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Biomedical subjects

M I Miller

Publications and source records attributed to M I Miller.

49 records · Page 3Linked to original sources

A personal computer based implementation of the maximum-likelihood method of analysis of electron microscope autoradiographs.

The maximum-likelihood (ML) method for the quantitative analysis of electron-microscopic autoradiographs has been shown to be substantially superior to the conventional crossfire (CF) method. It can generate reliable and accurate tracer concentration estimates with far fewer micrographs and produce valid estimates even at counts low enough to preclude the use of the crossfire method while eliminating the need for special ad hoc treatment of narrow membranous structures as well as the secondary verification of the tracer concentration estimates. Despite these significant advantages, the large computational requirements of the ML method has to date hampered its widespread use. In this paper, we present a new line-integration method that allows us to reduce the computational requirements of the ML method to a point where it becomes feasible to implement it on a small computer system of the type typically available to a laboratory user of EM autoradiography. We present the complete line-integration method for the particular case of EM autoradiography with tritium, and show how it can be adapted to other isotopes. We have constructed a software package that implements the complete maximum-likelihood method on the IBM PC class of machines using our line-integration method. Features of this software package which are of particular importance to the research community are device independence, which makes it usable with a large variety of currently available laboratory equipment, and easy portability of the software and data between different computer systems.

Algorithms↗

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↗

A statistical study of cochlear nerve discharge patterns in response to complex speech stimuli.

Cochlear nerve discharge patterns in response to the synthesized consonant-vowel stimulus /da/ were collected from a population of 223 auditory-nerve fibers from a single cat. For each nerve fiber, discharges were measured from multiple, independent stimulus presentations, with the means and variances of the post-stimulus time histograms and Fourier transforms of response generated from the ensemble of stimulus presentations. The statistics were not consistent with those predicted via an inhomogeneous Poisson counting process model. Specifically, the synchronized components as measured by the Fourier transforms of post-stimulus time histogram responses have variances that are as much as a factor of 3 times lower than the predicted by the Poisson model. To account for the non-Poisson nature of the statistics, the Markov process model of Siebert/Gaumond was adopted. Using the maximum-likelihood and minimum description length algorithms, introduced by Miller [J. Acoust. Soc. Am. 77, 1452-1464 (1985)] and Mark and Miller [J. Acoust. Soc. Am. 91, 989-1002 (1992)], estimates of the stimulus and recovery functions were computed for each nerve fiber. Then, Markov point processes were simulated with the stimulus and recovery functions generated from these nerve fibers. The statistics of the simulated Markov processes are shown to have almost identical first- and second-order statistics as those measured for the population of auditory-nerve fibers, and demonstrates the effectiveness of the Markov point process model in accounting for the correlation effects associated with the discharge history-dependent refractory properties of auditory nerve response.

Acoustic Stimulation↗

Regularized linear method for reconstruction of three-dimensional microscopic objects from optical sections.

The inverse problem involving the determination of a three-dimensional biological structure from images obtained by means of optical-sectioning microscopy is ill posed. Although the linear least-squares solution can be obtained rapidly by inverse filtering, we show here that it is unstable because of the inversion of small eigenvalues of the microscope's point-spread-function operator. We have regularized the problem by application of the linear-precision-gauge formalism of Joyce and Root [J. Opt. Soc. Am. A 1, 149 (1984)]. In our method the solution is regularized by being constrained to lie in a subspace spanned by the eigenvectors corresponding to a selected number of large eigenvalues. The trade-off between the variance and the regularization error determines the number of eigenvalues inverted in the estimation. The resulting linear method is a one-step algorithm that yields, in a few seconds, solutions that are optimal in the mean-square sense when the correct number of eigenvalues are inverted. Results from sensitivity studies show that the proposed method is robust to noise and to underestimation of the width of the point-spread function. The method proposed here is particularly useful for applications in which processing speed is critical, such as studies of living specimens and time-lapse analyses. For these applications existing iterative methods are impractical without expensive and/or specially designed hardware.

Computer Simulation↗

Bayesian image reconstruction for emission tomography incorporating Good's roughness prior on massively parallel processors.

