Biomedical subjects

D C Hood

Publications and source records attributed to D C Hood.

At least 55 records · Page 3Linked to original sources

PubMed1995

Phototransduction in human cones measured using the alpha-wave of the ERG.

To study human cone phototransduction, the alpha-wave of the ERG was recorded from color normals, dichromats, and patients with retinitis pigmentosa. A model of the activation phase of phototransduction, previously fitted to responses from single rods and the rod alpha-wave, was modified and fitted to the human cone alpha-wave. The modified model fits the cone alpha-wave well and allows questions about human cone phototransduction to be addressed. In particular, we conclude that: (1) the amplification of the activation phase of human cone transduction is comparable to that of the human rods. (2) Steady lights have relatively little effect on the amplification of cone transduction. (3) The normal alpha-wave elicited by red flashes is dominated by the L cones, consistent with a ratio of L:M cones of > 1. (4) Retinitis pigmentosa caused by mutations of the rhodopsin gene can affect cone phototransduction. Finally, a simpler computational expression is shown to approximate the modified model's responses.

Adult↗

PubMed1995

Testing a computational model of light-adaptation dynamics.

Experiments from the periodic and aperiodic traditions were used to guide the development of a quantitatively valid model of light adaptation dynamics. Temporal contrast sensitivity data were collected over a range of 3 log units of mean luminance for sinusoids of 2 to 50 Hz. Probe thresholds on flashed backgrounds were collected over a range of stimulus-onset asynchronies and background intensities from 0.1 to 1000 td. All experiments were performed foveally in the photopic range and used a consistent stimulus paradigm and psychophysical method. The resulting model represents a merging of elements from both traditions, and consists of a frequency-dependent front-end followed by a subtractive process and static nonlinearity.

Adaptation, Ocular↗

PubMed1995

Enhanced S cone syndrome: evidence for an abnormally large number of S cones.

The cellular basis of the hypersensitivity of the S (blue) cone system in patients with enhanced S cone syndrome was examined by analyzing ERGs from three patients. The patients had large alpha-waves in response to the blue and white flashes. These alpha-waves were shown to be driven nearly entirely by the S cones. Although these S cone alpha-waves were 4-6 times the size of the normal L/M cone alpha-wave, they are of the same form, and could be quantitatively described with the same model previously shown to fit cone alpha-waves. We propose that the retina of these patients has many more S cones than the normal retina and that these cones replace some of the normal L/M cones and many of the rods.

Adolescent↗

PubMed1995

Shades of gray matter: noninvasive optical images of human brain responses during visual stimulation.

Recent theories about human brain function emphasize the need for imaging methods that allow the study of dynamic interactions among different structures. In this paper, we report on a new technique, based on the measurement of parameters of migration of near-infrared photons, that yields functional images of the human occipital cortex, combining a spatial resolution of 0.5 cm and a temporal resolution of 50 ms. This technique appears to be suitable for studying the dynamics of cortical activation.

Adult↗

PubMed1995

Rod transduction parameters from the a wave of local receptor populations.

The analysis of electroretinogram a waves from locally stimulated populations of rods is complicated by the presence of scattered light within the eye. Scattered-light and cone contributions can be assessed after brief flashes of light designed to saturate only rods in the locally stimulated area. Subtracting the scattered-light and the cone responses from the local electroretinogram gives a pure rod a wave that can be fitted with models of photoreceptor activity. We demonstrate the feasibility of this technique by recording local rod a waves from a group of five normal subjects and by fitting the a waves with the rod model to derive transduction parameters. The local rod a waves are compared with expected responses derived from simulations in which the response of the entire retina to heterogeneous illumination is mimicked.

Adult↗

PubMed1995

Abnormal activation and inactivation mechanisms of rod transduction in patients with autosomal dominant retinitis pigmentosa and the pro-23-his mutation.

