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Luminance-onset, pattern-onset and pattern-reversal evoked potentials in human albinos demonstrating visual system anomalies
LUMINANCE-ONSET, PATTERN-ONSET AND PATTERN-REVERSAL EVOKED POTENTIALS IN HUMAN ALBINOS DEMONSTRATING VISUAL SYSTEM ANOMALIES Donnell Creel
Most fish, amphibians, reptiles and birds have laterally placed eyes and primarily panoramic vision. These vertebrates usually have complete crossing of optic fibres at the chiasm, i.e., optic ganglion fibres originating from each eye terminate in visual centres of the contralateral hemisphere. One of the features of the mammalian visual system is the appearance of an uncrossed optic projection terminating in visual centres of the ipsilateral hemisphere. As the eyes shift to a more frontal position on the head the number of ganglion fibres originating in temporal retinae increases. Concomitantly, stereoscopic vision and binocular overlap of visual fields increase. The number of optic fibres that do not cross at the chiasm varies: approximately l-5 percent in guinea pigs and mice, 5-10 percent in rats, 20 percent in dogs and horses, 30-40 percent in domestic cats, 4030 percent in primates (Giolli. and Creel, 1973; Hayhow et al, 1960; Polyak, 1957). Sheridan (1965) reported that uncrossed optic fibres are functionally incompeteni in an albino rat and predicted anatomical differences between visual systems of albino and pigmented rats. Lund (1965) verified Sheridan’s hypothesis anatomically. The finding of reduced uncrossed optic projections in albino rats was reconfirmed in behavioural (Creel and Sheridan, 1966), electrophysiological (Montero, ~_ 1968) and anatomical studies. (Creeland Giolli, 1976) Visual system anomalies in albino mammals are now known to include: (a) reduced numbers of uncrossed optic projections to dorsal and ventral portions of the lateral geniculate nuclei, anterior and posterior pretectal nuclei and superior colliculus; (b)disorganization of patterningilamination) of optic terminations in dorsal and ventral lateral geniculate nuclei; and (c) disorganization of projections from dorsal lateral geniculate nucleus to visual cortex. Abnormalities have been verified in nine species of mammals: cat, rat, ferret, tiger, mouse, mink, guinea pig, rabbit and humans. (Guillery et al., 1975). All albino mammals examined have shown one or more of these anomalies. Considerable research has been conducted using Siamese cats. The Siamese cat is representative of the Veterans Administration Medical Center, Salk Lake City, Ut 84148, U.S.A. This paper was presented at the International Symposium cm Evoked Potentials in Nottingham, UK, September 1978, the proceedings of which are available from the BES.
100
J. Biomed. Eng. 1979, Vol. 1, No. 2, April
Himalayan (C” C”) allele of the albino series which permits pigment to form only on the cooler parts of the body, including the face, ears, tail and feet because of a thermolabile tyrosinase enzyme. The eyes lack retinal pigment. As far as their visual systems are concerned they are albino. The disorganization of the visual systems of Siamese cats and other albino mammals is not random. There is an excessive number of optic afferents crossing at the optic chiasm and an insufficient number of optic afferents that do not cross. The misrouted optic fibres originate from approximately the first ZOoofthe temporal retina (Guillery and Kaas, 1971)Many of these fibres erroneously cross at the optic chiasm and terminate in a portion of the dorsal lateral geniculate nucleus (LGNd) normally reserved for uncrossed optic afferents. These terminations fragment the retinotopic organization of the LGNd, producing a disruption of retinotopically organized projections to striate cortex. It has been demonstrated that evoked potentials recorded from the visual area of albino rats (Creel et al., 2970) guinea pigs (Creel and Giolli, 1972) and Siamese