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Vision and cognition in Alzheimer's disease.

Alzheimer's disease (AD) is known to affect visual pathways, but potential concomitant effects on vision and cognitive performance are not well understood. We studied 43 individuals with AD of mild severity and 22 individuals without dementia on a battery of tests designed to measure multiple aspects of basic and higher-order visual perception and cognition. All subjects performed on the same visual and cognitive test batteries. The results showed no differences between groups on tests of static visual acuity, stereoacuity, dynamic visual acuity or motion direction discrimination. However, individuals with AD performed significantly worse on tests of static spatial contrast sensitivity, visual attention, shape-from-motion, color, visuospatial construction and visual memory. Correlation analyses showed strong relationships between visual and cognitive scores. The findings show that AD affects several aspects of vision and are compatible with the hypothesis that visual dysfunction in AD may contribute to performance decrements in other cognitive domains. The pattern of involvement indicates that AD affects multiple visual neural pathways and regions. It is possible that better understanding of vision-related dysfunction could aid diagnosis and interventions to improve functional capacity in patients with dementia.

Aged↗

The representation of objects in the human occipital and temporal cortex.

Recently, we identified, using fMRI, three bilateral regions in the ventral temporal cortex that responded preferentially to faces, houses, and chairs [Ishai, A., Ungerleider, L. G., Martin, A., Schouten, J. L., & Haxby, J. V. (1999). Distributed representation of objects in the human ventral visual pathway. Proceedings of the National Academy of Sciences, U.S.A., 96, 9379--9384]. Here, we report differential patterns of activation, similar to those seen in the ventral temporal cortex, in bilateral regions of the ventral occipital cortex. We also found category-related responses in the dorsal occipital cortex and in the superior temporal sulcus. Moreover, rather than activating discrete, segregated areas, each category was associated with its own differential pattern of response across a broad expanse of cortex. The distributed patterns of response were similar across tasks (passive viewing, delayed matching) and presentation formats (photographs, line drawings). We propose that the representation of objects in the ventral visual pathway, including both occipital and temporal regions, is not restricted to small, highly selective patches of cortex but, instead, is a distributed representation of information about object form. Within this distributed system, the representation of faces appears to be less extensive as compared to the representations of nonface objects.

Adult↗

Bilateral optic nerve cryptococcosis in sudden blindness in patients with acquired immune deficiency syndrome.

PURPOSE: A neuroanatomic study was undertaken to search for the cause of sudden, simultaneously bilateral blindness in a patient with acquired immune deficiency syndrome who had cryptococcal meningitis. METHODS: Careful gross examination was performed, and microscopic sections were cut at 50- to 100-microns intervals of the entire visual pathway. RESULTS: Focal cryptococcosis destroyed segments of the right intracanalicular optic nerve and the left intraorbital optic nerve adjacent to the optic canal. The meninges were heavily infiltrated by Cryptococcus organisms around the optic tracts, optic nerves, and optic chiasm; however, only a few scattered cryptococcal organisms were found in the periphery of the chiasm contiguous with heavy meningeal infection. Blood vessels supplying the chiasm appeared normal. Generalized cerebral edema and focal vacuolization of periventricular white matter were evident. CONCLUSION: The authors believe that sudden, simultaneously bilateral visual loss in this patient was caused by focal but fulminant necrosis of both optic nerves. However, the presence of cryptococcal organisms throughout the basal meninges and in the sheaths of both optic nerves suggests that cryptococcosis may produce visual loss by damaging multiple areas of the anterior visual pathway.

AIDS-Related Opportunistic Infections↗

Synaptic integration fields and associative plasticity of visual cortical cells in vivo.

