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Biomedical subjects

W H Merigan

Publications and source records attributed to W H Merigan.

At least 37 records · Page 2Linked to original sources

Selective damage to large cells in the cat retinogeniculate pathway by 2,5-hexanedione.

The neurotoxic hexacarbon 2,5-hexanedione (2,5-HD), which produces transport abnormalities and swellings in the large diameter fibers of the peripheral nervous system, was administered to cats in an attempt to produce similar selective effects in the optic tract. Anatomical findings indicate damage to one type of retinal ganglion cell, the large (alpha) or Y-cell class, both during dosing and after a long recovery period. This selective involvement of the large ganglion cells during dosing was shown by decreased retrograde transport of HRP in these cells relative to smaller cells. Such selectivity was not apparent in axonal swellings and neurofilament accumulations which were present in fibers of all diameters in the distal optic tract. Visual threshold studies during dosing showed a loss of flicker resolution with preservation of visual acuity, a result consistent with the different physiological properties of alpha and beta ganglion cells. In one cat, which survived dosing for a period of 8 months, there was a dramatic reduction in the number of large cells and a pronounced shrinkage of those that remained, but no observed changes in other cell types. Thus, this intoxication caused (1) axonal swellings which were not selective for fiber size; (2) a selective defect in axonal transport with later neuronal degeneration and shrinkage that were limited to large cells; and (3) a loss of flicker resolution that may reflect dysfunction of large ganglion cells.

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Recent observations on the neurobehavioral toxicity of carbon disulfide.

Visual thresholds, fluorescein angiography, color fundus photography and tests of motor function were used to examine the effects of carbon disulfide (CS2) on macaque monkeys. After reliable baseline measures were obtained, two monkeys were exposed to 256 ppm CS2, 6 hours a day, 5 days each week for 7 weeks. A third monkey was tested similarly but received a sham exposure over the same period. Visual acuity of the exposed monkeys dropped more than 5 fold during exposure and showed a partial subsequent recovery only in one monkey. Flicker resolution, on the other hand, was only slightly and transiently impaired. Tests of motor function also showed only brief and partial disruption. No evidence was seen in either exposed monkey of the retinal vascular changes that are currently the major diagnostic signs in human carbon disulfide poisoning.

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Acrylamide effects on the macaque visual system. I. Psychophysics and electrophysiology.

Oral acrylamide produces axonal swelling and later degeneration and gliosis in the distal optic tract, especially within the lateral geniculate nucleus, of macaque monkeys. Measures of visual thresholds and cortical-evoked potentials were used to study the time course of visual changes during exposure to acrylamide in macaque monkeys. Contrast sensitivity, visual acuity, and flicker fusion frequency were reduced during exposure, and only flicker fusion recovered rapidly and completely after exposure. Pattern-reversal-evoked responses exhibited increased latency and reduced amplitude during dosing but substantially recovered after exposure. Visual acuity and contrast sensitivity for high spatial frequencies were decreased throughout the 140 days of testing after dosing. These results suggest an acute general depression of visual capacities as the initial effect of acrylamide exposure, whereas later effects were confined to high spatial frequencies.

Acrylamide↗

Acrylamide effects on the macaque visual system. II. Retinogeniculate morphology.

Oral acrylamide dosing for 6-10 weeks produced axonal swellings with neurofilament accumulation in the distal optic tract and lateral geniculate nucleus of macaques. No swellings were seen in the retina or optic nerve. Monkeys that were killed 6-8 months after similar dosing showed a marked neuronal degeneration in the visual pathways that was more pronounced after two than after a single period of exposure. This degeneration was characterized by the following: loss of ganglion cells in central retina with relative sparing of other retinal neurons; disproportionate degeneration of temporal to central optic nerve and the dorsal optic tract; and neuronal atrophy in parvocellular layers of the lateral geniculate nucleus, with relative sparing of magnocellular layers. The pattern of neuronal loss suggests that one type of retinal ganglion cell or its axon may be especially vulnerable to damage by acrylamide. The selective neuronal damage produced by acrylamide may help explain the nature of the visual dysfunction associated with this intoxication.

Acrylamide↗

Effects of stimulus speed on direction discriminations.

