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Biomedical subjects

David P Crewther

Publications and source records attributed to David P Crewther.

At least 19 recordsLinked to original sources
PubMed2006

Ionic control of ocular growth and refractive change.

The physiological mechanisms underlying the abnormal vitreal and ocular growth and myopic refractive errors induced under conditions of visual form deprivation in many animal species, including humans, are unknown. This study demonstrates, using energy dispersive x-ray microanalysis, a systematic pattern of changes in the elemental distribution of K, Na, and Cl across the entire retina in experimental form deprivation myopia and in the 5 days required for refractive normalization after occluder removal. In our report we link the ionic environment associated with physiological activity of the retina under a translucent occluder to refractive change and describe large but reversible environmentally driven increases in potassium, sodium, and chloride abundances in the neural retina. Our results are consistent with the notion of ionically driven fluid movements as the vector underlying the myopic increase in ocular size. New treatments for myopia, which currently affects nearly half of the human population, may result.

Animals↗
PubMed2006

Pre- and post-critical period induced reduction of Cat-301 immunoreactivity in the lateral geniculate nucleus and visual cortex of cats Y-blocked as adults or made strabismic as kittens.

PURPOSE: To test the post-critical period stability of perineuronal nets by comparing the expression of antigens on aggrecan (a chondroitin sulfate proteoglycan (CSPG) recognized by the monoclonal antibody Cat-301) in the lateral geniculate nucleus (LGN) and striate cortex (A17) of adult Y-blocked cats and cats made strabismic and amblyopic as kittens. The comparison tested the idea that pre- and post-critical period loss of synchronous activity would differentially affect the perineuronal net of Y-type neurons in LGN and A17. METHODS: Seven adult cats, two normal, three convergent strabismic amblyopic, and two monocularly Y-blocked cats, were used in this study. The strabismic amblyopic cats had been made monocularly esotropic (by tenotomy) at 14 days of age. The Y-block was created acutely by a pressure cuff placed on the optic nerve behind the left eye in adult cats. The efficacy of both procedures was tested electrophysiologically. Frontal frozen sections were incubated with the Cat-301 antibody and the labeling visualized using a DAB kit. The sections were counterstained with cresyl violet. In each section, Cat-301-stained cells with well-defined nucleoli were counted under a 20x objective with a computer-based quantitative microscope image analysis system. RESULTS: The percentage of positively labeled cells was reduced in LGN laminae that received input from the deviated eye in amblyopic cats and from the pressure-blocked eye in Y-blocked cats compared with normal cats. Surprisingly, the non-blocked laminae of the Y-blocked cats also showed a significant reduction in positively labeled neurons when compared to normals or to strabismic cats. In the visual cortex of both hemispheres of strabismic and Y-blocked cats, the density of immunopositive neurons was significantly reduced compared with normal. The effect was most pronounced in layers IV-VI for Y-blocked cats and in layer IV for strabismic amblyopic cats. CONCLUSIONS: The results demonstrate that surface expression of aggrecan in adult cat LGN and A17 of adult cat is reduced both by chronic developmental loss of synchronous input from the two eyes and by acute changes in synchronous input in adulthood. Thus both pre- and post-critical plasticity in the expression of epitopes of aggrecan can be demonstrated. The uniform distribution of Cat-301 labeling tangentially within cortical layers of strabismic amblyopic cats indicates that the reduction in immunoreactivity observed with strabismus induced early in life is not simply eye-specific. Indeed, comparison of the immunopositivity of Y-blocked and strabismic animals, both in LGN and cortex, suggests that even after the critical period is ended, the physical removal of monocular Y-type afferent activity and weakening of binocular feedback connections between cortex and thalamus can alter the stability of the perineuronal nets surrounding the affected neurons.

Aggrecans↗
PubMed2006

Parietal function in good and poor readers.