Two major constraints in connectivity decide the spatial extent of visual cortical receptive fields, both during development and adult functioning: 1) feedforward input, extrinsic to visual cortex, is organized in an orderly projection to form a point-to-point mapping of the retina onto the cortical mantle and constitutes the core of the minimal discharge field (MDF) after amplification by local intracortical circuits; and 2) a second type of connectivity consists of long distance horizontal intracortical connections which are thought to favor the binding of local visual operations occurring simultaneously in different parts of the visual field. We review here possible factors, intrinsic to the considered cortical cell, that may control the effectiveness of post-synaptic integration. Their expression during sensory recognition could depend on the spatio-temporal distribution of active inputs onto the target cell dendrite and on their interplay with non-linearities of the membrane properties. On the basis of intracellular recordings in cat area, 17, we have observed that peripheral responses (excitatory and inhibitory) could be boosted by coincident postsynaptic depolarization. This effect is lost if the response and the postsynaptic depolarization are mismatched by 1,000 ms, suggesting that temporal correlation of central and peripheral responses could regulate in a non-linear manner the gain of center-surround interactions. This temporal selectivity is compatible with up-regulation of composite potentials by the transient voltage-dependent activation of slowly inactivating conductances in visual cortical neurons. A direct consequence of these different considerations is that the receptive field (RF) of neurons in visual pathways should not be considered as a static hardwired window probing the outer environment, but as an active filter which may continuously adapt and be updated as a function of global context and past experience.

Animals↗

Orbit and optic nerve.

The optic nerve is a fiber tract of the brain, and is not a true cranial nerve. Primary pathologic processes seen in the central nervous system and its linings can therefore affect the optic nerve. Along their course the fibers of the visual pathways are also susceptible to secondary extrinsic processes. The MR appearance of many of the primary and secondary processes that affect the optic nerve are characteristic. Where the imaging features of a process are not characteristic, a fairly narrow differential diagnosis can be suggested depending on the imaging appearance and anatomic location of the pathologic entity. This article is a categorical overview of the disease entities that may affect the optic nerve and tracts. Pathologic processes are organized according to the typical sites of involvement along the visual pathways, from the retina to the occipital cortex. Medical imaging, pathologic, clinical, and epidemiological highlights are presented.

Brain Diseases↗

Dissociation of discrimination thresholds for time to contact and for rate of angular expansion.

It is well known that, if a rigid sphere is moving at constant speed towards the eye along the line of sight then, for small values of theta, T = theta/theta, where T is the time to contact, theta is the instantaneous angular size and theta is the rate of increase of angular size. We describe a rationale and an experimental procedure for demonstrating empirically when subjects base discrimination of time to contact on trial-to-trial variations of (theta/theta) rather than on variations of theta or on variations of delta theta (the change of angular size during a presentation). Discrimination threshold for the ratio (theta/theta) was 0.070-0.13, and was independent of mean time to contact over a range of at least T = 1.0-4.0 sec. We conclude that the human visual pathway contains a mechanism that is sensitive to the ratio (theta/theta) rather independently of the values of theta and theta. Using a different procedure we demonstrated empirically that subjects based discriminations of rate of expansion on trial-to-trial variations of theta rather than variations of time to contact or on variations of delta theta. Discrimination threshold for rate of expansion was 0.85-0.14, and was independent of mean time to contact over a range of at least T = 1.0-4.0 sec. We conclude that the human visual pathway contains a mechanism that is sensitive to rate of expansion rather independently of time to contact or absolute change in size. When rate of expansion and time to contact were both available as cues, discrimination threshold was on average lower than when only one of the two cues was present. We conclude that there is some summation of the two cues. Our data can be explained by a small modification to a model previously put forward to account for data on threshold elevations and aftereffects caused by adapting to changing-size stimulation. This model incorporates a filter that is strongly activated by isotropic, homogeneous two-dimensional expansion of the retinal image and whose output is inversely proportional to time to contact (i.e. the more urgent the demand for evasive action, the stronger the output of the filter).

Discrimination, Psychological↗

Health-related quality of life of children with vision impairment or blindness.