PURPOSE: The leading edge of the rod a-wave in normal human subjects can be fit with a computational model of the activation phase of transduction to provide parameters analogous to those obtained from individual photoreceptors. The authors extend this work to the kinetics of recovery after saturating flashes. METHODS: Electroretinograms were recorded from three patients with autosomal dominant retinitis pigmentosa and the pro-23-his rhodopsin mutation, two patients with rod monochromatism, and five normal subjects. Rod-only a-waves were obtained for a series of flashes ranging from 4.4 to 10.1 ln (1.9 to 4.4 log) scot td-sec. One set of parameters describing the activation process was derived from fits to the a-wave model. A double-flash paradigm was used to study inactivation mechanisms. The first flash was achromatic and varied in intensity (I(f)) from 6.1 to 13.9 ln (2.6 to 6.0 log) scot td-sec. The second flash was a short-wavelength probe held constant at 9.3 ln (4.0 log) scot td-sec. Cone components were elicited with a photopically matched long-wavelength stimulus and were computer subtracted. Recovery at each I(f) was followed by measuring the amplitude to the probe flash at various interstimulus intervals (ISI). The critical time (Tc) before the initiation of rod recovery was determined from the function relating relative rod amplitude to ISI. RESULTS: Recovery from activation was similar in normal subjects and in patients with rod monochromatism. Over a large range of I(f) above rod saturation, Tc increased in proportion to ln I(f). The mean slope of the function relating Tc to I(f) was 2.3 s/ln I(f) when I(f) varied between 11 and 13.9 ln scot td-sec. Patients with retinitis pigmentosa and the pro-23-his rhodopsin mutation had a decrease in the gain of activation. They also had significantly slower than normal recovery after high test flash intensities, such that the slope of the function relating Tc to ln I(f) was 12.1 seconds. CONCLUSION: Available data from other species imply that complete, transient activation of transducin (T saturation) occurs within or below the investigated range of flash intensities. Based on the slope of the delay function (delta Tc/ delta ln I(f)) above 11 ln scot td-sec, the authors hypothesize that the lifetime of activated rhodopsin (R) in normal human rods is approximately 2.3 seconds. In patients with the pro-23-his mutation, the gain of the activation mechanism is reduced and the reaction determining the delta Tc/ delta ln I(f) slope is markedly slowed. The activated species that exhibits this prolonged lifetime could be the mutant rhodopsin itself.

Adolescent↗

PubMed1995

Rod phototransduction in retinitis pigmentosa. Distinguishing alternative mechanisms of degeneration.

PURPOSE: To test alternative hypotheses concerning the mechanisms of rod degeneration in retinitis pigmentosa (RP). METHODS: Full-field rod electroretinograms and rod visual fields were measured for 15 patients with RP and a normal control group. The rod a-wave was fitted with a computational model based on known transduction biochemistry. The values of td (the initial delay), S (a sensitivity parameter), and RmP3 (the maximum amplitude) were estimated. Rod b-wave amplitudes were fitted with the Michaelis-Menten equation, and the parameters Kbw (the semisaturation intensity--a sensitivity parameter) and Vmax (the maximum amplitude) were estimated. RESULTS: The patients all had significantly reduced values of RmP3, indicating rod receptor damage, and a wide range of S values. Three patients had S values in the normal range. Four had abnormal S values but normal thresholds in some locations in their visual field. The remaining patients had abnormal values of S and entirely abnormal visual fields. Three of those had a history of large elevations in Kbw. For all patients, the changes in Kbw and Vmax followed closely the changes in S and RmP3, respectively. CONCLUSION: Retinitis pigmentosa has a varying initial impact on the activation phase of rod transduction. Available evidence suggests that the activation of transduction is initially normal in most patients with RP. In some patients, RP appears to result in a reduced transduction amplification from birth. In all patients, subsequent degeneration of the rods effects progressive reductions in transduction amplification but no other major functional changes. Outer segment shortening and local dropout of rods appear to have little functional impact.

