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Visual loss with Langerhans cell histiocytosis: multifocal central nervous system involvement.

A 42-year-old woman with a 6-year history of diabetes insipidus and progressive hypersomnolence presented with visual loss. Neuroimaging showed infiltration in the hypothalamus, the optic nerve, and the chiasm, as well as multiple lesions in other areas of the brain parenchyma. Biopsy showed Langerhans cell histiocytosis. This is an unusual presentation of Langerhans cell histiocytosis, involving the visual pathways without manifestations outside of the central nervous system. The differential diagnosis and the magnetic resonance imaging findings will be discussed.

Administration, Oral↗

Visual lateralization in birds: from neurotrophins to cognition?

Birds which are tested monocularly in visual discrimination tasks generally show higher performance levels with the right eye seeing. Due to the virtual complete decussation of the optic nerves, a right eye superiority is probably related to a left hemisphere dominance. If visual processes between the hemispheres differ, each half-brain might be differently prone to be deceived by visual illusions. Indeed pigeons tested with the herringbone illusions are deceived to a stronger extent with the right eye. These functional asymmetries are accompanied by anatomical left-right differences in the ascending thalamo- and tectofugal visual pathways in chicks and pigeons, respectively. The neuroanatomical and behavioral assymmetries result from an asymmetrical posture before hatching in which the embryo keeps his head turned to the right, such that the right eye is stimulated by light shining through the shell. The lateralization of adult animals are induced by this prehatching asymmetric photic stimulation since dark incubation abolishes behavioral and anatomical asymmetries. It is conceivable that the asymmetrical embryonal light stimulation increases the release of neurotrophins in the developing avian visual system in an activity dependent matter. Neurotrophins play an important role in neuronal survival and morphology and thus might represent a molecular switch bridging the gap from embryonal light stimulation to asymmetries of visual cognition in adults.

Animals↗

Intermodal selective attention in monkeys. I: distribution and timing of effects across visual areas.

This study quantified the magnitude and timing of selective attention effects across areas of the macaque visual system, including the lateral geniculate nucleus (LGN), lower cortical areas V1 and V2, and multiple higher visual areas in the dorsal and ventral processing streams. We used one stimulus configuration and behavioral paradigm, with simultaneous recordings from different areas to allow direct comparison of the distribution and timing of attention effects across the system. Streams of interdigitated auditory and visual stimuli were presented at a high rate with an irregular interstimulus interval (mean of 4/s). Attention to visual stimuli was manipulated by requiring subjects to make discriminative behavioral responses to stimuli in one sensory modality, ignoring all stimuli in the other. The attended modality was alternated across trial blocks, and difficulty of discrimination was equated across modalities. Stimulus presentation was gated, so that no stimuli were presented unless the subject gazed at the center of the visual stimulus display. Visual stimuli were diffuse light flashes differing in intensity or color and subtending 12 degrees centered at the point of gaze. Laminar event-related potential (ERP) and current source density (CSD) response profiles were sampled during multiple paired penetrations in multiple visual areas with linear array multicontact electrodes. Attention effects were assessed by comparing responses to specific visual stimuli when attended versus when visual stimuli were looked at the same way, but ignored. Effects were quantified by computing a modulation index (MI), a ratio of the differential CSD response produced by attention to the sum responses to attended and ignored visual stimuli. The average MI increased up levels of the lower visual pathways from none in the LGN to 0.0278 in V1 to 0.101 in V2 to 0.170 in V4. Above the V2 level, attention effects were larger in ventral stream areas (MI = 0. 152) than in dorsal stream areas (MI = 0.052). Although onset latencies were shortest in dorsal stream areas, attentional modulation of the early response was small relative to the stimulus-evoked response. Higher ventral stream areas showed substantial attention effects at the earliest poststimulus time points, followed by the lower visual areas V2 and V1. In all areas, attentional modulation lagged the onset of the stimulus-evoked response, and attention effects grew over the time course of the neuronal response. The most powerful, consistent, and earliest attention effects were those found to occur in area V4, during the 100-300 ms poststimulus interval. Smaller effects occurred in V2 over the same interval, and the bulk of attention effects in V1 were later. In the accompanying paper, we describe the physiology of attention effects in V1, V2 and V4.

Animals↗

Neural correlates of incongruous visual information. An event-related fMRI study.