The aims of the study were to describe the functional ability, health status, and health-related quality of life (HRQL) of young children with a vision impairment or blindness (VI/BL) and to examine the effect of different types of ophthalmic condition and the presence of other impairments or systemic disorders. A cross-sectional community survey of children aged 3 to 8 years with VI/BL was conducted in four areas of England using the Health Utilities Index Mark 3 system. Seventy-nine children (47 males, 32 females; mean age 6 y 2 mo [SD 1 y 6 mo]) met the selection criteria: 43% had a visual pathway condition, 38% a condition of the eye, and 19% nystagmus alone; and 61% had additional impairments/disorders. Eighty per cent had functional limitations on at least two of the following attributes: vision, hearing, speech, cognition, ambulation, dexterity, emotion, and pain. Forty-four per cent had functional limitations on four or more attributes. Children with nystagmus alone had significantly higher mean HRQL utility scores (0.80 [SD 0.26]) than children with a condition of the eye (0.45 [SD 0.33]), who, in turn, had higher scores than children with a visual pathway condition (0.05 [SD 0.33], p=0.002). Children with an isolated VI/BL had significantly higher mean scores (0.73 [SD 0.21]) than those with additional impairments/disorders (0.09 [SD 0.34], p<0.001). These findings underline the need for a broad assessment of each child with VI/BL and a multidisciplinary approach to care.

Blindness↗

Visual function and brain organization in non-decussating retinal-fugal fibre syndrome.

Functional neuroimaging, psychophysical and electrophysiological investigations were performed in a patient with non-decussating retinal-fugal fibre syndrome, an inborn achiasmatic state in which the retinal projections of each eye map entirely to the ipsilateral primary visual cortex. Functional magnetic resonance imaging (fMRI) studies showed that for monocularly presented simple visual stimuli, only the ipsilateral striate cortex was activated. Within each hemisphere's striate cortex, the representation of the two hemifields overlapped extensively. Despite this gross miswiring, visual functions that require precise geometrical information (such as vernier acuity) were normal, and there was no evidence for the confounding of visual information between the overlapping ipsi-lateral and contralateral representations. Contrast sensitivity and velocity judgments were abnormal, but their dependence on the orientation and velocity of the targets suggests that this deficit was due to ocular instabilities, rather than the miswiring per se. There were no asymmetries in performance observed in visual search, visual naming or illusory contour perception. fMRI analysis of the latter two tasks under monocular viewing conditions indicated extensive bilateral activation of striate and prestriate areas. Thus, the remarkably normal visual behavior achieved by this patient is a result of both the plasticity of visual pathways, and efficient transfer of information between the hemispheres.

Adolescent↗

Vector analysis of visual evoked potentials elicited by pattern reversal and photic stimuli.

OBJECTIVE: The 2D VEPs to pattern reversal (PR) and LED goggle were studied in order to obtain a stable parameter for the functional assessing of posterior visual pathways regardless of the stimulus type used. DESIGN AND METHODS: Apex c latency, bc segment amplitude (V), and bc vector orientation angle (theta) in voltage space were computed from VEPs recorded in 50 normal human beings and two patients with left posterior brain lesions, in an orthogonal Fpz-Oz and T3-T4 montage and displayed as a two channel Lissajous' trajectory. The effects of stimulus type and stimulated eye were analyzed in the normal group by a two-way ANOVA. RESULTS: The stimulated eye had no effect on any parameter. Apex c latency was slightly longer, and V was greater and more variable in the responses to goggle stimuli, but there was no significant difference in theta, oriented to mid-occipital scalp with very low variability for both stimulus types. The patients showed significant deviations of theta towards the affected hemisphere. CONCLUSIONS: The bc vector orientation (theta) is a stable parameter for the evaluation of the posterior visual pathways using both pattern reversal and LED stimuli, specially the latter, useful in unconscious or uncooperative patients.

Adolescent↗

Visual system degeneration induced by blast overpressure.