cats (Creel, 1971) reflect the anatomically verified reduction and disorganization of uncrossed optic fibres. The evoked potential technique therefore provides a method for evaluating visual system anomalies in humans. By covering an eye so that only one eye is photically stimulated and at the same time recording visually evoked potentials from scalp overlying visual areas of both hemispheres the relative contribution of optic projections from uncrossed optic fibres may be compared. Visually evoked potentials (VEPs) have been recorded from 60 human oculocutaneous (total) albinos of four types’which can be distinguished from each other on the basis of biochemical, clinical, genetic, and ultrastructural characteristics (Creel et al., 1974). We have also recorded VEPs from 12 human ocular albinos of two types, Xlinked ocular albinism and a newly described autosomal recessively inherited ocular albinism (Creel et a1.,1978) Thirty normally pigmented browneyed individuals participated as control subjects. METHOD Each subject was seated in a padded chair in a
Visual Evoked Potentials:
Several methods of photic stimulation were used. Luminance onset-offset was produced by placing the lamp of a photostimulator behind a white plastic diffusing screen. Pattern-luminance onsetoffset was produced by placing checkerbpard patterns in front of the lamp of the photostimulator. Pattern reversal was produced using a Digitimer pattern reversal stimulator. Individual check size was varied from 15 min. to 2”. Total field of stimulation was varied from 15Oto 80° The calculated flash illuminance was varied from approximately 0.3 lux to 2.5 lux. The subjects were not dark-adapted, although the room was dark during testing. The lamp of the photostimulator was enclosed in polyethylene foam to attenuate sounds. Luminance onset-offset and pattern-luminance onset-offset stimuli were produced by the lamp of a Grass photostimulator at a rate of one flash approximately every two seconds. Sixty to 100 flashes were averaged. The Digitimer pattern-reversal stimulator was set to reverse the checkerboard every 600 msec. Two hundred reversals were averaged. Binocular visually evoked potentials were recorded. One eye was then covered with several layers of opaque material consisting of a gauze pad, a black eye patch and adhesive eye patches which covered facial areas around the eye. The efficiency of the occlusion process was checked for each subject. Brain activity was amplified by a Grass EEG and recorded on an FM tape recorder. Care was taken that channel-to-channel bias in the calibration of the EEG did not affect recording to differences of evoked potentials between hemispheres. Electrical responses were averaged by a signal averager set to analyse electrocortical activity for 500 msec following each flash of light. The averaged response was plotted by an X-Y plotter. In addition to visual inspection, statistical comparisons were made between recordings of evoked potentials from each hemisphere. Each regularly appearing component was examined for latency and amplitudinal changes. Components were considered significantly reduced if attenuation exceeded 50 percent. RRSULTS
For all control subjects and most albinos, there was no significant hemispheric VEP amplitude asymmetries with binocular stimulation. When evoked potentials were recorded with one eye again there were still no hemispheric asymmetries for the
Monocular
Binocular
sound-attenuated room. Placement of electrodes was according to the lo-20 International System (Jasper, 1958). Several electrode montages with several reference points were explored. Silver disc electrodes were attached bilaterally to the scalp with nonflexible collodion at 01,02, Oz, AI, A2,6, FI, 05 and 06. We use 05 and 05 and 06 to desingnate the positionhalfway between electrodes 01-T5 and Oa-Ts. Ipsilateral ears, linked ears, and Fr were used as reference electrodes for 01,02, OZ.05 and 06.
