How parallel are the primate visual pathways?
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Animals↗
Biomedical subjects
W H Merigan
Publications and source records attributed to W H Merigan.
Visual effects of lesions of cortical area V2 in macaques.
Ibotenic acid lesions were placed in two monkeys in a portion of cortical area V2 that corresponds to a lower quadrant of the visual field extending approximately 3-7 degrees from the fovea. For purposes of comparison, another lesion was placed in area V1 in one animal. A wide range of visual capacities were then measured, using a discrimination between vertical and horizontal orientation, in and near the affected regions of the visual field. Visual acuity declined sharply as the test stimulus approached the visual field location corresponding to the V1 lesion, and no threshold could be measured at its center. In contrast, lesions of area V2 caused no measurable decrease in acuity, nor was there any substantial effect on several measures of contrast sensitivity. Subsequently, two types of more complex visual discriminations were measured (also using a vertical-horizontal discrimination), and these discriminations were severely disrupted by V2 lesions. The first discrimination was of the orientation of two parallel lines of five colinear dots each. We measured the number of background dots that would bring the discrimination to threshold, and this number of dots was greatly decreased by a V2 lesion. The second discrimination was of the orientation of a group of three distinctive texture elements embedded in a six by six element texture. This task could not be done in the visual field region affected by the V2 lesion when the distinctive elements differed in orientation from the others. Control experiments showed that the discrimination could be done when the three distinctive elements differed in size or color. These results suggest that cortical area V2 is not needed for some low-level discriminations, but may be essential for tasks involving complex spatial discriminations.
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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↗
Does primate motion perception depend on the magnocellular pathway?
This study examined the importance of the primate magnocellular retinocortical pathway in the perception of moving stimuli. A portion of the magnocellular pathway was permanently and selectively interrupted by ibotenic acid injections in the LGN of macaque monkeys. We then tested contrast sensitivity for detecting moving stimuli, as well as two indices of motion perception, contrast sensitivity for opposite direction discrimination and speed difference thresholds, in the affected portion of the visual field. Magnocellular lesions greatly reduced detection contrast sensitivity at high temporal and low spatial frequencies and had a similar effect on contrast sensitivity for opposite direction discrimination under these same stimulus conditions. Consequently, opposite direction discriminations could be made at contrast threshold, suggesting that magnocellular lesions reduced the visibility of stimuli used to test direction perception, but did not act directly on direction perception. Magnocellular lesions also elevated speed difference thresholds under some stimulus conditions. However, this deficit was reduced or eliminated by raising the contrast of the test stimulus. Together, these findings suggest that magnocellular lesions reduce the visibility of stimuli used to test motion perception but that they do not appear to alter motion perception otherwise.
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The effects of parvocellular lateral geniculate lesions on the acuity and contrast sensitivity of macaque monkeys.
The effects of ablating the visual pathway that passes through the parvocellular (dorsal) LGN were tested in 2 macaque monkeys by measuring acuity and both luminance and chromatic contrast sensitivity. Thresholds were tested monocularly before and after ibotenic acid was used to lesion parvocellular layers 4 and 6 of the contralateral geniculate. The injections were centered at the representation of 6 degrees in the temporal field on the horizontal meridian, and vision was tested with localized stimuli at this location. In addition, in one of the monkeys, a lesion was made in magnocellular layer 1 of the opposite geniculate, and the same thresholds were tested. Physiological and anatomical reconstructions demonstrated complete destruction of the target layers in 1 parvocellular lesions and in the magnocellular lesion, and sparing of the nontarget layers in the tested region. Parvocellular lesions caused a 3-4-fold reduction in visual acuity within the affected part of the visual field, while the magnocellular lesion did not affect acuity. Both luminance and chromatic contrast sensitivity, tested with stationary gratings of 2 c/degree, were severely reduced by parvocellular lesions, but not affected by the magnocellular lesion. However, when luminance contrast sensitivity was tested with 1 c/degree gratings, counterphase modulated at 10 Hz, it was reduced by both parvocellular and magnocellular lesions. This study demonstrates that the parvocellular pathway dominates chromatic vision, acuity, and contrast detection at low temporal and high spatial frequencies, while the magnocellular pathway may mediate contrast detection at higher temporal and lower spatial frequencies.
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Spatial resolution across the macaque retina.
