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Results for “Likelihood Functions”

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PubMed2001

An analysis of neural receptive field plasticity by point process adaptive filtering.

Neural receptive fields are plastic: with experience, neurons in many brain regions change their spiking responses to relevant stimuli. Analysis of receptive field plasticity from experimental measurements is crucial for understanding how neural systems adapt their representations of relevant biological information. Current analysis methods using histogram estimates of spike rate functions in nonoverlapping temporal windows do not track the evolution of receptive field plasticity on a fine time scale. Adaptive signal processing is an established engineering paradigm for estimating time-varying system parameters from experimental measurements. We present an adaptive filter algorithm for tracking neural receptive field plasticity based on point process models of spike train activity. We derive an instantaneous steepest descent algorithm by using as the criterion function the instantaneous log likelihood of a point process spike train model. We apply the point process adaptive filter algorithm in a study of spatial (place) receptive field properties of simulated and actual spike train data from rat CA1 hippocampal neurons. A stability analysis of the algorithm is sketched in the. The adaptive algorithm can update the place field parameter estimates on a millisecond time scale. It reliably tracked the migration, changes in scale, and changes in maximum firing rate characteristic of hippocampal place fields in a rat running on a linear track. Point process adaptive filtering offers an analytic method for studying the dynamics of neural receptive fields.

Adaptation, Physiological↗

PubMed2005

Identification of four gene variants associated with myocardial infarction.

Family history is a major risk factor for myocardial infarction (MI). However, known gene variants associated with MI cannot fully explain the genetic component of MI risk. We hypothesized that a gene-centric association study that was not limited to candidate genes could identify novel genetic associations with MI. We studied 11,053 single-nucleotide polymorphisms (SNPs) in 6,891 genes, focusing on SNPs that could influence gene function to increase the likelihood of identifying disease-causing gene variants. To minimize false-positive associations generated by multiple testing, two studies were used to identify a limited number of nominally associated SNPs; a third study tested the hypotheses that these SNPs are associated with MI. In the initial study (of 340 cases and 346 controls), 637 SNPs were associated with MI (P<.05); these were evaluated in a second study (of 445 cases and 606 controls), and 31 of the 637 SNPs were associated with MI (P<.05) and had the same risk allele as in the first study. For each of these 31 SNPs, we tested the hypothesis that it is associated with MI, using a third study (of 560 cases and 891 controls). We found that four of these gene variants were associated with MI (P<.05; false-discovery rate <10%) and had the same risk allele as in the first two studies. These gene variants encode the cytoskeletal protein palladin (KIAA0992 [odds ratio (OR) 1.40]), a tyrosine kinase (ROS1 [OR 1.75]), and two G protein-coupled receptors (TAS2R50 [OR 1.58] and OR13G1 [OR 1.40]); all ORs are for carriers of two versus zero risk alleles. These findings could lead to a better understanding of MI pathophysiology and improved patient risk assessment.

Aged↗

PubMed2005

Figure-ground segmentation from occlusion.

Layered video representations are increasingly popular; see [2] for a recent review. Segmentation of moving objects is a key step for automating such representations. Current motion segmentation methods either fail to segment moving objects in low-textured regions or are computationally very expensive. This paper presents a computationally simple algorithm that segments moving objects, even in low-texture/low-contrast scenes. Our method infers the moving object templates directly from the image intensity values, rather than computing the motion field as an intermediate step. Our model takes into account the rigidity of the moving object and the occlusion of the background by the moving object. We formulate the segmentation problem as the minimization of a penalized likelihood cost function and present an algorithm to estimate all the unknown parameters: the motions, the template of the moving object, and the intensity levels of the object and of the background pixels. The cost function combines a maximum likelihood estimation term with a term that penalizes large templates. The minimization algorithm performs two alternate steps for which we derive closed-form solutions. Relaxation improves the convergence even when low texture makes it very challenging to segment the moving object from the background. Experiments demonstrate the good performance of our method.