85
D. Creel
%_L
ti
67 w %f
5pV 100
I
200
Figure 1. Visually evoked potentials recorded from both hemispheres (OI-AI and Oz-AZ)of four normally pigmented subjects under conditions of binocular and monocular illumination. Horizontal time base250msec. Negative isup. Stimulation luminanceonsetoffset 0.5lsec (N=IOO). control subjects (Figure 1). In contrast, approximately 70 percent of human oculocutaneous and ocular albinos (50 of 72) showed asymmetry between hemispheres following monocular stimulation, with one or more components of the VEP missing or significantly attenuated. The degree of hemispheric asymmetry of monocularly evoked potentials was significantly greater than that observed in normally pigmented men with one eye enucleated, and for most albinos was as severe as that which is seen in neurologic patients with lesions of the optic pathways resulting in visual field defects. All three stimulation techniques (luminance onset-offset, pattern-luminance onsetoffset and pattern reversal) produced essentially the same results. Even with binocular stimulation it is not unusual to record occasional asymmetry of VEPS between hemispheres in humans. A distinctive feature of the human albino is the dramatic change in the VEP following monocular stimulation as compared to the effects of monocular stimulation in normally
J. Biomed. Eng. 1979, Vol. 1, No. 2, April
101
Visual Evoked Potentials:
D. Creel
Binocular
Monocular
pigmented humans. Monocular stimulation reveals the discontinuity and fragmentation of the retinotopic organization of the albino’s visual projections between eye and cortex (Figure 2). Most changes in the VEP are seen in those components appearing in the first 125 msec. Figure 3 illustrates the VEPs of an adult human albino presented with luminance onset-offset, pattern-luminance onset-offset and pattern reversal stimuli. Changes in the monocular VEP of this Figure 2. Visually evoked potentials recorded from both hemispheres (Or-Al and Oz-AZ)of four albino subjects under conditions of binocular and monocular illumination. Monocularly evoked potentials recorded from the hemisphere receiving uncrossed optic fibres have the missing components indicated by dotted lines. Horizontal time base 250 msec. Negative is up. Stimulation luminance onset-offset 0.5lsec. (N=lOO). Figure 3.
A44
Pattern
Luminance
I
I
100
200
Ymsec
102
J. Biomed. Eng. 1979, Vol. 1, No. 2, April
Visually evoked potentials recorded from both hemispheres of an albino under conditions of binocular and monocular (right eye) illumination. Components missing from the monocular evoked potentials are indicated by dotted lines. Horizontal time base 250 msec. Negative is up. Total field size 15’. Illumination 0.3 lux in darkness. Luminance onset-offset 0.5lsec (N=50). Pattern-luminance onset-offset 1’ checkerboard O.S/sec (N=50). Pattern reversal 2Ocheckerboard, reversal rate 600 msec (N=500).
Pattern
reversal
Visual Evoked Potentials: D. Creef
potentials of monocularly illuminated human albinos demonstrates a disorganization of uncrossed optic fibres similar to that reported for other albino mammals. Guillery, Okoro and Witkop (1975) have anatomically verified anomalous ops projections in several brains of human albinos. Anatomically visual systems of albino humans appear to include the anomaly described for the Siamese cat, i.e., laminae of the dorsal lateral geniculate nucleus receiving ganglion fibres from the ipsilateral eue are fragmented.
Binocular
I
I
too
I
I
200 msec
Figure 4. Visually evoked potentials recorded from both hemis$heres of an albino under conditions of binocular and monocular illumination. The component missingfrom the binocular evokedpotential is indicated by a dotted line. Horizontal time base 300 msec. Negative isup. Stimulation luminanceonsetoffset 0.5lsec (N=60). albino include reversal of polarity of early components with discordance present beyond 250 msec. It is unusual to see significant alteration of the VEP beyond 125 msec. Monocular stimulation of each eye often results in differential effects in the VEP. Stimulation of one eye may result in reversal of polarity of several components, whereas monocular stimulation of the other eye may result in minimal effects. Another unusual feature of the human albino’s VEP is that approximately 1 in 10 demonstrates asymmetric evoked potentials between hemispheres with binocular stimulation that then become symmetric when only on eye is stimulated (Figure 4). This suggests significant asymmetry in the geniculostriate projections between hemispheres of these individuals. DISCUSSION The bilaterally
