Biomedical subjects

E Ruppin

Publications and source records attributed to E Ruppin.

At least 37 records · Page 2Linked to original sources

PubMed1998

Spreading depression in focal ischemia: a computational study.

When a cerebral infarction occurs, surrounding the core of dying tissue there usually is an ischemic penumbra of nonfunctional but still viable tissue. One current but controversial hypothesis is that this penumbra tissue often eventually dies because of the metabolic stress imposed by multiple cortical spreading depression (CSD) waves, that is, by ischemic depolarizations. We describe here a computational model of CSD developed to study the implications of this hypothesis. After simulated infarction, the model displays the linear relation between final infarct size and the number of CSD waves traversing the penumbra that has been reported experimentally, although damage with each individual wave progresses nonlinearly with time. It successfully reproduces the experimental dependency of final infarct size on midpenumbra cerebral blood flow and potassium reuptake rates, and predicts a critical penumbra blood flow rate beyond which damage does not occur. The model reproduces the dependency of CSD wave propagation on N-methyl-D-aspartate activation. It also makes testable predictions about the number, velocity, and duration of ischemic CSD waves and predicts a positive correlation between the duration of elevated potassium in the infarct core and the number of CSD waves. These findings support the hypothesis that CSD waves play an important causal role in the death of ischemic penumbra tissue.

Cerebral Infarction↗

PubMed1998

Neuronal regulation versus synaptic unlearning in memory maintenance mechanisms.

Hebbian learning, the paradigm of memory formation, needs further mechanisms to guarantee creation and maintenance of a viable memory system. One such proposed mechanism is Hebbian unlearning, a process hypothesized to occur during sleep. It can remove spurious states and eliminate global correlations in the memory system. However, the problem of spurious states is unimportant in the biologically interesting case of memories that are sparsely coded on excitatory neurons. Moreover, if some memories are anomalously strong and have to be weakened to guarantee proper functioning of the network, we show that it is advantageous to do that by neuronal regulation (NR) rather than synaptic unlearning. Neuronal regulation can account for dynamical maintenance of memory systems that undergo continuous synaptic turnover. This neuronal-based mechanism, regulating all excitatory synapses according to neuronal average activity, has recently gained strong experimental support. NR achieves synaptic maintenance over short time scales by preserving the average neuronal input field. On longer time scales it acts to maintain memories by letting the stronger synapses grow to their upper bounds. In ageing, these bounds are increased to allow stronger values of remaining synapses to overcome the loss of synapses that have perished.

Adult↗

PubMed1997

A computational model of acute focal cortical lesions.

BACKGROUND AND PURPOSE: Determining how cerebral cortex adapts to sudden focal damage is important for gaining a better understanding of stroke. In this study we used a computational model to examine the hypothesis that cortical map reorganization after a simulated infarct is critically dependent on perilesion excitability and to identify factors that influence the extent of poststroke reorganization. METHODS: A previously reported artificial neural network model of primary sensorimotor cortex, controlling a simulated arm, was subjected to acute focal damage. The perilesion excitability and cortical map reorganization were measured over time and compared. RESULTS: Simulated lesions to cortical regions with increased perilesion excitability were associated with a remapping of the lesioned area into the immediate perilesion cortex, where responsiveness increased with time. In contrast, when lesions caused a perilesion zone of decreased activity to appear, this zone enlarged and intensified with time, with loss of the perilesion map. Increasing the assumed extent of intracortical connections produced a wider perilesion zone of inactivity. These effects were independent of lesion size. CONCLUSIONS: These simulation results suggest that functional cortical reorganization after an ischemic stroke is a two-phase process in which perilesion excitability plays a critical role.

Animals↗

PubMed1996

Neuronal-based synaptic compensation: a computational study in Alzheimer's disease.

In the framework of an associative memory model, we study the interplay between synaptic deletion and compensation, and memory deterioration, a clinical hallmark of Alzheimer's disease. Our study is motivated by experimental evidence that there are regulatory mechanisms that take part in the homeostasis of neuronal activity and act on the neuronal level. We show that following synaptic deletion, synaptic compensation can be carried out efficiently by a local, dynamic mechanism, where each neuron maintains the profile of its incoming post-synaptic current. Our results open up the possibility that the primary factor in the pathogenesis of cognitive deficiencies in Alzheimer's disease (AD) is the failure of local neuronal regulatory mechanisms. Allowing for neuronal death, we observe two pathological routes in AD, leading to different correlations between the levels of structural damage and functional decline.