Grating acuity was measured as a function of eccentricity from the fovea in two macaques. A vertical-horizontal orientation discrimination was used to determine acuity, and the retinal locus of the test grating was controlled by training them to fixate a spot placed at various distances from the stimulus. Their head was fixed in place and fixation was monitored with a scleral search coil. The acuity of monkeys across the retina was similar to that previously measured in human subjects, reaching a peak of about 38 c/deg at the fovea, and decreasing about 10-fold by 30 deg eccentricity. Acuity was slightly higher in the temporal than in the nasal visual field. The shape of the acuity-eccentricity function suggested a dependence on cone density near the fovea, and on the density of P ganglion cells at eccentricities beyond 10 deg. Existing physiological data suggest the possibility that macaque acuity may also be limited in part by spatial averaging across the receptive field of retinal ganglion cells.
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Macaque vision after magnocellular lateral geniculate lesions.
Ibotenic-acid lesions of the magnocellular portion of the macaque lateral geniculate nucleus were used to examine the role of the M-cell pathway in spatio-temporal contrast sensitivity. A lesion was placed in layer 1 of the lateral geniculate of each of two monkeys. Physiological mapping in one animal demonstrated that the visual-field locus of the lesion was on the horizontal meridian, approximately 6 deg in the temporal field. Visual thresholds were tested monocularly in the contralateral eye, and fixation locus was monitored with a scleral search coil to control the retinal location of the test target. Three threshold measures were clearly disrupted by the magnocellular lesions. Contrast sensitivity for a 1 cycle/deg grating that drifted at 10 Hz was reduced from about twofold greater than, to about the same as, that for 10-Hz counterphase modulated gratings. Sensitivity for a very low spatial frequency (Gaussian blob), 10-Hz flickering stimulus was reduced so severely that no threshold could be measured. In addition, flicker resolution was greatly reduced at lower modulation depths (0.22), but not at higher depths (1.0). Two of the measured thresholds were unaffected by the lesions. Contrast sensitivity for 2 cycle/deg stationary gratings remained intact, and little or no effect on sensitivity was found for 1 cycle/deg, 10-Hz counterphase modulated gratings. Together, these results suggest that the magnocellular pathway makes little contribution to visual sensitivity at low to moderate temporal frequencies. On the other hand, some contribution to detection sensitivity is evident at lower spatial and high temporal frequencies, especially for drifting stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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Selective degeneration of the parvocellular-projecting retinal ganglion cells in a New World monkey, Saimiri sciureus.
Selective degeneration of retinal ganglion cells projecting to parvocellular layers of the dorsal lateral geniculate nucleus (LGN) was observed in squirrel monkeys (Saimiri sciureus) exposed to a range of doses of acrylamide monomer. Similar acrylamide-induced neuronal loss has previously been reported in parvocellular-projecting ganglion cells of macaques, but no such selective degeneration has been found in acrylamide-dosed rats, squirrels, rabbits or cats. The extent of ganglion cell loss observed in the present study suggests that in the squirrel monkey, as in the macaque, a majority of ganglion cells project to parvocellular layers of the LGN. The locus of optic tract degeneration suggests that the squirrel monkey parvocellular pathway passes in dorsolateral optic tract, as does that of the macaque. Patterns of decreases in cytochrome oxidase activity confirm that, in both of these primates, geniculocortical pathways driven by these vulnerable neurons project to cortical layers 4A and 4C beta. These results suggest close parallels in the neuroanatomical projections and toxic vulnerability of the parvocellular-projecting pathway in New and Old World monkeys. They indicate that acrylamide intoxication can be used to selectively damage this pathway in order to study the functional roles of parallel visual pathways in both New and Old World monkeys.
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Subchronic dosing of macaques with 2,5-hexanedione causes long-lasting motor dysfunction but reversible visual loss.
Visual sensitivity and neurological status were monitored in four female macaque monkeys dosed orally with 2.5-hexanedione (0.64 mM/kg, 5 days per week) for 15 or 17 weeks. The first sign of toxicity was intention tremor seen after 3 months of dosing. This was followed, a week later, by a moderate decrease in visual contrast sensitivity, which returned to baseline 6 to 11 weeks after the end of dosing. Acuity and flicker resolution were not disrupted. A progressive general weakness ensued for 5 to 7 weeks after dosing had ended. Some slow recovery was seen, although the animals remained severely disabled 20 weeks after dosing was discontinued. Pathologic changes were examined 3 weeks (one monkey) and 20 weeks (three monkeys) after dosing. Soon after the end of dosing, axonal swellings were present throughout the distal optic tracts, peripheral nerves, and long tracts of the spinal cord. Twenty weeks after dosing, there was no indication of degeneration in the retinocortical pathway. Peripheral nerves showed widespread axonal loss, residual ongoing degeneration, and only slight regeneration. Axon loss and gliosis were evident in distal dorsal columns, and to a lesser extent, dorsal spinocerebellar and corticospinal tracts. These effects of 2,5-hexanedione on the macaque differ from those found previously for two other axonotoxic compounds, acrylamide monomer and carbon disulfide, which caused marked permanent degeneration that was most prominent in the visual system.
