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MR of vasculitis-induced optic neuropathy.

PURPOSE: To describe the MR characteristics of optic neuropathy caused by vasculitis. METHODS: Nine cases of optic neuropathy with diagnosis of vasculitis (six with systemic lupus erythematosis and one each with rheumatoid arthritis, Sjögren disease, and radiation vasculitis) were reviewed retrospectively. Patients were 31 to 62 years old, and all but one were women. All patients had MR imaging through the orbits and anterior visual pathways, five with fat suppression, with and without gadopentetate dimeglumine. Five patients also had MR imaging of the entire brain. The size and enhancement of various segments of the optic nerve and anterior visual pathways were studied. RESULTS: MR imaging with contrast material showed enhancement and enlargement of segments of the optic nerves and/or chiasm in six of the nine patients (all but three with systemic lupus erythematosis). Enlargement of a segment of the anterior visual pathway never occurred without enhancement, but enhancement alone did occur in three cases. Of the five patients who had MR imaging of the whole brain, abnormalities were seen in three: periventricular hyperintensity in two and a lacunar infarct in one; none had vessel abnormalities. CONCLUSION: Because the MR enhancement seen represents disruption of the blood-brain barrier within the optic nerve, MR imaging with gadopentetate dimeglumine and fat suppression should be performed to detect increased permeability of the blood-brain barrier in acute optic neuropathy.

Adult↗

Shifter circuits: a computational strategy for dynamic aspects of visual processing.

We propose a general strategy for dynamic control of information flow between arrays of neurons at different levels of the visual pathway, starting in the lateral geniculate nucleus and the geniculorecipient layers of cortical area V1. This strategy can be used for resolving computational problems arising in the domains of stereopsis, directed visual attention, and the perception of moving images. In each of these situations, some means of dynamically controlling how retinal outputs map onto higher-level targets is desirable--in order to achieve binocular fusion, to allow shifts of the focus of attention, and to prevent blurring of moving images. The proposed solution involves what we term "shifter circuits," which allow for dynamic shifts in the relative alignment of input and output arrays without loss of local spatial relationships. The shifts are produced in increments along a succession of relay stages that are linked by diverging excitatory inputs. The direction of shift is controlled at each stage by inhibitory neurons that selectively suppress appropriate sets of ascending inputs. The shifter hypothesis is consistent with available anatomical and physiological evidence on the organization of the primate visual pathway, and it offers a sensible explanation for a variety of otherwise puzzling facts, such as the plethora of cells in the geniculorecipient layers of V1.

Animals↗

[Optic nerve regeneration in Bcl-2 overexpressing mice].

OBJECTIVE: To determine whether overexpression of Bcl-2 is sufficient to support optic nerve regeneration in mouse in the early neonatal stage, when the brain environment remains permissive for axonal growth, and whether regenerating axons follow the guidance cues to reach the appropriate targets in the brain. METHODS: Optic nerve crush was performed in wild-type (C57BL/6J) and Bcl-2 transgenic mouse pups at 3 days after birth (P3). To assess optic nerve regeneration, mouse pups were allowed to survive for 1-4 days post-surgery. An anterograde tracer-cholera toxin B subunit (CTB) and anti-GAP-43 immunofluorescence were applied to reveal regenerating axons. RESULTS: In wild-type mice, severed optic nerves failed to regenerate, and most severed axons retracted within 24 hour post-surgery. In contrast, in all of the Bcl-2 transgenic mice examined, optic nerves regenerated robustly over long distances and reached their brain targets in 4 days after optic nerve crush. However, the majority of regenerating axons, appearing to follow the existing optic tract and visual pathways, entered the visual targets that were ipsilateral to the nerve injury. Much less number of regenerating axons innervated their contralateral visual targets. CONCLUSION: Overexpression of Bcl-2 is sufficient to support the intrinsic growth mechanisms of retinal ganglion cell axons and enables robust optic nerve regeneration over long distances in vivo if the injury is incurred at 3 days after birth. However, the regenerating axons appear to follow the existing CNS pathways and innervate uninjured brain areas.

Animals↗

Erythrocyte docosahexaenoic acid correlates with the visual response of healthy, term infants.

