal electroencephalographic (EEG) alpha variants appear during relaxed wakefulness with closed eyes, drowsiness period at sleep onset, and rapid eye movement (REM) sleep in bursts without arousal signals. Previous results revealed that fronto-occipital and fronto-frontal alpha coherences became weaker from wakefulness to drowsiness, and finally to REM sleep. The present work was aimed at determining whether a generalized or a unidirectional deactivation of the long fronto-occipital fasciculi, previously proposed to be involved in the alpha rhythm generation, could explain the above-mentioned results. Polynomial regression analyses, applied to the change of alpha coherence with distance along the antero-posterior axis, suggested that the anterior and posterior local circuits show a similar level of activation in all brain states. Bivariate partial correlation analyses between local alpha coherences revealed that such local circuits maintain a reciprocal dependency during wakefulness, but unidirectional during drowsiness (anterior-to-posterior, A-P) and REM sleep (posterior-to-anterior, P-A). From these findings, both anterior and posterior cortical structures are suggested as being involved in the generation of the three alpha variants. If the implication of a double cortical generation source (anterior and posterior) of alpha variants is assumed, these two generators seem to maintain a mutual inter-dependency during wakefulness, whereas during the transition to human sleep, the anterior areas work quite independently of the posterior regions. Finally, the occipital structures may be the driving force for the REM-alpha bursts generation, since involvement of frontal regions demonstrated a high dependence on the posterior neural circuits in the genesis of this sleep event.

Adult↗

Absence of c-fos induction in neonatal rat brain after seizures.

Induction of the proto-oncogene c-fos is often considered to be a marker of increased neuronal activity. We have used in situ hybridization to study the pattern of c-fos expression in limbic structures following kainic acid-induced seizures during the postnatal period in the rat. Prior to postnatal day 13 (P13), seizure activity did not result in c-fos induction in any limbic structure. Between P13 and P25, a gradual increase in c-fos expression was observed in hippocampus and cortical structures. These results were corroborated by nuclear run-off transcription assay. Thus, alterations in c-fos transcription that may facilitate stimulus-transcription coupling occur during postnatal development. The possible relationship between the postnatal maturation of c-fos expression and the increase in susceptibility of specific neuronal populations to seizure-induced cell damage is discussed.

Age Factors↗

The three cortical membranes of the gregarines (parasitic protozoa). Characterization of the membrane proteins of gregarina blaberae.

GREGARINES, WHICH ARE PARASITIC PROTOZOA LIVING IN INVERTEBRATES, POSSESS A CORTICAL STRUCTURE SPECIFIC TO THEIR VEGETATIVE STAGE: namely two additional cytomembranes are lying just under the plasma membrane. This cortical complex has been isolated by centrifugation on discontinuous sucrose gradients and characterized chemically. Its integrity was tested by electron microscopy. Ghost proteins were resolved by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. About 30 polypeptides of mol.wt. 15000-300000 were present in this fraction and four glycoproteins were detected after periodate/Schiff staining. Ten major proteins were labelled after lactoperoxidase-catalysed iodination. The GP(2) glycoprotein (41000-49000 apparent mol.wt.) appears to be a major component of the cell surface. Effects of trypsin and Pronase digestion on ghosts and cells were monitored by gel electrophoresis and by electron microscopy. Ghosts treated with low trypsin or Pronase concentrations (10-25mug/ml) became drastically disorganized; many proteins were vigorously attacked in comparison with those of control ghosts. Variations in proteinase-sensitivity of proteins are pointed out. The GP(3) glycoprotein (130000-160000 apparent mol.wt.) seemed to be the only glycoprotein released from the cell surface by trypsin. Whole cells treated under the same conditions or with higher proteinase concentrations (up to 1mg/ml) do not exhibit morphological modifications of the cell surface; furthermore, no discernible cleavage of membrane proteins was indicated by electrophoretograms. It is postulated that cell-surface proteins are protected by the dense carbohydrate cell coat. By using various different methods (change of ionic strength, detergent, denaturing agent, labelling experiment) it was possible to localize several major proteins within the protozoon cortical membranes.

Animals↗

A unique achiasmatic anomaly detected in non-albinos with misrouted retinal-fugal projections.