Adolescent↗

PubMed1994

Understanding changes in the b-wave of the ERG caused by heterogeneous receptor damage.

PURPOSE: To understand better the relationship between heterogeneous receptor damage and the changes in the b-wave of the rod ERG. METHODS: A computational model of the b-wave is used to simulate b-waves from retinas with two regions (a healthier and a more affected region) differing in area and sensitivity. The peak-to-peak amplitudes of the simulated b-waves are fitted with a Naka-Rushton equation, and the parameters log K and Vmax are estimated. Insights gained from these simulations are tested against rod ERGs and rod visual fields from patients with autosomal dominant retinitis pigmentosa (n = 11) and cone-rod dystrophy (n = 17). RESULTS: In the simulated retinas, Vmax decreases when the more affected region of receptors is less sensitive than the healthier region by more than 0.5 log unit. However, the relative change in Vmax does not match the relative area of the more affected region unless this region is depressed by 2.0 log units or more. As the more affected region loses sensitivity, log K at first increases but then decreases and approaches the log K of the healthier region for losses greater than 2.0 log units or so relative to the healthier region. For the patients' data, the simulations predict the general relationships observed between the summary statistics of the visual fields (e.g., area of field and mean of log sensitivity changes in the field) and the changes in log K and Vmax. CONCLUSION: A decrease in Vmax indicates that regions of the patient's retina have lost 0.5 log unit or more of sensitivity. An increase in log K indicates that either the healthiest part of the patient's retina is abnormal by at most delta log K, a large part of the retina has lost considerable sensitivity (i.e., 0.5 to 2.0 log units) but is still contributing to the response, or both.

Adolescent↗

PubMed1994

Rod phototransduction in retinitis pigmentosa: estimation and interpretation of parameters derived from the rod a-wave.

PURPOSE: Relationships between the Lamb and Pugh model of transduction in single rod photoreceptors and the parameters derived from human rod a-waves are examined to evaluate transduction abnormalities in retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). METHODS: ERGs were obtained from 15 patients, 11 with RP and 4 with CRD, and from 15 normal subjects. Rod-only responses were derived from responses to blue (W47B) flashes over a wide range of flash energies by computer-subtracting estimates of the cone contribution. A model of the rod's response was fitted to the a-waves of the rod-only responses as well as to the responses to the blue flashes by estimating three parameters-sensitivity (S), delay (td), and maximum response (RmP3). To assess the limits of the cone contributions to the parameters of the model, ERGs were obtained from two of the patients, two normal subjects, and three additional patients with nondetectable rod responses using white flashes. RESULTS: All patients had significantly decreased values of RmP3, and eight had significantly decreased values of S compared to the control subjects. The values of the parameters estimated from the responses to the blue flashes were reasonably similar to those for the rod-only responses except in patients with nondetectable rod signals. For the white flashes, the estimate of S was considerably larger and the fit of the model noticeably poorer. CONCLUSIONS: The authors reached two conclusions. First, some forms of RP and CRD alter the activation stages of transduction. Transduction appears normal in other patients, despite extensive receptor damage as indicated by markedly reduced RmP3 values. Second, the cone contribution to a blue flash only affects the estimate of the key parameters in patients in whom the rod component is minimal. The cone contribution to a white flash contaminates the fit and the estimate of the parameters in all patients and normal subjects.

Adolescent↗

PubMed1993

Light adaptation of human rod receptors: the leading edge of the human a-wave and models of rod receptor activity.

The human rod receptors can be studied by measuring the leading edge of the rod a-wave of the ERG. Computational models, previously shown to fit the recordings from single rods, are fitted to dark-adapted a-wave responses. A model proposed by Lamb and Pugh [(1992) Journal of Physiology, 499, 719-758] fits slightly better than the traditional models based upon n-stage exponential filters. To test alternative models of rod light adaptation, a-waves were recorded to flashes presented upon steady adapting lights. Steady adapting lights decrease the rods' sensitivity. Human rods must adapt as response compression alone predicts far greater decreases in sensitivity. The evidence suggests that the mechanism(s) of adaptation include a change in the time-course of the rod's response. Human rods appear to adapt in much the same manner as do the rods of other vertebrates.