Algorithms↗

PubMed1978

Febrile convulsions followed by nonfebrile convulsions: analysis based on a maximum likelihood method and discriminant function.

Two hundred sixty-two nontreated patients with febrile convulsions only and 107 with later nonfebrile convulsions were analyzed based on a maximum likelihood method and discriminant function. The formula for discrimination is as follows: y = 2.9193 x (basic EEG abnormality at the first examination) + 2.2134 x (more than 20 minutes in duration of convulsion) + 1.7358 (fever under 38.4 degrees C before convulsion) + 1.7005 x (specific EEG abnormality at the first examination) + 1.6703 x (more than 5 recurrences) + 1.5610 x (over 4 years of age at the last convulsion) + 1.4921 x (exogenous causes) + 0.3741 x (family histroy of febrile convulsions among second or third relatives)--3.0397. If an item is positive, coefficient x 1 is to be used, and if it is negative, coefficient x 0 is to be applied. When one classifies patients with y greater than 0 as the FCC group, and those with y less than 0 as the FC group, misclassification may be theoretically expected in 18.9% of cases (accuracy in 81.1%).

Age Factors↗

PubMed2005

Analyzing functional connectivity using a network likelihood model of ensemble neural spiking activity.

Analyzing the dependencies between spike trains is an important step in understanding how neurons work in concert to represent biological signals. Usually this is done for pairs of neurons at a time using correlation-based techniques. Chornoboy, Schramm, and Karr (1988) proposed maximum likelihood methods for the simultaneous analysis of multiple pair-wise interactions among an ensemble of neurons. One of these methods is an iterative, continuous-time estimation algorithm for a network likelihood model formulated in terms of multiplicative conditional intensity functions. We devised a discrete-time version of this algorithm that includes a new, efficient computational strategy, a principled method to compute starting values, and a principled stopping criterion. In an analysis of simulated neural spike trains from ensembles of interacting neurons, the algorithm recovered the correct connectivity matrices and interaction parameters. In the analysis of spike trains from an ensemble of rat hippocampal place cells, the algorithm identified a connectivity matrix and interaction parameters consistent with the pattern of conjoined firing predicted by the overlap of the neurons' spatial receptive fields. These results suggest that the network likelihood model can be an efficient tool for the analysis of ensemble spiking activity.

Action Potentials↗

PubMed2003

QMLE: fast, robust, and efficient estimation of distribution functions based on quantiles.

Quantile maximum likelihood (QML) is an estimation technique, proposed by Heathcote, Brown, and Mewhort (2002), that provides robust and efficient estimates of distribution parameters, typically for response time data, in sample sizes as small as 40 observations. In view of the computational difficulty inherent in implementing QML, we provide open-source Fortran 90 code that calculates QML estimates for parameters of the ex-Gaussian distribution, as well as standard maximum likelihood estimates. We show that parameter estimates from QML are asymptotically unbiased and normally distributed. Our software provides asymptotically correct standard error and parameter intercorrelation estimates, as well as producing the outputs required for constructing quantile-quantile plots. The code is parallelizable and can easily be modified to estimate parameters from other distributions. Compiled binaries, as well as the source code, example analysis files, and a detailed manual, are available for free on the Internet.

Data Interpretation, Statistical↗

PubMed1996

Comparing non-hierarchical models: application to non-linear mixed effects modeling.

There is no method available to compare the fit of two non-hierarchical non-linear mixed effects models, although the common practice is to select the model with the lower objective function. Bootstrapping the log-likelihood differences (LLDs) of non-hierarchical models and constructing a bootstrap confidence interval on the LLDs is proposed for comparing the goodness-of-fit of such models. This is illustrated with different parameterizations of clearance models for an anti-infective agent in a longitudinal pharmacokinetic study which are compared. Additive and exponential models of creatinine clearance as a predictor of clearance are used as examples.