In mammals with binocular vision, projections of retinal axons to primary retino-recipient nuclei establish a strict visuotopic and eye-segregated arrangement. Normal primate visual pathway organization is characterized by orderly hemiretina separation in which nasal-retinal axons cross at the optic chiasm and project to primary contralateral subcortical and cortical structures while temporal-retinal fibres project ipsilaterally to corresponding visual structures. We report here, in two unrelated children, an unusual visual pathway malformation in which nasal-retinal cortical projections, unable to decussate due to the inborn absence of an optic chiasm, erroneously route ipsilaterally to visual projection targets. We have termed this newly documented achiasmatic condition the non-decussating retinal-fugal fibre syndrome (Apkarian et al., Invest. Ophthalmol. Vis. Sci., 34, Suppl., 711, 1993).

Adolescent↗

Delta 9-tetrahydrocannabinol alters cerebral metabolism in a biphasic, dose-dependent manner in rat brain.

delta 9-tetrahydrocannabinol (THC)-induced alterations in limbic and neocortical function are associated with deficiencies in short-term memory and recall. The 2-deoxy-D-glucose (2DG) autoradiographic method was used to examine the effect of acute THC administration (0, 0.2, 0.5, 2.0, 10.0 mg/kg) on regional brain metabolism in limbic and cortical brain regions of male rats. THC altered 2DG uptake in a biphasic, dose-dependent manner in most limbic and cortical structures, however most diencephalic and brainstem structures examined were unaffected. The 0.2 mg/kg THC dose significantly increased 2DG uptake relative to vehicle treatment in all cortical and selected limbic regions, whereas the 2.0 and 10.0 mg/kg THC doses decreased 2DG uptake in most of these regions. Certain limbic regions, particularly the hippocampus, are more sensitive to THC suggesting a selective regional action of the drug at lower doses. The incidence of enhanced metabolic activity in limbic and cortical regions is consistent with the occurrence of high density cannabinoid receptors in these regions.

Animals↗

[Hemodynamic component in cerebral compensatory processes following unilateral exclusion of the somatosensory cortex].

In experiments on anesthetised and awake cats the dynamics of the cerebral blood flow was studied by the thermoelectric method in one hemisphere in experimental lesion of the somatosensory zone of the opposite one. Temporary exclusion of the cortical area by cold produced evident hemodynamic changes, i. e. a two-phase vasoreaction and an initial blood flow decrease followed by a prolonged increase of blood supply, in the other hemisphere. Analogous vasoreactions were seen on unilateral extirpation of the cortical layer of the somatosensory zone, as well. Such vasoreactions indicate enhanced activity of the cortical structures in the intact hemisphere and may be considered as a compensatory reaction to the local lesion of certain cortical areas.

Animals↗

Functional mapping of the rat brain during vocalizations: a 2-deoxyglucose study.

Autoradiographic [14C]2-deoxyglucose (2-DG) procedures were used to map the functional activity in the CNS during vocalizations elicited by electrical stimulation of the midbrain reticular formation (MRF) in behaving rats. Following injection of 2-DG, rats received MRF stimulation through stainless steel electrodes over 90 min. Yoked controls received 2-DG injection followed by playback of the recorded vocalizations. Relative differences in peak isotope uptake (gray/white matter ratios) in 22 structures related to vocalization were compared between the two groups. The major findings were localized to hypothalamus, midbrain and brainstem structures. Significant increases in 2-DG uptake were noted in the following structures in MRF stimulated rats: dorsolateral central gray (PAG), MRF, lateral hypothalamus (LH), ventromedial hypothalamus (VmH), paraventricular nucleus (PVN) and nucleus ambiguus (NA). Cortical structures were not activated during MRF stimulation. The PAG and NA are known to be important relays in the production of vocalizations. MRF stimulation, therefore, activates the motor output pathways for vocalization, but does not appear to activate cortical and limbic motivational centers.

Animals↗

Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development.

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal-recessive disorders in Japan, is characterized by congenital muscular dystrophy associated with brain malformation due to a defect during neuronal migration. Through positional cloning, we previously identified the gene for FCMD, which encodes the fukutin protein. Here we report that chimeric mice generated using embryonic stem cells targeted for both fukutin alleles develop severe muscular dystrophy, with the selective deficiency of alpha-dystroglycan and its laminin-binding activity. In addition, these mice showed laminar disorganization of the cortical structures in the brain with impaired laminin assembly, focal interhemispheric fusion, and hippocampal and cerebellar dysgenesis. Further, chimeric mice showed anomaly of the lens, loss of laminar structure in the retina, and retinal detachment. These results indicate that fukutin is necessary for the maintenance of muscle integrity, cortical histiogenesis, and normal ocular development and suggest the functional linkage between fukutin and alpha-dystroglycan.

