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PubMedDate not supplied

Developmental dyslexia and animal studies: at the interface between cognition and neurology.

Recent findings in autopsy studies, neuroimaging, and neurophysiology indicate that dyslexia is accompanied by fundamental changes in brain anatomy and physiology, involving several anatomical and physiological stages in the processing stream, which can be attributed to anomalous prenatal and immediately postnatal brain development. Epidemiological evidence in dyslexic families led to the discovery of animal models with immune disease, comparable anatomical changes and learning disorders, which have added needed detail about mechanisms of injury and plasticity to indicate that substantial changes in neural networks concerned with perception and cognition are present. It is suggested that the disorder of language, which is the cardinal finding in dyslexic subjects, results from early perceptual anomalies that interfere with the establishment of normal cognitive-linguistic structures, coupled with primarily disordered cognitive processing associated with developmental anomalies of cortical structure and brain asymmetry. This notion is supported by electrophysiological data and by findings of anatomical involvement in subcortical structures close to the input as well as cortical structures involved in language and other cognitive functions. It is not possible at present to determine where the initial insult lies, whether near the input or in high-order cortex, or at both sites simultaneously.

Animals↗
PubMed2000

Conditions for noise reduction and stable encoding of spatial structure by cortical neural networks.

Cortical circuits have been proposed to encode information by forming stable spatially structured attractors. Experimentally in the primary somatosensory cortex of the monkey, temporally invariant stimuli lead to spatially structured activity patterns. The purpose of this work is to study a recurrent cortical neural network model with lateral inhibition and examine what effect additive random noise has on the networks' ability to form stable spatially structured representations of the stimulus pattern. We show numerically that this network performs edge enhancement and forms statistically stationary, spatially structured responses when the lateral inhibition is of moderate strength. We then derive analytical conditions on the connectivity matrix that ensure stochasticly stable encoding of the stimulus spatial structure by the network. For stimuli whose strength falls in the near linear region of the sigmoid, we are able to give explicit conditions on the eigenvalues of the connection matrix. Finally, we prove that a network with a connection matrix, where the total excitation and inhibition impinging upon a neural unit are nearly balanced, will yield stable spatial attractor responses.

Animals↗
PubMed2006

Rtn1p is involved in structuring the cortical endoplasmic reticulum.

The endoplasmic reticulum (ER) contains both cisternal and reticular elements in one contiguous structure. We identified rtn1Delta in a systematic screen for yeast mutants with altered ER morphology. The ER in rtn1Delta cells is predominantly cisternal rather than reticular, yet the net surface area of ER is not significantly changed. Rtn1-green fluorescent protein (GFP) associates with the reticular ER at the cell cortex and with the tubules that connect the cortical ER to the nuclear envelope, but not with the nuclear envelope itself. Rtn1p overexpression also results in an altered ER structure. Rtn proteins are found on the ER in a wide range of eukaryotes and are defined by two membrane-spanning domains flanking a conserved hydrophilic loop. Our results suggest that Rtn proteins may direct the formation of reticulated ER. We independently identified Rtn1p in a proteomic screen for proteins associated with the exocyst vesicle tethering complex. The conserved hydophilic loop of Rtn1p binds to the exocyst subunit Sec6p. Overexpression of this loop results in a modest accumulation of secretory vesicles, suggesting impaired exocyst function. The interaction of Rtn1p with the exocyst at the bud tip may trigger the formation of a cortical ER network in yeast buds.

Endoplasmic Reticulum↗
PubMed1997

Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells.