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Chromatic and achromatic vision of macaques: role of the P pathway.
Chromatic and achromatic contrast sensitivity were measured in a human observer, 2 normal macaque monkeys, and 3 monkeys with severe toxicant-induced damage to the parvocellular projecting retinogeniculate pathway (P cell-deficient monkeys). Damage to the P pathway was produced by the oral administration of acrylamide monomer (Eskin and Merigan, 1986). Contrast sensitivity was measured in all subjects with isochromatic luminance gratings, as well as isoluminant chromatic gratings, modulated along several directions of a color space that represents color-opponent and luminance contrast (Krauskopf et al., 1986). The chromatic and achromatic sensitivity of the control monkeys was virtually identical to that of the human observer. Chromatic sensitivity of the P cell-deficient monkeys, measured at a low spatial frequency (0.3 c/deg), along a constant-blue color axis, was 0.9-1.5 log units lower than that of controls. Similar losses were seen along a tritanopic confusion axis and along 2 intermediate axes of color direction. Chromatic thresholds measured at higher spatial frequency (2.0 c/deg) were similarly reduced. Counterphase-modulated chromatic gratings were used to test color sensitivity over a range of temporal frequencies up to 15 Hz, and the loss of color vision was substantial over the entire range of frequencies. The luminance contrast sensitivity of the P cell-deficient monkeys for stationary gratings decreased after exposure by 0.5-0.8 log units. These results indicate that the chromatic and achromatic spatial vision of macaques is very similar to that of humans. They also suggest that the P pathway plays an important role in macaque chromatic sensitivity at all spatial frequencies, as well as achromatic sensitivity at high spatial and lower temporal frequencies.
Acrylamide↗
Carbon disulfide effects on the visual system. II. Retinogeniculate degeneration.
We examined the morphological effects of carbon disulfide exposure on neurons and vasculature of the visual system of macaque monkeys. Five monkeys were exposed to 256 ppm carbon disulfide (CS2) by inhalation for 6 hr a day, 5 days a week. One monkey, sacrificed immediately after exposure, had numerous axonal swellings in the distal optic tract. Four other monkeys survived the exposure period for at least 1 year and were found to have suffered marked degeneration of central retinal ganglion cells, with little or no effect on other neurons in the retina. No evidence was found for arteriosclerotic or aneurysmal changes, suggesting that visual system injury in primates induced by carbon disulfide exposure is not dependent on the occurrence of structural changes in retinal blood vessels.
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Carbon disulfide effects on the visual system. I. Visual thresholds and ophthalmoscopy.
The visual effects of carbon disulfide exposure were studied in macaque monkeys with measurements of visual thresholds, fluorescein angiography and fundus photography. Five monkeys were exposed by inhalation for 6 hr a day, 5 days a week to 256 ppm carbon disulfide (CS2). The motor dysfunction observed in these monkeys appeared to be entirely reversible. All five suffered severe reductions in visual acuity and contrast sensitivity although flicker resolution was not affected. Visual loss was found to be irreversible, with degeneration of substantial numbers of retinal ganglion cells (companion paper) in those monkeys permitted to survive after the termination of exposure. None of the monkeys developed retinal microaneurysms or hemorrhages, major accepted signs of visual toxicity in CS2 exposed humans; thus, permanent visual loss may result from carbon disulfide exposure even in the absence of retinal vascular effects.
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Selective acrylamide-induced degeneration of color opponent ganglion cells in macaques.
P beta (color opponent) retinal ganglion cells in macaques were found to degenerate as a result of oral administration of acrylamide. Histological examination, wheat germ agglutinin-horseradish peroxidase transport and cytochrome oxidase histochemistry indicate that other retinal ganglion cells and other neurons in the visual pathways were spared.
Acrylamide↗
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↗
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↗