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The possible relationship between visual deficits and dyslexia: examination of a critical assumption.

Numerous studies have found that visual deficits are associated with dyslexia. The prevailing theory regarding this association is that dyslexia is the result of a deficit in the magnocellular system (earlier called the transient system) in the visual pathway. An essential assumption of this theory is that the parvocellular system (formerly called the sustained system) is suppressed by the magnocellular system at the time of saccadic eye movements. This assumption is examined on the basis of published studies of saccadic suppression. The evidence from six studies indicates quite unequivocally that the magnocellular system, not the parvocellular system, is suppressed during saccadic eye movements. It seems, therefore, that an essential premise of the magnocellular deficit theory of dyslexia is incorrect.

Dyslexia↗

Intensity modulation technique using the complementary boost-fields for ethmoid sinus cancer.

PURPOSE: To explore a static intensity-modulated radiation therapy (IMRT) technique of a more homogeneous isodose distribution to an irregular-shaped tumour of the ethmoid sinus, with concomitantly sparing the adjacent critical normal organs including the orbit. METHODS AND MATERIALS: We conducted a static IMRT technique adding 2 or smaller complementary boost-fields to the underdosed volume in the PTV, which resulted from complete blocking of the orbits in all coplanar or non-coplanar main ports of the standard 3-D CRT. The standard 3-D CRT plans (Plan A) and IMRT plans adding complementary boost fields (Plan B) were established for 10 patients with ethmoid sinus cancer. Two sets of different plans for each patient were compared using isodose distribution, dose statistics, and dose volume histogram (DVH) of the planning target volume (PTV) and also using dose statistics and DVH of the adjacent critical structures. RESULTS: The IMRT plans adding 2 or more complementary boost-fields (Plan B) for each patient demonstrated better coverage and improved dose homogeneity of the PTV compared to the standard 3-D CRT plan (Plan A). Moreover, the radiation doses to adjacent normal tissue organs, such as the orbits, optic nerves, brain stem and optic chiasm were similarly spared in both plans. CONCLUSION: With concomitantly sparing the surrounding visual pathway structures, our IMRT technique using the complementary boost-fields was quantitatively better than current standard 3-D CRT technique with respect to the dose homogeneity within the PTV. Therefore, we believe that our technique, though still not ideal, is thorough enough to be used routinely in treatment of ethmoid sinus tumour.

Adult↗

Magnocellular channel subserves the human contrast-sensitivity function.

There is evidence that the human contrast-sensitivity function (CSF) is mediated by the spatiotemporal characteristics of magno and parvo neurons early in the visual pathway. In this study we use a measure of contrast gain derived from simple reaction times, to investigate the neural substrates of suprathreshold performance. The results reveal the activity of two mechanisms having distinctly different contrast-gain characteristics. Comparing these to neurophysiological data, we find that the magnocellular system dominates close-to-threshold detection and probably forms the basis of the achromatic CSF, whereas the parvocellular system dominates detection at higher contrasts, when the magnocellular system saturates.

Adult↗

Red-green chromatic mechanisms in normal aging and glaucomatous observers.

PURPOSE: This study was designed to determine whether normal aging and glaucoma are associated with red-green (R/G) chromatic processing abnormalities, a function that is primarily performed by the parvocellular visual pathway. METHODS: Chromatic processing mechanisms were examined in 98 glaucomatous observers (between the ages of 49 and 93 years; mean age, 70.8 +/- 9.4 [SD]) and 67 normal observers (between the ages of 49 and 88; mean age, 70.6 +/- 10.6 years) with the use of the minimum-motion and motion-nulling paradigms. Phakic glaucomatous (n = 60; mean age, 68.7 +/- 8.9 years) and normal (n = 32; mean age, 69.8 +/- 10.6 years) and pseudophakic glaucomatous (n = 38; mean age, 74 +/- 9.4 years) and normal (n = 35; mean age, 71.4 +/- 10.6 years) subjects were tested to evaluate the effects of lenticular aging on color perception. RESULTS: Phakic observers (normal or glaucomatous) displayed significantly different minimum-motion values than did both their younger counterparts and all the pseudophakic subjects. These results suggest that normal aging with the presence of a natural lens is accompanied by a significant decrease in green-light sensitivity, an effect that is not exacerbated by glaucoma and is primarily related to optical factors. The data also revealed no differences in color motion perception between groups, indicating that the higher cortical mechanisms of the parvocellular pathway implicated in the analysis of information about the middle and long wavelengths of the visible spectrum are not selectively affected by the disease process and normal aging. CONCLUSIONS: Normal aging and glaucoma do not produce significant R/G chromatic processing deficits at retinal and postretinal levels when optical factors are excluded. The authors propose the hypothesis that glaucoma-related effects on motion perception and blue-on-yellow perimetry should be viewed as evidence of loss of ganglion cells that necessitates integration of information over larger retinal areas and more receptor cells than in the R/G chromatic system. Ganglion cells with large receptive fields involve more neural connections and are less numerous than those that respond to R/G information. The functional consequence of this could be that the loss of a single ganglion cell with a larger receptive field would have a greater impact on visual function than the loss of a ganglion cell with a smaller receptive field, such as the ones that process R/G information. The authors believe that glaucoma-induced functional loss is best viewed as related to receptive field structure and function rather than to anatomic cell-type damage.