The mechanisms through which the small GTPases Rac1 and Cdc42 regulate the formation of membrane ruffles, lamellipodia, and filopodia are currently unknown. The p21-activated kinases (PAKs) are direct targets of active Rac and Cdc42 which can induce the assembly of polarized cytoskeletal structures when expressed in fibroblasts, suggesting that they may play a role in mediating the effects of these GTPases on cytoskeletal dynamics. We have examined the subcellular localization of endogenous PAK1 in fibroblast cell lines using specific PAK1 antibodies. PAK1 is detected in submembranous vesicles in both unstimulated and stimulated fibroblasts that colocalize with a marker for fluid-phase uptake. In cells stimulated with PDGF, in v-Src-transformed fibroblasts, and in wounded cells, PAK1 redistributed into dorsal and membrane ruffles and into the edges of lamellipodia, where it colocalizes with polymerized actin. PAK1 was also colocalized with F-actin in membrane ruffles extended as a response to constitutive activation of Rac1. PAK1 appears to precede F-actin in translocating to cytoskeletal structures formed at the cell periphery. The association of PAK1 with the actin cytoskeleton is prevented by the actin filament-disrupting agent cytochalasin D and by the phosphatidylinositol 3-kinase inhibitor wortmannin. Co-immunoprecipitation experiments demonstrate an in vivo interaction of PAK1 with filamentous (F)-actin in stimulated cells. Microinjection of a constitutively active PAK1 mutant into Rat-1 fibroblasts overexpressing the insulin receptor (HIRcB cells) induced the formation of F-actin- and PAK1-containing structures reminiscent of dorsal ruffles. These data indicate a close correlation between the subcellular distribution of endogenous PAK1 and the formation of Rac/Cdc42-dependent cytoskeletal structures and support an active role for PAK1 in regulating cortical actin rearrangements.

3T3 Cells↗
PubMed1977

[Topography and cytoarchitectonics of the main cortical zones of the turtle forebrain].

The description of cytoarchitectonics and topography of the three principle cortical zones of the forebrain of Emys orbicularis reveals that the cortical structures in the species are precisely distinguished with respect to their neuronal characteristics, density and the situation of cellular elements. Emys orbicularis occupies an intermediate position among the species of the order Chelonia described in the literature as regards the level of development of the forebrain cellular structures. Emys orbicularis is less progressive in respect to the structure of telencephalic cortical formations than Testudo carolina and has a number of progressive properties as compared with Testudo geometrica. Testudo graeca seems to be close to Emys orbicularis in the development of forebrain cellular structures.

Animals↗
PubMed1996

A comparison of the effects of two fimbria-fornix lesion techniques on beam-walking performance in the rat: aspiration versus electrolysis.

This experiment was aimed at comparing the sensorimotor correlates of fimbria-fornix lesions made with either a classical aspiration technique that also removes part of the overlying cortical structures, or an electrolytic one that does not encroach upon these cortical structures. About 4 months after lesion surgery, Long-Evans female rats which had sustained an aspiration or an electrolytic fimbria-fornix lesion at the age of 90 days were tested to measure their beam-walking performance as an index for their sensorimotor capabilities. We found that after an aspiration lesion, the rats presented sensorimotor deficits which did not occur after an electrolytic lesion. After having found that electrolytic lesions of the fimbria and the fornix produced neurochemical deficits (in the dorsal hippocampus) and cognitive alterations close to those resulting from aspiration lesions, it is concluded from the present experiment that the electrolytic lesion technique is an interesting alternative to an aspiration technique, essentially because the former does not induce the sensorimotor deficits due to the partial damage that an aspiration technique produces in the medial parietal cortex. As the electrolytic lesion technique may minimize the risk of introducing a sensorimotor bias in the accuracy of cognitive evaluations, the present result might be of interest to neuroscientist using a fimbria-fornix lesion paradigm in order to investigate the efficacy of drugs, grafts or other treatments on the recovery from cognitive deficits.

Animals↗
PubMed1982

The structure of cerebral cortex in the rat following prenatal administration of 6-hydroxydopamine.

The early, prenatal formation of noradrenergic projections to the forebrain has led to the proposition that these axons exert a trophic influence on cerebral cortex during ontogeny. To test this hypothesis, we have examined a number of different structural features of cortical development following prenatal lesions of the ascending noradrenergic axons. The parameters that were analyzed include cytoarchitecture, dendritic morphology, and the distribution of monoaminergic and nonmonoaminergic cortical afferents. Rat fetuses were administered the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) by transuterine, intraperitoneal injection on embryonic day 17. Vehicle-injected controls and fetuses treated with the catecholamine uptake inhibitor desmethylimipramine (DMI) prior to 6-OHDA were prepared. After reaching maturity (200-300 g), the brain of treated and control rats were examined using Nissl and Golgi preparations (for cytoarchitecture and dendritic morphology), histofluorescence (for monoaminergic afferents, especially dopaminergic axons), and serotonin and dopamine-beta-hydroxylase (DBH) immunocytochemistry. Effective lesioning of the ascending noradrenergic system was confirmed in each case, using DBH immunocytochemistry. Prenatal treatment with 6-OHDA resulted in complete and long-lasting destruction of the noradrenergic innervation of the cerebral cortex, along with hyperinnervation of the diencephalon and brain stem. Despite the widespread denervation of cerebral cortex, no significant alterations in cytoarchitecture, dendritic morphology, or spine counts were found in treated brains. In particular, no abnormalities were observed in the apical dendrites of layer VI pyramidal cells, based on qualitative criteria. The distribution, density and morphology of serotonergic and dopaminergic afferents were unaffected. Thalamocortical afferents had developed normally as reflected by the cortical barrels. In 33% of the 6-OHDA-treated fetuses foci of ectopic neurons were found at the cortical surface. The ectopias contain neuronal processes, somata, and synapses interspersed with collagen and other connective tissue elements. While the ectopias may result from selective damage to the noradrenergic neurons, the finding of similar (but smaller) malformations in DMI-protected animals is equally consistent with a non-specific effect of 6-OHDA upon non-adrenergic cells. The examination of intervening stages will be needed to resolve this question. Based on the parameters of cortical structure analyzed in this study we conclude that the neocortex develops normally even in the absence of the noradrenergic system.