Difference thresholds for the direction of movement of moving isotropic dot patterns were measured over a wide range of stimulus speeds. These measurements were made in human subjects, in normal cats and in visually deprived cats with abnormalities in neuronal directional response. For all subjects, direction thresholds were inversely related to stimulus speed at low drift rates. Above a "critical speed", direction thresholds were independent of stimulus speed. Between group differences in critical speed parallel differences in visual acuity and absolute thresholds for direction of motion. However, asymptotic direction thresholds appear to be unrelated to acuity and motion detection thresholds. It is argued that the basis for the differences in asymptotic direction thresholds between the groups are differences in properties of directional mechanisms.

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The role of area centralis in the spatial vision of the cat.

Spatial contrast sensitivity was measured over a 6 log unit luminance range in two cats before and after bilateral 4-5 deg radius argon laser lesions were placed in area centralis. The lesions reduced high luminance contrast sensitivity by approximately 0.3-0.4 log units at the low and middle spatial frequencies and by 0.5-1.0 log unit at the highest spatial frequencies. The loss of visual acuity was 0.4 octave in the cat with the smaller lesions and 0.8 octave in the cat whose lesions were larger. At lower luminance, little loss in contrast sensitivity was seen and no change was detectable at scotopic luminance levels. Visual acuity, on the other hand, was decreased at higher scotopic conditions, but unaffected at the lowest luminance levels tested (16 X 10(-6) cd/m2). These data indicate that area centralis plays an important role in detecting both high and low spatial frequencies under high luminance conditions but contributes only to spatial resolution at low luminance levels. This result is consistent with known anatomical and physiological properties of the cat area centralis.

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Motion mechanisms in strobe-reared cats: psychophysical and electrophysical measures.

Cats were reared from birth to at least 12 months of age in a visually static environment (illuminated 40/min by a 3 mu sec strobe flash). Single unit recordings from these animals revealed abnormalities in spatial and directional properties of cortical neurons. In an attempt to find psychophysical correlates of these neural deficits, spatial contrast sensitivity and motion detection thresholds were measured behaviorally. Both spatial vision and motion detection were greatly impaired. While spatial deficits failed to recover, motion thresholds improved greatly following extended training. These improvements in behavioral motion response were accompanied by the recovery of cortical directional selectivity. The recovery of motion thresholds and directional selectivity was direction specific: the distribution of the preferred directions of cortical neurons and motion thresholds were sharply biased towards the direction first seen in training. Thus, directional mechanisms of adult motion deprived cats may be modified if following deprivation the animals are trained to detect moving stimuli.

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Spatial and temporal vision of macaques after central retinal lesions.

Spatial contrast and temporal modulation sensitivity of two macaque monkeys were measured at three luminance levels before and after binocular laser coagulation of the fovea. The radius of the lesions ranged from 1.6 to 2.2 deg from the center of the fovea. After placement of the lesions, the visibility of high spatial frequencies was greatly reduced, although sensitivity at middle and low spatial frequencies was unaffected. No loss of spatial resolution was found at the lowest luminance tested. When temporal modulation sensitivity was tested with 4 deg targets, foveal lesions had no effect at any temporal frequency or luminance. However, with a 0.57 deg target, sensitivity to lower frequencies was impaired. Thus visual loss after destruction of the fovea is limited to high luminance, small targets, and the resolution of fine detail.

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Movement detection by cats: invariance with direction and target configuration.

Absolute thresholds for movement detection were measured in three cats and two human subjects under similar conditions. A two-alternative spatial forced-choice procedure was used with the method of constant stimuli. When targets were moving random-dot patterns, cat thresholds ranged from .6 degrees to 2.3 degrees/sec, while human thresholds were approximately .05 degrees/sec. Similar thresholds were found for cats tested with square wave gratings ranging in spatial frequency from .18 to 1 cycle/degree. Neither cats nor humans showed any directional asymmetry for motion detection.

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Effects of toxicants on visual systems.

The analysis of visual toxicity is complicated by the heterogeneity of visual capacities in different regions of the visual field. Since various toxicants may impair different functions allied to localized portions of the visual field, it is important to explore the relationship of field defects to residual visual abilities. We have begun this exploration by studying methylmercury poisoning in macaque monkeys. Extended exposure to this toxicant produces a marked concentric constriction of visual fields, a result similar to that found in human victims. In addition, visual sensitivity is greatly reduced on those tests in which the periphery of the visual field is more sensitive than the center. Our findings suggest simple but reliable clinical tests for screening suspected victims of substances impairing peripheral vision.

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