Recent studies have reported that formula-fed preterm infants score lower on visual and developmental tests relative to breast-fed preterm infants. This phenomenon has been associated with the presence of docosahexaenoic acid (DHA), an omega-3 fatty acid, in breast milk and its absence from infant formula. To investigate the possibility that DHA status of healthy, term infants is also related to neuronal function of the visual pathway, we studied the erythrocyte fatty acid profiles of 16 infants at 22.3 +/- 3.9 wk of age and related these to maturity of the visual pathway as assessed by visual-evoked potentials. Healthy, term infants fed breast milk had better visual-evoked potential acuity (p < 0.05) and higher DHA levels (p < 0.001) than infants who received infant formula as their major energy source. There was a positive correlation between erythrocyte DHA and visual-evoked potential acuity (p < 0.01). The data are preliminary and the long-term effects as yet unknown. However, our results suggest that there is an urgent need to evaluate the dietary fatty acid supply of formula-fed term infants.

Breast Feeding↗

Eye position affects activity in primary auditory cortex of primates.

BACKGROUND: Neurons in primary auditory cortex are known to be sensitive to the locations of sounds in space, but the reference frame for this spatial sensitivity has not been investigated. Conventional wisdom holds that the auditory and visual pathways employ different reference frames, with the auditory pathway using a head-centered reference frame and the visual pathway using an eye-centered reference frame. Reconciling these discrepant reference frames is therefore a critical component of multisensory integration. RESULTS: We tested the reference frame of neurons in the auditory cortex of primates trained to fixate visual stimuli at different orbital positions. We found that eye position altered the activity of about one third of the neurons in this region (35 of 113, or 31%). Eye position affected not only the responses to sounds (26 of 113, or 23%), but also the spontaneous activity (14 of 113, or 12%). Such effects were also evident when monkeys moved their eyes freely in the dark. Eye position and sound location interacted to produce a representation for auditory space that was neither head- nor eye-centered in reference frame. CONCLUSIONS: Taken together with emerging results in both visual and other auditory areas, these findings suggest that neurons whose responses reflect complex interactions between stimulus position and eye position set the stage for the eventual convergence of auditory and visual information.

Acoustic Stimulation↗

[Correlated study of visual evoked potentials-polyneuropathy in diabetic patients without retinopathy].

The functional study of visual pathways by means of pattern reversals VEPs (visual evoked potentials) was used as a noninvasive method in the study of diabetic patients, but the correlations between alterations in VEPs and the involvement of peripheral nervous system were not explored. Among 35 diabetic patients not suffering from retinopathy, we tested early deteriorations in visual pathways by means of pattern reversals VEPs and we considered similarities between these alterations, clinical metabolic parameters of the disease and clinical and paraclinical aspects of polyneuropathy (PNP). Four of these patients were insulin-dependent and 31 non-insulin-dependent, all with normal electroretinography and fluorangiography. Monitoring control of diabetes was performed by measuring hemoglobin HbA1. The control group was composed of 35 healthy subjects with normal neurologic and ophthalmologic examinations and normal visual acuity. In all subjects we tested four peripheral nerve conduction velocities (PNCV) (sensory and motor conduction of median nerve, motor conduction of peroneal nerve, anthidromic sensory conduction of sural nerve) diabetic patients were distributed in two groups according to the presence (group A, 15 patients) or absence (group B, 20 patients) of polyneuropathy. Pattern reversals PEVs were recorded after mono and binocular stimulation; screen was 25 x 18 cm with black and white check board pattern, check size 1.1 cm. Subject-to-stimulus distance was 1 m, corresponded to a visual angle of 38 degrees. Active electrode were located in Oz, O1 and O2, reference electrode in Fz.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence of optic pathway gliomas after previously negative neuroimaging.

PURPOSE: The authors emphasize the potential for the development of anterior visual pathway gliomas, evidenced by computed tomography (CT) or magnetic resonance imaging (MRI) scans, in neurofibromatosis type 1 (NF1) patients who previously had normal neuroimaging studies. METHODS: The clinic charts and CT and MRI scans were retrospectively reviewed for all patients evaluated at the neurofibromatosis clinic of one referral center over a period of 7 years. Patients with neuroimaging studies demonstrating anterior visual pathway gliomas who previously had normal scans were identified, and their cases are described in detail. A similar, previously reported series, from the pediatric literature, was also reviewed. RESULTS: Eight percent (28/360) of patients had CT or MRI scans revealing optic gliomas. Two of these patients had normal neuroimaging studies previously. CONCLUSION: A negative neuroimaging study in an NF1 patient does not exclude the future development of an optic glioma.

Antineoplastic Combined Chemotherapy Protocols↗

Spatio-temporal vision of macaques with severe loss of P beta retinal ganglion cells.