Afferent Pathways↗
PubMed2004

Analysis of the morphological substrate for information processing in the pallidal nuclear complex of the dog brain in terms of the organizational characteristics of its afferent projections.

Axonal transport of retrograde markers was used to study the distribution of the afferent projections of the nuclei of the pallidal complex (the globus pallidus, the entopeduncular nucleus, and the ventral pallidum) from functionally diverse cortical and subcortical structures (cortical fields, substantia nigra, ventral tegmental field, and thalamus) in the dog brain. The results were used to analyze the morphological aspects both of the functional heterogeneity of the pallidum and integrative information processing, which underlie the mechanisms of adaptive behavior.

Adaptation, Psychological↗
PubMed1998

The neuropsychology of REM sleep dreaming.

Recent PET imaging and brain lesion studies in humans are integrated with new basic research findings at the cellular level in animals to explain how the formal cognitive features of dreaming may be the combined product of a shift in neuromodulatory balance of the brain and a related redistribution of regional blood flow. The human PET data indicate a preferential activation in REM of the pontine brain stem and of limbic and paralimbic cortical structures involved in mediating emotion and a corresponding deactivation of dorsolateral prefrontal cortical structures involved in the executive and mnemonic aspects of cognition. The pontine brainstem mechanisms controlling the neuromodulatory balance of the brain in rats and cats include noradrenergic and serotonergic influences which enhance waking and impede REM via anticholinergic mechanisms and cholinergic mechanisms which are essential to REM sleep and only come into full play when the serotonergic and noradrenergic systems are inhibited. In REM, the brain thus becomes activated but processes its internally generated data in a manner quite different from that of waking.

Animals↗
PubMed1979

The origin of the hind limb vasodilatation evoked by stimulation of the motor cortex in the cat.

In cats under Althesin anaesthesia, the hind limb area of the motor cortex has been stimulated by means of monopolar, semi-micro-electrodes with careful experimental control so as to avoid reflex effects evoked through stimulation of meningeal afferent fibres or stimulus spread to non-cortical structures. 2. Localized cortical stimulation which elicited muscle contractions in the contralateral hind limb also elicited vasodilation in the same limb: the stimulus threshold was the same for both effects, and the magnitude of the dilatation was related to the strength of contraction. 3. Reduction of the somatic motor response, caused by lesions in the medullary pyramidal tract, was accompanied by a parallel reduction of the vascular response. 4. Prevention of the motor response by gallamine or by spinal cord section at L4--L5 (which leaves the sympathetic outflow to the hind limbs intact) led to abolition of the vascular response. During recovery from gallamine, contraction and vasodilatation returned in parallel. 5. The muscle vasodilatation was insensitive to atropine or guanethidine. 6. It is concluded that the hind limb vasodilatation observed on stimulation of the motor cortex is simply a post-contraction hyperaemia, and that it is independent of the sympathic nervous system. Previous conclusions of a sympathetically mediated vasodilatation probably resulted from inadequate control of the stimulus or a failure to recognize weak muscle contractions.

Animals↗
PubMed2002

N400 event-related potential reduction indexes: early central nervous system impairment in HIV.

