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Delineation of brain structures from positron emission tomography images with deformable models.

Segmentation of positron emission tomography (PET) images is a difficult task. In this study, we propose a new method for delineation of brain structures according to the tracer uptake. The method is based on a new deformable model which is particularly designed for extracting surfaces automatically from noisy images. The automation is achieved by using a global optimization algorithm for minimizing the energy of the deformable model. As an example, the coarse cortical structure was extracted from FDG PET brain images by delineating first the brain surface and then the white matter surface. We have tested the method with the image of the brain phantom and images from a small number (N = 17) of FDG brain studies. The cortical structure was automatically and reliably found from all the images. The proposed method provides new opportunities for automatic and repeatable structure extraction applicable for regional quantification of the tracer uptake.

Brain↗

Morphology and development of left-handed singlets derived from mirror-image doublets of Stylonychia mytilus.

Mirror-image doublets of Stylonychia mytilus include 2 sets of cortical structures, one with the normal "right-handed" (RH) arrangement, the other with a reversed "left-handed" (LH) arrangement. These sets, however, are incomplete, with certain structures, most notably cirri of the right marginal type, missing near the line of symmetry. When a mirror-image doublet is bisected longitudinally to separate the RH and LH components physically, each fragment undergoes a regeneration process that restores a complete set of cortical structures, including the previously missing cirri of the right marginal type. In the resulting LH cell, all ciliary structures are present in an arrangement that is globally reversed in relation to that found in RH cells; in particular, marginal cirri of the left-marginal type are formed at the cell's right margin, and marginal cirri of the right-marginal type are produced at the cell's left margin. Whereas the regenerated RH fragment always divides and initiates a clone of normal singlets, the LH fragment, though structurally nearly complete, in all cases eventually dies without dividing. The cause of death is starvation due to the formation of an abnormal oral apparatus. In the Discussion, we consider the nature and consequences of a reversal of global positional information.

Animals↗

The role of corticothalamic coupling in human temporal lobe epilepsy.

The EEG activity of the thalamus and temporal lobe structures (hippocampus, entorhinal cortex and neocortex) was obtained using intracerebral recordings (stereoelectroencephalography, SEEG) performed in patients with TLE seizures undergoing pre-surgical evaluation. Synchrony was studied using a statistical measure of SEEG signal interdependencies (non-linear correlation). The results demonstrated an overall increase of synchrony between the thalamus and temporal lobe structures during seizures. Moreover, although there was great inter-individual variability, we found that values from seizure onset period were significantly higher than values from the background period (P = 0.001). Values at the end of seizure were significantly higher than values from the seizure onset (P < 0.0001). Several indices were also defined in order to correlate some clinical features to the degree of coupling between cortical structures and the thalamus. In patients with mesial TLE seizures, a correlation was found between the degree of thalamocortical synchrony and the presence of an early loss of consciousness but not with other clinical parameters. In addition, surgical prognosis seemed better in patients with low values of thalamocortical couplings at the seizure onset. This report demonstrates that the thalamus and remote cortical structures synchronize their activity during TLE seizures and suggest that the extension of the epileptogenic network to the thalamus is a potential important factor determining surgical prognosis.

Adolescent↗

Transmitter systems in the primate dentate gyrus.

While the dentate gyrus is clearly the simplest of the cortical fields that constitute the hippocampal formation, it nonetheless occupies a pivotal position in the flow of information through this region. Though it has been the subject of anatomical study for over a century and its major connections have been known for almost as long, the use of newly developed histochemical and immunohistochemical techniques have demonstrated many new facets of its intrinsic connectivity and afferent innervation. These techniques have established that it is innervated by cholinergic, noradrenergic, serotonergic and dopaminergic fibers. More recent studies have shown that fibers and cell bodies of the dentate gyrus are immunoreactive for variety of neuroactive substances including the excitatory amino acids glutamate and aspartate, the inhibitory transmitter GABA, as well as peptides of many types including the opioid peptides, enkephalin and dynorphin, several forms of somatostatin, neuropeptide Y, cholycystokinin, vasoactive intestinal peptide and substance P. In this review, we will briefly summarize the distribution of each of these putative transmitter systems within the dentate gyrus. The perspective emerges that the plethora of newly identified and chemically specific fiber systems enriches the classical understanding of the organization of this relatively simple cortical structure. Since there is thus far no evidence for the exclusion from the dentate gyrus of any class of transmitter bearing fiber or neuron found in the neocortex, it can be viewed as a relatively simple model system for studying the interactions of specific transmitter systems in a laminated, cortical structure.