asymmetric,
photically
evoked
The point to point representation of the visual field upon the geniculate nuclei and striate cortex can be detected u&g scalp-recordedVEPs. Some components of the VEP change polarity in normally pigmented humans when left-right half-field stimulation is used (Spekreijse, 1977). The effect of misrouting of optic afferents in the albino is similar to shifting the visual field midline (O” meridian ) up to 20”. In the albino this shift is analogous to the effect of partial field stimulation in a normally pigmented human. Misrouting of retinogeniculostriate projections alters the location of cortical generators of evoked potentials. An albino limited to monocular stimulation produces changes in components of the occipital VEP similar to those reported for normally pigmented humans following partial left-right field stimulation. As one might expect, the changes in components of the VEP of monocularly stimulated human albinos are also similar to those changes in the VEP of patients with homonymous hemianopsia or localized unilateral macular scotoma affecting the first 20” of the horizontal field (Harding, 1977). There is probably extreme anatomical variability in the retinogeniculostriate projections of human albinos, even more than that reported for hypopigmented laboratory mammals. (Creel and Giolli; 1976). Anatomical variability confounds the detection of anomalies in man and the identification of the underlying electronic source of affected components in the scalp-recorded VEP. Among human albinos, there is probably considerable variation in the retinal point of origin and proportion of uncrossed fibres in the organization of the geniculate laminae and in the organization of genidulostrlate projections. Further, the juxtaposition of the cortical generators of the VEP probably varies considerably. The distribution of striate cortex varies between hemispheres, as do the cortical sulci. Variation in location and orientation of cortical generators would affect the form of scalprecorded VEP. Anatomic variability may be only partially responsible for anomalies not being detected in 30% of human albinos using scalp-recorded VEPs. Perhaps modulated light or other methods of pattern stimulation such as appearance disappearance would be more effective stimuli, producing a detection rate of even greater than 70% in human albinos.
J. Biomed.
Eng. 1979, Vol. 1, No. 2, April
103
Visual Evoked Potentials:
D. Creel
REFERENCES Creel, D. J. and Sheridan, C.L. (1966). Monocular acquisition and interocular transfer in albino rats with unilateral striate ablations. Psychonomic. Sci., 6,89. Creel, D.J.. Dustman, R.E. and Beck, EC. (1970). Differences in visually evoked responses in albino versus hooded rats. Exp. Newel., 29,298. Creel, D. J. (1971). Visual system anomaly associated with albinism in the cat. Nature, 231,465. Creel, D.J. and Giolli, R.A. (1972). Retinogeniculostriate projections in guinea pigs: albino and pigmented strains compared. Exp. Neural., 36,411. Creel, D. J., Witkop, C. J. and King, R.A. (1974). Asymmetric visually evoked potentials in human albinos: evidence for visual system anomalies. Invest. Ophthalmol., 13,430-440. Creel, D. J. and Giolli, R.A. (1976). Retinogeniculate projections in albino and ocularly hypopigmented rats. J. Camp. Neural., l&445-456. Creel, D., O’Donnell, R.E., Jr. and Witkop, C.J., Jr (1978). Visual system anomalies in human ocular albinos. Science, 201,931-933. Giolli, R.A. and Creel, D. J. (1973). The primary optic projections in pigmented and albino guinea pigs: an experimental degeneration study. Brain Res., 55,25. Guillery, R.W. and Kass, J.H. (1971). A study of normal and congenitally abnormal retinogeniculate projections incats. J. Camp. Neural., 143,73.