BACKGROUND: While there are many psychophysical reports of impaired magnocellular pathway function in developmental dyslexia (DD), few have investigated parietal function, the major projection of this pathway, in good and poor readers closely matched for nonverbal intelligence. In view of new feedforward-feedback theories of visual processing, impaired magnocellular function raises the question of whether all visually-driven functions or only those associated with parietal cortex functions are equally impaired and if so, whether parietal performance is more closely related to general ability levels than reading ability. METHODS: Reading accuracy and performance on psychophysical tasks purported to selectively activate parietal cortex such as motion sensitivity, attentional tracking, and spatial localization was compared in 17 children with DD, 16 younger reading-age matched (RA) control children, and 46 good readers of similar chronological-age (CA) divided into CA-HighIQ and a CA-LowIQ matched to DD group nonverbal IQ. RESULTS: In the age-matched groups no significant differences were found between DD and CA controls on any of the tasks relating to parietal function, although performance of the DD group and their nonverbal IQ scores was always lower. As expected, CA and RA group comparisons indicated purported parietal functioning improves with age. No difference in performance was seen on any of the parietally driven tasks between the DD and age-nonverbal IQ matched groups, whereas performance differentiated the DD group from the age-matched, higher nonverbal IQ group on several such tasks. An unexpected statistical difference in performance between lower reading age (DD and RA children) and all higher reading age (CA) children was seen on a test of chromatic sensitivity, whereas when high and low nonverbal IQ normal readers were compared performance was not different CONCLUSION: The results indicate that performance on purported parietal functions improves with age and may be more associated with nonverbal mentation than reading accuracy. Performance on a cognitively demanding task, traditionally considered to rely on ventral stream functions, was more related to reading accuracy.

Journal Article↗
PubMed2006

Low frequency temporal modulation of light promotes a myopic shift in refractive compensation to all spectacle lenses.

Emmetropization, the process by which ocular growth of young animals adapts to ensure focussed retinal images, can be disrupted by high frequency flicker, causing a hypermetropic shift. Emmetropization can also be disrupted differentially, in a sign dependent manner, by pharmacological alteration of the balance of activation of the ON and OFF retinal sub-systems in normal light or by rearing in an environment with a moving spatiotemporally varied diamond pattern (yielding local sawtooth illumination on the retina). Thus the aim of this experiment was to determine whether low frequency temporal modulation alone was sufficient to cause defocus sign-dependent interference with compensation. Chicks were reared for 6 or 7 days with monocular +/-10 D, 0 D, or No Lenses in a 12h light/dark cycle. Luminance of the environment was temporally modulated during the light cycle with a non-square wave profile pulse of 250 msec duration, with the illumination fluctuating between 1.5 and 180 lux at 1 Hz, 2 Hz, 4 Hz or with no flicker (0 Hz-180 lux). Final refractive state and ocular dimensions, measured using retinoscopy and A-scan ultrasonography, demonstrated that in the absence of temporal luminance modulation (0 Hz), chicks compensated to induced defocus in the expected sign-dependent manner. However, under 1, 2 and 4 Hz flickering light conditions, there was an overall myopic offset of approximately 6D across lens groups with refractive compensation to positive lenses more strongly inhibited. This myopic offset was reflected by increases in the depth of both vitreous and anterior chambers. However, luminance modulation had no effect on refraction or ocular parameters in the No Lens conditions. This is a hitherto unreported strong interaction between lens wear and low frequency temporally modulated light, with the refractive compensation mechanism being overridden by a generalized myopic shift.

Accommodation, Ocular↗
PubMed2006

Wots that werd? Pseudowords (non-words) may be a misleading measure of phonological skills in young learner readers.

Pseudoword (non-word) reading tasks are a commonly used measure of phonological processing across diverse fields of reading research. However, whether pseudoword reading gives any more information about phonological processing in young learner readers than does the reading of real words has seldom been considered. Here we show that pseudoword and real word reading are so strongly correlated (r=0.94) in the first 4 years of school as to be representative of the same construct. Two of the subskills of phonological processing, phonological awareness and rapid automatic naming also predict almost identical amounts of variance in pseudoword and real word reading. A divergence in the correlations between word and pseudoword reading and phonological awareness and rapid naming only emerges in the fourth year, while a significant correlation between phonological awareness and rapid automatic naming is evident only in the first year of schooling. Thus these results suggest that, at least in young children learning to read, care should be taken when using pseudoword reading to measure either phonological processing ability or phonological awareness as this may misinform the choice of therapy for a child showing symptoms of dyslexia.