Incongruous information is better remembered than ordinary information. This result has been attributed both to semantic incongruity and surprise. To determine the contribution of each factor, we performed a functional magnetic resonance imaging study in which participants viewed pictures depicting ordinary and incongruous objects (e.g., head of a wrench fused onto a sheep body). To maximize surprise we administered novel incongruent pictures infrequently in an initial scan. (This scan also included infrequent color-inverted pictures as a control for frequency.) To obtain a pure measure of the effect of incongruity we conducted a second scan in which participants viewed equal numbers of ordinary and incongruous pictures. Signal increases were greater for incongruous versus ordinary and oddball stimuli throughout the ventral and dorsal visual pathways, and in prefrontal cortex bilaterally. Signal decreases were larger for incongruous than for ordinary stimuli bilaterally in lateral parietal regions. A subset of regions near the right frontal operculum and extending laterally responded only to, or more strongly to, infrequent incongruous pictures. A second, purely behavioral, experiment involving a separate group of participants demonstrated that incongruous pictures were better recognized than ordinary pictures. We interpret our results as suggesting that, although correlates of a surprise response can be observed, better memory for incongruous visual information is attributable mainly to more processing and, consequently, better encoding.

Adult↗

Neurophysiologic mechanisms of attention: a selective review of early information processing in schizophrenics.

Attention is an integral component of information processing. A pronounced attention deficit exists among people with schizophrenia and their first-degree relatives as compared to persons without this pathology. Schizophrenics demonstrate marked deficiencies on psychophysical tasks that require temporal and / or spatial integration, properties that are associated with the two primary visual pathways composed of magnocellular (M) and parvocellular (P) cells, respectively. The deficit expresses itself as a dysfunctional information processing system that affects higher order processes, for example, perceptual ability and memory. The focus of this review is to integrate results from several divergent areas of research to include those studies that identify the contributions of the M and P pathways associated with information processing and the attention deficit. The diverse approaches reviewed in this chapter converge to provide a neurophysiologic explanation of the attention deficit in schizophrenia.

Attention↗

Brainstem control of response modes in neurons of the cat's lateral geniculate nucleus.

The visual pathway from retina through the lateral geniculate nucleus to visual cortex in the cat is comprised of several parallel neuronal streams that independently analyze different aspects of the visual scene. The best known of these are the X and Y pathways that relay through the geniculate A laminae. Recent receptive-field studies of retinal and geniculate neurons suggest that there is a further elaboration of cell types at the level of the lateral geniculate nucleus. That is, two types of geniculate X cells with different temporal patterns of responses to visual stimuli are recognized, one with "nonlagged" features, exhibiting shorter response latencies and another with "lagged" features; all retinal X cells are nonlagged. We asked whether nonlagged and lagged responses represent different cell classes or two response modes of the same cells, perhaps under the control of nonretinal afferents to these relay cells. Accordingly, we studied the effects on appropriate receptive-field properties of electrical activation of the midbrain parabrachial region, which is a major nonretinal input to relay cells. Such parabrachial stimulation made each of the eight lagged X cells much more like nonlagged cells, and this stimulation completely transformed the lagged response profiles of six of the eight cells to nonlagged. We thus conclude that the property of lagged responsiveness, which is an emergent property of the lateral geniculate nucleus, is a different response mode of the same cells that can also display nonlagged responses, rather than representing different cell classes; furthermore, this switching between response modes is, at least partly, under the control of afferents from the parabrachial region.

Animals↗

Spatial neural modulation transfer function of human foveal visual system for equiluminous chromatic gratings.

To determine the spatial modulation transfer function (MTF) of the human foveal visual system for equiluminous chromatic gratings we measured contrast sensitivity as a function of retinal illuminance for spatial frequencies of 0.125-4 c/deg with equiluminous red-green and blue-yellow gratings. Contrast sensitivity for chromatic gratings first increased with luminance, obeying the Rose-DeVries law, but then the increase saturated and contrast sensitivity became independent of light level, obeying Weber's law. Critical retinal illuminance (I(c)) marking the transition point between the laws was found to be independent of spatial frequency at 165 phot. td. According to our detection model of human spatial vision the MTF of the retina and subsequent neural visual pathways (P(c)) is directly proportional to radicalI(c). Hence, P(c) is independent of spatial frequency, reflecting the lack of precortical lateral inhibition for equiluminous chromatic stimuli in spatiochromatically opponent retinal ganglion cells and dLGN neurons.

Adult↗

Edridge-Green Lecture. Competition and cooperation in visual development.