Animals↗

[Classical and current aspects of the formation of motor dominance in man].

In the paper, significance of driving phenomenon for formation of motor dominant is considered and experimentally corroborated with the aid of autocorrelation and spectral analysis of the working man's EEG. The A.A. Ukhtomsky classical postulate has been complemented by contemporary ideas of the role of phasic relationships between the cortical activity for extablishing intercentral interconnections and the functional differentiation of working and irrelevant cortical structures. Data of correlation, crosscorrelation, and coherent EEG analysis enable to ascertain stages of formation of motor dominants at the cortical level and to judge of possible mechanisms of concentration of the dominant consstellations, as well as to show significance of the coadjustment for a common rhythm and of coincidence in phase of oscillations for improvement of the effectiveness of motor activity in man.

Dominance, Cerebral↗

Where and how does grammatically geared processing take place-and why is Broca's area often involved. A coordinated fMRI/ERBP study of language processing.

We address the possibility of combining the results from hemodynamic and electrophysiological methods for the study of cognitive processing of language. The hemodynamic method we use is Event-Related fMRI, and the electrophysiological method measures Event-Related Band Power (ERBP) of the EEG signal. The experimental technique allows us to approach the relation between cortical structure and cognitive function in a sophisticated way. In particular, we can formulate original working hypotheses about the language-induced changes in the ongoing brain dynamics. We show, on the basis of electrophysiological data collected in an experiment on language production, that synchronized cortical networks code cognitive processes induced by language in form of power modulations of specific frequency bands. The hemodynamic (fMRI) data collected in the same task point to the existence of a central processor for the phrase structure assignment. We conceptualize such a central processor as a frequency scanner, a cortical device designed to pick up synchronized brain activity over a specific range of frequencies. We discuss the experimental designs which result from this set of hypotheses and show their relevance for the models of language processing.

Adult↗

Functional magnetic resonance imaging in a stereotactic setup.

The localization of critical structures within the brain is important for the planning of therapeutic strategies. Functional MRI is capable to assess functional response of cortical structures to certain stimuli. The authors present two techniques for functional MRI (fMRI) in a stereotactic set-up. The skull of the patients has been immobilized for stereotactic treatment planning either with a self developed stereotactic ceramic frame and bony fixation or with an individual precision mask system made of light cast. It has been shown that this frame does not produce any image distortion. fMRI was performed using a modified FLASH sequence on a conventional 1.5 T MRI scanner with a specially developed linear polarized head coil. The imaging technique used was an optimized conventional 2D and 3D, first order flow rephased, gradient echo sequence (FLASH) with fat-suppression and reduce bandwidth (16-28 Hz/pixel) and TR = 80-120 ms, TE = 60 ms, flip angle = 40 degrees, matrix = 128 x 128, FOV = 150-250 mm, slice-thickness = 2-5 mm, NEX = 1, and a total single scan time for one image of about 7 sec. The motor cortex stimulation was achieved by touching each finger to thumb in a sequential, self-paced, and repetitive manner. Statistical parametric maps based on student's test were calculated. Pixels with a highly significant signal increase (p < 0.001) are overlaid on T1w SE images. The primary motor and sensory cortex could be visualized with this method in all 10 patients that were imaged in this study. Due to tight fixation of the patient's skull there have been no motion artifacts. These results show that functional MRI is feasible in an stereotactic set-up with an standard 1.5 T scanner. This is a prerequisite for the exact pre therapeutic assessment of the function of cortical centers.

Brain↗

Experimental study of the mechanism and indices of harmful effects of certain chemical substances on the central nervous system.