The effect of blast overpressure on visual system pathology was studied in 14 male Sprague-Dawley rats weighing 360-432 g. Blast overpressure was simulated using a compressed-air driven shock tube, with the aim of studying a range of overpressures causing sublethal injury. Neither control (unexposed) rats nor rats exposed to 83 kiloPascals (kPa) overpressure showed evidence of visual system pathology. Neurological injury to brain visual pathways was observed in male rats surviving blast overpressure exposures of 104-110 kPa and 129-173 kPa. Optic nerve fiber degeneration was ipsilateral to the blast pressure wave. The optic chiasm contained small numbers of degenerated fibers. Optic tract fiber degeneration was present bilaterally, but was predominantly ipsilateral. Optic tract fiber degeneration was followed to nuclear groups at the level of the midbrain, midbrain-diencephalic junction, and the thalamus where degenerated fibers arborized among the neurons of: (i) the superior colliculus, (ii) pretectal region, and (iii) the lateral geniculate body. The superior colliculus contained fiber degeneration localized principally to two superficial layers (i) the stratum opticum (layer III) and (ii) stratum cinereum (layer II). The pretectal area contained degenerated fibers which were widespread in (i) the nucleus of the optic tract, (ii) olivary pretectal nucleus, (iii) anterior pretectal nucleus, and (iv) the posterior pretectal nucleus. Degenerated fibers in the lateral geniculate body were not universally distributed. They appeared to arborize among neurons of the dorsal and ventral nuclei: the ventral lateral geniculate nucleus (parvocellular and magnocellular parts); and the dorsal lateral geniculate nucleus. The axonopathy observed in the central visual pathways and nuclei of the rat brain are consistent with the presence of blast overpressure induced injury to the retina. The orbital cavities of the human skull contain frontally-directed eyeballs for binocular vision. Humans looking directly into an oncoming blast wave place both eyes at risk. With bilateral visual system injury, neurological deficits may include loss or impairments of ocular movements, and of the pupillary and accommodation reflexes, retinal hemorrhages, scotomas, and general blindness. These findings suggest that the retina should be investigated for the presence of traumatic or ischemic cellular injury, hemorrhages, scotomas, and retinal detachment.

Air Pressure↗

"Tho' she kneel'd in that place where they grew..." The uses and origins of primate colour vision.

The disabilities experienced by colour-blind people show us the biological advantages of colour vision in detecting targets, in segregating the visual field and in identifying particular objects or states. Human dichromats have especial difficulty in detecting coloured fruit against dappled foliage that varies randomly in luminosity; it is suggested that yellow and orange tropical fruits have co-evolved with the trichromatic colour vision of Old World monkeys. It is argued that the colour vision of man and of the Old World monkeys depends on two subsystems that remain parallel and independent at early stages of the visual pathway. The primordial subsystem, which is shared with most mammals, depends on a comparison of the rates of quantum catch in the short- and middle-wave cones; this system exists almost exclusively for colour vision, although the chromatic signals carry with them a local sign that allows them to sustain several of the functions of spatiochromatic vision. The second subsystem arose from the phylogenetically recent duplication of a gene on the X-chromosome, and depends on a comparison of the rates of quantum catch in the long- and middle-wave receptors. At the early stages of the visual pathway, this chromatic information is carried by a channel that is also sensitive to spatial contrast. The New World monkeys have taken a different route to trichromacy: in species that are basically dichromatic, heterozygous females gain trichromacy as a result of X-chromosome inactivation, which ensures that different photopigments are expressed in two subsets of retinal photoreceptor.

Animals↗

Identification of contrast-defined letters benefits from perceptual learning in adults with amblyopia.

Amblyopes show specific deficits in processing second-order spatial information (e.g. Wong, Levi, & McGraw (2001). Is second-order spatial loss in amblyopia explained by the loss of first-order spatial input? Vision Research, 41, 2951-2960). Recent work suggests there is a significant degree of plasticity in the visual pathway that processes first-order spatial information in adults with amblyopia. In this study, we asked whether or not there is similar plasticity in the ability to process second-order spatial information in adults with amblyopia. Ten adult observers with amblyopia (five strabismic, four anisometropic and one mixed) were trained to identify contrast-defined (second-order) letters using their amblyopic eyes. Before and after training, we determined observers' contrast thresholds for identifying luminance-defined (first-order) and contrast-defined letters, separately for the non-amblyopic and amblyopic eyes. Following training, eight of the 10 observers showed a significant reduction in contrast thresholds for identifying contrast-defined letters with the amblyopic eye. Five of these observers also showed a partial transfer of improvement to their fellow untrained non-amblyopic eye for identifying contrast-defined letters. There was a small but statistically significant transfer to the untrained task of identifying luminance-defined letters in the same trained eye. Similar to first-order spatial tasks, adults with amblyopia benefit from perceptual learning for identifying contrast-defined letters in their amblyopic eyes, suggesting a sizeable degree of plasticity in the visual pathway for processing second-order spatial information.