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J. Biomed. Eng. 1979, Vol. 1, No. 2, April
Guillery, R.W., Okoro, An. N. and Witkop, C. J. (1975). Abnormal visual pathways in the brain of a human albino. Brain Res., 96.373-377. Harding, G.F.A. (1977). The use of visual evoked potentials to flash stimuli in the diagnosis of visual defects. In Visual Evoked Potentials in Man: New Developments’, Ed. J.E. Desmedt, Clarendon. Oxford: 500-508. Hayhow, W.R., Webb, C. and Jervie, A. (1966). Theaccessory optic fiber system of the rat. J. Comp. Neurol., 115,187. Jasper, H.H. (1958). The ten-twenty electrode system of the international federation. Electroencephalogr. Clin. hreurophysiol., 10,371. Lund, R.D. (1965). Uncrossed visual pathways of hooded and albino rats. Science 149.1506. Montero, V.M., Brugge, J.F. and Beitel, R.E. (1968). Relation of the visual field to the lateral geniculate body of the albino rat. J. Neurophysiol., 31,221. Polyak, S. (1957). In ‘The Vertebrate Visual System’, Ed. H. Kluver University of Chicago Press. Chicago. Sheridan, C.L. (1965). Interocular transfer of brightness and pattern discriminations in normal and corpus callosumsectioned rats. J. Comp. Physiol. Psychol., 59,292. Spekreijse, H., Estevez, 0. and Reits, D. (1977). Visual evoked potentials and the physiological analysis of neuronal processes in man. In Visual Evoked Potentials in Man: New Developments, Ed. J.E. Desmedt, Clarendon,Oxford, 16-89.
Most fish, amphibians, reptiles and birds have laterally placed eyes and primarily panoramic vision. These vertebrates usually have complete crossing of optic fibres at the chiasm, i.e., optic ganglion fibres originating from each eye terminate in visual centres of the contralateral hemisphere. One of the features of the mammalian visual system is the appearance of an uncrossed optic projection terminating in visual centres of the ipsilateral hemisphere. As the eyes shift to a more frontal position on the head the number of ganglion fibres originating in temporal retinae increases. Concomitantly, stereoscopic vision and binocular overlap of visual fields increase. The number of optic fibres that do not cross at the chiasm varies: approximately l-5 percent in guinea pigs and mice, 5-10 percent in rats, 20 percent in dogs and horses, 30-40 percent in domestic cats, 4030 percent in primates (Giolli. and Creel, 1973; Hayhow et al, 1960; Polyak, 1957). Sheridan (1965) reported that uncrossed optic fibres are functionally incompeteni in an albino rat and predicted anatomical differences between visual systems of albino and pigmented rats. Lund (1965) verified Sheridan’s hypothesis anatomically. The finding of reduced uncrossed optic projections in albino rats was reconfirmed in behavioural (Creel and Sheridan, 1966), electrophysiological (Montero, ~_ 1968) and anatomical studies. (Creeland Giolli, 1976) Visual system anomalies in albino mammals are now known to include: (a) reduced numbers of uncrossed optic projections to dorsal and ventral portions of the lateral geniculate nuclei, anterior and posterior pretectal nuclei and superior colliculus; (b)disorganization of patterningilamination) of optic terminations in dorsal and ventral lateral geniculate nuclei; and (c) disorganization of projections from dorsal lateral geniculate nucleus to visual cortex. Abnormalities have been verified in nine species of mammals: cat, rat, ferret, tiger, mouse, mink, guinea pig, rabbit and humans. (Guillery et al., 1975). All albino mammals examined have shown one or more of these anomalies. Considerable research has been conducted using Siamese cats. The Siamese cat is representative of the Veterans Administration Medical Center, Salk Lake City, Ut 84148, U.S.A. This paper was presented at the International Symposium cm Evoked Potentials in Nottingham, UK, September 1978, the proceedings of which are available from the BES.