Studies of the effect of visual deprivation on cells in the lateral geniculate nucleus (LGN) show that there are two distinct sensitive periods in the monkey during which different reactions between the visual pathways related to the two eyes predominate and requirements for recovery from deprivation differ. The first extends from birth to about 8 weeks of age. The main interaction between the pathways from the two eyes is competitive, segregation of cortical ocular dominance columns occurs during this early period and monocular deprivation results initially in hypertrophy of undeprived LGN cells, with later parallel shrinkage of both deprived and undeprived parvocellular cells. Simply reopening the closed eye produces no recovery but reverse suture is effective in reversing some of the changes. The second sensitive period starts from about 8 weeks of age, although the peak of the later sensitivity appears to be at 7-9 months of age and some effect is still present at 12-18 months. During this later phase a cooperative interaction between the pathways related to the two eyes is necessary for normal development and in the absence of this selective shrinkage of both deprived and undeprived parvocellular LGN cells occurs. Simply reopening an eye during this late sensitive period allows recovery of these cells to normal size.

Animals↗

Schizophrenia and red light: fMRI evidence for a novel biobehavioral marker.

Previous research has demonstrated the ability of diffuse red light to suppress activity in the magnocellular (M) visual pathway. An earlier psychophysical study found that a subset of nonpsychotic relatives of persons with schizophrenia showed the opposite effect when compared to healthy adults (Bedwell et al., 2003), suggesting a novel biobehavioral marker for the disorder. The present study attempted to replicate and explore the mechanism for this effect using fMRI. Results provide physiological evidence that the M pathway response to red light is in the opposite direction than expected in a subset of nonpsychotic relatives of persons with schizophrenia.

Adult↗

Pattern of convergence of the receptors of the barnacle's three ocelli onto second-order cells.

The giant barnacle, Balanus nubilus, has three simple eyes, two lateral and one median. We have studied the convergence of the receptors of these ocelli by recording from the second-order cell (I-cell) and from the receptors' terminals. The I-cell's responses to illumination of the median and lateral eyes are similar in shape, dynamic range, and reversal potential, but the response to lateral input has a longer latency, a slower rise time, and a smaller amplitude. These differences primarily reflect the different voltage changes in the terminals of the decrementally conducting median and lateral receptors. Simultaneous recordings from the terminals of median and lateral receptors showed that the responses to light recorded in lateral terminals had a longer latency, a slower rise time, and smaller amplitude than signals in median terminals. The differences in the I-cell's responses to median and lateral input were essentially eliminated by stimulating the median and lateral ocellar nerves with extracellular suction electrodes positioned at equal distances from the receptors' terminals. The similarity of the I-cell's responses to median and lateral input suggests that lateral photoreceptors, like median receptors, contact the I-cell directly. No evidence was found for interaction between median and lateral receptors. Simultaneous fills of median and lateral receptors with cobalt showed minimal overlap between their terminal arbors. No voltage change was detected in the second receptor when the voltage in the first was changed with current pulses or when action potentials were elicited in the presence of tetraethylammonium ions. The absence of a detectable response in the terminals of one eye's receptors when the receptors of the other eye were stimulated with current or light suggests that there is no feedback from the I-cell to the receptors. Simultaneous illumination of the median and lateral eyes produced responses in the I-cell expected from two independent inputs. The first synaptic stage of the visual pathway in the barnacle is thus unusually simple, consisting of a small number of electrically isolated photoreceptors converging upon the same pair of second-order cells with no feedback interaction.

Animals↗

Critical frequency of photic driving in the diagnosis of multiple sclerosis. A comparison to pattern evoked responses.

Patients with known or suspected multiple sclerosis (MS) were tested for abnormalities in visual evoked potentials. We compared the critical frequency of photic driving (CFPD) with pattern reversal visual evoked potentials (PVER). We found the CFPD to be somewhat more sensitive than PVER for detecting abnormalities in the visual pathways of patients with MS. When used together, the two were complementary, each fining abnormalities that the other missed. When evaluating patients with MS with evoked potentials, both PVER and CFPD should be tested.

Cerebral Cortex↗

Visual evoked response in diagnosis of multiple sclerosis.

The diagnostic value of the pattern-evoked response has been assessed in 73 patients referred because of suspected multiple sclerosis. Altogether 52 had delayed responses. Fifty-one patients in the group satisfied McAlpine's criteria for diagnosing definite, probable, or possible multiple sclerosis. Of these, all but two had delayed responses in one or both eyes, while only three of the remaining 22 patients had delays. In those patients with multiple sclerosis but without any history of optic neuritis the incidence of delayed responses was only slightly less. Of 51 patients with delayed responses 23 had normal discs. Thus subclinical lesions of the visual pathways can be readily detected with this test. The high incidence of abnormal pattern responses, even in patients with no other ocular signs or symptoms, suggests that the test is of value in establishing the diagnosis.

