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PubMed1996

Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites.

1. Excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage clamp from granule cells in slices of rat cerebellum. EPSCs from individual mossy fibre inputs were identified by their all-or-none appearance in response to a graded stimulus. Excitatory synaptic transmission was investigated at room temperature (approximately 24 degrees C) and at near-physiological temperature (approximately 34 degrees C) by analysing current fluctuations in the peak and decay of the non-N-methyl-D-aspartate (non-NMDA) component of EPSCs. 2. In a subset of synapses the mean EPSC amplitude remained unchanged as the probability of transmitter release was substantially lowered by raising the extracellular [Mg2+] and lowering [Ca2+]. These synapses were considered to have only one functional release site. Single-site synapses had small EPSCs (139 +/- 16 pS, n = 5, at 24 degrees C) with a large coefficient of variation (c.v. = 0.23 +/- 0.02, n = 5) and an amplitude distribution that was well fitted by a Gaussian distribution in four out of five cases. The EPSC latency had a unimodal distribution and its standard deviation had a temperature dependence with a temperature coefficient (Q10; range, 24-35 degrees C) of 2.4 +/- 0.4 (n = 4). 3. Peak-scaled non-stationary fluctuation analysis of single-site EPSCs indicated that the mean conductance of the underlying non-NMDA channels was 12 +/- 2 pS (n = 4) at 35 degrees C. Upper and lower limits for mean channel open probability (Po), calculated from fluctuations in the EPSC peak amplitude, were 0.51 and 0.38, respectively. These estimates, together with the open probability of the channel when bound by transmitter, suggest that only about 50% of the non-NMDA channels were occupied following the release of a quantum of transmitter. 4. At some multi-site synapses EPSCs had a low c.v. (0.4 +/- 0.01, n = 5) at 34 degrees C and non-stationary fluctuation analysis gave a parabolic variance-mean current relationship. This suggests that practically all of the non-NMDA receptors were occupied by glutamate at the peak of EPSC. The channel open probability (Po = 0.84 +/- 0.03, n = 5) at these 'saturated' multi-site synapses will therefore equal the open probability of the channel when bound by transmitter (Po,max). 5. Non-stationary fluctuation analysis of EPSCs from 'saturating' multi-site synapses indicated that 170 +/- 40 postsynaptic non-NMDA channels were exposed to transmitter at the peak of the EPSC. The mean conductance of the synaptic channels was 10 +/- 2 pS (n = 5) at 34 degrees C. 6. At synapses with multiple release sites the EPSC decay time became faster when release probability was lowered (by reducing the external [Ca2+]/[Mg2+] ratio), indicating that the transmitter concentration profile depended on release probability. No such speeding of the EPSC decay was observed at single-site synapses. 7. Our results suggest that release of a packet of transmitter from a single release site does not saturate postsynaptic non-NMDA receptors at cerebellar mossy fibre-granule cell synapses. However, at multi-site synapses transmitter released from neighbouring sites can overlap, changing the transmitter concentration profile in the synaptic cleft. We conclude that the level of postsynaptic receptor occupancy can depend on the probability of transmitter release at individual multi-site synapses.

Animals↗
PubMedDate not supplied

Post-test probability for pulmonary embolism after ventilation-perfusion scan assessed by nuclear medicine physicians.