We examined event-related potential (ERP) measures of priming in a lexical decision task in which two-thirds of the words were presented as sequential antonym pairs. HIV-1+ subjects were divided into cognitively normal and cognitively impaired subgroups on the basis of a neuropsychological battery. Cognitively impaired HIV-1+ subjects showed reduced priming, associated with reduced N400 ERP component amplitudes, suggesting that the processing of linguistic stimuli in these patients may involve reduced activation of semantic networks. Cognitively normal HIV-1+ subjects showed a reduction in N400 amplitude, but no reduction in performance, suggesting that some reduction in neural signal may occur earlier in the course of HIV-1 central nervous system disease than behavioral priming deficit. As the known neurological deficit in HIV-1 disease is primarily in the basal ganglia and periventricular white matter, we propose that a functional disconnection of subcortical and frontal structures from posterior cortical structures underlies this reduction in semantic activation.

AIDS Dementia Complex↗
PubMed1985

[Various patterns in structural changes in the cortex and subcortical structures of the human brain during the aging process].

The authors examined the structural organization of cortical and subcortical formations (fields 4, 6, 8, 44, 47, 39, the head of the caudate nucleus and thalamic nuclei) of the right and left hemispheres of the brain of 6 mentally normal subjects aged 30 to 90 years. In sections 20 millimicron thick and stained by Nissl's method the authors measured the density of neurons in subcortical nuclei, in layers III and V of the cortical fields, as well as the number of neurons containing lipofuscin. The identified characteristics indicate heterochronicity of the process of ageing in different portions of the brain: motor and, particularly, cortical structures are involved in this process earlier and more intensively than others.

Adult↗
PubMed1980

[Comparative ontogeny of the human and monkey hippocampus, hypothalamus, entorhinal and limbic cortex].

Studies of the ontogenesis of the limbic and entorhinal cortex, the hippocamp and the hypothalamus in man and monkeys in the pre- and postnatal periods revealed substantial differences in their development. The architectonic structures of the monkey brain develop in the prenatal period, and by the time of the birth they have already been formed to a greater degree than the analogous structures in the human newborn. A substantial difference of the ontogenesis of the above cortical structures in man consists in development of limitrophe structures and appearance of new structural units. A specific feature of the development of the limbic and entorhinal cortex and the hippocampus of the human brain, as compared with that in rhesus macacas, is a longer duration of their postnatal ontogenesis. The main development of the cortical structures of the human brain proceeds after the birth.

Animals↗
PubMed1998

Limbic-cortical neuronal damage and the pathophysiology of schizophrenia.

Neurobiological studies of patients with schizophrenia suggest that abnormalities of both anatomy and function occur in limbic-cortical structures. An anatomical circuit links the functioning of the ventral striatum (i.e., nucleus accumbens) with the hippocampus and other limbic-cortical structures where neurobiological abnormalities have been found. In animals, lesions of limbic-cortical neurons cause decreases in glutamatergic input to the nucleus accumbens and are also associated with decreases in presynaptic dopamine release, increases in the density of D2-like dopamine receptors, and insensitivity to the actions of dopamine antagonists such as haloperidol. These experiments suggest a plausible pathophysiology of schizophrenia, in that schizophrenic symptoms may be caused by an abnormal dopaminergic state brought about by a primary limbic-cortical lesion and deficits in glutamatergic inputs to the ventral striatum.

Animals↗
PubMed1991

The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischemia.

We report the effects of intravenous infusion of CGS-19755, a potent competitive N-methyl-D-aspartate (NMDA) antagonist, on local cerebral pH (LCpH) and local CBF (LCBF) in rats with occluded left middle cerebral and common carotid arteries. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique 4 h after vascular occlusion in three groups: no treatment, carrier infused, and a group receiving CGS-19755 at 10 mg/kg bolus immediately after occlusion followed by infusion at 5 mg kg-1 h-1 for 4 h. Compared with rats receiving carrier, several cortical structures on the side of occlusions showed significantly higher CBF in rats receiving CGS-19755. This drug also corrected the pH in several left cortical structures to values significantly higher than in the rats receiving carrier. The correction in LCpH was not limited to those regions showing significant elevations in LCBF. In the nonoccluded hemisphere, CGS-19755 significantly increased the hemispheric mean blood flow from 122 +/- 17 to 221 +/- 64 ml 100 g-1 min-1 (mean +/- SD of all structures, p less than 0.01) without any changes in LCpH. Cortical but not basal ganglia infarct volume was significantly smaller in rats receiving CGS-19755 than in the carrier-treated group. These results suggest that, at least partially, the neuroprotective effect of CGS-19755 in ischemia may be related to changes in CBF and pH in addition to its antagonist effect on the NMDA receptor.