Acetylcholine↗

The structure of cortical cytoplasm.

Actin-rich cortical cytoplasm of phagocytic leucocytes forms pseudopodia and controls cell shape and movement by generating directional propulsive and contractile forces. Proteins purified from leucocytes form and deform an actin matrix. Actin-binding protein (ABP) cross-links actin filaments into a three-dimensional lattice with perpendicular branches. This structure, which can be visualized in the electron microscope, is consistent with physical properties of actin-ABP matrices. Gelsolin binds one end of actin filaments with high affinity in the presence of calcium; acumentin, another protein, constitutively binds the other end with low affinity. Together these proteins can control actin filament length and thereby regulate expansion (propulsion) or collapse of the actin network. The assembly state of the network also controls myosin-based contractile forces. A tug-of-war decides the direction of lattice movement, regions of lesser structure tending to move toward regions of greater structure.

Actins↗

Lack of changes in cortical [3H]-muscimol binding in rats sensitized to nicotine-induced enhancement of dopamine metabolism.

It was proposed that chronic nicotine treatment may induce adaptive changes in GABAA receptors, thus leading to the attenuation of a GABAergic inhibition of dopaminergic neurons. This putative mechanism might underlie the sensitization to nicotine-induced increase in locomotor activity and dopamine metabolism; i.e. phenomena highly significant to the dependence-producing effects of this psychostimulant. To test this hypothesis, in the present study we have analyzed the influence of acute and repeated treatment of rats with nicotine on the binding of a highly selective and competitive GABAA receptor agonist, [3H]-muscimol. The binding was investigated by autoradiography in different brain cortical structures. It was found that nicotine given at the dose stimulating locomotor activity (0.6 mg/kg, sc), markedly increased striatal HVA concentration in the group of animals chronically pretreated (for 6 days) with this psychostimulant. Neither acute nor repeated nicotine administration changed in a significant way the [3H]-muscimol binding to brain cortical structures. Thus, the hypothesis about the role of adaptive changes in GABAA receptors in the enhancement of the biochemical and behavioral effects of nicotine was not confirmed.

Animals↗

The functions of the preplate in development and evolution of the neocortex and hippocampus.

Recently, it has been shown that the early developmental organization of the archicortical hippocampus resembles that of the neocortex. In both cortices at embryonic stages, a preplate is present, which is split by the formation of the cortical plate into a marginal zone and a subplate layer. The pioneer neurons of the preplate are believed to form a phylogenetically ancient cortical structure. Neurons in these preplate layers are the first postmitotic neurons and have important roles in the development of the cerebral cortex. Cajal-Retzius cells in the marginal zone regulate the phenotype of radial glial cells and may direct neuronal migration establishing the inside-out gradient of corticogenesis. Furthermore, pioneer neurons form the initial axonal connections with other (sub)cortical structures. A significant difference between the hippocampus and neocortex, however, is that in the hippocampus, most afferents are guided by the pioneer neurons in the prominent marginal zone, while in the neocortex most ingrowing afferent axons enter via the subplate. At later developmental periods, most pioneer neurons disappear by cell death or transform into other neuronal shapes. Here, we review the early developmental organization of the mammalian cerebral cortex (both neocortex and hippocampus) and discuss the functions and fate of pioneer neurons in cortical development, in particular that of Cajal-Retzius cells. Evaluating the developmental properties of the hippocampus and neocortex, we present the hypothesis that the distribution of the main ingrowing afferent systems in the developing neocortex, which differs from the one in the hippocampal region, may have enabled the specific evolution of the neocortex.

Animals↗

Increase in excitability of cortical nonspecific structures in the presence of a decreased level of influences from the brainstem reticular formation.

The results of the measurement of the threshold of electrical stimulation of the cortex sufficient to elicit the EEG activation reaction in the norm and under conditions of the reduction of influences from the brainstem of the reticular formation are presented. A decrease in the thresholds was observed in those conditions which are regarded as evidence of an increase in the excitability of the nonspecific cortical formations. The increase was uneven: it was maximal in the sensorimotor and minimal in the visual cortex. It is hypothesized that the data obtained in brain preparations with a decreased level of brainstem reticular influences may be applied to the understanding of certain phenomena of neurotic pathology in its neurophysiological aspect.