Brain Stem↗

Assessment of patients with suspected non-organic visual loss using pattern appearance visual evoked potentials.

BACKGROUND: The aim of the study was to validate the use of the short duration pattern onset visual evoked potential (PappVEP) in the objective assessment of visual acuity (VA) in patients referred with presumed non-organic visual loss. METHODS: The combination of minimum check size and minimum contrast required to elicit a consistently discernible PappVEP (amplitude >or=5 microV) were measured in ten normal subjects under conditions of induced optical blur (0 to +3 dioptres) and the relationship to Snellen VA established. The data from 100 consecutive patients (167 eyes) referred for possible non-organic visual loss (NOVL) and 20 patients with confirmed visual pathway dysfunction were reviewed in relation to the results in normal subjects. RESULTS: Snellen VA, under conditions of blur, could be predicted in normal subjects from the check size and contrast required to elicit a criterion PappVEP. These data were tabulated and a quantitative guideline established for the estimation of VA in the patients referred with suspected NOVL. Most (88%) patients referred with suspected NOVL had normal electrophysiology and PappVEPs consistent with normal Snellen VA. In others, they suggested a degree of non-organic overlay. In 20 cases of organic visual loss, PappVEPs were in close agreement with subjective VA. CONCLUSIONS: The short duration pattern onset visual-evoked potential is confirmed as a clinically useful tool in the objective assessment of patients with suspected non-organic visual loss.

Adolescent↗

Directional tuning of motion-sensitive cells in the anterior superior temporal polysensory area of the macaque.

An investigation was made into the directional sensitivity of cells in the macaque anterior superior temporal polysensory region (STPa) to the motion of objects. The cells studied were sensitive to the presence of motion but showed little or no selectivity for the form of the stimulus. Directional tuning was not continuously distributed about all possible directions. The majority of cells were most responsive to motion in a direction within 15 degrees of one of the three cartesian axes (up/down, left/right, towards/away). Tuning to direction varied in sharpness. For most (34/37) cells the angular change in direction required to reduce response to half maximal was between 45 and 70 degrees (for 3/37 cells it was > 90 degrees). The estimates of the directionality (median Id = 0.97) of STPa cells was similar to that reported for posterior motion processing areas (the middle temporal area, MT, and the medial superior temporal area, MST). The tuning for direction (sharpness, distribution and discrimination) of the motion-sensitive STPa cells were found to be similar to the tuning for perspective view of STPa cells selective for static form of the head and body. On average the STPa responses showed a 100- to 300-ms transient burst of activity followed by a tonic discharge maintained at approximately 20% of the peak firing rate for the duration of stimulation. The responses of motion-sensitive STPa cells occurred at an earlier latency (mean 91 ms) than responses of cells selective for static form (mean 119 ms), but the time course of responses of the two classes of cell were similar in many other respects. The early response latency and directional selectivity indicate that motion sensitivity in STPa cells derives from the dorsal visual pathway via MT/MST. The similarity of tuning for direction and perspective view within STPa may facilitate the integration of motion and form processing within this high-level brain area.

Acoustic Stimulation↗

Asymptomatic visual loss in multiple sclerosis.

Visual disturbances are common in multiple sclerosis (MS) and often a result of acute demyelinating optic neuropathy. Careful examination of MS patients, who have never suffered optic neuritis, may also reveal asymptomatic visual loss. This type of silent disease activity was investigated by computerised resolution perimetry, which has the potential to reflect the percentage of functional retino-cortical neural channels. The time of onset and the evolution of asymptomatic visual loss was investigated. One approach was to retrospectively select patients who never had suffered acute optic neuritis from a closely monitored MS population and re-examine them again. Sixteen patients were identified and vision was evaluated during a period of 5.5-9 years of follow-up and compared with that in 14 healthy controls. The mean channel percentage of the MS group was 89 +/- 19 % (SD) on entry into the study, compared with 110 +/- 15% (SD) of controls (p < 0.003). At termination of the study the mean percentage was essentially unchanged both in MS patients (87 +/- 21%, SD) and controls (110 +/- 19%, SD). The second approach was to test a group of 7 patients with MS or strongly suspected MS, with the same method, in close connection with their first clinical exacerbation. All cases lacked visual symptoms and none had previously had acute visual loss. Again, virtually all performed subnormally in the vision tests, and to the same degree as in the first group of patients. Results were compared with those obtained from 25 MS patients who had experienced one or more attacks of optic neuritis. Compared with controls the loss of functional retino-cortical neural channels was 20% in patients without a previous history of optic neuritis and 30 % in patients who previously had experienced optic neuritis. We conclude that asymptomatic visual loss seems to be a universal feature of MS and has a substantial impact on the visual pathways, that it is present already at the time of clinical onset of the disease, and that any progression thereafter is slow enough to elude detection during several years of follow-up.