Aged↗

A computational model to link psychophysics and cortical cell activation patterns in human texture processing.

The human visual system uses texture information to automatically, or pre-attentively, segregate parts of the visual scene. We investigate the neural substrate underlying human texture processing using a computational model that consists of a hierarchy of bi-directionally linked model areas. The model builds upon two key hypotheses, namely that (i) texture segregation is based on boundary detection--rather than clustering of homogeneous items--and (ii) texture boundaries are detected mainly on the basis of a large scenic context that is analyzed by higher cortical areas within the ventral visual pathway, such as area V4. Here, we focus on the interpretation of key results from psychophysical studies on human texture segmentation. In psychophysical studies, texture patterns were varied along several feature dimensions to systematically characterize human performance. We use simulations to demonstrate that the activation patterns of our model directly correlate with the psychophysical results. This allows us to identify the putative neural mechanisms and cortical key areas which underlie human behavior. In particular, we investigate (i) the effects of varying texture density on target saliency, and the impact of (ii) element alignment and (iii) orientation noise on the detectability of a pop-out bar. As a result, we demonstrate that the dependency of target saliency on texture density is linked to a putative receptive field organization of orientation-selective neurons in V4. The effect of texture element alignment is related to grouping mechanisms in early visual areas. Finally, the modulation of cell activity by feedback activation from higher model areas, interacting with mechanisms of intra-areal center-surround competition, is shown to result in the specific suppression of noise-related cell activities and to improve the overall model capabilities in texture segmentation. In particular, feedback interaction is crucial to raise the model performance to the level of human observers.

Action Potentials↗

[Dissociation of visual evoked responses to hemi-field or full-field flash-checkerboard stimulation].

Unexpected visual evoked responses (VERs) were recorded in 5 subjects with tumoral, ischemic or hemorrhagic lesions of the retrochiasmatic visual pathways. The flash pattern stimulation was always binocular and involved full-field and half-field stimuli. In these 5 cases, the total field VER was asymmetrical with anomalies on the affected occipital region. However half-field VERs P100 contralateral to the stimulus were noted both on the normal and on the affected occipital region. One can ask if this is not an electrophysiological equivalent of the clinical relative hemianopsia.

Adult↗

[Indications for electrophysiologic studies of the eye].

The phenomena of light-evoked electrical activity of the retinal pigment epithelium, retina, and visual cortex can be used for specific diagnostic testing. The EOG, with standing potential and light peak, reflects the functional state of the pigment epithelium; the ERG reflects the function of the photoreceptors (a-wave) and inner nuclear layer (b-wave), and the visual evoked response (VER) provides information on signal conduction along the entire visual pathway. The indications for electroretinography are discussed in detail, resulting in a broad spectrum including degenerative, metabolic, inflammatory and toxic changes of the retina. In addition, a condensed table of diagnoses that can hardly be established without ERG is proposed. The value of ERG recordings is extended by the possibility to document rate of progression and relative involvement of the rod- and/or the cone system of the retina. VER procedures are mainly directed towards demyelinating diseases of the CNS. We attempt to interpret results of electrophysiologic testing synoptically with subjective complaints and clinical observations.

Electroretinography↗

Spatial distribution of evoked potentials in the inferior olivary nucleus by stimulation of the visual afferents in the rat.