OBJECTIVE: The objective of this prospective study was to compare assessments of pre- and post-ventilation-perfusion (V/Q) scan probabilities for pulmonary embolism (PE) by the nuclear medicine physician and the referring physician. MATERIALS AND METHODS: Seventy-nine patients (41 females, 38 males, mean age 49 years) referred for V/Q scans over a period of 6 months and suspected of PE were included in the study. The pre-test likelihood was determined independently by a consultant nuclear physician and a referring physician prior to the V/Q scan. The scan was performed according to a standard protocol using 8 view technetium-99m diethylenetriamine pentaacetic acid aerosol ventilation study followed by a technetium-99m macroaggregated albumin perfusion study. The scan was interpreted according to prospective investigation of pulmonary embolism diagnosis criteria. The post-scan probability was calculated. The probability of PE was quoted as low, intermediate and high. Agreement or disagreement in assessing the pre- and post-scan probability was classified according to the degree of difference (no difference: 0; minor difference: 1, and major difference: 2 grades). RESULTS: The agreement between the nuclear medicine and referring physicians on clinical probability of PE was moderate (63%) before the scan and good (90%) after the scan. The disagreement in assessing the clinical probability between the referring physician and the nuclear medicine physician was predominantly minor. Only 5 and 1% of the disagreement was major in pre-scan and post-scan probabilities, respectively. CONCLUSION: The data show that nuclear medicine physicians can use the assessment of pre-scan clinical likelihood to determine the post-scan probability of PE.

Adult↗
PubMed1987

Probability and delay in commitment.

In the first stage of a two-stage choice, human subjects chose between probabilistic access to a second choice (between a small high-probability reward and a large low-probability reward) and commitment to the large low-probability reward. When confronted with the second-stage choice, subjects strongly preferred the small high-probability reward. When the first-stage probability (of access to the second stage) was high, subjects strongly preferred the path leading to the choice in the second stage. But when the first-stage probability was low, subjects committed themselves to the large low-probability reward. These results parallel those obtained by Rachlin and Green (1972) with pigeons and constitute some evidence that probabilities may be interpreted as delays.

Journal Article↗
PubMed1994

Bias in self-evaluation: Signal probability effects.

Two experiments examined apparent signal probability effects in simple verbal self-reports. After each trial of a delayed matching-to-sample task, young adults pressed either a "yes" or a "no" button to answer a computer-presented query about whether the most recent choice met a point contingency requiring both speed and accuracy. A successful matching-to-sample choice served as the "signal" in a signal-detection analysis of self-reports. Difficulty of matching to sample, and thus signal probability, was manipulated via the number of nonmatching sample and comparison stimuli. In Experiment 1, subjects exhibited a bias (log b) for reporting matching-to-sample success when success was frequent, and no bias or a bias for reporting failure when success was infrequent. Contingencies involving equal conditional probabilities of point consequences for "I succeeded" and "I failed" reports had no systematic effect on this pattern. Experiment 2 found signal probability effects to be evident regardless of whether referent-response difficulty was manipulated in different conditions or within sessions. These findings indicate that apparent signal probability effects in self-report bias that were observed in previous studies probably were not an artifact of contingencies intended to improve self-report accuracy or of the means of manipulating signal probability. The findings support an analogy between simple self-reports and psychophysical judgments and bolster the conclusion of Critchfield (1993) that signal probability effects can influence simple self-reports much as they do reports about external stimuli in psychophysical experiments.

Journal Article↗
PubMed2005

A randomized trial of ways to describe test accuracy: the effect on physicians' post-test probability estimates.

BACKGROUND: Some people believe that likelihood ratios provide diagnostic information that is more useful than sensitivity and specificity estimates. OBJECTIVE: To assess how physicians' estimates about probability of illness are affected by the presentation of a diagnostic test's value as an estimate of sensitivity and specificity versus a likelihood ratio or an inexact numerical graphic. DESIGN: Random assignment of vignettes with different presentation formats of diagnostic test accuracy. SETTING: Auditorium at a continuing medical education conference. PARTICIPANTS: 183 physicians. INTERVENTION: After estimating probabilities of 6 common illnesses described in patient vignettes, physicians reviewed pertinent test results presented in 1 of 3 formats. MEASUREMENTS: Physicians' probability estimates of illness before and after receiving test information, and post-test probability estimates based on the Bayes theorem. RESULTS: Absolute percentage point differences between the physicians' estimated and the Bayes-based post-test probabilities varied from -7 to 31, from -7 to 28, and from 1 to 29 for the sensitivity and specificity, likelihood ratio, and graphical groups, respectively. Mean differences of probability estimates between the sensitivity and specificity and the likelihood ratio groups were small for all vignettes (-2 to 3 percentage points; summary mean z value across the 6 vignettes, 0.04 [95% CI, -0.14 to 0.21]). LIMITATIONS: The small pool of participants (who were potentially selected) and the limited number of vignettes prevented a more detailed analysis of relationships between the interpreted strength of diagnostic evidence and estimations of illness probability. CONCLUSIONS: These findings suggest that presenting diagnostic test accuracy with likelihood ratios does not affect some physicians' estimates of illness probability compared with presenting diagnostic test results as sensitivity and specificity.