Alzheimer Disease↗

PubMed1996

Pathogenesis of schizophrenic delusions and hallucinations: a neural model.

We implement and study a computational model of Stevens' theory of the pathogenesis of schizophrenia. This theory hypothesizes that the onset of schizophrenia is associated with reactive synaptic regeneration in brain regions that receive degenerating temporal lobe projections. Concentrating on one such area, the frontal cortex, we model a frontal module as an associative memory neural network whose input synapses represent incoming temporal projections. Modeling Stevens' hypothesized pathological synaptic changes in this framework results in adverse side effects similar to hallucinations and delusions seen in schizophrenia: spontaneous, stimulus-independent retrieval of stored memories focused on just a few of the stored patterns. These could account for the delusions and hallucinations that occur in schizophrenia without any apparent external trigger and for their tendency to concentrate on a few central cognitive and perceptual themes. The model explains why the positive symptoms of schizophrenia tend to wane as the disease progresses, why delayed therapeutic intervention leads to a much slower response, and why delusions and hallucinations may persist for a long time when they do occur.

Brain↗

PubMed1996

Frequency-spatial transformation: a proposal for parsimonious intra-cortical communication.

This work examines a neural network model of a cortical module, where neurons are organized on a 2-dimensional sheet and are connected with higher probability to their spatial neighbors. Motivated by recent findings that cortical neurons have a resonant peak in their impedance magnitude function, we present a frequency-spatial transformation scheme that is schematically described as follows: An external input signal, applied to a small input subset of the neurons, spreads along the network. Due to a stochastic component in the dynamics of the neurons, the frequency of the spreading signal decreases as it propagates through the network. Depending on the input signal frequency, different neural assemblies will hence fire at their specific resonance frequency. We show analytically that the resulting frequency-spatial transformation is well-formed; an injective, fixed, mapping is obtained. Extensive numerical simulations demonstrate that a homogeneous, well-formed transformation may also be obtained in neural networks with cortical-like "Mexican-hat" connectivity. We hypothesize that a frequency-spatial transformation may serve as a basis for parsimonious cortical communication.

Cell Communication↗

PubMed1995

Compensatory mechanisms in an attractor neural network model of schizophrenia.

We investigate the effect of synaptic compensation on the dynamic behavior of an attractor neural network receiving its input stimuli as external fields projecting on the network. It is shown how, in the face of weakened inputs, memory performance may be preserved by strengthening internal synaptic connections and increasing the noise level. Yet, these compensatory changes necessarily have adverse side effects, leading to spontaneous, stimulus-independent retrieval of stored patterns. These results can support Stevens' recent hypothesis that the onset of schizophrenia is associated with frontal synaptic regeneration, occurring subsequent to the degeneration of temporal neurons projecting on these areas.

Brain↗

PubMed1995

Patterns of functional damage in neural network models of associative memory.

Current understanding of the effects of damage on neural networks is rudimentary, even though such understanding could lead to important insights concerning neurological and psychiatric disorders. Motivated by this consideration, we present a simple analytical framework for estimating the functional damage resulting from focal structural lesions to a neural network model. The effects of focal lesions of varying area, shape, and number on the retrieval capacities of a spatially organized associative memory are quantified, leading to specific scaling laws that may be further examined experimentally. It is predicted that multiple focal lesions will impair performance more than a single lesion of the same size, that slit like lesions are more damaging than rounder lesions, and that the same fraction of damage (relative to the total network size) will result in significantly less performance decrease in larger networks. Our study is clinically motivated by the observation that in multi-infarct dementia, the size of metabolically impaired tissue correlates with the level of cognitive impairment more than the size of structural damage. Our results account for the detrimental effect of the number of infarcts rather than their overall size or structural damage, and for the "multiplicative" interaction between Alzheimer's disease and multi-infarct dementia.

Algorithms↗

PubMed1995

A neural model of memory impairment in diffuse cerebral atrophy.