Visual pathways (optic disc, optic nerve and pretectal regions) were electrically stimulated and evoked potentials were explored throughout the inferior olive in the anesthetized rat. Responsive areas were identified as the caudal half of the dorsal cap, nucleus beta and the most caudal region of subnucleus c of the medial accessory olive. No field potentials were identified in the rostral half of the dorsal cap, its ventrolateral outgrowth or the dorsomedial cell column. Contralateral retinal afferents were only effective all over the responsive areas.

Animals↗

Identification of differentially expressed genes in the visual structures of brain using high-density cDNA grids.

The hybridization patterns of 18,371 high-density-grid-arrayed non-redundant complementary DNA (cDNA) clones were examined using three different sources of cDNA probes. The first set of probes was synthesized from mRNA isolated from visual brain areas MT and V4 of Vervet monkey. The second set of probes was derived from cDNA libraries constructed from two micro dissected sets of layers of the monkey Lateral Geniculate Nucleus layers within the visual pathway, namely the magnocellular and parvocellular layers. The third set of cDNA probes was synthesized from the subtracted fractions of the cDNAs enriched for either the magnocellular or the parvocellular layers of the Lateral Geniculate Nucleus. Software, linked directly to the Genbank database, was developed to aid in the rapid identification of both expressed and differentially expressed genes. Our results indicate that both the cDNA probes synthesized from mRNA and cDNA libraries can identify similar fractions of expressed genes. However, the subtracted cDNA probes improve the efficiency of detection for those genes that are expressed at much lower abundance. Analyses of these results for the differential expression patterns of these genes were validated by semi-quantitative PCR on the DNA derived from the whole tissue cDNA libraries. A list of some known genes that are statistically differentially expressed within the magnocellular layers of the LGN and area MT in the primate visual areas is derived.

Animals↗

The pattern of callosal connections in posterior neocortex of congenitally anophthalmic rats.

In an effort to assess the innate capacity of the central visual system to specify corticocortical connectivity in the absence of retinal afferents, we examined the tangential distribution of callosal cells and terminations in posterior neocortex of congenitally anophthalmic rats. Although our results indicate that the callosal pattern is clearly anomalous in these rats, all features of the normal visual callosal pattern are recognizable in mutant rats, indicating that central visual pathways can generate many aspects of normal interhemispheric connectivity in the absence of input from the periphery. On the other hand, the presence of anomalies in the pattern indicates that the eyes are necessary to fine-tune the distribution of callosal connections at some developmental stage. Moreover, the fact that abnormalities in the callosal pattern of mutant rats are the same as those previously described in rats enucleated at birth suggests that the eyes begin to exert their influence on callosal development after birth.

Agenesis of Corpus Callosum↗

Postnatal development of quantitative morphological parameters in the lateral geniculate nucleus of the marmoset monkey.

Quantitative morphological parameters were studied in the lateral geniculate nucleus (LGN) of the marmoset monkey (Callithrix jacchus) during development, using a series of 14 animals, at ages from birth to adulthood. They include the volume of the LGN and of its layers and interlaminar zones, their neuronal content expressed as numerical density and total number, and the density and number of glial cells in the nucleus as a whole. The volume of the LGN increases rapidly after birth, reaches a maximum at 6 months of age, and then decreases to its adult value of about 11 mm3. Neuronal density follows a reciprocal curve, reaching an adult value of about 41,000 neurons/mm3, so that the total number of about 440,000 neurons per LGN remains constant throughout life although large interindividual variations, especially in juveniles, do not allow unequivocal statements about total neuronal number to be made. Parvocellular layers occupy most of the geniculate volume, and contain about 74% of its neurons in the adult. We found no difference in their development pattern compared with the magnocellular component. The 'superficial' layers and interlaminar zones contain more than 15% of the geniculate neurons, and they could therefore play an important functional role in the primary visual pathway of New World primates. The number of glial cells nearly triples during the first 6 weeks and stabilizes around 800,000 in the LGN of one hemisphere. As the same brains were used as in a previous study on the area 17 of the marmoset (Dev. Brain Res., 29 (1986) 173-188) direct comparisons of the development of cortex and thalamus can be made. Their development is parallel in time, and in both cases the adult values for volume, neuronal density and glial numbers are reached several months postnatally.

Animals↗

Neuropathology of experimental vitamin B12 deficiency in monkeys.