Since the introduction by Shepp and Vardi [Shepp, L. A. & Vardi, Y. (1982) IEEE Trans. Med. Imaging 1, 113-121] of the expectation-maximization algorithm for the generation of maximum-likelihood images in emission tomography, a number of investigators have applied the maximum-likelihood method to imaging problems. Though this approach is promising, it is now well known that the unconstrained maximum-likelihood approach has two major drawbacks: (i) the algorithm is computationally demanding, resulting in reconstruction times that are not acceptable for routine clinical application, and (ii) the unconstrained maximum-likelihood estimator has a fundamental noise artifact that worsens as the iterative algorithm climbs the likelihood hill. In this paper the computation issue is addressed by proposing an implementation on the class of massively parallel single-instruction, multiple-data architectures. By restructuring the superposition integrals required for the expectation-maximization algorithm as the solutions of partial differential equations, the local data passage required for efficient computation on this class of machines is satisfied. For dealing with the "noise artifact" a Markov random field prior determined by Good's rotationally invariant roughness penalty is incorporated. These methods are demonstrated on the single-instruction multiple-data class of parallel processors, with the computation times compared with those on conventional and hypercube architectures.

Algorithms↗

Data acquisition system for maximum-likelihood analysis of electron microscopic autoradiographs.

EMAMAP is a program for the data acquisition phase of maximum-likelihood analysis of electron microscope autoradiographs. This program is written in C and has been implemented on a Masscomp MC-500 which supports a graphics processor and a digitizing tablet. The image analysis is automated at a low level: the program operator outlines the edges of the structures of interest using the digitizing tablet, while contiguous regions formed by closed contours are automatically filled by the software. The resulting image is compressed for efficient storage by a quadtree encoding technique for which data compression ratios of greater than 25:1 have been achieved. In practical terms, this implies that the data from a typical experiment of 50 autoradiographs could be stored on a single floppy disk. The system is currently in use for acquiring actual biological experimental data.

Autoradiography↗

Multiple myeloma presenting with primary meningococcal arthritis.

A 64-year-old white man presented with Neisseria meningitidis primary septic arthritis. Further evaluation revealed multiple myeloma. Increased susceptibility to infection occurs early in multiple myeloma; thus, a rare cause of primary septic arthritis, such as N. meningitidis, warrants a full evaluation for immunocompromise.

Arthritis, Infectious↗

Recruitment of internal oblique and transversus abdominis muscles during the eccentric phase of the curl-up exercise.

The purpose of this study was to analyze the results of a training method to increase voluntary recruitment of internal oblique and transversus abdominis muscles. Forty volunteers were assigned to either a Control or an Experimental Group. Training consisted of multisensory (auditory, tactile, visual, and kinesthetic) cuing focused on the lower abdominal muscles during the slow curl-back (eccentric) phase of curl-up exercises with the subjects' feet unsupported. We recorded integrated electromyographic (IEMG) values using surface electrodes from internal oblique and transversus abdominis muscles during pretest and posttest exercises. Using an analysis of covariance, posttest IEMG values of the Experimental Group were significantly higher (p less than .001) than the Control Group. Our results reveal that multisensory cuing with the feet unsupported during the curl-back is an effective method of increasing combined recruitment of internal oblique and transversus abdominis muscles. Motor skills developed by this technique are discussed in relation to optimal trunk function and rehabilitation.

Abdominal Muscles↗

Strategies for the representation of a tone in background noise in the temporal aspects of the discharge patterns of auditory-nerve fibers.

The responses of populations of auditory-nerve fibers to both a 1.0-kHz tone, and 1.0-kHz tone in broadband noise, have been measured. Period histograms were generated from fiber spike trains and discrete Fourier transforms (DFTs) with a resolution of 125 Hz were computed from each histogram. Sample mean and sample variance statistics were generated for period histograms of response and for temporal response measures derived from discrete Fourier transforms. It is demonstrated how the statistical properties of auditory-nerve fiber response determine the strategy for the estimation and discrimination of particular stimulus components. When the tone is presented alone, the entire population of auditory-nerve fibers provides statistically reliable estimates of the 1.0-kHz tone. Upon addition of the broadband noise stimulus only those units with characteristic frequencies which are close in frequency to the 1.0-kHz stimulus provide spectral estimates which have high signal-to-noise ratios (mean-squared-to-variance ratios). Estimates of the 1.0-kHz-tone stimulus derived from auditory-nerve fibers with characteristic frequencies which are far from the 1.0-kHz stimulus are statistically unreliable. Based on the responses of the population of auditory-nerve fibers, the strategy for estimating the 1.0-kHz-tone stimulus is to derive estimates of the 1.0-kHz stimulus from the subpopulation of neurons with characteristic frequencies close to the 1.0-kHz stimulus. It is concluded that neurons which are tuned close to 1.0-kHz provide the central nervous system (CNS) with the most salient information about the 1.0-kHz stimulus in the presence of the broadband background.

