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Multicystic encephalomalacia of infancy: clinico-pathological report of 7 cases.

Clinical follow up and complete neuropathological examination was made on seven cases of multicystic encephalomalacia of infancy. Etiological factors were carefully studied in all the cases. They consisted of prenatal injuries presenting as a cord prolapse, in 3 cases; prolonged labour with marked cyanosis; abdominal trauma during gestation, and various maternal infections at different stages of pregnancy. Pathological interest is centred on the variable involvement of different areas of the brain, generally sparing the cerebellum and brain stem, and being minimal or absent in the occipito-temporal areas. This distribution may be explained by a different effect of the "causal agency" on these different areas, or by a different capacity of these regions to react against injury. Among the etiological factors reviewed in the literature, the anoxic theory appears the most probable, as there was a close parallelism between lesions and vascular areas, mainly the carotid and vertebro-basilar systems.

Asphyxia Neonatorum↗

Vasopressin and amphetamine, but not desglycinamide vasopressin, impair positively reinforced visual attention performance in rats.

Rats were trained to respond to the lever above which a light stimulus was briefly (0.5 s) presented at unpredictable times. Once the task had been learned to criterion, subjects were injected, intra-peritoneally, with arginine8-vasopressin, desglycinamide arginine8-vasopressin (AVP or DGAVP: 0, 5, 10 or 20 micrograms/kg) or D-amphetamine (AMP: 0, 0.75, 1.5 or 3 mg/kg) prior to test. Attention performance was assessed using several different indices, including percent corrects, sensitivity and responsivity measures derived from signal detection theory, the recently described probability of (response) repetition and switching, and latency to respond. AVP had a disruptive effect on percent corrects at the highest dose and increased response latencies, but DGAVP, which lacks pressor activity, had no behavioral effects. AMP markedly impaired most aspects of performance, and was the only substance to alter response strategies by inducing bias and repetitive responding. It is concluded that (1) contrary to some recent reports, visual attention is disrupted, not improved, by peripherally injected AVP, (2) these effects reflect pressor potency, (3) the disruption induced by AMP reflects response alterations, while the peptide probably affects more cognitive mechanisms, and (4) certain recently described indices are more sensitive than others in detecting response bias.

Animals↗

The electroencephalogram in the prediction of human reaction time during growth and development.

Characteristics of the distributions of electroencephalographic (EEG) half waves recorded in children during performance of a simple auditory reaction time (RT) task were investigated. The purpose was to determine the extent to which difference in these distributions could account for children's slow RT. The durations of a sample of 760 EEG half waves in each of a group of 41 healthy children aged 5-17 yr were measured and distributed into an interval histogram, and the first four central moments of the 41 distributions were computed. All four of the moments-which measure the central tendency, dispersion, skewness and kurtosis of the distributions-proved to be significantly correlated (p less than 0.01) with RT. The multiple correlation (R) between RT and the four moments was equal to 0.68 and was statistically significant. R was unchanged when only the measures of dispersion, skewness and kurtosis were used as predictor variables, suggesting that the predictive value of the central tendency is low. The predictive capability of a multiple regression equation based on these three predictor variables was tested in an independent group of 42 children also aged 5-17 yr. EEGs and RTs were recorded and this group was treated in exactly the same way as the other group. The correlation between these children's average RTs and their RTs as estimated from the other group's regression equation was 0.53. These findings suggested that knowing the degree of dispersion, skewness and kurtosis of the children's EEG distributions reduces from chance by about 28% the error of predicting their RTs.

Adolescent↗

Novel approach to a quantitative treatment of the quantal transmitter release at the frog neuromuscular junction.

To explain the discrepancy between estimates of parameters of quantal transmitter release received by different techniques the paper postulates a novel concept for quanta mobilization, which assumes that a quantum emitted by a vesicle transiently acquires a transition state in which it is immediately available for release. The working particle model is formulated in terms of probabilities of inter-state quanta transitions. The parameters of the model are determined by fitting solutions to the experimental curves representing short-term changes of synaptic efficacy at the frog neuromuscular junction as well as taking into account the morphologically estimated number of releasable vesicles. The value of the model is demonstrated by successful prediction of the estimates of the parameters of the quantal transmitter release suggested by evidence received from different lines of research.

Animals↗

Hypothesis generation, probability judgment, and individual differences in working memory capacity.

This research examined the role of working memory (WM) in probability judgment and hypothesis generation using a simulated task that involved estimating the likelihood that particular menu items would be ordered by customers at a dinner. Five main findings were observed. First, judgments of the likelihood of individual items were made relative to alternatives retrieved from long-term memory. Second, the number of alternatives retrieved was positively correlated with a measure of WM-capacity (the operation-span task). Third, participants' probability judgments were subadditive (summing to well over 100%). Fourth, the degree to which participants' judgments were subadditive was affected by the number and strength of the alternatives retrieved from long-term memory. Fifth, the degree to which participants were subadditive was negatively correlated with WM-capacity. The results suggest that individual differences in WM-capacity are fundamental to hypothesis generation and probability judgment.

Humans↗

Statistical models of synaptic transmission evaluated using the expectation-maximization algorithm.

Amplitude fluctuations of evoked synaptic responses can be used to extract information on the probabilities of release at the active sites, and on the amplitudes of the synaptic responses generated by transmission at each active site. The parameters that describe this process must be obtained from an incomplete data set represented by the probability density of the evoked synaptic response. In this paper, the equations required to calculate these parameters using the Expectation-Maximization algorithm and the maximum likelihood criterion have been derived for a variety of statistical models of synaptic transmission. These models are ones where the probabilities associated with the different discrete amplitudes in the evoked responses are a) unconstrained, b) binomial, and c) compound binomial. The discrete amplitudes may be separated by equal (quantal) or unequal amounts, with or without quantal variance. Alternative models have been considered where the variance associated with the discrete amplitudes is sufficiently large such that no quantal amplitudes can be detected. These models involve the sum of a normal distribution (to represent failures) and a unimodal distribution (to represent the evoked responses). The implementation of the algorithm is described in each case, and its accuracy and convergence have been demonstrated.