Awareness↗
PubMed2006

Monocular and binocular thresholds for abruptly and gradually presented illusory contours.

BACKGROUND: In this study, monocular thresholds and binocular summation for abrupt onset/offset versus gradually revealed phantom letter E (illusory contours) stimuli are compared to determine the suitability of these stimuli for assessment of the integrity of two of the major retinal streams: the magnocellular and the parvocellular pathways. Such tests are important in progressive retinal disease where disease severity may differ between the classes of retinal ganglion cells and between the two eyes. Abrupt onset phantom contours have long been considered to activate the magnocellular visual pathway and we propose that gradually revealed high contrast ramped onset/offset stimuli are more likely to promote the more sustained processing of the parvocellular stream. METHODS: Contrast discrimination thresholds for monocular and binocular viewing were compared in a counter-balanced order in 70 young normal subjects, using tests of contrast threshold for a flicker-defined letter E produced by alternation of light and dark dots. Three onset/offset conditions were used - abrupt onset that was maintained for 34 milliseconds (four frames of 8.5 milliseconds) then discontinued, ramped onset over 34 milliseconds (four frames) with offset over 34 milliseconds and ramped onset over 85 milliseconds (10 frames) with offset over 85 milliseconds. RESULTS: Contrast thresholds for identification of the orientation of the E, when presented with four frames ramped onset and offset when compared to the four frames abrupt onset/offset were three times higher, irrespective of monocular or binocular viewing conditions. Threshold contrasts were seven times higher when the 10 frames ramped onset/offset stimuli were compared to abrupt four frames onset/offset. Binocular contrast thresholds were reduced by approximately 40 per cent compared to monocular thresholds for all conditions. The binocular increase in contrast sensitivity is approximately equal for abrupt transiently presented stimuli and for gradually presented more sustained stimuli. DISCUSSION: The results indicate that the same mechanisms of monocular processing and binocular summation are used for identification of a flickering contrast-defined phantom contour under presentation conditions, which are characteristic of the temporal and contrast preferences of the primate magnocellular and parvocellular visual pathways. This suggests that the phantom contour E test may be useful for clinical differentiation of the integrity of the M and P retinal ganglion-derived visual pathways, regardless of whether it is applied monocularly or binocularly.

Adult↗
PubMed2005

Measurement error: Implications for diagnosis and discrepancy models of developmental dyslexia.

The diagnosis of developmental dyslexia (DD) is reliant on a discrepancy between intellectual functioning and reading achievement. Discrepancy-based formulae have frequently been employed to establish the significance of the difference between 'intelligence' and 'actual' reading achievement. These formulae, however, often fail to take into consideration test reliability and the error associated with a single test score. This paper provides an illustration of the potential effects that test reliability and measurement error can have on the diagnosis of dyslexia, with particular reference to discrepancy models. The roles of reliability and standard error of measurement (SEM) in classic test theory are also briefly reviewed. This is followed by illustrations of how SEM and test reliability can aid with the interpretation of a simple discrepancy-based formula of DD. It is proposed that a lack of consideration of test theory in the use of discrepancy-based models of DD can lead to misdiagnosis (both false positives and false negatives). Further, misdiagnosis in research samples affects reproducibility and generalizability of findings. This in turn, may explain current inconsistencies in research on the perceptual, sensory, and motor correlates of dyslexia.

Child↗
PubMed2005

Changes in ocular accommodation when shifting between global and local attention.