Adaptation, Ocular↗

PubMed1993

Heterogeneity in retinal disease and the computational model of the human-rod response.

Abnormal rod-receptor activity can be quantitatively assessed in humans by fitting a computational model of the rod's response to the leading edge of the a wave of the electroretinogram. One purpose of the present study was to compare two procedures for fitting the model to the electroretinogram. A computationally simpler method gives comparable results to the more labor-intensive method used previously. This finding holds for both normal observers and patients with retinodegenerative disease that affects the receptors unevenly. A second purpose of the present study was to consider the effects of a heterogeneous disease process on the parameters of the model. a waves from a heterogeneous retina are computer simulated and are fitted with the receptor model. This analysis suggests that the model will overestimate the change in the healthiest rods and will underestimate the percentage of the rods that are significantly affected.

Adult↗

PubMed1993

Chromatic and luminance sensitivity in diabetes and glaucoma.

The effects of glaucoma and diabetes on the sensitivities of the opponent and achromatic systems were investigated by measuring thresholds along theoretically defined axes in a three-dimensional color space. Thresholds were measured along two equiluminant chromatic axes and one achromatic axis in patients with diabetes or glaucoma and in glaucoma suspects. The results were compared with measures of sensitivities of short- and middle-wavelength-sensitive-cone pathways [S (Stiles pi 1) and M (Stiles pi 4), respectively] and with measures of hue discrimination by use of the Farnsworth-Munsell 100-hue test. The glaucoma suspects and diabetic patients showed preferential S-cone-pathway sensitivity losses. For glaucoma patients, however, these losses were associated with significant decreases in the sensitivity of the L-M opponent system and with decreased sensitivity to achromatic contrast.

Adolescent↗

PubMed1993

Sites of cone system sensitivity loss in retinitis pigmentosa.

PURPOSE: To examine the sites of cone sensitivity loss in patients with retinitis pigmentosa by comparing focal electroretinographic and psychophysical modulation thresholds. METHODS: Both psychophysical and electrophysiologic increment threshold curves were obtained in retinitis pigmentosa patients and a group of age-matched, normally-sighted adults. RESULTS: The majority of the retinitis pigmentosa data could be accounted for by a vertical displacement of the normal curve. The retinitis pigmentosa patients showed similar patterns of cone sensitivity losses using both techniques. CONCLUSIONS: The combined electrophysiologic and psychophysical results provide support for an outer retina locus for these cone sensitivity losses. The data suggest that these deficits may be caused by a spatially independent loss of cone photoreceptors with normal adaptation properties in the remaining photoreceptors.

Adaptation, Ocular↗

PubMed1992

Temporal frequency dependent adaptation at the level of the outer retina in humans.

The focal electroretinogram (FERG) was used to examine temporal frequency tuning at the outer retinal level in humans by measuring temporal modulation thresholds. Changes in FERG thresholds as a function of ambient light level were compared to temporal modulation thresholds obtained psychophysically using the same stimuli. At lower temporal frequencies, both FERG and psychophysical thresholds changed sensitivity proportional to the mean illuminance level. At higher illuminance levels, both threshold measures were relatively independent of illuminance. The comparison of the FERG to the behavioral data suggest that most of the adaptation-dependent changes in temporal sensitivity in humans occur at the level of the photoreceptor complex.

Adaptation, Ocular↗

PubMed1992

Quantal noise and decision rules in dynamic models of light adaptation.