BACKGROUND: Computer-supported neural network models have been subjected to diffuse, progressive deletion of synapses/neurons, to show that modelling cerebral neuropathological changes can predict the pattern of memory degradation in diffuse degenerative processes such as Alzheimer's disease. However, it has been suggested that neural models cannot account for more detailed aspects of memory impairment, such as the relative sparing of remote versus recent memories. METHOD: The latter claim is examined from a computational perspective, using a neural associative memory model. RESULTS: The neural network model not only demonstrates progressive memory deterioration as diffuse network damage occurs, but also exhibits differential sparing of remote versus recent memories. CONCLUSIONS: Our results show that neural models can account for a large variety of experimental phenomena characterising memory degradation in Alzheimer's patients. Specific testable predictions are generated concerning the relation between the neuraonatomical findings and the clinical manifestations of Alzheimer's disease.

Aged↗

PubMed1993

A neural model of the dynamic activation of memory.

We study an Attractor Neural Network that stores natural concepts, organized in semantic classes. The concepts are represented by distributed patterns over a space of attributes, and are related by both semantic and episodic associations. While semantic relations are expressed through an hierarchical coding over the attribute space, episodic links are realized via specific synaptic projections. Due to dynamic thresholds expressing neuronal fatigue, the network's behavior is characterized by convergence toward the concept patterns on a short time scale, and by transitions between the various patterns on a longer time scale. In its baseline, undamaged state, the network manifests semantic, episodic, and random transitions, and demonstrates the phenomenon of priming. Modeling possible pathological changes, we have found that increasing the 'noise' level or the rate of neuronal fatigue decreases the frequency of semantic transitions. When neurons characterized by large synaptic connectivity are deleted, semantic transitions decay before the episodic ones, in accordance with the findings in patients with Alzheimer's disease.

Alzheimer Disease↗

PubMed1993

Examining the volume efficiency of the cortical architecture in a multi-processor network model.

The convoluted form of the sheet-like mammalian cortex naturally raises the question whether there is a simple geometrical reason for the prevalence of cortical architecture in the brains of higher vertebrates. Addressing this question, we present a formal analysis of the volume occupied by a massively connected network or processors (neurons) and then consider the pertaining cortical data. Three gross macroscopic features of cortical organization are examined: the segregation of white and gray matter, the circumferential organization of the gray matter around the white matter, and the folded cortical structure. Our results testify to the efficiency of cortical architecture.

Animals↗

PubMed1992

Extra-pyramidal symptoms in Alzheimer's disease: a hypothesis.

Recent studies have shown that compensatory processes have an important role in counteracting the neurodegenerative changes underlining Alzheimer's disease (AD), much like their well known role in Parkinson's disease (PD). In the light of these reports, we review the findings of the positive correlation existing between the appearance of extra-pyramidal symptoms and an increased rate of progression in AD patients. We propose that this correlated symptomatology arises from the wasting of globally shared compensatory resources, manifested both in an increasing inability to compensate for persisting sub-clinical nigral lesions, and in enhanced AD deterioration rate. Our hypothesis gains support from various clinical reports and by the neural modeling of synaptic changes in AD.

Alzheimer Disease↗

PubMed1989

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies.

We carried out a prospective, randomized, double-blind, placebo-controlled study to investigate the capacity of aspirin to prevent pregnancy-induced hypertension and to alter prostaglandin metabolism. A total of 791 pregnant women with various risk factors for pre-eclamptic toxemia were screened with use of the rollover test (a comparison of blood pressure before and after the woman rolls from her left side to her back) during week 28 or 29 of gestation. Of 69 women with abnormal results (an increase in blood pressure during the rollover test), 65 entered the study and were treated with a daily dose of either aspirin (100 mg; 34 women) or placebo (31 women) during the third trimester of pregnancy. The number of women in whom pregnancy-induced hypertension developed was significantly lower among the aspirin-treated than among the placebo-treated women (4 [11.8 percent] vs. 11 [35.5 percent]; P = 0.024); the same was true for the incidence of preeclamptic toxemia (1 [2.9 percent] vs 7 [22.6 percent]; P = 0.019). The mean ratio of serum levels of thromboxane A2 to serum levels of prostacyclin metabolites after three weeks of treatment decreased by 34.7 percent in the aspirin-treated group but increased by 51.2 percent in the placebo-treated group. No serious maternal or neonatal side effects of treatment occurred in either group. We conclude that low daily doses of aspirin taken during the third trimester of pregnancy significantly reduce the incidence of pregnancy-induced hypertension and pre-eclamptic toxemia in women at high risk for these disorders, possibly through the correction of an imbalance between levels of thromboxane and prostacyclin.