BACKGROUND: The link between cognitive changes in attentional focus and the physiological parameters of the eye is not well understood. The aim of the current work was to examine the role of ocular accommodation, that is, the process of changing the shape of the crystalline lens in order to focus an image onto the retina, in active shifts of visual attention between global and local information. METHOD: Ten adult participants (aged 19 to 27) viewed sequences of complex global/local figures presented at the same location. They were asked to identify either a global or local red target letter and to look for either a global or local letter x (probe) in the sequence following. Target and probe items were separated by a temporal gap of approximately one second. Refraction was measured using a Canon Autorefractor R1 at the time of target appearance and again at the time of probe presentation. Particular interest was paid to trials where participants were required to shift attention either from a local to global level or in the reverse direction. The difference between the two measurements of refraction gave a 'change score' which provided an indication of the change of accommodation. RESULTS: No significant change in refraction was observed when shifting from the local to the global condition. A mean change in refraction of -0.128 dioptres was observed for the global to local condition. The 95 per cent confidence interval for this difference did not overlap zero, indicating a significant change in refraction, which was attributed to an increase in accommodation. DISCUSSION: The results suggest that while a change in accommodation occurs in shifting attention from the global to the local aspect of the complex figures, a similar change is not observed in the reverse direction. These results are consistent with the hypothesis that it is more difficult to restrict attentional focus than it is to widen it.

Accommodation, Ocular↗
PubMed2004

Clinical application of the multifocal visual evoked potential.

BACKGROUND: Measures of visual function thresholds such as visual acuity and visual fields are generally dependent on subjective responses and assume maintenance of fixation, attention and motivation. In the young, elderly, cognitively impaired or malingering populations, such measures may be inaccurate or difficult to obtain. The Visual Evoked Response Imaging System (VERIS) has been claimed to give more objective topographic recordings of retinal and cortical function. This paper aims to explore the adequacy of this technique in four unusual, unrelated, clinically difficult cases. METHODS: Multifocal visual evoked potentials (mfVEPs) recorded on the VERIS System 3.01 are used to assess visual function in four cases with contradictory clinical findings or unreliable subjective responses. RESULTS: Patient 1 had sustained a head injury and had normal ocular and pupil examination but light perception in the right eye and 6/5 acuity in the left. Multifocal VEPs showed a marked depression of the right visual field with little macular response. Patient 2 had sustained a head injury, had a left field hemianopia, possible macular sparing and loss of much of the right field, reduced but variable visual acuities, good near vision and normal ocular fundi. Multifocal VEPs showed a severe depression in both visual fields (L more than R) with little macular response. Patient 3 had a left optic nerve meningioma and experienced great difficulty with visual field assessment. mfVEPs showed a bilateral depression in the superior field particularly the left field, with a larger deficit in the left eye. Patient 4 had unexplained visual acuity and peripheral field deficits. mfVEP results were inconclusive in this case. DISCUSSION: Where there is difficulty performing traditional techniques or conflicting clinical findings, mfVEPs may provide additional objective information to aid in the assessment of patients.

Adult↗
PubMed2004

Structural and elemental evidence for edema in the retina, retinal pigment epithelium, and choroid during recovery from experimentally induced myopia.

PURPOSE: The purpose of this study was to monitor temporal changes in the retina, retinal pigment epithelium (RPE), and choroid of chick eyes using biometric, ultrastructural, and elemental microanalysis techniques as a means of visualizing more detailed signs of the physiological processes underlying choroidal expansion and refractive normalization during recovery from form deprivation. METHODS: Axial dimensions and refractions were measured on form-deprived and fellow eyes of 117 experimental chickens reared with monocular translucent occlusion from days 1 to 15 and given different lengths of visual experience (T = 0-144 hours) before death. Tissue was analyzed ultrastructurally by electron microscopy and relative sodium (Na) and chloride (Cl) ion abundances, by using x-ray microanalysis to determine changes in the presence of these indicators of tissue hydration. RESULTS: Refractive error decreased from more than 20 D of myopia almost linearly over the first 144 hours after occlusion. Concurrent changes in thickness in the retina, RPE, and choroid were seen as a series of thickness increases and edema, which returned to normal thickness, first in the retina, and did not reach maximum until 3 days after occluder removal in the choroid. In freeze-dried tissue, Na and Cl ion concentrations were greatest in the RPE photoreceptor outer segments and extravascular choroid at T = 0, decreasing toward fellow eye levels by T = 48 in the RPE and choroid. Na and Cl ion abundances in the frozen lymph of choroidal lymphatics were nearly at control levels (T = 0) and increased later as the vessels became more distended after the extravascular edema became significant. CONCLUSIONS: The results suggest that occluder removal induces edema across the retina and choroid and that this fluid may be the vector eliciting choroidal expansion during recovery from form deprivation possibly driven by the hyperosmolarity in the choroid, RPE, and photoreceptor outer segments that accompanies deprivation.