Animals↗

Activities of the EM10 protein from Echinococcus multilocularis in cultured mammalian cells demonstrate functional relationships to ERM family members.

The ezrin-radixin-moesin (ERM) homolog EM10 is expressed by the larval stage of the parasite E. multilocularis and shows 46.9% overall identity in the primary structure with human ezrin. To determine whether EM10 has similar activities to ERM proteins, we investigated properties of the protein expressed in mammalian cells. In particular, we transiently expressed haemagglutinin-tagged (HA-tagged) versions of the full-length EM10 as well as the amino- and the carboxy-terminal halves of EM10 in HtTA-1 cells. In addition we stably transfected NIH-3T3 cells with untagged full-length EM10. The data demonstrate that EM10 polypeptides behave like their corresponding portions of radixin when transiently expressed in mammalian cells. The full-length and amino-terminal EM10 polypeptides were localized to cortical structures. Cells expressing the carboxy-terminal polypeptide of EM10 showed long actin-filled protrusions. Cells expressing full-length EM10 showed a reduction in endogenous moesin-staining at cortical structures. In stably transfected NIH-3T3 cells EM10 was not crisply localized but rather was diffuse throughout the cytoplasm. These cells showed a conspicuous loss of stress-fibers, a phenotype that was not seen in analogous experiments with ERM proteins. The results demonstrate both similarities and differences between the functional properties of EM10 and ERM proteins expressed in vertebrate cells.

3T3 Cells↗

Impaired renal blood flow and cortical pressure autoregulation in contralateral kidneys of Goldblatt hypertensive rats.

Experiments were conducted on two-kidney, one clip renal vascular hypertensive rats to assess the ability of the kidney contralateral to renal vascular stenosis to autoregulate renal blood flow (RBF), glomerular filtration rate (GFR), and hydrostatic pressures in cortical structures during conditions of acutely reduced renal arterial blood pressure (BP). When observed at their respective, spontaneous BPs, RBF and GFR were not different in the contralateral kidneys of the hypertensive rats (n = 11) compared to normal animals (n = 7). However, the contralateral kidneys exhibited a significantly higher renal vascular resistance (RVR), 28.9 +/- 2.8 mm Hg . min/ml than the control animals, 23.1 +/- 1.5 mm Hg . min/ml. At spontaneous BP (169 +/- 5 mm Hg), urine flow, absolute and fractional sodium excretion, and absolute and fractional potassium excretion were all significantly greater in the contralateral kidneys of hypertensive rats than in kidneys of normal rats. Hydrostatic pressures in cortical structures were similar in the two groups. When BP was reduced acutely, the kidney contralateral to the renal artery stenosis achieved only small decreases in RVR that failed to allow RBF, GFR, or cortical pressures to be maintained. In contrast, normal rats efficiently autoregulated RBF and GFR. In addition, hydrostatic pressures in proximal tubules, distal tubules, and first order peritubular capillaries were maintained during reductions in BP to as low as 100 mm Hg. Urine flow and electrolyte excretion decreased to a greater extent in the hypertensive kidneys, such that at comparable BP these indices of excretory function were not different in the two groups. These observations indicate that the capacity of the contralateral kidney to maintain hemodynamic and glomerular function at reduced BP is compromised severely and suggest the possibility that the impaired autoregulatory capability may contribute to the maintenance of hypertension observed in this model.

Animals↗

Measurements of the microscopic structure of cortical bone.

A technique is described in which the microstructure of cortical bone is analysed in terms of distributions of possible paths which ionizing particles take as they transverse the soft-tissue cavities and mineralized component. Measurements are restricted to transverse planes in the long bones, but a method is suggested for generating approximate omnidirectional path-length distributions from the measured transverse distributions. Results are presented for some long bones of a 50 year old man, a 9 year old boy and a young adult beagle, and these suggest that considerable structural differences occur between the two species. Values of some commonly quoted structural parameters are also given. For example, mean transverse cavity path lengths range between 67 and 99 micron in the long bones of the adult man compared with 29 micron in the beagle femur; the corresponding mean path lengths through the mineralized component are 830-1040 and 1500 micron. Finally, the total cavity plus periosteal surface for cortical bone in adult man is estimated to be about 6 m2.