Adult↗

PubMed1984

[Significance of hormones in the amniotic fluid. 1. Insulin and C-peptide].

Samples of amniotic fluid of 275 healthy women were used to establish a standard profile of amniotic fluid insulin and C-peptide concentrations versus gestational age. The reasons for amniocentesis were: exclusion of chromosomal defects, rhesus immunisation, and determination of the L/S ratio. The concentrations of both peptides which were measured in the amniotic fluid in diabetics were compared with the normal profile. We found that long-term blood glucose control as estimated by the concentration of glycosylated haemoglobins in maternal blood is not well correlated with amniotic fluid insulin or C-peptide, respectively. In a few cases with poor metabolic control, we found normal insulin values, and vice versa. Since elevated insulin and C-Peptide levels in amniotic fluid correlate well with diabetic foetopathy, we conclude that measurement of both peptides provides a useful parameter in the management of a diabetic pregnancy.

Amniocentesis↗

PubMed1981

[A double blind study of the treatment of threatened abortion with fenoterol hydrobromide (author's transl)].

UNLABELLED: To study the effectiveness of Fenoterol Hydrobromide in the treatment of threatened abortion a double blind trial was performed. A total of 112 patients was examined. A comprehensive statistical analysis was made including Chi square and Student's t-test to provide a valid comparison of both, trial and control groups, in order to eliminate any possible statistical bias, as seen in many of the former studies of this topic. RESULTS: 1. The number of surviving children during the perinatal period did not differ significantly in the placebo and Fenoterol groups. 2. Fenoterol did not influence the course of pregnancy, full term delivery or fetal outcome, unless early abortion occurred. 3. Pregnancies resulting in abortions obviously were not prolonged by Fenoterol treatment. 4. Histology of aborted pregnancies revealed major pathological findings in more than 99% of the cases. So it may be presumed, that pharmacological treatment was bound to fail in these cases.

Abortion, Threatened↗

PubMed1979

[The syndrome of acute fatty liver in pregnancy].

It is reported on the syndrome of the acute fatty liver of pregnancy and pointed out that early diagnosis, subsequent early termination of pregnancy and intensive treatment of complications, especially of hepatic and renal failure and disturbed blood clotting could reduce the mortality from almost 90 to 45 per cent within the recent years.

Acute Disease↗

PubMed1978

[On the use of fenoterolhydrobromide in the treatment of imminent abortion (author's transl)].

A report was made about the retrospective comparison of a purely hormonal and a hormonal-tocolytic therapy of abortus imminens in 153 patients. The statistical comparison of the two groups was later specified. As a successful criterion, the successful childbirth was based upon. In this case it was found out, that an additional tocolytic medication of the final result was insignificantly affected, rather the hospital admittance under the tocolysis was significantly lengthened and the number of pregnancies which ended through abortion was reduced. Through this clear indication, it could be said, that pregnancies with delicate prognosis through tocolytic therapy are possibly unnecessarily lengthened and the final result is not better.

Abortion, Threatened↗

PubMed1976

[A comparison between so-called triple-diagnosis and surgical biopsy in diagnosis of the female breast (author's transl)].

A comparison of 265 cases of tripel-diagnosis and 112 surgical biopsies of the female breast is reported. In 89,83% of these 265 cases the correct diagnosis was found, in 9,43% the result was doubtful, in 0,75% completely wrong. In 3,77% of these doubtful results the repetition of the tripel-diagnosis gave the correct diagnosis, in 4,15% surgical biopsy we found 2,68% wrong diagnosis. This fact shows the certainty of tripel-diagnosis. In addition the highly significant lower rate of complications, the avoidance of the risk of narcosis and scars and the lower amount of costs show the high clinical value of the so-called tripel-diagnosis.

Biopsy↗