Adult↗
PubMed2003

Variable dopamine release probability and short-term plasticity between functional domains of the primate striatum.

Release of the neuromodulator dopamine (DA) is critical to the control of locomotion, motivation, and reward. However, the probability of DA release is not well understood. Current understanding of neurotransmitter release probability in the CNS is limited to the conventional synaptic amino acid transmitters (e.g., glutamate and GABA). These fast neurotransmitters are released with a repertoire of probabilities according to synapse type, and these probabilities show activity-dependent plasticity according to synapse use. Synapses for neuromodulators such as DA, however, are designed for signaling that diverges temporally and spatially from that for fast neurotransmitters: DA receptors are exclusively metabotropic and at sites that extend to extrasynaptic locations and neighboring synapses. In this study, the release probability of DA was explored in real time in limbicversus motor-associated functional domains of the striatum of a primate (marmoset; Callithrix jacchus) using fast-scan voltammetry at a carbon-fiber microelectrode. We show that the probability of axonal DA release varies with striatal domain. Furthermore, release probability exhibits a short-term, activity-dependent plasticity that ranges from depression to facilitation in motor-through limbic-associated regions, respectively. Rapid plasticity does not result from metabotropic D2-like DA receptor activation or ionotropic GABA(A) receptor effects but is dependent on Ca2+ availability. These data reveal that rapid dynamics in DA release probability will participate in the transmission of the patterns and frequencies encoded by DA neuron action potential discharge. Furthermore, the regional variation in these features indicates that limbic-versus motor-associated DA neurons are permitted to generate diverse DA signals in response to a given firing pattern.

Animals↗
PubMed2004

Diagnostic testing, pre- and post-test probabilities, and their use in clinical practice.

In the process of establishing a diagnosis, the clinician calculates the disease probabilities, which keep changing as data is gathered from clinical history, physical examination and laboratory and imaging data. This paper sets out to explain, in a simple and practical way, how the characteristics of a test can be applied in order to determine post-test probability, that is, the probability of a specific disease being present. Before applying the test, we start with a pretest probability that corresponds to the prevalence of the disease. With each additional test this probability changes, until a threshold is reached that includes or excludes the clinical diagnosis. To calculate the post-test probabilities, the sensitivity and specificity of the test are used to calculate the positive and negative predictive values for a determined pretest probability, as well as likelihood ratios (through graphics or nomograms, approximations or equations). Among the test characteristics, the most useful for calculating post-test probabilities are likelihood ratios, which have several advantages over sensitivity and specificity.

Clinical Medicine↗
PubMed2004

Probability detection mechanisms and motor learning.

The automatic detection of patterns or regularities in the environment is central to certain forms of motor learning, which are largely procedural and implicit. The rules underlying the detection and use of probabilistic information in the perceptual-motor domain are largely unknown. We conducted two experiments involving a motor learning task with direct and crossed mapping of motor responses in which probabilities were present at the stimulus set level, the response set level, and at the level of stimulus-response (S-R) mapping. We manipulated only one level at a time, while controlling for the other two. The results show that probabilities were detected only when present at the S-R mapping and motor levels, but not at the perceptual one (experiment 1), unless the perceptual features have a dimensional overlap with the S-R mapping rule (experiment 2). The effects of probability detection were mostly facilitatory at the S-R mapping, both facilitatory and inhibitory at the perceptual level, and predominantly inhibitory at the response-set level. The facilitatory effects were based on learning the absolute frequencies first and transitional probabilities later (for the S-R mapping rule) or both types of information at the same time (for perceptual level), whereas the inhibitory effects were based on learning first the transitional probabilities. Our data suggest that both absolute frequencies and transitional probabilities are used in motor learning, but in different temporal orders, according to the probabilistic properties of the environment. The results support the idea that separate neural circuits may be involved in detecting absolute frequencies as compared to transitional probabilities.