Adaptation, Ocular↗

Retrospective review of MEG visual evoked hemifield responses prior to resection of temporo-parieto-occipital lesions.

Visual evoked cortical magnetic field (VEF) waveforms were recorded from both hemifields in 21 patients with temporo-parieto-occipital mass lesions to identify preserved visual pathways. Fifteen patients had visual symptoms pre-operatively. Magnetoencephalographic (MEG) VEF responses were detected, using single equivalent current dipole (ECD), in 17/21 patients studied. Displaced or abnormal responses were seen in 15 patients with disruption of pathway in one patient. Three of 21 patients had alterations in the surgical approach or the planned resection based on the MEG findings. The surgical outcome for these three patients suggests that the MEG study may have played a useful role in pre-surgical planning.

Adult↗

Neurons of the central complex of the locust Schistocerca gregaria are sensitive to polarized light.

The central complex is a topographically ordered neuropil structure in the center of the insect brain. It consists of three major subdivisions, the upper and lower divisions of the central body and the protocerebral bridge. To further characterize the role of this brain structure, we have recorded the responses of identified neurons of the central complex of the desert locust Schistocerca gregaria to visual stimuli. We report that particular types of central complex interneurons are sensitive to polarized light. Neurons showed tonic responses to linearly polarized light with spike discharge frequencies depending on e-vector orientation. For all neurons tested, e-vector response curves showed polarization opponency. Receptive fields of the recorded neurons were in the dorsal field of view with some neurons receiving input from both compound eyes and others, only from the ipsilateral eye. In addition to responses to polarized light, certain neurons showed tonic spike discharges to unpolarized light. Most polarization-sensitive neurons were associated with the lower division of the central body, but one type of neuron with arborizations in the upper division of the central body was also polarization-sensitive. Visual pathways signaling polarized light information to the central complex include projections via the anterior optic tubercle. Considering the receptive fields of the neurons and the biological significance of polarized light in insects, the central complex might serve a function in sky compass-mediated spatial navigation of the animals.

Action Potentials↗

Organization, sequence, and expression of a gene encoding goldfish neurofilament medium protein.

The goldfish visual pathway displays a remarkable capacity for continuous neurogenesis, plasticity, and regeneration. The intermediate filament protein composition of this system differs from that of higher vertebrates, which lack the capacity for continued nerve growth and development. In an effort to determine how intermediate filament proteins are regulated during nerve growth, we isolated and characterized cDNA and genomic clones representing the goldfish neurofilament medium (NF-M) protein. The tissue-specific expression of goldfish NF-M mRNA was analyzed by RNase protection assays and by in situ hybridization. The expression of goldfish NF-M is qualitatively the same as in other species. Although the intermediate filament protein composition of the goldfish visual pathway is unusual when compared with higher vertebrates, the goldfish NF-M protein is similar to higher vertebrate NF-M proteins. In addition, the organization of the goldfish NF-M gene is identical to the NF-M genes in all other vertebrate species. In contrast, the promoter region of the goldfish NF-M gene has several potential regulatory sequences that are not found in the promoter regions of higher vertebrate NF-M genes.

Amino Acid Sequence↗

Dendritic field size and morphology of midget and parasol ganglion cells of the human retina.