Anatomical and physiological studies indicate major structural and functional differences between the two parallel retinogeniculate visual pathways in the macaque. We have examined the contribution of these pathways to achromatic visual capacities by behaviorally testing spatio-temporal vision in monkeys with severe damage to the P beta (medium cell) pathway. This loss was produced by systemic administration of a neurotoxicant, acrylamide monomer, a treatment that apparently spares other visual system neurons. Monkeys dosed with acrylamide showed large reductions of contrast sensitivity at high spatial as well as low temporal frequencies. On the other hand, they had normal sensitivity for stimuli of high temporal, low spatial frequency. In addition, dosed monkeys retained normal flicker resolution thresholds for unpatterned stimuli. These findings suggest that the medium cell retinogeniculate pathway contributes primarily to the detection of higher spatial, lower temporal frequencies, while the large cell pathway is involved primarily in sensitivity to lower spatial and higher temporal frequencies.

Acrylamide↗

An alternate pathway for visual signal integration into the hypothalamo-pituitary axis: retinorecipient intergeniculate neurons project to various regions of the hypothalamus and innervate neuroendocrine cells including those producing dopamine.

Using tract tracing and immunocytochemistry, this study explored the connectivity between lateral geniculate efferents and neurons of the hypothalamus, including those producing dopamine, that have direct access to fenestrated capillaries. It was also determined whether the intergeniculate neurons that give rise to hypothalamic projections are targeted by retinal axons. Within the hypothalamus, Phaseolus vulgaris leucoagglutinin-labeled, lateral geniculate efferents were observed in the suprachiasmatic nucleus, subparaventricular area, periventricular nuclei, medial preoptic areas, and between the arcuate and ventromedial nuclei. In these sites, intergeniculate efferents contacted populations of neurons that were retrogradely labeled from fenestrated capillaries by the intraperitoneal injection of fluorogold. Hypothalamic dopamine neurons, a population of which was neuroendocrine, were also synaptic targets of lateral geniculate efferents. After injection of the retrograde tracer fluorogold into these hypothalamic projection sites in parallel with bilateral enucleation, retrogradely labeled perikarya were restricted to the intergeniculate leaflet. All of the labeled perikarya contained infolded nuclei, and their distal dendrites were frequently found to be contacted by degenerated, retinal fibers. This study provides morphological evidence for a signaling pathway from the retina through the intergeniculate leaflet to hypothalamic cells that participate in neuroendocrine regulations. These observations raise the possibility that visual signals independent of the circadian clock may also influence the hypothalamo-pituitary axis. In light of the overlapping distribution of intergeniculate and suprachiasmatic efferents in the hypothalamus and their similar relationship with neuroendocrine cells, it is suggested that integration of circadian and visual signals can occur outside of the suprachiasmatic nucleus to regulate endocrine rhythms.

Animals↗

Cortical dynamics.

Our ability to interpret visual scenes involves assembling the components of objects into a unified percept and segregating them from background, storing information about earlier visual experiences and testing our interpretations of the visual world against incoming sensory input. The influences of context, experience and expectation are reflected in the response properties of cells at early stages in the visual pathway. The responses of cells in primary visual cortex depend not only on the attributes of features lying within the classical receptive field but also on the global characteristics of the contours and surfaces within which these features are embedded. The substrate for lateral interactions includes a plexus of long-range horizontal connections within each cortical area that links columns of similar orientation specificity and cells with widely separated receptive fields. The horizontal connections also play a role in the plasticity of receptive field structure and of cortical functional architecture, induced over long time scales by retinal lesions and over short time scales by patterned visual stimulation. The long-term changes are associated with synaptogenesis; and the short-term changes with an increase in synaptic effectiveness. The dynamics of cortical function persist throughout adulthood and are general to all cortical areas, including primary sensory cortices.

Animals↗

Cortical streams of visual information processing in primates.

1. The topographic organization of the cortical visual areas in the Cebus monkey and their anatomical connections support the subdivision of the visual pathways into ventral and dorsal streams of visual information processing. 2. We propose that the dorsal stream, as defined by Ungerleider and Mishkin (In: Ingle DJ, Goodale MA and Mansfield RJW (Editors), Analysis of Visual Behavior. MIT Press, Boston, 1982), be subdivided into dorsolateral and dorsomedial streams, which are concerned with different aspects of the processing of motion and spatial perception. 3. The data support the hypothesis of concurrent, modular processing of visual attributes in cortical visual areas in the different streams, and highlight some features of the visual field representation in each area which may reflect functional specialization of these streams. 4. The visual topography is locally disrupted in some cortical areas by the existence of functionally different modules. However, a global visuotopic organization is preserved in most areas. 5. The visuotopic organization may provide the address of space coordinates to integrate information concerning the same retinotopic locus across different visual areas.