100
J. Biomed. Eng. 1979, Vol. 1, No. 2, April
Himalayan (C” C”) allele of the albino series which permits pigment to form only on the cooler parts of the body, including the face, ears, tail and feet because of a thermolabile tyrosinase enzyme. The eyes lack retinal pigment. As far as their visual systems are concerned they are albino. The disorganization of the visual systems of Siamese cats and other albino mammals is not random. There is an excessive number of optic afferents crossing at the optic chiasm and an insufficient number of optic afferents that do not cross. The misrouted optic fibres originate from approximately the first ZOoofthe temporal retina (Guillery and Kaas, 1971)Many of these fibres erroneously cross at the optic chiasm and terminate in a portion of the dorsal lateral geniculate nucleus (LGNd) normally reserved for uncrossed optic afferents. These terminations fragment the retinotopic organization of the LGNd, producing a disruption of retinotopically organized projections to striate cortex. It has been demonstrated that evoked potentials recorded from the visual area of albino rats (Creel et al., 2970) guinea pigs (Creel and Giolli, 1972) and Siamese cats (Creel, 1971) reflect the anatomically verified reduction and disorganization of uncrossed optic fibres. The evoked potential technique therefore provides a method for evaluating visual system anomalies in humans. By covering an eye so that only one eye is photically stimulated and at the same time recording visually evoked potentials from scalp overlying visual areas of both hemispheres the relative contribution of optic projections from uncrossed optic fibres may be compared. Visually evoked potentials (VEPs) have been recorded from 60 human oculocutaneous (total) albinos of four types’which can be distinguished from each other on the basis of biochemical, clinical, genetic, and ultrastructural characteristics (Creel et al., 1974). We have also recorded VEPs from 12 human ocular albinos of two types, Xlinked ocular albinism and a newly described autosomal recessively inherited ocular albinism (Creel et a1.,1978) Thirty normally pigmented browneyed individuals participated as control subjects. METHOD Each subject was seated in a padded chair in a
Visual Evoked Potentials:
Several methods of photic stimulation were used. Luminance onset-offset was produced by placing the lamp of a photostimulator behind a white plastic diffusing screen. Pattern-luminance onsetoffset was produced by placing checkerbpard patterns in front of the lamp of the photostimulator. Pattern reversal was produced using a Digitimer pattern reversal stimulator. Individual check size was varied from 15 min. to 2”. Total field of stimulation was varied from 15Oto 80° The calculated flash illuminance was varied from approximately 0.3 lux to 2.5 lux. The subjects were not dark-adapted, although the room was dark during testing. The lamp of the photostimulator was enclosed in polyethylene foam to attenuate sounds. Luminance onset-offset and pattern-luminance onset-offset stimuli were produced by the lamp of a Grass photostimulator at a rate of one flash approximately every two seconds. Sixty to 100 flashes were averaged. The Digitimer pattern-reversal stimulator was set to reverse the checkerboard every 600 msec. Two hundred reversals were averaged. Binocular visually evoked potentials were recorded. One eye was then covered with several layers of opaque material consisting of a gauze pad, a black eye patch and adhesive eye patches which covered facial areas around the eye. The efficiency of the occlusion process was checked for each subject. Brain activity was amplified by a Grass EEG and recorded on an FM tape recorder. Care was taken that channel-to-channel bias in the calibration of the EEG did not affect recording to differences of evoked potentials between hemispheres. Electrical responses were averaged by a signal averager set to analyse electrocortical activity for 500 msec following each flash of light. The averaged response was plotted by an X-Y plotter. In addition to visual inspection, statistical comparisons were made between recordings of evoked potentials from each hemisphere. Each regularly appearing component was examined for latency and amplitudinal changes. Components were considered significantly reduced if attenuation exceeded 50 percent. RRSULTS
For all control subjects and most albinos, there was no significant hemispheric VEP amplitude asymmetries with binocular stimulation. When evoked potentials were recorded with one eye again there were still no hemispheric asymmetries for the
Monocular
Binocular
sound-attenuated room. Placement of electrodes was according to the lo-20 International System (Jasper, 1958). Several electrode montages with several reference points were explored. Silver disc electrodes were attached bilaterally to the scalp with nonflexible collodion at 01,02, Oz, AI, A2,6, FI, 05 and 06. We use 05 and 05 and 06 to desingnate the positionhalfway between electrodes 01-T5 and Oa-Ts. Ipsilateral ears, linked ears, and Fr were used as reference electrodes for 01,02, OZ.05 and 06.