We have produced severe vitamin B12 deficiency in rhesus monkeys by feeding them a defined experimental diet under controlled conditions. Five years after institution of the deficient diet, the morphology and counts of peripheral blood and bone marrow are normal. Gross visual impairment appeared in five of the monkeys between 33 and 45 months after the institution of the vitamin B12 deficient diet. Subsequently, in three of the visually impaired animals, a gradually progressive spastic paralysis of their hind limbs developed. Autopsies of six deficient animals showed degeneration of the peripheral visual pathway in all and of white matter in the spinal cord in four. Degeneration of several cranial nerve roots was found in four monkeys and a mild diffuse degeneration of cerebral white matter in four. The lesions in all affected parts of the central nervous system were bilaterally symmetrical and were indistinguishable from those due to B12 deficiency in the human. No abnormalities were found in one B12 supplemented control animal.

Animals↗

Efficient coding of natural scenes in the lateral geniculate nucleus: experimental test of a computational theory.

A recent computational theory suggests that visual processing in the retina and the lateral geniculate nucleus (LGN) serves to recode information into an efficient form (Atick and Redlich, 1990). Information theoretic analysis showed that the representation of visual information at the level of the photoreceptors is inefficient, primarily attributable to a high degree of spatial and temporal correlation in natural scenes. It was predicted, therefore, that the retina and the LGN should recode this signal into a decorrelated form or, equivalently, into a signal with a "white" spatial and temporal power spectrum. In the present study, we tested directly the prediction that visual processing at the level of the LGN temporarily whitens the natural visual input. We recorded the responses of individual neurons in the LGN of the cat to natural, time-varying images (movies) and, as a control, to white-noise stimuli. Although there is substantial temporal correlation in natural inputs (Dong and Atick, 1995b), we found that the power spectra of LGN responses were essentially white. Between 3 and 15 Hz, the power of the responses had an average variation of only +/-10.3%. Thus, the signals that the LGN relays to visual cortex are temporarily decorrelated. Furthermore, the responses of X-cells to natural inputs can be well predicted from their responses to white-noise inputs. We therefore conclude that whitening of natural inputs can be explained largely by the linear filtering properties (Enroth-Cugell and Robson, 1966). Our results suggest that the early visual pathway is well adapted for efficient coding of information in the natural visual environment, in agreement with the prediction of the computational theory.

Animals↗

Visual field preservation after multisession cyberknife radiosurgery for perioptic lesions.

OBJECTIVE: The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings. METHODS: Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months. RESULTS: After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes. CONCLUSION: Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

Adolescent↗

Neurotoxic effects of neonatal injections of monosodium L-glutamate (L-MSG) on the retinal ganglion cell layer of the golden hamster: anatomical and functional consequences on the circadian system.

In rodents, daily injection of neurotoxic monosodium L-glutamate (MSG) during the postnatal period induces retinal lesions, optic nerve degeneration with an alteration of visual pathway and an absence of the b-wave in the electroretinogram. Despite this damage, electrophysiological responses subsist in the lateral geniculate bodies and synchronization of circadian rhythms to the light/dark cycle can still occur. Using two formal properties of the circadian system (entrainment and phase-shift by light), we assessed the functionality of retinal projections to the circadian clock in MSG-treated hamsters. Displaced amacrine and ganglion cell populations were quantified and retinal terminals in the suprachiasmatic nuclei were estimated. Animals received daily doses of glutamate during the first ten days after birth according to two protocols. The two treatments similarly destroyed 56% of the overall population of the ganglion cell layer: 30% of displaced amacrine and 89% of ganglion cells. Surviving ganglion neurons (7,500 cells) were evenly distributed across the entire retina except in one area of high cell density located in the temporoventral quadrant. Retinal projections of the "image-forming" pathway were drastically reduced in the dorsal lateral geniculate bodies, less in their ventral part. The "nonimage-forming" pathway was also affected since the volume of labeled terminals in the suprachiasmatic nuclei was reduced by one-half to one-third. Nevertheless, treated hamsters exhibited a free-running locomotor activity rhythm after several months in constant darkness, could be entrained by the light/dark cycle and phase-shifted by light pulses. These results suggest that a damaged retinohypothalamic tract can still assume the photic entrainment of the circadian clock.

Animals↗

Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis.