Animals↗

Development of visual system - comparison of monkey and man.

In Golgi preparations of the lateral geniculate nucleus of adult humans and monkeys several types of neuron are described. Multipolar neurons have a "radiate" or "tufted" dendritic arbor. The next commonest class is the bipolar neuron with two or three thick dendrites arising from opposite poles of the soma. A few examples of rare medium-sized neurons with beaded dendrites are found. There are also small neurons with fine "axon-like" dendritic processes. Some have long, untapered dendrites and others shorter dendritic arbors. A class of large, capsular neurons is found in the circumgeniculate capsule. Maturation of lateral geniculate nucleus neurons in baby humans and monkeys was studied in Golgi preparations. They pass through post-natal stages characterised by dendritic growth cones and a profusion of spine-like protuberances on dendrites and somata. The mature form is found by the second month in monkey and about one year in man. The morphological changes in the thalamus are paralleled by synaptogenesis in the visual cortex. In man synaptic density reaches a maximum at about one year of age, declines later in childhood and stabilises at adult levels by about 11 years of age. In both monkey and man the period of morphological maturation in the visual pathways corresponds to a time of increasing visual acuity when visual deprivation is most likely to have permanent harmful effects.

Adolescent↗

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↗

Sensitive and vulnerable periods in the development of the visual system.

In advanced mammals the visual system consists of a number of parallel channels for the efficient processing of different aspects of the visual scene. Much of the basic anatomical structure of the visual pathway is constructed before birth. A wave of maturation sweeps through the system, from the eye to the visual cortex, the correct formation of connections depending on precisely timed interactions between axons and their targets. Competition between growing axons (apparently dependent on spontaneous impulse activity in those axons), cell death (partly influenced by competition between those cells' axons), axon withdrawal, trophic interactions--these and other mechanisms play a part in constructing the visual pathway and laying down basic 'maps' of the visual field before birth. Disturbances in such processes might underlie disorders of the genesis of the nervous system. At the level of the visual cortex, synaptic plasticity continues after birth and may permit cortical neurons to refine their processing capacities on the basis of information provided by the visual environment. This makes the young animal vulnerable to disturbances of visual experience early in life, which can cause virtually irreversible deficits in stereoscopic vision, visual resolution and sensitivity to contrast (amblyopia) in adult life.

Animals↗

Visual effects of damage to P ganglion cells in macaques.

Four indices of visual performance were measured in control macaques and in macaques that had been exposed to monomeric acrylamide, a neurotoxicant that preferentially damages P retinal ganglion cells. Morphological examination of the retina and visual pathways of these monkeys showed virtually complete loss of P ganglion cells over a region extending to at least 40 deg from the fovea, and relative sparing of M ganglion cells. The four tests examined visual functions for which the visual pathway from P ganglion cells might be of great importance: visual acuity, contrast discrimination, hyperacuity, and shape discrimination. In the acrylamide-dosed monkeys, visual acuity was reduced slightly more than fourfold, a somewhat larger reduction than that seen previously after ibotenic-acid lesions of the P pathway in the geniculate. The residual acuity was in good agreement with the Nyquist frequency calculated from the density of ON or OFF M ganglion cells. Contrast increment thresholds were elevated for the dosed monkeys only in one of the two conditions tested. The elevation was found only under those spatiotemporal conditions for which we have previously shown that contrast thresholds are increased by acrylamide exposure, and was most marked at low background contrasts. Vernier acuity was elevated in one dosed monkey, but not affected in a second monkey that also had severe loss of P ganglion cells. Finally, we found no effect of acrylamide exposure on the number of training trials required to learn simple or complex shape discriminations. These results support previous findings in showing that the P pathway mediates visual acuity, and they show that several other important aspects of visual perception are not exclusively dependent on the P pathway.

Acrylamide↗

Magnocellular contributions to impaired motion processing in schizophrenia.