85
D. Creel
%_L
ti
67 w %f
5pV 100
I
200
Figure 1. Visually evoked potentials recorded from both hemispheres (OI-AI and Oz-AZ)of four normally pigmented subjects under conditions of binocular and monocular illumination. Horizontal time base250msec. Negative isup. Stimulation luminanceonsetoffset 0.5lsec (N=IOO). control subjects (Figure 1). In contrast, approximately 70 percent of human oculocutaneous and ocular albinos (50 of 72) showed asymmetry between hemispheres following monocular stimulation, with one or more components of the VEP missing or significantly attenuated. The degree of hemispheric asymmetry of monocularly evoked potentials was significantly greater than that observed in normally pigmented men with one eye enucleated, and for most albinos was as severe as that which is seen in neurologic patients with lesions of the optic pathways resulting in visual field defects. All three stimulation techniques (luminance onset-offset, pattern-luminance onsetoffset and pattern reversal) produced essentially the same results. Even with binocular stimulation it is not unusual to record occasional asymmetry of VEPS between hemispheres in humans. A distinctive feature of the human albino is the dramatic change in the VEP following monocular stimulation as compared to the effects of monocular stimulation in normally
J. Biomed. Eng. 1979, Vol. 1, No. 2, April
101
Visual Evoked Potentials:
D. Creel
Binocular
Monocular
pigmented humans. Monocular stimulation reveals the discontinuity and fragmentation of the retinotopic organization of the albino’s visual projections between eye and cortex (Figure 2). Most changes in the VEP are seen in those components appearing in the first 125 msec. Figure 3 illustrates the VEPs of an adult human albino presented with luminance onset-offset, pattern-luminance onset-offset and pattern reversal stimuli. Changes in the monocular VEP of this Figure 2. Visually evoked potentials recorded from both hemispheres (Or-Al and Oz-AZ)of four albino subjects under conditions of binocular and monocular illumination. Monocularly evoked potentials recorded from the hemisphere receiving uncrossed optic fibres have the missing components indicated by dotted lines. Horizontal time base 250 msec. Negative is up. Stimulation luminance onset-offset 0.5lsec. (N=lOO). Figure 3.
A44
Pattern
Luminance
I
I
100
200
Ymsec
102
J. Biomed. Eng. 1979, Vol. 1, No. 2, April
Visually evoked potentials recorded from both hemispheres of an albino under conditions of binocular and monocular (right eye) illumination. Components missing from the monocular evoked potentials are indicated by dotted lines. Horizontal time base 250 msec. Negative is up. Total field size 15’. Illumination 0.3 lux in darkness. Luminance onset-offset 0.5lsec (N=50). Pattern-luminance onset-offset 1’ checkerboard O.S/sec (N=50). Pattern reversal 2Ocheckerboard, reversal rate 600 msec (N=500).
Pattern
reversal
Visual Evoked Potentials: D. Creef
potentials of monocularly illuminated human albinos demonstrates a disorganization of uncrossed optic fibres similar to that reported for other albino mammals. Guillery, Okoro and Witkop (1975) have anatomically verified anomalous ops projections in several brains of human albinos. Anatomically visual systems of albino humans appear to include the anomaly described for the Siamese cat, i.e., laminae of the dorsal lateral geniculate nucleus receiving ganglion fibres from the ipsilateral eue are fragmented.