Animals↗
PubMed2003

Change detection is impaired in children with dyslexia.

The severe deficits in rapid automatized naming demonstrated by children with developmental dyslexia has usually been interpreted in terms of a deficit in speed of access to the lexicon rather than as a possible deficit in speed of visual object recognition. Yet fluent reading requires rapid visual recognition and semantic interpretation of new letters and words appearing in successive fixations of the eyes. Thus we wondered whether change detection performance was related to reading ability. We investigated whether children with developmental dyslexia (DD) were less able to detect change in a simple display--gap--display paradigm than normal reading (NR) children of the same age and children with impaired reading and mentation (LD). In a first experimental phase, the DDs required a longer initial exposure of four letter items in order to detect change of a single letter at a level of 71% correct, compared with NRs performing at the same level. Thus the deficit in reading in DD is associated with a deficit in early processes associated with visual recognition. In a second experimental phase (using the individual target display exposures measured in the first phase), cues appeared during the 250 ms gap for a period of either 0 (no cue), 50 or 200 ms immediately prior to the presentation of the second (comparison) display. Children of all groups showed dependence on the presence of the cue to help make a judgement of change (versus no change), with the NRs least affected. When change was detected in the presence of a cue, the NRs were better able to identify the new letter than either of the other groups. However, only about 50% of the correct detections were accompanied by a correct identification. Despite published reports of a mini-neglect for left visual field in dyslexic adults, none of our groups showed such an effect. However, a significant upper visual field (UpVF) advantage in change detection performance was found across groups, which we interpret in terms of the interactions of the ventral and dorsal streams.

Adolescent↗
PubMed2002

Temporal processing of global and local information varies with global precedence.

The concept of global precedence, which suggests that the global aspect of a scene is processed more rapidly than local details, was examined using the attentional blink paradigm. Eighteen adult subjects observed multiple sequences of complex global-local letter figures to see whether the attentional blink duration would be affected by the visual angle size of the stimulus. Within each sequence, the subject was directed to identify either a global or local red target letter and to detect whether a global or local probe letter (X) was presented in the sequence following the target letter. Stimuli were presented at three different sizes. Results showed significantly higher probe detection rates for global probes than for local at small stimulus sizes. However, using large stimulus sizes, mean correct probe detection was significantly higher in conditions requiring local attention compared to global. No significant difference in probe detection performance was observed between global and local conditions at medium stimulus sizes. The results suggest that the rate of visual information processing varies according to the visual angle of the particular information. The results support the suggestion that the precedence of information is an important factor in the temporal processing of global-local information.

Adolescent↗
PubMed2002

Normal readers have an upper visual field advantage in change detection.

The ability to detect change has not been well studied in children.A research paradigm was used involving search for a change made to one of four letter targets, presented twice, with a gap of 250 ms.Sixty-one schoolchildren, aged 7.3 - 12.9 years,participated in the study. The duration of the first presentation was such that each child was detecting change at a rate of 71% correct. The mean duration was 0.91 s (SD = 0.58 s),with older children not significantly faster in detecting change. In the second phase, using the duration established in the first phase, the effect of cue condition on detection was studied. An upper visual field advantage for change detection was clearly evident for un-cued trials. The most likely explanation derives from the masking produced by the reappearance of the four targets, which interferes with the process of change detection. The greater dorsal pathway representation of the lower visual field implies greater masking there, yielding better change detection in the upper visual field.

