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R D Hamer

Publications and source records attributed to R D Hamer.

31 records · Page 2Linked to original sources

Spatial summation in dark-adapted human infants.

Behavioral measures of spatial summation in 4- and 11-week old human infants were obtained using the forced-choice preferential looking technique. Infants exhibit complete spatial summation over large areas (4 weeks: 8.9 degrees; 11 weeks: 5.5 degrees), much larger than those of adults tested in the same apparatus (2.6 degrees). Thus, infants' summation areas are larger than adults' by factors of 12 at 4 weeks and 4 at 11 weeks. It is argued that at most, one-half of this difference between the infant and adult data may be due to optical factors (e.g. defocus and small eye size). The remainder probably reflects differences in the neural organization of the immature and mature visual systems.

Adult↗

Absolute thresholds in human infants exposed to continuous illumination.

Continuous illumination at low-to-moderate photopic levels can cause damage to the visual system in nonhuman species. Therefore, the authors sought to determine whether behaviorally measurable visual deficits occurred in young human infants who had been exposed to long-term, continuous illumination in a neonatal intensive care unit (NICU). Using the forced-choice, preferential-looking technique, the authors measured absolute thresholds for detection of a 502 nm stimulus in nine preterm infants who had been exposed to 13 to 46 days of continuous room illumination. Nine infants born at term, who had experienced less than or equal to 5 days of continuous illumination, served as controls. The thresholds for the light-exposed and control infants did not differ. In addition, the light-exposed infants did not differ from control infants in their performance on a rapid acuity screening under photopic conditions. Thus, the present data provide no evidence of functional damage to either rod or cone vision in infants who had been exposed to continuous illumination in an NICU. Some limitations to the generality of these conclusions are discussed.

Female↗

Vibrotacile masking of Pacinian and non-Pacinian channels.

Vibrotactile masking functions were determined using sinusoidal and noise maskers. Results were nearly identical within the Pacinian (P) and non-Pacinian (NP) channels. At low maskers SLs there was a substantial amount of negative masking which proved not be an artifact of stimulus definition. The critical parameters for successful prediction of the data were a peripheral threshold and internal Gaussian noise. Threshold shifts in cross-channel stimulation can be attributed to the masker exceeding the detection threshold of the signal channel.

Adult↗

Rayleigh discriminations in young human infants.

The capacity of young infants to discriminate 3 x 3 degrees broadband red or 550 nm green squares from a 589 nm yellow surround was tested by means of the forced-choice preferential looking technique. All 3-month olds, about 3/4 of the 2-month olds, and just under half of the one-month-olds could make at least one of these discriminations. Taken together with other known properties of infant color vision, the failures of discrimination shown by the younger infants are more readily modeled as immaturities of neural processing than as an absence of anomaly of LWS or MWS cones.

Adult↗

The effects of a surround on vibrotactile thresholds.

Psychophysical thresholds for the detection of vibration on the thenar eminence were measured as a function of stimulus frequency. As has been found in earlier studies, the threshold functions had two separate branches: one relatively flat branch at low frequencies and a U-shaped branch at higher frequencies. When the rigid surround which is used to confine the stimulus to the region of the vibrator contactor was removed and vibration was allowed to spread freely over the surface of the skin, thresholds along the relatively flat segment of the curve increased while thresholds along the U-shaped segment decreased. The results were interpreted in terms of the duplex model of mechanoreception.

Adult↗

Enhancement of vibrotactile sensation magnitude and predictions from the duplex model of mechanoreception.

The degree to which the sensation magnitude of a vibrotactile stimulus is enhanced by a prior stimulus was studied for vibration of the thenar eminence of the right hand. Enhancement was measured by a psychophysical matching procedure in which two brief stimuli separated by a variable time interval were presented to the skin and the subject adjusted a third stimulus to match the sensation magnitude of the second stimulus. By this procedure, it is possible to determine functional relationships between enhancement and the time interval between stimuli, the intensity of the stimuli, and the frequency of the stimuli. The results were consistent with the duplex model of mechanoreception.

Differential Threshold↗

Phototransduction: modeling the primate cone flash response.