Algorithms↗

Probabilistic secretion of quanta: spontaneous release at active zones of varicosities, boutons, and endplates.

The amplitude-frequency histogram of spontaneous miniature endplate potentials follows a Gaussian distribution at mature endplates. This distribution gives the mean and variance of the quantum of transmitter. According to the vesicle hypothesis, this quantum is due to exocytosis of the contents of a single synaptic vesicle. Multimodal amplitude-frequency histograms are observed in varying degrees at developing endplates and at peripheral and central synapses, each of which has a specific active zone structure. These multimodal histograms may be due to the near synchronous exocytosis of more than one vesicle. In the present work, a theoretical treatment is given of the rise of intraterminal calcium after the stochastic opening of a calcium channel within a particular active zone geometry. The stochastic interaction of this calcium with the vesicle-associated proteins involved in exocytosis is then used to calculate the probability of quantal secretions from one or several vesicles at each active zone type. It is shown that this procedure can account for multiquantal spontaneous release that may occur at varicosities and boutons, compared with that at the active zones of motor nerve terminals.

Animals↗

Effects of variance in mini amplitude on stimulus-evoked release: a comparison of two models.

The strength of synaptic connections between two neurons is characterized by the number of release sites (N) on the presynaptic cell, the probability (p) of transmitter release at those sites in response to a stimulus, and the average size (A) of the postsynaptic response from each site. Quantal analysis can determine N, p, and A, but the large variance in the amplitudes of minis at central synapses is predicted to obscure quantal peaks and render quantal analysis unusable. Recently it has been suggested that the variance in mini amplitude is generated by differences between release sites, rather than by quantum-to-quantum fluctuations at identical sites, and that this form of variance in mini amplitude reduces the amount of variance expected in quantal peaks. Using simulations, we examine the possibility of resolving quantal peaks assuming either form of variance in mini amplitude. We find that individual quantal peaks are resolvable in neither case, provided that the uniquantal distribution is similar to the mini distribution. Because this lack of resolution compromises the utility of quantal analysis, we develop a general description that can solve N and p, given the statistical parameters of the mini distribution and the evoked distribution. We find that this description is relatively insensitive to the source of variance in mini amplitude.

Analysis of Variance↗

Accounting for the shapes and size distributions of miniature endplate currents.

The current model does not account adequately for the characteristics of miniature endplate currents (MEPCs). We do not understand their relatively slow rise, the shape of their rise, their variable and sometimes prolonged decay, and the correlation between amplitude and decay time. If we assume that ACh is released from the vesicle through a pore and that the vesicle enlarges as it takes on additional transmitter, the predictions are more like MEPCs. However, previous measurements showed that after quantal size was increased the vesicles in the terminal were not enlarged. This need not be a problem, because some of the ACh is added to vesicles positioned at the active zones, a process known as second-stage loading. By using the false transmitter precursor monoethylcholine we provide additional evidence for second-stage loading. The distribution of quantal sizes at the junction usually does not follow a normal probability distribution; it is skewed to the right. The skew can be accounted for by a model incorporating second-stage loading in which the vesicles are released randomly, without regard to their ACh content. If the vesicles increase in size when they contain more transmitter, only vesicles at the active zone need swell.

Acetylcholine↗

Probabilistic secretion of quanta and the synaptosecretosome hypothesis: evoked release at active zones of varicosities, boutons, and endplates.

A quantum of transmitter may be released upon the arrival of a nerve impulse if the influx of calcium ions through a nearby voltage-dependent calcium channel is sufficient to activate the vesicle-associated calcium sensor protein that triggers exocytosis. A synaptic vesicle, together with its calcium sensor protein, is often found complexed with the calcium channel in active zones to form what will be called a "synaptosecretosome." In the present work, a stochastic analysis is given of the conditions under which a quantum is released from the synaptosecretosome by a nerve impulse. The theoretical treatment considers the rise of calcium at the synaptosecretosome after the stochastic opening of a calcium channel at some time during the impulse, followed by the stochastic binding of calcium to the vesicle-associated protein and the probability of this leading to exocytosis. This allows determination of the probabilities that an impulse will release 0, 1, 2,... quanta from an active zone, whether this is in a varicosity, a bouton, or a motor endplate. A number of experimental observations of the release of transmitter at the active zones of sympathetic varicosities and boutons as well as somatic motor endplates are described by this analysis. These include the likelihood of the secretion of only one quantum at an active zone of endplates and of more than one quantum at an active zone of a sympathetic varicosity. The fourth-power relationship between the probability of transmitter release at the active zones of sympathetic varicosities and motor endplates and the external calcium concentration is also explained by this approach. So, too, is the fact that the time course of the increased rate of quantal secretion from a somatic active zone after an impulse is invariant with changes in the amount of calcium that enters through its calcium channel, whether due to changes consequent on the actions of autoreceptor agents such as adenosine or to facilitation. The increased probability of quantal release that occurs during F1 facilitation at the active zones of motor endplates and sympathetic boutons is predicted by the residual binding of calcium to a high-affinity site on the vesicle-associated protein. The concept of the stochastic operation of a synaptosecretosome can accommodate most phenomena involving the release of transmitter quanta at these synapses.

Action Potentials↗