Animals↗

Differences in cortical actin structure and dynamics document that different types of blebs are formed by distinct mechanisms.

Bleb formation has been studied by specifically targeting major factors controlling this process, such as microtubule disassembly, local actin depolymerization, and increased pressure. At least two different types of blebs (types 1 and 2) formed by different mechanisms and possibly a third type (type 3) can be documented at the front of living polarized cells expressing green fluorescent protein-actin and/or in fixed and stained cells. Type 1 blebs (membrane/cortex dissociation blebs) formed by dissociation of the plasma membrane from cortical actin develop cytoplasmic actin layers associated with restriction rings. They can be induced by the microtubule-disassembling agent colchicine. Type 2 blebs (cortical actin disassembly blebs) form after disassembly of the cortical actin layer in the presence of latrunculin A. Restriction rings without a cytoplasmic actin layer occur in a transition zone between the intact cortical actin layer of the cell body and the compromised actin layer of the bleb. Evidence for a third type of bleb (type 3), showing an intact cortical actin layer but no cytoplasmic actin layer and no recognizable relationship between the actin cytoskeleton and the restriction ring, has been obtained by passive cell deformation in micropipettes, which increases pressure. Repolymerization of the cortical actin layer does not necessarily result in bleb retraction. Once formed, restriction rings do not narrow, suggesting that they result from isometric contraction. A simplified classification scheme has been developed to relate the type of bleb to specific signals or cell functions. Its application shows that spontaneously blebbing cells form almost exclusively type 1 blebs.

Actinin↗

[Corticofugal influences on pontine neuronal activity].

Reactions of neurons of pons varolii reticular and proprial nuclei to stimulation of the frontobasal regions of the cortex (proreal, orbital and basal temporal regions) and dorsal hippocampus were studied in cat. The stimulation of various cortical structures caused phasic and rarely tonic reactions of these neurons. Primary excitation was the dominant type of reactions in the reticular nuclei and primary inhibition--in the proprial nuclei. The greatest number of responding neurons was observed during stimulation of the proreal gyrus. In the cerebro-cerebellar system the most responsible neurons were those of nucleus reticularis tegmenti pontis and ventromedial part of the pontine grey matter. The regions of dominant influence from the cortical structures were in the same zones of the pontine reticular formation, where neurons with rostral projection are localized.

Animals↗

Functional neuroanatomy of human vocalization: an H215O PET study.

Vocalization in lower animals is associated with a well-described visceromotor call system centered on the mesencephalic periacqueductal grey matter (PAG), which is itself regulated by paramedian cortical structures. To determine the role this phylogenetically older system plays in human phonation, we contrasted voiced and unvoiced speech using positron emission tomography and then evaluated functional connectivity of regions that significantly differentiated these conditions. Vocalization was associated with increased and highly correlated activity within the midline structures--PAG and paramedian cortices--described in lower mammalian species. Concurrent activation and connectivity of neocortical and subcortical motor regions--medial and lateral premotor structures and elements of basal ganglia thalamocortical circuitry--suggest a mechanism by which this system may have come under an increasing degree of voluntary control in humans. Additionally, areas in the temporal lobe and cerebellum were selectively activated during voiced but not unvoiced speech. These regions are functionally coupled to both visceromotor and neocortical motor areas during production of voiced speech, suggesting they may play a central role in self-monitoring and feedback regulation of human phonation.

Adult↗

Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings.

BACKGROUND: Schizophrenia is a highly heritable disorder associated with structural brain abnormalities. The aim of this study was to establish if the gene(s) for schizophrenia are associated with specific abnormalities of brain structure. SUBJECTS: Six sibships from multiple affected families were recruited. Each sibship consisted of one patient with schizophrenia, one "obligate carrier" without the disorder but with an affected child, and one "non-affected non-carrier". Such sibships are very rare, but present a powerful opportunity to separate the associations of genotype and phenotype. Obligates presumably have the gene(s) but not the disorder, affected siblings have both, whereas non-affected non-carrier siblings have neither. METHOD: Brain MRI was conducted with a semiautomated region of interest analysis. The risk of false positive findings was reduced by collapsing brain regions and sides into five regions and comparing groups by repeated measures analysis of variance. RESULTS: In terms of whole brain volumes and volumes of cortical structures, obligates resembled their non-affected non-carrier siblings, both groups having significantly greater volumes than their schizophrenic siblings (p=0.01 and p=0.04). Obligates also had significantly smaller ventricles than their schizophrenic siblings (p=0.03). However, with respect to the amygdalohippocampal complex, the obligates' brains resembled those of their schizophrenic siblings, both groups showing a significant reduction in volume when compared with their non-affected non-carrier siblings (p=0.001). CONCLUSIONS: In the families studied, reductions in volumes of cortical structures and reductions in whole brain volume seem to be associated with the phenotype of schizophrenia. By contrast, reduced volume of the amygdalohippocampal complex seems to be associated with genetic risk for the disorder even in the absence of disease.