We have developed a new model of phototransduction that accounts for the dynamics of primate and human cone flash responses in both their linear and saturating range. The model incorporates many of the known elements of the phototransduction cascade in vertebrate photoreceptors. The input stage is a new analytic expression for the activation and inactivation of cGMP-phosphodiesterase (PDE). Although the Lamb and Pugh (1992) model (of a delayed ramp for the rising phase of the PDE response in amphibian rods) provided a good fit for the first 2 log units of stimulus intensity without parameter adjustments, the remaining 4 log units of the data required nonlinear modifications of both delay and gain (slope). We show that this nonlinear behavior is a consequence of the delay approximation and develop a completely linear model to account for the rising phase of amphibian rod photocurrent responses over the full intensity range (approximately 6 log units). We use the same dynamic model to account for primate cone responses by decreasing the time constants of PDE activation and introducing an enhanced inactivation process. This PDE response activates a nonlinear calcium feedback stage that modulates guanylate cyclase synthesis of cyclic GMP. By adjustment of the throughput and feedback parameters, the full model successfully captures most of the features of the primate and human cone flash responses throughout their dynamic range. Our analysis suggests that initial processes in the transduction cascade may be qualitatively different from comparable processes in rods.

3',5'-Cyclic-GMP Phosphodiesterases↗

Computational analysis of vertebrate phototransduction: combined quantitative and qualitative modeling of dark- and light-adapted responses in amphibian rods.

We evaluated the generality of two models of vertebrate phototransduction. The approach was to quantitatively optimize each model to the full waveform of high-quality, dark-adapted (DA), salamander rod flash responses. With the optimal parameters, each model was then used to account for signature, qualitative features of rod responses from three experimental paradigms (stimulus/response, "S/R suite"): (1) step responses; (2) the intensity dependence of the period of photocurrent saturation (Tsat vs. ln(I)); and (3) light-adapted (LA) incremental flash sensitivity as a function of background intensity. The first model was the recent successful model of Nikonov et al. (1998). The second model replaced the instantaneous Ca2+ buffering used in the Nikonov et al. model with a dynamic buffer. The results showed that, in the absence of the dynamic Ca2+ buffer, the Nikonov et al. model does not have sufficient flexibility to provide a good fit to the flash responses, and, using the same parameters, reproduce the salient features of the S/R suite--critical features at step onset and offset are absent; the Tsat function has too shallow a slope; and the model cannot generate the empirically observed I-range of Weber-Fechner LA behavior. Some features could be recovered by changing parameters, but only at the expense of the fit to the reference (Ref) data. When the dynamic buffer is added, the model is able to achieve an acceptable fit to the Ref data while reproducing several features of the S/R suite, including an empirically observed Tsat function, and an extended range of LA flash sensitivity adhering to Weber's law. The overall improved behavior of the model with a dynamic Ca2+ buffer indicates that it is an important mechanism to include in a working model of phototransduction, and that, despite the slow kinetics of amphibian rods, Ca2+ buffering should not be simulated as an instantaneous process. However, neither model was able to capture all the features with the same parameters yielding the optimal fit to the Ref data. In addition, neither model could maintain a good fit to the Ref data when five key biochemical parameters were held at their current known values. Moreover, even after optimization, a number of important parameters remained outside their empirical estimates. We conclude that other mechanisms will need to be added, including additional Ca2+-feedback mechanisms. The present research illustrates the importance of a hybrid qualitative/quantitative approach to model development, and the limitations of modeling restricted sets of data.

Adaptation, Ocular↗

Toward a unified model of vertebrate rod phototransduction.

Recently, we introduced a phototransduction model that was able to account for the reproducibility of vertebrate rod single-photon responses (SPRs) (Hamer et al., 2003). The model was able to reproduce SPR statistics by means of stochastic activation and inactivation of rhodopsin (R*), transducin (G alpha ), and phosphodiesterase (PDE). The features needed to capture the SPR statistics were (1) multiple steps of R* inactivation by means of multiple phosphorylations (followed by arrestin capping) and (2) phosphorylation dependence of the affinity between R* and the three molecules competing to bind with R* (G alpha, arrestin, and rhodopsin kinase). The model was also able to account for several other rod response features in the dim-flash regime, including SPRs obtained from rods in which various elements of the cascade have been genetically disabled or disrupted. However, the model was not tested under high light-level conditions. We sought to evaluate the extent to which the multiple phosphorylation model could simultaneously account for single-photon response behavior, as well as responses to high light levels causing complete response saturation and/or significant light adaptation (LA). To date no single model, with one set of parameters, has been able to do this. Dim-flash responses and statistics were simulated using a hybrid stochastic/deterministic model and Monte-Carlo methods as in Hamer et al. (2003). A dark-adapted flash series, and stimulus paradigms from the literature eliciting various degrees of light adaptation (LA), were simulated using a full differential equation version of the model that included the addition of Ca2+-feedback onto rhodopsin kinase via recoverin. With this model, using a single set of parameters, we attempted to account for (1) SPR waveforms and statistics (as in Hamer et al., 2003); (2) a full dark-adapted flash-response series, from dim flash to saturating, bright flash levels, from a toad rod; (3) steady-state LA responses, including LA circulating current (as in Koutalos et al., 1995) and LA flash sensitivity measured in rods from four species; (4) step responses from newt rods ( Forti et al., 1989) over a large dynamic range; (5) dynamic LA responses, such as the step-flash paradigm of Fain et al. (1989), and the two-flash paradigm of Murnick and Lamb (1996); and (6) the salient response features from four knockout rod preparations. The model was able to meet this stringent test, accounting for almost all the salient qualitative, and many quantitative features, of the responses across this broad array of stimulus conditions, including SPR reproducibility. The model promises to be useful in testing hypotheses regarding both normal and abnormal photoreceptor function, and is a good starting point for development of a full-range model of cone phototransduction. Informative limitations of the model are also discussed.