Adolescent↗
PubMedDate not supplied

Clinical usefulness of D-dimer depending on clinical probability and cutoff value in outpatients with suspected pulmonary embolism.

BACKGROUND: We evaluated whether a highly sensitive D-dimer test is clinically useful and safe for ruling out pulmonary embolism (PE) in patients with a high clinical probability and whether adopting different cutoff values according to the clinical probability category might increase the proportion of patients in whom PE is ruled out. METHODS: We retrospectively analyzed the databases of 2 outcome studies on the diagnosis of PE with a 3-month follow-up that included 1409 patients. We evaluated the usefulness of D-dimer testing by calculating the number needed to test to rule out one PE, and its safety by measuring the 3-month thromboembolic risk in patients not treated by anticoagulant agents based on a normal D-dimer level. RESULTS: The sensitivity of D-dimer was 100% in all clinical probability categories, but the number needed to test increased with increasing clinical probability of PE. The 95% confidence interval (0%-23%) of the 3-month thromboembolic risk (0%) among 13 of 121 patients with a normal D-dimer level and a high clinical probability of PE was wide. Increasing the cutoff value to 700 mug/L in patients with a low clinical probability would rule out PE in an additional 5% of the entire patient cohort at the expense of a lower sensitivity (93% [95% confidence interval, 83%-97%]). CONCLUSIONS: The safety of D-dimer testing in patients with a high clinical probability of PE is not established, and testing results are rarely negative in such patients. Increasing the enzyme-linked immunosorbent assay D-dimer cutoff value only marginally increased the test's usefulness.

Aged↗
PubMed2004

Measuring Alzheimer's disease progression with transition probabilities in the Taiwanese population.

BACKGROUND: The transition probability of Alzheimer's disease (AD) is defined as the likelihood that the disease progresses from one stage to another in a given time period. OBJECTIVE: To estimate the separate stage-to-stage and stage-to-death transition probabilities for Taiwanese patients with AD and to evaluate the hazard ratios of age, sex, behavioral symptoms, and medications on disease progression. METHOD: We examined data (severity of dementia, hallucinations or delusions, use of cholinesterase inhibitors [CEIs], survival) in 365 patients with probable AD at baseline and at follow-Gup (mean +/- SD 29 +/- 17 months, range 3-109 months). RESULTS: Modified survival analysis revealed that transition probabilities of Taiwanese patients were similar to those of Western patients. The probability of dementia remaining at the same stage was higher in patients taking CEIs than in other. Men had a higher probability of dying in the mild stage. CONCLUSION: Transition probabilities can be used to measure AD progression. CEIs used to treat AD might alter the disease course.

Age Factors↗
PubMed1999

On the shape of the probability weighting function.

Empirical studies have shown that decision makers do not usually treat probabilities linearly. Instead, people tend to overweight small probabilities and underweight large probabilities. One way to model such distortions in decision making under risk is through a probability weighting function. We present a nonparametric estimation procedure for assessing the probability weighting function and value function at the level of the individual subject. The evidence in the domain of gains supports a two-parameter weighting function, where each parameter is given a psychological interpretation: one parameter measures how the decision maker discriminates probabilities, and the other parameter measures how attractive the decision maker views gambling. These findings are consistent with a growing body of empirical and theoretical work attempting to establish a psychological rationale for the probability weighting function.

Humans↗
PubMedDate not supplied

Patients' interpretations of probability terms.