The visual system of the macaque monkey has provided a useful model for understanding the neural basis of human vision, yet, there are few detailed comparisons of neural populations other than photoreceptors for the two species. Using intracellular staining in an in vitro preparation of the isolated and intact human retina, we have characterized the relationship of dendritic field size to retinal eccentricity for the two major ganglion cell classes, the midget and the parasol cells. We report three findings. (i) The difference in dendritic field diameter between the parasol and midget cells increases from a ratio of approximately 3:1 in the retinal periphery to approximately 10:1 at 3 degrees eccentricity, suggesting that human midget cells may outnumber parasol cells by as much as 30:1 in the central retina. (ii) The dendritic fields of human ON-center parasol and midget cells are 30-50% larger in diameter than their OFF-center counterparts, suggesting a distinct asymmetry in the human ON-OFF visual pathways. (iii) The dendritic fields of parasol cells, but not midget cells, are larger in humans than in macaques. The difference increases from approximately 20% in the retinal periphery to approximately 90% at 5 degrees eccentricity. This result predicts that the human parasol cells should show a lower resolving ability and an increased sensitivity to luminance contrast than their equivalents in the macaque.

Animals↗

Gefiltin in zebrafish embryos: sequential gene expression of two neurofilament proteins in retinal ganglion cells.

Neurogenesis is correlated with the progressive synthesis of diverse neuronal intermediate filaments (IF) proteins. This apparent developmental regulation of IF protein gene expression suggests that specific neurofilament proteins impart unique structural attributes that support the staged growth of the neuron. In the teleost visual pathway, the sequential expression of two IF genes, plasticin and gefiltin, is linked to the age of retinal ganglion cells (RGCs) and to the regeneration of optic axons after nerve injury. Given this pattern of plasticin and gefiltin expression, we hypothesized that the two proteins would be sequentially expressed in zebrafish retina during development. We analyzed the pattern of gefiltin expression during zebrafish development and compared it to our previous determination of plasticin expression (Canger et al. 1998). Gefiltin is expressed after plasticin, during the later stages of retinal development when axons grow past the optic chiasm and innervate their targets. Thus, during RGC development, expression of plasticin and gefiltin resembles that with optic nerve regeneration. Outside of the visual pathway, gefiltin is predominantly expressed in the central nervous system whereas plasticin is primarily expressed in the peripheral nervous system. These results suggest that the expression of these genes is regulated in a neuron-specific manner. In addition, since plasticin and gefiltin are co-expressed during RGC development, these findings suggest a more complex mechanism of transcriptional regulation which orchestrates the sequential expression of these genes.

Animals↗

[Neuro-ophthalmologic initial presentation of sarcoidosis].

PURPOSE: To describe different forms of neuro-ophthalmologic onset of sarcoidosis: clinical signs, means of diagnosis, treatment, and progression. PATIENTS AND METHODS: Retrospective study of 13 patients with neuro-ophthalmologic initial onset of sarcoidosis diagnosed in three departments between 1997 and 2003. RESULTS: There were ten women and three men, with a mean age of 36 years. Six patients suffered from diplopia. In three cases, the cavernous sinus was involved; the three other patients with diplopia had meningoradiculitis. Nine patients had infiltration of the anterior visual pathway: the optic nerve was involved in five cases, the chiasm in two cases, and two patients had papilledema. Two patients also had both symptoms. The dosage of the angiotensin-converting enzyme level was evaluated in 11 patients and was elevated in six cases. Nine patients underwent a lumbar puncture; the cerebrospinal fluid protein was high in seven cases. Chest radiography and CT were abnormal in nine cases of 11. Ten patients had histological proof of sarcoidosis; the three others had enough evidence to support this diagnosis. All of them were treated with systemic corticosteroids. The diplopia improved for the six patients. Among the seven patients with optic nerve or chiasmal infiltration, one recovered completely, two were partially improved, and four remained stable. CONCLUSIONS: Diplopia and anterior visual pathway abnormalities can be the manifestation of initial onset of sarcoidosis; therefore this diagnosis must be kept in mind when these frequent neuro-ophthalmologic signs are encountered. Complementary exams, mainly biopsy of the involved areas with histological analysis, are needed to confirm this diagnosis. Corticosteroid treatment is generally followed by improvement, but relapses may occur.

Adult↗