Adult↗

On the significance of temporally structured activity in the dorsal lateral geniculate nucleus (LGN).

Higher organisms perceive information about external or internal physical or chemical stimuli with specialized sensors that encode characteristics of that stimulus by a train of action potentials. Usually, the location and modality of the stimulus is represented by the location and specificity of the receptor and the intensity of the stimulus and its temporal modulation is thought to be encoded by the instantaneous firing rate. Recent studies have shown that, primarily in cortical structures, special features of a stimulus also are represented in the temporal pattern of spike activity. Typical attributes of this time structure are oscillatory patterns of activity and synchronous discharges in spatially distributed neurons that respond to inputs evoked by a coherent object. The origin and functional significance of this kind of activity is less clear. Cortical, subcortical and even very peripheral sources seem to be involved. Most of the relevant studies were devoted to the mammalian visual system and cortical findings on temporally structured activity were reviewed recently (Eckhorn, 1994, Progr. Brain Res., Vol. 102, pp. 405-426; Singer and Gray, 1995, Annu. Rev. Neurosci., Vol. 18, pp. 555-586). Therefore, this article is designed to give an overview, especially of those studies concerned with the temporal structure of visual activity in subcortical centers of the primary visual pathway, which are the retina and the dorsal lateral geniculate nucleus (LGN). We discuss the mechanisms that possibly contribute to the generation and modulation of the subcortical activity time structure and we try to relate to each other the subcortical and cortical patterns of sensory activity.

Action Potentials↗

Pupil light reflex in normal and diseased eyes: diagnosis of visual dysfunction using waveform partitioning.

OBJECTIVE: To evaluate changes in pupil size (corresponding to neuronal firing) within different time windows of the pupil light reflex in patients and normal subjects to understand which segments of the pupil waveform are best able to differentiate normal from abnormal subjects. DESIGN: Comparative, observational case series. PARTICIPANTS: Forty-nine normal subjects and 25 patients with known unilateral or asymmetric visual field damage were tested. METHODS: A dual-channel infrared pupillograph was used to simultaneously record the right and left pupil diameters at a rate of 60 Hz. Each eye was stimulated alternately (30 degrees full-field, 200 milliseconds duration every 3 seconds) over 10 different stimulus intensities. The recorded waveform of the pupil light reflex was subdivided into six time windows based on landmarks corresponding to contraction onset, maximum contraction velocity, peak contraction, and maximum dilation velocity to assess which portion was most affected by disease. MAIN OUTCOME MEASURES: The linear correlation between pupil contractions elicited by right versus left full-field stimulation at different light intensities provided diagnostic parameters (slope, intercept, and correlation coefficient R(2)) that were useful for differentiating normal subjects from patients and for categorizing disease. Sensitivity and specificity of the time windows were evaluated with receiver-operator curve analysis. RESULTS: The diagnosis of asymmetric disease was greatest at time windows that included pupil contraction but not dilation. When the contraction phase was subdivided into an early phase and into a late phase, the late phase was the most diagnostic compared with the entire phase of contraction amplitude (onset to peak contraction). CONCLUSIONS: By use of a range of light intensity, the change in pupil size measured between the time at which maximum contraction velocity occurs and the time to peak contraction provided the best response parameter for objective diagnosis of asymmetric disease of the anterior visual pathway. The waveform of the pupil light reflex may be an expression of the firing of retinal ganglion cells. Therefore, understanding which segment of the pupil light reflex provides maximal diagnostic power may give insight into how disease affects the pattern of neuronal firing rate.

Diagnostic Techniques, Ophthalmological↗

Disruption of orientation tuning in visual cortex by artificially correlated neuronal activity.

In the primary visual cortex, the development of orientation selectivity is influenced by patterns of neural activity. The introduction of artificially correlated activity into the visual pathway (through synchronous activation of retinal ganglion cell axons in the optic nerve) substantially weakens the orientation selectivity of neurons in superficial and deep cortical layers. This is consistent with activity having an instructive role in shaping cortical neuron receptive field tuning properties.

Action Potentials↗