Analysis of Variance↗

Algorithms for removing recovery-related distortion from auditory-nerve discharge patterns.

The probability that a cochlear nerve fiber discharges during some specified time interval depends on both the acoustic stimulus and on refractory effects due to earlier spike discharges. With the objective of separating the stimulus-related effects from refractory-related effects seen in poststimulus-time histograms, various maximum-likelihood estimation schemes have been developed. By modeling auditory-nerve fiber discharges as a self-exciting point process in which the intensity depends on both the time during stimulation and the history of discharge, we have been able to independently verify the likelihood estimates of Gaumond et al. [J. Acoust. Soc. Am. 74, 1392-1398 (1983)] under conditions when the recovery function is known. Secondly by maximizing the likelihood function of the neural event process subject to periodic stimulus constraints we have derived estimates which as the number of stimulus presentations and or stimulus periods increase are free from the effects of both absolute and relative recovery-related distortion. Under conditions when the recovery function is unknown, a recursive algorithm is proposed that yields the joint maximum-likelihood estimates of both the stimulus-and recovery-related components in the response histograms. We state the conditions under which unique maximum-likelihood estimates exist and prove that the recursive algorithm converges to those unique estimates.

Acoustic Stimulation↗

Representation of voice pitch in discharge patterns of auditory-nerve fibers.

Responses of populations of auditory-nerve fibers were measured for synthesized consonant-vowel stimuli. This paper explores the encoding of fundamental frequency (pitch) in these responses. Post-stimulus time (PST) histograms were computed from 25 ms segments of the spike trains. Discrete Fourier transforms with a 40 Hz resolution were computed from the histograms. Two representations of pitch are considered. The first representation is based on the pitch-related temporal properties of the speech signal. Histograms for individual units can show envelope modulations directly related to the pitch period. These modulations reflect the responses of these fibers to a number of stimulus harmonics near fiber CF. Responses of fibers near formant frequencies are dominated by a single large harmonic component, and thus show small or no pitch-related enveloped modulations. Envelope modulations are reduced in the presence of background noise. The second representation uses both temporal properties of auditory-nerve responses and cochlear place to encode the pitch-related harmonic structure of speech. As a measure of the response of the population of fibers to each harmonic of 40 Hz the magnitude of the component of the Fourier transform at that frequency was averaged across all fibers whose characteristic frequencies were within one-fourth octave of that harmonic. We call this measure the average localized synchronized rate (ALSR). The ALSR provides a good representation of stimulus spectrum, even in the presence of background noise. From the harmonic structure of the ALSR, we are able to extract the stimulus pitch frequency. The relationship of these two representations to pitch perception in both acoustic and electrical stimulation (via cochlear implants) is discussed.

Acoustic Stimulation↗

Representation of stop consonants in the discharge patterns of auditory-nerve fibers.

The representation of the speech syllables /da/ and /ba/ in populations of auditory-nerve fibers was studied. Post-stimulus-time histograms were computed from 20-ms segments of fiber spike trains occurring in response to the stimulus. Discrete Fourier transforms with a resolution of 50 Hz were computed from each histogram. As a measure of the response of the population of fibers to each harmonic of the 50-Hz resolution frequency of the transform, the magnitude of the response to that frequency was averaged across all fibers whose characteristic frequencies were within one-fourth octave of that harmonic. We have previously called this measure the average localized synchronized rate (ALSR). Response profiles for the 20-ms segments of the stimulus were generated by plotting the ALSR versus frequency. Time-varying spectral features of the /da/ and /ba/ stimuli are well preserved by such profiles. For example, the onset spectrum and formant transitions of the consonant-vowel syllable are well represented. Furthermore, the fine structure in the speech spectrum related to the pitch of the excitation source is maintained in these ALSR plots. Average discharge rate profiles were generated in a manner similar to that for the ALSR; in this case average rate replaces Fourier transform components as response measure. Such average rate profiles can represent the transitions of at least formants two and three. However, such average rate profiles do not represent the steady-state formants or the voice pitch.

Animals↗