Adult↗

PubMed2003

Hazard regression for interval-censored data with penalized spline.

This article introduces a new approach for estimating the hazard function for possibly interval- and right-censored survival data. We weakly parameterize the log-hazard function with a piecewise-linear spline and provide a smoothed estimate of the hazard function by maximizing the penalized likelihood through a mixed model-based approach. We also provide a method to estimate the amount of smoothing from the data. We illustrate our approach with two well-known interval-censored data sets. Extensive numerical studies are conducted to evaluate the efficacy of the new procedure.

Biometry↗

PubMed2004

A maximum likelihood method for detecting functional divergence at individual codon sites, with application to gene family evolution.

The tailoring of existing genetic systems to new uses is called genetic co-option. Mechanisms of genetic co-option have been difficult to study because of difficulties in identifying functionally important changes. One way to study genetic co-option in protein-coding genes is to identify those amino acid sites that have experienced changes in selective pressure following a genetic co-option event. In this paper we present a maximum likelihood method useful for measuring divergent selective pressures and identifying the amino acid sites affected by divergent selection. The method is based on a codon model of evolution and uses the nonsynonymous-to-synonymous rate ratio (omega) as a measure of selection on the protein, with omega = 1, < 1, and > 1 indicating neutral evolution, purifying selection, and positive selection, respectively. The model allows variation in omega among sites, with a fraction of sites evolving under divergent selective pressures. Divergent selection is indicated by different omega's between clades, such as between paralogous clades of a gene family. We applied the codon model to duplication followed by functional divergence of (i) the epsilon and gamma globin genes and (ii) the eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) genes. In both cases likelihood ratio tests suggested the presence of sites evolving under divergent selective pressures. Results of the epsilon and gamma globin analysis suggested that divergent selective pressures might be a consequence of a weakened relationship between fetal hemoglobin and 2,3-diphosphoglycerate. We suggest that empirical Bayesian identification of sites evolving under divergent selective pressures, combined with structural and functional information, can provide a valuable framework for identifying and studying mechanisms of genetic co-option. Limitations of the new method are discussed.

Amino Acids↗

PubMed1995

A spatial oculomotor memory-task performance produces a task-related slow shift in human electroencephalography.

Electroencephalographic (EEG) deflections in humans related to the performance of memory-guided saccades were studied in this work. The EEG deflections were recorded during 2 spatial oculomotor delayed response tasks in which the subject was instructed to make a saccade either to the right or to the left depending on the spatial location of the cue which had been shown in the beginning of the delay period. The EEG deflections were compared to those recorded during a control task in which the subject also made a saccade to the right or to the left after a delay but the requirement to keep spatial information actively in mind was minimized. A slow delay-related shift was recorded during all task conditions. The slow shift was positive in the most frontal and negative in the more posterior recording sites. The negative slow shift in the more posterior recording sites was larger in the memory tasks than in the control task. Since the memory and the control tasks differed mainly in their requirement to hold spatial information in mind it is suggested that the difference in the magnitude of slow shifts between the memory and the control tasks reflects neural activity related to spatial working memory. But although the oculomotor responses in all tasks were similar, the preparatory activities for the impending eye movements may not have been similar and in addition to working memory may have contributed to the observed differences in the slow shifts.

Adult↗

PubMed1990

Features of "near-death experience" in relation to whether or not patients were near death.

The medical records of 58 patients, most of whom believed they were near death during an illness or after an injury and all of whom later remembered unusual experiences occurring at the time, were examined. 28 patients were judged to have been so close to death that they would have died without medical intervention; the other 30 patients were not in danger of dying although most of them thought they were. Patients of both groups reported closely similar experiences but patients who really were close to death were more likely than those who were not to report an enhanced perception of light and enhanced cognitive powers. The claim of enhancement of cognitive functions despite the likelihood that brain function had probably become disturbed and possibly diminished, deserves further investigation.