Patients with schizophrenia show impairments in motion processing, along with deficits in lower level processing primarily involving the magnocellular visual pathway. The present study investigates potential magnocellular contributions to impaired motion processing in schizophrenia using a combined neurophysiological and behavioral approach. As compared to prior motion studies in schizophrenia, thresholds were determined for both incoherent and coherent visual motion. In this study, velocity discrimination thresholds were measured for schizophrenia patients (n=14) and age-matched normal control subjects (n=16) using a staircase procedure. Early visual processing was evaluated using steady-state visual evoked potentials (ssVEP), with stimuli biased toward activation of either the magnocellular or parvocellular visual pathways through luminance contrast manipulation. Patients with schizophrenia showed poor velocity discrimination for both incoherent and coherent motion, with no significant group x task interaction. Further, when coherent motion performance was measured at individually determined incoherent motion thresholds, accuracy levels for patients were similar to controls, also indicating similarity of deficit for incoherent vs. coherent motion discrimination. Impairments in velocity discrimination correlated significantly with reduced amplitude of ssVEP elicited by magnocellular -- but not parvocellular -- selective stimuli. This study demonstrates that deficits in motion processing in schizophrenia are significantly related to reduced activation of the magnocellular visual system. Further, this study supports and extends prior reports of impaired motion processing in schizophrenia, and indicates significant bottom-up contributions to higher-order cognitive impairments.

Adult↗

Monoclonal antibody Cat-301 identifies Y-cells in the dorsal lateral geniculate nucleus of the cat.

In mammalian visual pathways, information is carried in parallel channels from the retina through the visual thalamus to visual cortex. The cat's visual pathway comprises at least three major channels that begin with the X, Y, and W ganglion cells in the retina. In the dorsal lateral geniculate nucleus (LGN) of the thalamus, neurons in the X, Y, and W channels receive input from their retinal counterparts and can be discriminated from one another on the basis of their anatomical and physiological properties. The search for molecular properties that might correlate with anatomically or physiologically defined classes of neuron has been a major area of research in recent years. Monoclonal antibody Cat-301 recognizes a neuronal surface-associated proteoglycan in many areas of the mammalian central nervous system. In the cat LGN Cat-301 immunoreactivity is restricted to a subset of neurons. We show here that the distribution, size, morphology, and cortical projection pattern of Cat-301-positive LGN neurons match those previously described for Y-cells. Taken together with our previous studies of the development of immunoreactivity and the sensitivity of Cat-301 staining to visual deprivation, these studies suggest that Cat-301 specifically recognizes Y-cells in the cat LGN. These results indicate that neurons within a physiologically and anatomically defined cell class share a molecular property. They further suggest that differences in molecular traits may reflect, and possibly subserve, differences in anatomical and physiological characteristics.

Animals↗

Transient patterns of serotonergic innervation in the rat visual cortex: normal development and effects of neonatal enucleation.

The transient aggregation of serotonin (5-HT)-containing fibers in the early development of rat visual cortex was examined immunohistochemically. The aggregation of 5-HT immunoreactive (IR) fibers consisted of three stages which were classified according to the course of time and degree of space occupied. The primary aggregation appeared in the subplate and moved upward along the development of the cortex. The aggregation proceeded to the secondary stage in presumptive layer IV. The fibers extended in a column-like structure following the secondary aggregation and formed the tertiary aggregation. The upper edge of the tertiary aggregation formed a lattice-like pattern in layer I and its structure was recognized to be similar to the structure of a 'blob' which characterizes the primary visual cortex in monkey. This transient aggregation of 5-HT-IR fibers began in the subplate of the anterior visual cortex on postnatal day 2 (PND 2) and progressed towards the posterior. On PND 11, the secondary and tertiary aggregations were completed in the entire region. No further aggregation of 5-HT-IR fibers was observed on PND 15. The anterior-to-posterior axis in the aggregation process corresponds to the direction of differentiation in the layer structure of cortex. In order to investigate the relationship between the transient aggregation of 5-HT-IR fibers and the development of the visual pathway, the secondary and tertiary aggregation on PND 11 were observed after postnatal monocular or binocular enucleation. Enucleation of eye balls did not affect either the area occupied by the 5-HT-IR fibers in the secondary aggregation or the number of column structures in the tertiary aggregation. However, the contralateral and ipsilateral cortices of monocularly enucleated cases were irregularly shaped in the secondary aggregation. The distribution of 5-HT-IR fiber terminals in the binocular area (Oc1B) increased in density on the contralateral side in the monocular enucleation, while that of both sides in the binocular enucleation was of non-homogeneous density and were shaped irregularly. The above results suggest that the transient aggregation of 5-HT-IR fibers observed in the early stage of development of visual cortex is regulated primarily by the intrinsic factors, and that extrinsic factors, such as visual pathway input, affect the aggregation within the boundary of such intrinsic factors. That is, the visual pathway input and the input balance from both eyes affect the distribution density of 5-HT-IR fibers and the shape of the visual cortex, respectively.

Animals↗