Adult↗

Primary hyperparathyroidism: iliac crest cortical thickness, structure, and remodeling evaluated by histomorphometric methods.

Iliac crest bone biopsies from 62 patients (42 women, 20 men; median age 59 years; range 17-79 years) with primary hyperparathyroidism (PHP) were examined. Static and structural parameters were compared with 30 age- and sex-matched normal controls. Eighteen sex-matched younger controls were used for evaluation of the dynamic controls. On the endocortical surface increase in extension of eroded (p < 0.01) and formative (p < 0.01) surfaces was found in PHPs compared with normals. Endocortical bone formation rate was increased in PHPs (p < 0.05), but mineral appositional rate and adjusted appositional rate were normal. On the periosteal surface very little remodeling activity was found. Although bone formation rate was found increased in PHPs (p < 0.05), more than half of the labeled biopsies were without periosteal tetracycline in patients, and only 2 of 18 biopsies from normals contained periosteal tetracycline labels. No significant decreases in cortical width or relative cortical width were found in PHPs. In both patients and controls an age-related decrease in relative cortical width cortical width were found in PHPs. In both patients and controls an age-related decrease in relative cortical width was noted for women (PHPs: r = -0.52, p < 0.01; controls: r = -0.59, p < 0.001), but not for men. Cortical porosity was about 30% increased in PHPs (p < 0.02). Only normal women showed a positive age-related increase in porosity (r = 0.61, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

How do we modulate our emotions? Parametric fMRI reveals cortical midline structures as regions specifically involved in the processing of emotional valences.

One of the major problems in affective neuroscience of healthy subjects as well as of patients with emotional dysfunctions is to disentangle emotional core functions and non-emotional processes. Emotional valence is considered an emotional key process. The present study employed a parametric functional magnetic resonance imaging (fMRI) study to address this question. Thirteen healthy volunteers were scanned during emotional stimulus processing (International Affective Picture System). The presented pictures covered the entire range of emotional valences. The fMRI data were consecutively subjected to a preliminary categorical (valence-independent) and a detailed parametric analysis, the latter using individual valence ratings as regressor. The parametric analysis revealed a linear valence-dependent modulation of the BOLD signal in the orbito- and dorsomedial prefrontal cortex (OMPFC, DMPFC), medial parietal cortex (MPC), and insula. In addition, we observed that emotional valence exerts its effects predominantly via modulation of signal decreases. We conclude that the psychological concept of emotional valence may be related to neural processing in cortical midline regions.

Adult↗

Lateral inhibition and habituation of the human auditory cortex.

The goal of this study was to compare the lateral inhibition and the habituation in the human auditory cortex, two important physiological effects during auditory processing that can be reliably measured by means of magnetoencephalography when recording auditory evoked fields. Applying 40-Hz amplitude-modulated stimuli allowed us to record simultaneously the slow transient evoked and the steady-state fields and thus to characterize the lateral inhibition and the habituation effect in primary and non-primary auditory cortical structures. The main finding of the study is that the lateral inhibition effect of non-primary auditory areas as measured on the major component of the slow transient auditory evoked field (N1) is significantly stronger than the corresponding habituation effect. By contrast, this effect was not observed for the 40-Hz steady-state fields, characterizing the activation of the primary auditory cortex in humans. The results might be interpreted as (i) evidence that the inhibition mediated by lateral connections is stronger than the habituation of excitatory neurons in the non-primary auditory cortex and (ii) the processing hierarchy in the human auditory cortex is demonstrated by the different behaviour of lateral inhibition and habituation in primary and non-primary auditory cortical structures.

Acoustic Stimulation↗