Child↗
PubMed2002

Effects of optical defocus and spatial contrast on anterior chamber depth in chicks.

The goal of this study was to investigate the effect of optical defocus and spatial contrast on refractive development and, in particular,on anterior chamber growth. Ninety chicks were raised from day 4-10 post-hatching wearing monocular lenses (+/-10 Dor 0 D), in an environment with either high, low or no spatial contrast patterns: 30%, 6% or 0% contrast, respectively. At day 10, the chicks' refractive state and ocular components were assessed using retinoscopy and A-scan ultrasonography. Ocular defocus resulted in sign-dependent significant differences in refractive error, axial length and vitreous chamber depth. Lens wear also led to significant spatial contrast dependent changes in anterior chamber depth. Varying ambient spatial contrast in the chick's environment did not inhibit emmetropization processes; however, anterior chamber growth was particularly susceptible to changes in spatial contrast.

Animals↗
PubMed2002

Separation of contour and area dependent components in the first and second order kernels of the multifocal pattern appearance evoked potential.

The non-linearities of the diffuse flash visual evoked potential (VEP) have been shown to generate separable waves corresponding to Magnocellular and Parvocellular contributions. The authors wished to investigate whether, under conditions of isoluminance, the chromatic pattern appearance VEP shows waveforms that are related to both the processing of contours (the pattern) and the processing of the diffuse stimulation (from the area lying between the contours). The VERIS multifocal system was used to record monocular VEP. Standard 2-ring, 3-ring, 5-ring and 7-ring VERIS pattern stimuli were employed with a cardboard circular aperture used to blank the stimulus monitor to a 9-cm diameter field. The results for four subjects were recorded. The first order kernel responses showed a significant increase in amplitude with total contour length. In comparison, the amplitudes of the first and second slices of the second order kernel did not increase with contour length. It appears that the contour-dependent component has negligible non-linear components. It is proposed that the constant, non-zero responses of the higher order kernel components reflects contributions from the diffuse chromatic VEP.

Adult↗
PubMed2002

Referral rates for a functional vision screening among a large cosmopolitan sample of Australian children.

The aim of this study was to investigate the incidence of functional vision problems in a large unselected cosmopolitan population of primary school-age children and to investigate whether constant clinical criteria for functional vision problems would be implemented by the practitioners involved in the screening. Refractive errors, near point of convergence, stereopsis, strabismus, heterophoria and accommodative facility were assessed for 2697 children (3-12 years) of varying racial backgrounds living in Australia. The spherical component of the refractive error ranged from -7.75 to +9.50 D (mean +0.54 D, +/-0.79) with a distribution skewed towards hypermetropia; astigmatism ranged from 0 to 4.25 D (mean -0.16 D, +/-0.35). There was a trend towards less hypermetropia and slightly more astigmatism with age. Mean near point of convergence was 5.4+/-2.9 cm, heterophoria at far and near was 0.12+/-1.58delta exophoria and 1.05+/-2.53delta exophoria, respectively, 0.55% of children exhibited vertical phoria at near >0.5delta, accommodative facility ranged from 0 to 24 cycles per minute (cpm) (mean 11.2 cpm, +/-3.7), stereopsis varied from 20 to 800 s (") of arc with 50% of children having 40" or better. The prevalence of strabismus was particularly low (0.3%). Twenty percent of the children were referred for further assessment based on criteria of one or more of: stereopsis >70", accommodative facility <8 cpm, near point of convergence (NPC) >9 cm, near exophoria >10delta or near esophoria >5delta, shift in eso or exophoria > or = 4delta between distance and near, astigmatism > or = 1 D, myopia more than -0.75 D, or hyperopia >+1.50 D. Post-hoc analysis of the record cards seeking the reason for further assessment indicates that referrals appear to have been based upon clinical intuition rather than on a set number of borderline or unsatisfactory results.

Accommodation, Ocular↗