The task of the second stage of Soviet-American cooperation on the problem of environmental health science was to explain the question of the comparative sensitivity of methods used in both countries, as well as the indices of harmful effects for the same toxic substance (carbon disulfide), with the purpose of determining the most informative methods of assessing the influence of atmospheric pollutants on organisms. The application of neurophysiological research methods (recording total electrical activity of the cortex and cortical structures of the brain, studying amplitude-time characteristics of averaged evoked potentials of the optical cortex, investigating sensory and convulsive thresholds) has made it possible to explain the neurophysiological basis of the effect of carbon disulfide on the central nervous system-the perturbation of cortical inhibition processes and the increase of excitation in amygdalate structures, both of which play an important role in the fixation process of temporary connection. The compilation of data from neurophysiological and neurochemical investigations show that neurophysiological changes are associated primarily with a decrease in enzymic breakdown of free neuraminic acid. The study of the average evoked potentials in humans during exposure to carbon disulfide concentrations of 0.09 mg/m(3) revealed a tendency to decrease the short latent amplitude components and increase the long latent amplitude components of the averaged evoked potentials. The study of operant behavior in rats revealed a characteristic change in the instrumental alimentary reactions under long-term (3 months) exposure of carbon disulfide to a concentration of 16 mg/m(3). IN THIS MANNER, THE FOLLOWING WERE DEVELOPED IN EXPERIMENTS WITH ANIMALS AND RESEARCH ON HUMANS: indices of the harmful effects of neurotropic toxic substances, a change in operant behavior, a decrease in the amplitude of total electrical activity, a change in time-amplitude parameters of evoked potentials, and a decrease in post-discharge convulsion thresholds in the cortical-medial nucleus of the amygdala. Neurophysiological and neurochemical research methods have proven to be the most sensitive and informative of the methods used. These criteria and methods are recommended for determining threshold levels of various neurotropic toxic substances which pollute the atmosphere.

Animals↗

Developmental abnormalities of mouse cerebellum induced by intracisternal injection of ochratoxin A in neonatal period.

Ochratoxin A, one of the food-contaminating mycotoxins, is known to impair brain development in mammals. Slc:ICR mice were treated intracisternally with a single dose of 5 micrograms ochratoxin A on day 0, 1, 2, 4, 5, or 7 after birth, in order to examine the direct effects of ochratoxin A on cerebellar development. The mice in each group were killed at 30 days of age, and the brains examined by light microscopy. Body and total brain weights were reduced (7 to 15%) in the treated groups. Cerebellar weight was also significantly reduced (18 to 27%) in all treated groups. In mice treated on day 0, 1, or 2, the layered structure of the vermis was well preserved, but some animals treated on day 4, 5, or 7 had cerebella with disarranged cortical structure. The number of folia decreased and the foliation index showed a significant decrease in the groups treated on days 0, 1, and 2.

Animals↗

How echogenic is echogenic? Quantitative acoustics of the renal cortex.

The echogenicity of the cortex is an important parameter in interpreting renal sonograms that suggest changes in cortical structure. Echogenicity is currently measured qualitatively, and no attempts have been made at quantification. We developed a method to quantify renal cortical echogenicity in reference to the liver and evaluated its reproducibility, dependence on scanning variables, and potential utility. Sonograms of the right kidney were digitized, and the mean pixel density of regions of the renal cortex and liver was measured and normalized to the gray scale. Echogenicity was expressed as the ratio of the brightness (inverse of mean pixel density) of the cortex to that of the liver. The mean coefficient of variation among measurements performed on multiple sonograms from the same study was 2.8%, and the coefficient of variation among multiple measurements performed on the same kidney over 1 year was 1.8%. The correlation between measurements obtained by two different individuals on identical images was 0.92, with a mean variation of 3.0%. Echogenicity was not significantly affected by type of scanner or probe frequency, but varied inversely with gain. However, the effect of gain was very small within the useful range. Water loading after an overnight fast increased echogenicity in all cases, with a mean increase of 6.4%. Echogenicity of normal kidneys was significantly less than that of the liver (range, 0.810 to 0.987), and in clinical sonograms analyzed retrospectively but blindly, echogenicity correlated with the qualitative gradations of echogenicity originally assigned. The most echogenic kidneys were 62% brighter than normal kidneys, many times greater than the variability of the measurement. We conclude that quantification of renal cortical echogenicity is feasible and reproducible and may be useful in detecting and following renal disease. Echogenicity of the renal cortex is less than that of the liver in healthy subjects and is influenced by the state of diuresis.

Adolescent↗