Animals↗
PubMedDate not supplied

[Reverse temporary connections and their role in human cortical reactions].

A number of experiments shows that the character of human cortical response to a conditioned stimulus is to a considerable degree determined by properties and significance of the second stimulus in the combined pair. In a combination of two stimuli differently expressed depression of cortical response to the first stimulus takes place. If the "reinforcing" stimulus is emotionally significant and is recognized then the changes of evoked cortical activity in response to conditioned stimulus are complex and of different signs; they result from simultaneous action on cortical structures of both inhibitory and activating "nonspecific" influences. In this case the facilitation of the cortical response is revealed by comparison with the tests of indifferent stimulus before pairing or with tests where association between two indifferent stimuli is formed. A considerable increase of evoked response after elimination of the "reinforcing" emotional stimulus testifies that this facilitation is merely relative, and along with activating influence via feedback has an inhibitory action on cortical structures which perceive the conditioned stimulus.

Adult↗
PubMed1997

Effect of estrogen deficiency on cancellous and cortical bone structure and strength of the femoral neck in rats.

Eighty mature Sprague-Dawley rats were weight matched before ovariectomy (Ovx) or Sham surgery (Sham). Sham rats had free access to food and water throughout the experiment, whereas Ovx rats were kept on the pair-fed diet. Rats were euthanized at 4, 8, and 12 weeks after surgery, and had received fluorochrome bone markers at 9 and 2 days prior to euthanasia. In addition 10 rats were euthanized at the time of surgery serving as baseline controls. All rats were also scanned for body composition and bone mineral parameters by DEXA before surgery and euthanasia. Left proximal femurs (femoral necks) were used for bone histomorphometry, whereas right femurs were used for in vitro DEXA measurements and mechanical testing. Despite pair-feeding, ovariectomized rats had increased body weights and fat body mass, whereas the percent lean body mass steadily declined throughout the experiment. Mineral density of the whole femur and femoral neck was significantly higher in the Sham rats relative to Ovx animals. Ovariectomy reduced trabecular number and thickness, and increased trabecular separation and bone marrow space at the femoral midneck location. The structure of the remaining trabeculae was dramatically changed toward simpler struts as revealed by nodal analyses. Cortical thickness in Ovx rats was reduced because of the high endocortical resorption, which, in addition to cancellous bone resorption, resulted in fewer endocortico-trabecular connections. Femoral necks obtained from ovariectomized rats had reduced strength and were less stiff relative to controls. Because of the enormous clinical significance of the proximal femur for osteoporosis in humans, and the opportunity for studying bone BMD, mass, structure, and strength at the same skeletal location, the femoral neck appears superior to other skeletal sites routinely used for bone histomorphometry or mechanical testing in the Ovx rat model.

Absorptiometry, Photon↗
PubMed2004

Multislice computed tomography of the distal radius metaphysis: relationship of cortical bone structure with gender, age, osteoporotic status, and mechanical competence.

We explore the relationship of region-specific densitometric and geometry-based (cortical) parameters at the distal radial metaphysis with gender, age, and osteoporotic status, using multislice computed tomography (CT). We specifically test the hypothesis that these parameters can improve the prediction of mechanical strength of the distal radius vs bone mass (bone mineral content [BMC]). The BMC was determined in 56 forearm specimens with peripheral dual-energy X-ray absorptiometry (DXA). Trabecular and cortical density and geometric properties of the metaphyseal cortex were determined using multislice CT and proprietary image analysis software. Specimens were tested to failure in a fall simulation, maintaining the integrity of the elbow joint and hand. Women displayed significantly lower failure strength (-34%), BMC (-35%), trabecular density (-26%), and cortical area (-12%) than men. The reduction of trabecular density with age and osteoporotic status was stronger than that of cortical density or thickness. DXA explained approx 50% (r2) of the variability in bone failure loads. This proportion was slightly increased (55%) when adding geometry-based parameters. The study suggests that high-resolution tomographic measurements with current clinical imaging methodology can marginally improve the prediction of mechanical failure strength. Further efforts are required to improve spatial resolution for determining metaphyseal cortical properties clinically.

Aged↗