Adolescent↗

PubMed2006

Classification images of two right hemisphere patients: a window into the attentional mechanisms of spatial neglect.

While spatial neglect most commonly occurs after right hemisphere lesions, damage to diverse areas within the right hemisphere may lead to neglect, possibly through different mechanisms. To identify potentially different causes of neglect, the visual information used (the 'perceptual template') in a cueing task was estimated with a novel technique known as 'classification images' for five normal observers and two male patients with right-hemisphere lesions and previous histories of spatial neglect (CM, age 85; HL, age 69). Observers made a yes/no decision on the presence of a 'White X' checkerboard signal (1.5 degrees ) at one of two locations, with trial-to-trial stimulus noise added to the 9 checkerboard squares. Prior to the stimulus, a peripheral precue (140 ms) indicated the signal location with 80% validity. The cueing effects and estimated perceptual templates for the normal observers showed no visual field differences. Consistent with previous studies of spatial neglect, both patients had difficulty with left (contralesional) signals when preceded by a right (ipsilesional) cue. Despite similar behavioral results, the patients' estimated perceptual templates in the left field suggested two different types of attentional deficits. For CM, the left template matched the signal with left-sided cues but was opposite in sign to the signal with right-sided cues, suggesting a severely disrupted selective attentional strategy. For HL, the left templates indicated a general uncertainty in localizing the signal regardless of the cue's field. In conclusion, the classification images suggested different underlying mechanisms of neglect for these two patients with similar behavioral results and hold promise in further elucidating the underlying attentional mechanisms of spatial neglect.

Adult↗

PubMed1998

Selecting linear-score distributions for modelling milk-culture results.

The data for this cross-sectional retrospective study are from surveys of 65 dairy-cattle herds in central New York, USA sampled between February, 1993 and March, 1995. The objective was to identify probability distributions of logarithmically transformed somatic-cell counts (linear score) for use in a simulation model of mastitis and milk quality. Probability density functions were estimated using maximum-likelihood estimators for the linear score of individual-cow composite-milk samples culture negative and culture positive for the pathogens Streptococcus agalactiae, Streptococcus non-agalactiae, Staphylococcus aureus, and coagulase-negative staphylococci for the complete dataset and by bulk-tank somatic-cell count group (< 500,000, > or = 500,000 SCC/ml). Based on the rankings of three goodness-of-fit tests (Anderson-Darling, Kolmogorov-Smirnov and chi 2), the Weibull distribution (among the three top-ranking distributions for 14 out of 15 cases) may be used to model the individual-cow linear-score response by culture-result-specific bulk-tank somatic-cell count group. A beta distribution was among the three top-ranking distributions for nine out of 15 culture-result-specific bulk-tank somatic-cell count groups and has a logical relationship to linear score because it is defined on a fixed interval. On the other hand, the normal distribution had a poorer fit than the Weibull and at least two other distributions for all culture negative and coagulase-negative staphylococci samples. We do not assume that the underlying biological processes are fully explained by either Weibull or beta distribution--but modelling the linear score for the above culture results with these distributions provided an adequate fit to the survey data, reduced the need for two-sided truncation that open intervals needed, and had errors that did not appear to be systematically positive or negative.

Animals↗

PubMedDate not supplied

Stress radionuclide imaging versus stress echocardiography: a framework for comparisons.

Comparisons of stress-imaging procedures require analyses based on their 2 principal applications: diagnostic and prognostic assessments. Besides comparing results reported in the literature--in which differences have been reported in the ability of stress nuclear versus stress echocardiographic imaging to predict a low risk of cardiac events-other factors often not reported may be important in discerning the relative efficacy of these tests. These include consideration of how these tests perform in specific, individualized patient scenarios; the effect of on-going technical advances on test usefulness; and evaluation of test worthiness according to such factors as cost-effectiveness and the magnitude of incremental test information that is provided. Furthermore, it is important to distinguish between a test's efficacy (ie, its intrinsic accuracy) and its effectiveness (ie, how it performs in the real world of clinical practice).