STUDY OBJECTIVES: To assess the meaning ascribed by patients to qualitative expressions of probability commonly used in medical care and to determine patient preferences for obtaining information when communicating with their physicians about medical risk numerically and/or qualitatively. DESIGN: Cross-sectional survey of consecutive patients. SETTING: A university-based Department of Veterans Affairs medical center. PARTICIPANTS: 133 patients sequentially seen in a general medicine clinic. MEASUREMENTS AND MAIN RESULTS: Subjects were given a randomly ordered list of 12 common terms, each a qualitative expression of probability. They were asked to indicate what they understood to be the numerical meaning of each word. The patients' probability estimates were found to comprise two groups of five terms each, with high intercorrelations among the probabilities assigned to the terms in each group. Mean probabilities assigned to terms in the first group all were greater than 60%, and mean probabilities assigned to terms in the second group all were below 50%. When asked whether they wanted chance information to be provided in numerical or qualitative terms, 32% reported that they wanted it only numerically; 35.3% wanted it only qualitatively; 21.8% wanted the information either way; and 8.3% wanted the information both ways. CONCLUSIONS: The numerical meanings that patients ascribe to probability terms fall into identifiable patterns. While patients vary in the actual values they assign to terms, the relative meanings of terms show consistent trends.

Analysis of Variance↗
PubMed1989

Effects of framing and level of probability on patients' preferences for cancer chemotherapy.

Although most clinicians agree that patients should be informed about treatment alternatives, little is known about the way patients perceive probabilistic information about treatment outcomes and how it influences the choices they make. The purpose of this study was to examine the influence of level and framing of probability on preferences for cancer treatment alternatives in which tradeoffs between quantity and quality of life are made. 129 healthy volunteers and 154 cancer patients indicated their preferences for a toxic treatment over a non-toxic treatment at varying survival probabilities. Subjects responded to questions in one of three randomly assigned conditions: (1) a positive frame in which the probability of survival was given; (2) a negative frame in which the probability of dying was given; and (3) a mixed frame in which the probability of surviving and dying were both given. The cancer patients' preferences for the more effective toxic treatment was significantly stronger than the healthy volunteers. Both groups were significantly influenced by the level of probability that was presented. Preferences for the toxic treatment were weaker when the chance of survival dropped below 50%. This weakening preference below 50% survival was enhanced for subjects who responded in the negative frame. A negative frame or probability level below 0.5 would seem to stimulate a "dying mode" type of value system in which quality of life becomes more salient in decision making than quantity of life. The implications in eliciting informed consent from patients are discussed.

Adolescent↗
PubMed2005

Anxiety, depression, and judgments about the probability of future negative and positive events in children.

Probability bias refers to the phenomenon that high-anxious individuals estimate future negative events as far more likely to occur, and in particular to themselves, than low-anxious individuals. The present study further examined this cognitive bias in a sample of non-clinical children aged between 10 and 13 years. Participants completed a scale for measuring symptoms of DSM-defined anxiety disorders and major depressive disorder, and a modified version of the Subjective Probability Questionnaire in order to assess probability estimates of future negative and positive events. Results showed that children's anxiety and depression symptoms were positively associated with probability estimates of future negative events, but only when these events referred to children themselves. Further, when controlling for concurrent depression symptoms, anxiety remained significantly linked to probability ratings of self-referent negative events. When controlling for concurrent anxiety symptoms, depression was no longer linked to probability estimates of negative events. Finally, depression symptoms were negatively related to probability ratings for future positive events.

Anxiety↗
PubMed2006

Prediction error as a linear function of reward probability is coded in human nucleus accumbens.

Reward probability has been shown to be coded by dopamine neurons in monkeys. Phasic neuronal activation not only increased linearly with reward probability upon expectation of reward, but also varied monotonically across the range of probabilities upon omission or receipt of rewards, therefore modeling discrepancies between expected and received rewards. Such a discrete coding of prediction error has been suggested to be one of the basic principles of learning. We used functional magnetic resonance imaging (fMRI) to show that the human dopamine system codes reward probability and prediction error in a similar way. We used a simple delayed incentive task with a discrete range of reward probabilities from 0%-100%. Activity in the nucleus accumbens of human subjects strongly resembled the phasic responses found in monkey neurons. First, during the expectation period of the task, the fMRI signal in the human nucleus accumbens (NAc) increased linearly with the probability of the reward. Second, during the outcome phase, activity in the NAc coded the prediction error as a linear function of reward probabilities. Third, we found that the Nac signal was correlated with individual differences in sensation seeking and novelty seeking, indicating a link between individual fMRI activation of the dopamine system in a probabilistic paradigm and personality traits previously suggested to be linked with reward processing. We therefore identify two different covariates that model activity in the Nac: specific properties of a psychological task and individual character traits.