Adaptation, Ocular↗

Polaroid photorefractive screening of infants.

We modified a Polaroid SE camera for use as a photoretinoscope. A total of 187 infants between 2 and 18 months of age were photographed using this device. About half of these infants (97) participated in a double blind study in which the results of photorefraction were compared with those of standard cycloplegic retinoscopy. Eighty-three infants were photographed without cycloplegia. Thirty-four infants were photographed while cyclopleged. Photographs were evaluated for significant refractive errors and other ocular abnormalities. The effectiveness of the camera system to screen for significant refractive errors without the use of cycloplegia was assessed. Infants were identified to be at risk by photorefraction if, in any photograph, a hyperopic bright crescent calculated to be greater than or equal to +1.25 D was present in the pupil. Clinically significant refractive errors were defined by the results of cycloplegic retinoscopy: "at-risk" infants had either 3.5 D or more hyperopia in either eye, or astigmatism in either eye greater than or equal to 2.5 D, or anisometropia greater than or equal to 1.5 D. With these clinical criteria and the above photographic screening criterion, the camera's sensitivity and specificity were 83% and 69%, respectively. The present system compares favorably with earlier, more sophisticated units in alerting practitioners to potentially significant refractive errors in infants. Additionally, as a screening tool, this device offers the benefits of being inexpensive and easy to use, and of providing immediate feedback.

Calibration↗

Comparison of on- and off-axis photorefraction with cycloplegic retinoscopy in infants.

We have compared the performance of an off-axis (knife-edge) photorefractor with that of an on-axis (isotropic) system. Normal infants and children between the ages of 8 and 208 weeks were photographed with each camera both with and without cycloplegia. Refractive errors were estimated for each technique based on equations derived from ray-tracing. These refractions were compared to the results of retinoscopy under cycloplegia. Sensitivity and specificity of the two photorefraction systems were evaluated as a function of the magnitude of meridional hyperopia defined by retinoscopy. We also examined the effect of varying the photorefraction screening criterion. Thirteen percent of the infants in the screening sample presented with +3.50 diopters or more of meridional hyperopia. Using this level of ametropia as a referral criterion, the sensitivity and specificity of the off-axis system for infants without cycloplegia were 83% and 72%, respectively. For the on-axis system, sensitivity and specificity values were 85% and 53%. The use of cycloplegics did not significantly improve the performance of either system, but rather their use degraded the specificity of the on-axis system in the presence of moderate refractive errors. The results of the present study indicate that both on- and off-axis systems are effective in identifying highly ametropic infants, but that the off-axis system results in significantly fewer false positives. Moreover, the off-axis system has the advantages of an inherently greater dynamic range for a fixed camera design, and also more easily interpreted photographs.

Child, Preschool↗

Preoperative alternate occlusion decreases motion processing abnormalities in infantile esotropia.

We have examined the effects of preoperative, full-time alternate occlusion on the development of visual motion processing mechanisms. Motion visual evoked potentials (MVEPs) were recorded longitudinally in 14 infantile esotropia patients during the course of standard preoperative occlusion therapy. The MVEP in these patients was initially asymmetric in a fashion consistent with a nasalward/temporalward response bias, with a motion asymmetry significantly higher than that of age-matched normals. The magnitude of the developmental motion asymmetry declined significantly after an average of 24 weeks of alternate occlusion. This result implies that the binocular motion-sensitive cells underlying the MVEP retain some degree of plasticity up to at least 1 year of age. Our data suggest further that the persistence of motion asymmetries in untreated infantile esotropia patients is maintained by an active process that can be disrupted by alternate occlusion. Alternate occlusion apparently eliminates a form of abnormal binocular interaction that supports the persistence of the motion asymmetry. We propose that one of the necessary pre-conditions for symmetricization of motion processing in infantile esotropia is the absence of abnormal competitive binocular interactions.

Child, Preschool↗