Coronary Disease↗

PubMed1999

Simultaneous maximum a posteriori reconstruction of attenuation and activity distributions from emission sinograms.

In order to perform attenuation correction in emission tomography an attenuation map is required. We propose a new method to compute this map directly from the emission sinogram, eliminating the transmission scan from the acquisition protocol. The problem is formulated as an optimization task where the objective function is a combination of the likelihood and an a priori probability. The latter uses a Gibbs prior distribution to encourage local smoothness and a multimodal distribution for the attenuation coefficients. Since the attenuation process is different in positron emission tomography (PET) and single photon emission tomography (SPECT), a separate algorithm for each case is derived. The method has been tested on mathematical phantoms and on a few clinical studies. For PET, good agreement was found between the images obtained with transmission measurements and those produced by the new algorithm in an abdominal study. For SPECT, promising simulation results have been obtained for nonhomogeneous attenuation due to the presence of the lungs.

Abdomen↗

PubMed1999

Modeling clustered, discrete, or grouped time survival data with covariates.

We have developed methods for modeling discrete or grouped time, right-censored survival data collected from correlated groups or clusters. We assume that the marginal hazard of failure for individual items within a cluster is specified by a linear log odds survival model and the dependence structure is based on a gamma frailty model. The dependence can be modeled as a function of cluster-level covariates. Likelihood equations for estimating the model parameters are provided. Generalized estimating equations for the marginal hazard regression parameters and pseudolikelihood methods for estimating the dependence parameters are also described. Data from two clinical trials are used for illustration purposes.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Bayesian model selection and minimum description length estimation of auditory-nerve discharge rates.

Auditory-nerve fiber discharges are modeled as self-exciting point processes with intensity given by the product of a stimulus-related function and a refractory-related function. Previous methods of estimating these two functions, based on the maximum-likelihood principle, have the problem of estimating more parameters than the data can support. A new procedure, based on a Bayes criterion for choosing the complexity of the model in addition to estimating the parameters, solves the over-parametrization problem. This procedure is seen to relate asymptotically to Rissanen's minimum description length (MDL) criterion. A performance comparison of the MDL procedure with previous maximum-likelihood algorithms promotes the adoption of the MDL procedure for simultaneous estimation of the stimulus and recovery properties of auditory-nerve discharge.

Algorithms↗

PubMed2004

Therapeutic delay and reduced functional status six months after thrombolysis for acute myocardial infarction.

Thrombolytic therapy decreases the mortality rate in patients with acute myocardial infarction (AMI), and the timing of thrombolysis has proved to be critical for decreasing the short-term mortality rate. Much less is known about the longer term consequences of delays in thrombolysis, particularly for outcomes other than the mortality rate. We assessed the effect of time to thrombolysis and other clinical predictors on cardiac functional status 6 months after AMI. We used InTIME II, a multicenter trial, to test the efficacy of alteplase and lanoteplase. This component of the trial was conducted in 147 North American centers. Patients were > or =18 years of age with ST-elevated AMI. Functional status was measured by the Duke Activity Status Index, which was administered 6 months after AMI. After multivariate adjustment for baseline characteristics, delay in presentation to hospital and delay in initiation of thrombolysis were significantly and independently associated with decreased cardiac functional status 6 months later. Each additional hour from symptom onset to hospital presentation was associated with a 16% increase (95% confidence interval 3% to 31%) in the likelihood of functional impairment (Duke Activity Status Index score < or =30). In addition, each additional delay of 1 hour from hospital presentation to thrombolysis independently increased the probability of functional impairment by 38% (12% to 71%). Thus, in patients with AMI, earlier presentation to the hospital and more rapid initiation of thrombolysis could prevent significant decreases in functional status months after the initial infarct.

Activities of Daily Living↗