Axonal damage is found in both acute and chronic lesions of multiple sclerosis. Direct axon counting in post-mortem tissue has suggested that smaller axons might have a greater susceptibility to damage, but methodological limitations have precluded unequivocal interpretation. However, as neuronal and axonal sizes are linked and neuronal changes would be expected with retrograde or transsynaptic degeneration following axon injury, we hypothesized that an alternative strategy for studying this phenomenon would be to define multiple sclerosis-associated changes in neurones. To test this hypothesis, we measured both axonal loss and neuronal size changes in the anterior optic pathway [including the optic nerve (ON), optic tract (OT) and lateral geniculate nucleus] of the brains of eight patients who died with multiple sclerosis and in eight control brains. The ONs and OTs in brains from the multiple sclerosis patients showed a trend to smaller mean cross-sectional areas (ON, multiple sclerosis = 6.84 mm(2), controls = 9.25 mm(2); and OT, multiple sclerosis = 6.45 mm(2), controls = 7.94 mm(2), P = 0.08) and had reduced axonal densities (ON, multiple sclerosis = 1.1 x 10(5)/mm(2), controls = 1.7 x 10(5)/mm(2); and OT, multiple sclerosis = 1.4 x 10(5)/mm(2), controls = 1.8 x 10(5)/mm(2), P = 0.006). Estimated total axonal counts were reduced by 32 (OT)-45% (ON) in the patients relative to controls (ON, multiple sclerosis = 8.1 x 10(5) axons, controls = 14.8 x10(5), P = 0.05; and OT, multiple sclerosis = 9.1 x 10(5), controls = 13.3 x 10(5), P = 0.02). The size distributions of the magnocellular cells in the lateral geniculate nucleus were similar for the two groups, but in multiple sclerosis brains the parvocellular cells were significantly smaller (mean sizes: multiple sclerosis = 226 microm(2), controls = 230 microm(2), P < 0.001) and had a larger variation in size, suggesting a greater proportion of atrophic neurones. Axon loss in the optic nerves of multiple sclerosis patients correlated strongly with measures of increased dispersion of cell sizes in the parvocellular layer (r = 0.8, P < 0.04). These data demonstrate that both atrophy and decreased density contribute to the substantial axonal loss in the anterior visual pathway of these patients. This appears related to a relatively selective atrophy of the smaller neurones of the parvocellular layer in the lateral geniculate nucleus, supporting the hypothesis that smaller axons may be preferentially susceptible to injury in multiple sclerosis.

Adult↗

Motion-onset VEPs reflect long maturation and early aging of visual motion-processing system.

Pattern-reversal and motion-onset visual evoked potentials (VEPs) were simultaneously tested in a group of 70 healthy subjects between the ages of 6-60 years to verify suspected differences in maturation and aging dynamics of the pattern and motion processing subsystems of the visual pathway. The motion-onset VEPs displayed dramatic configuration development and shortening of latencies up to 18 years of age (correl. coeff. -0.85; p < 0.001) and systematic prolongation from about 20 years of age (correl. coeff. 0.70; p < 0.001). This confirms long-lasting maturation of the magnocellular system and/or motion processing cortex and their early age related changes. Less significant changes of pattern-reversal VEPs in the tested age range can be interpreted as a sign of early maturation of the parvocellular system and its enhanced functional endurance in the elderly.

Adolescent↗

The source of reactive cells during central Wallerian degeneration in the goldfish: a differential irradiation protocol.

We have used a partial irradiation paradigm to examine the provenance of cells that participate in Wallerian cellular responses in the goldfish visual system. Animals which received 50 Gy whole-body gamma-irradiation showed virtually complete inhibition of the proliferative burst usually seen after optic nerve section. These animals did, however, show a robust hyperplastic response in the optic tract that we believe represents the migration of nearby microglial cells into the affected tract. When only the postcephalic body was irradiated, proliferating cells in the major hematopoietic organs of the fish, the kidney and pronephros, were substantially inhibited. Despite this, the Wallerian cellular response in the visual paths was essentially normal. Thus, there is no obligate requirement for peripheral proliferative cells to participate in central Wallerian degeneration in the fish. However, when only the head was irradiated, and the hematopoietic organs were spared, there was a proliferative response in the visual system. We believe this represents the invasion of the visual pathways by peripheral blood cells through the optic nerve lesion and blood vessels in the nerve itself. This invasion, however, is not sufficient to generate substantial hyperplasia. In summary, although we find evidence for a small contribution by exogenous cells, the major source of reactive cells during central Wallerian degeneration in the fish is the endogenous microglia. Our data underscore the importance of elucidating the mechanisms by which microglial cells are activated and the role that they play in regeneration.

Animals↗