To evaluate some of the consequences of including probabilistic processes (e.g. quantal noise) in a computable model of light-adaptation dynamics, we considered the behavior of a general class of models. These models contain four stages: (1) early noise; (2) a deterministic filtering and gain-changing stage; (3) late noise; (4) a decision rule that is either an ideal (signal-known-exactly) detector or a peak-trough detector. With the ideal detector and without late noise, the observer's sensitivity as a function of mean luminance and temporal frequency is not affected by the filtering and gain-changing stage. Consequently, if the early noise is entirely quantal fluctuations, sensitivity will always be a square-root function of mean luminance and a uniform (flat) function of temporal frequency. This latter prediction is contradicted by all known data; either the ideal-detector is the wrong decision rule or sensitivity is almost always limited by sources of noise other than quantal fluctuations. With the peak-trough detector, however, with or without late noise, the observer's sensitivity as a function of temporal frequency does reflect the sensitivity of the low-level filtering and gain-changing stage. Late noise is needed, however, if the observer's sensitivity as a function of mean luminance is to go through both a square-root and a Weber region. Comparing these conclusions to similar work on the spatial frequency dimension highlights differences between the spatial and temporal frequency domains. Finally, on the basis of these analyses and evidence from the literature, we question whether quantal fluctuations limit visual sensitivity under any condition.

Adaptation, Ocular↗

PubMed1992

Modeling the dynamics of light adaptation: the merging of two traditions.

Light adaptation has been studied using both aperiodic and periodic stimuli. Two well-documented phenomena are described: the background-onset effect (from an aperiodic-stimulus tradition) and high-temporal-frequency linearity (from the periodic-stimulus tradition). These phenomena have been explained within two different theoretical frameworks. Here we briefly review those frameworks. We then show that the models developed to predict the phenomenon from one tradition cannot predict the phenomenon from the other tradition, but that the models from the two traditions can be merged into a class of models that predicts both phenomena.

Adaptation, Ocular↗

PubMed1992

A computational model of the amplitude and implicit time of the b-wave of the human ERG.

To improve the usefulness of the ERG in identifying the sites and mechanisms of adaptation, development, and disease processes, a theoretical framework based upon Granit's analysis of the ERG was evaluated. The framework assumes that the ERG is the sum of two potentials, one, P3, generated by the receptors and the other, P2, generated by the cells of the INL. Hood and Birch (1990a, b) demonstrated that the leading edge of the a-wave can be quantitatively described by a model used to describe the response from single rod receptors. This model provides P3(t), a theoretical receptor response as a function of time, for any given flash intensity. The ERGs from normal observers and patients with retinal diseases were analyzed in this framework, first by deriving P2 by computer subtracting the predicted P3(t) responses. This analysis was successful and a computational model of the ERG was then derived. The model of P2(t) was constructed with linear filters and a static nonlinearity and using P3(t) as the input. The ERG for any given flash intensity is then P3(t) + P2(t). The model describes (1) the change both in implicit times and in trough-to-peak b-wave amplitudes with flash intensity for the normal, dark-adapted observers; and (2) the changes in b-wave implicit times and amplitudes for three patients with retinal diseases. Among the implications drawn from these analyses were as follows: (1) The fits of the Naka-Rushton equation to trough-to-peak b-wave amplitudes must be interpreted with great care. (2) When the INL is affected by retinal disease, the b-wave may be a very poor reflection of INL activity. (3) The implicit time of the b-wave can provide a measure of receptor sensitivity.

Adult↗

PubMed1992

Psychophysical evidence for post-receptoral sensitivity loss in diabetics.

Although numerous reports show that the sensitivity of the S cone system is decreased in diabetic patients, few studies have been directed toward identifying the possible sites of the sensitivity loss. In this study, a psychophysical technique was used to test hypotheses about sites of S cone system sensitivity loss in a group of patients with early diabetic retinopathy. A model of the S cone system was assumed and the experimental conditions were chosen to distinguish between explanations for S cone sensitivity loss at the receptor level from explanations for loss at a post-receptoral level. Within the context of the model, the data were consistent with S cone system sensitivity loss occurring at a post-receptoral level.

Adult↗