Binocular
I
I
too
I
I
200 msec
Figure 4. Visually evoked potentials recorded from both hemis$heres of an albino under conditions of binocular and monocular illumination. The component missingfrom the binocular evokedpotential is indicated by a dotted line. Horizontal time base 300 msec. Negative isup. Stimulation luminanceonsetoffset 0.5lsec (N=60). albino include reversal of polarity of early components with discordance present beyond 250 msec. It is unusual to see significant alteration of the VEP beyond 125 msec. Monocular stimulation of each eye often results in differential effects in the VEP. Stimulation of one eye may result in reversal of polarity of several components, whereas monocular stimulation of the other eye may result in minimal effects. Another unusual feature of the human albino’s VEP is that approximately 1 in 10 demonstrates asymmetric evoked potentials between hemispheres with binocular stimulation that then become symmetric when only on eye is stimulated (Figure 4). This suggests significant asymmetry in the geniculostriate projections between hemispheres of these individuals. DISCUSSION The bilaterally
asymmetric,
photically
evoked
The point to point representation of the visual field upon the geniculate nuclei and striate cortex can be detected u&g scalp-recordedVEPs. Some components of the VEP change polarity in normally pigmented humans when left-right half-field stimulation is used (Spekreijse, 1977). The effect of misrouting of optic afferents in the albino is similar to shifting the visual field midline (O” meridian ) up to 20”. In the albino this shift is analogous to the effect of partial field stimulation in a normally pigmented human. Misrouting of retinogeniculostriate projections alters the location of cortical generators of evoked potentials. An albino limited to monocular stimulation produces changes in components of the occipital VEP similar to those reported for normally pigmented humans following partial left-right field stimulation. As one might expect, the changes in components of the VEP of monocularly stimulated human albinos are also similar to those changes in the VEP of patients with homonymous hemianopsia or localized unilateral macular scotoma affecting the first 20” of the horizontal field (Harding, 1977). There is probably extreme anatomical variability in the retinogeniculostriate projections of human albinos, even more than that reported for hypopigmented laboratory mammals. (Creel and Giolli; 1976). Anatomical variability confounds the detection of anomalies in man and the identification of the underlying electronic source of affected components in the scalp-recorded VEP. Among human albinos, there is probably considerable variation in the retinal point of origin and proportion of uncrossed fibres in the organization of the geniculate laminae and in the organization of genidulostrlate projections. Further, the juxtaposition of the cortical generators of the VEP probably varies considerably. The distribution of striate cortex varies between hemispheres, as do the cortical sulci. Variation in location and orientation of cortical generators would affect the form of scalprecorded VEP. Anatomic variability may be only partially responsible for anomalies not being detected in 30% of human albinos using scalp-recorded VEPs. Perhaps modulated light or other methods of pattern stimulation such as appearance disappearance would be more effective stimuli, producing a detection rate of even greater than 70% in human albinos.
J. Biomed.
Eng. 1979, Vol. 1, No. 2, April
103
Visual Evoked Potentials:
D. Creel
REFERENCES Creel, D. J. and Sheridan, C.L. (1966). Monocular acquisition and interocular transfer in albino rats with unilateral striate ablations. Psychonomic. Sci., 6,89. Creel, D.J.. Dustman, R.E. and Beck, EC. (1970). Differences in visually evoked responses in albino versus hooded rats. Exp. Newel., 29,298. Creel, D. J. (1971). Visual system anomaly associated with albinism in the cat. Nature, 231,465. Creel, D.J. and Giolli, R.A. (1972). Retinogeniculostriate projections in guinea pigs: albino and pigmented strains compared. Exp. Neural., 36,411. Creel, D. J., Witkop, C. J. and King, R.A. (1974). Asymmetric visually evoked potentials in human albinos: evidence for visual system anomalies. Invest. Ophthalmol., 13,430-440. Creel, D. J. and Giolli, R.A. (1976). Retinogeniculate projections in albino and ocularly hypopigmented rats. J. Camp. Neural., l&445-456. Creel, D., O’Donnell, R.E., Jr. and Witkop, C.J., Jr (1978). Visual system anomalies in human ocular albinos. Science, 201,931-933. Giolli, R.A. and Creel, D. J. (1973). The primary optic projections in pigmented and albino guinea pigs: an experimental degeneration study. Brain Res., 55,25. Guillery, R.W. and Kass, J.H. (1971). A study of normal and congenitally abnormal retinogeniculate projections incats. J. Camp. Neural., 143,73.
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