Adult↗
PubMed2002

Practical diagnostic management of patients with clinically suspected deep vein thrombosis by clinical probability test, compression ultrasonography, and D-dimer test.

PURPOSE: To evaluate a new noninvasive diagnostic strategy for ruling out deep vein thrombosis consisting of either a combination of low clinical probability and normal ultrasonography or a combination of moderate-to-high clinical probability, normal ultrasonography, and a normal D-dimer test. SUBJECTS AND METHODS: We studied 811 patients with clinically suspected deep vein thrombosis using a diagnostic management strategy that combined clinical probability, ultrasonography, and measurement of D-dimers. The primary endpoint was venous thromboembolism occurring during a 3-month follow-up. RESULTS: Of the 280 patients (35%) with a low clinical probability, 30 (11%) had an abnormal initial ultrasonography and were treated. Of the other 250 untreated patients with low clinical probability and a normal ultrasonography, 5 (2%; 95% confidence interval [CI]: 1% to 5%) developed a nonfatal venous thromboembolism during follow-up. Of the 531 patients (65%) with a moderate-to-high clinical probability, 300 (56%) had an abnormal ultrasonography. Of the remaining 231 patients with a normal ultrasonography, 148 had a normal D-dimer test; none of these patients developed deep vein thrombosis during follow-up (0%; 95% CI: 0% to 3%). Of the 83 patients with an abnormal D-dimer test, 77 underwent repeat ultrasonography about 1 week later; none of the 64 patients with a second normal ultrasound developed symptomatic deep vein thrombosis during follow-up (0%; 95% CI: 0% to 6%). CONCLUSIONS: This management strategy, which combines clinical probability, ultrasonography, and D-dimer measurements, is practical and safe in ruling out deep vein thrombosis in patients with clinically suspected thrombosis and reduces the need for repeat ultrasonography.

Adult↗
PubMed1992

Calculated enhancement of open base pair probability downstream of a (TATA)2 box.

The modified self-consistent phonon approximation is generalized to calculate the open base pair probability of a (TATA)2 insert between two semi-infinite poly(dA-dC) . poly(dG-dT) helices. An iterative method based entirely on the Green's function method is developed to compute the open interbase hydrogen bond probability of the insert and near bases versus temperature. The open interbase hydrogen bond probability is calculated for two temperatures and compared with perfect homopolymer open base pair probabilities at room temperature. The probability of opening is enhanced by a factor of two for the major groove bond of the AT pair at the transcriptional downstream end of the (TATA)2 insert. The total base pair opening probability of that pair is enhanced by 54%. The probability of the next inline GC base pair to be open is increased by a factor of ten.

Base Composition↗
PubMed2002

The effect of stimulus probability on pupillary response as an indicator of cognitive processing in human learning and categorization.

Stimuli presented with a low probability of occurrence elicit larger pupillary dilations than those presented with a high frequency. Utilizing this stimulus probability effect, we conducted two Go/NoGo reaction time experiments to analyze category learning and compound coding in the context of associative learning. Experiment 1 showed no stimulus probability effect when participants used an abstract rule to classify stimuli with different probabilities into the same category. When no rules could be applied, however, the stimulus probability effect was observed. Hence, this effect can be utilized to identify the application of rules in category learning. Experiment 2 demonstrated that the stimulus probability effect can also be used in determining whether compounds are processed in terms of elemental stimuli or as new entities. The results of Experiment 2 supported elemental rather than configural processing. Obviously, the probability effect can be used as a tool for the evaluation of categorization and compound processing.

Adult↗