Vision Res. Vol. 31, No. 11, pp. 1851-1857, 1991 Printed in Great Britain. All rights reserved
Copyright
0042-6989/91 53.00 + 0.00 Pergamon Press pic
© 1991
THE EFFECT OF A SLOW FLICKER ON THE HUMAN PHOTOPIC OSCILLATORY POTENTIALS PIERRE LACHAPELLE
Department of Ophthalmology, McGill University and Montreal Children's Hospital, Montreal, Canada H3H IP3 (ReceIVed 19 November 1990; in reVIsed form 4 February 1991)
Abstract-Flicker-induced modifications of the human photopic oscillatory potentials (OPs) were investigated with the use of flash stimuli of 0.89 and 8.9 cd m- 2 sec in strength. When the dimmest stimulus is used, increasing the rate of presentation from 0.5 to 20 Hz augments the amplitude and peak time of OP2 • For a brighter stimulus, the 10 Hz flicker significantly reduces the amplitude of OP2 and OPJ , increases the peak time of OP2 and reduces that of OP4 • The 20 Hz flicker increases the peak time and reduces the amplitude of OP 2 and completely abolishes OP J , while it has no significant impact on the amplitude and timing of OP4 • The data presented support the claim that each OP making the photopic response represent independent electrophysiological entities. Oscillatory potentials
Electroretmogram
Photopic
INTRODUCTION
Few studies have specifically examined the oscillatory potentials evoked to a flicker stimulus. Anderson, Troelstra and Garcia (1979) compared the waveforms of human ERG signals evoked to a singie flash and to a 24 Hz stimulus. Although no specific reference is made to the OPs, their illustration (their Fig. 1) clearly shows that two OPs are seen on the ascending limb of the b-wave of the single flash ERG, while none are seen on the 24 Hz b-wave. Similarly, Winkler (1972) showed in rabbits that, for a flicker rate of 10 flashes/sec, the resulting b-wave was without OPs on its ascending limb. Analysis of the flicker-evoked retinal potentials with the use of an OP specific recording bandwidth was also performed by Nagata (1963), and more recently by Kojima and Zrenner (1978). They showed that, with a progressive increase in the flicker rate, there is an increase in the peak time of the short latency OPs and, at the same time, a shortening in the timing of the long latency OPs. Interestingly, both studies made use of a similar methodological approach where the retina was first darkadapted, and light-adaptation was progressively obtained by using the flickering stimulus. It is now well documented that following a period of dark-adaptation, the retina needs to be light-adapted for at least 10 min before photopic signals of maximal amplitudes are
Flicker
Intensity
Retina
Human
obtained (Gouras & MacKay, 1989; Lachapelle, 1987; Miyake, Horiguchi, Ota & Takabayashi, 1988; Peachey, Alexander, Fishman & Derlacki, 1989). This light-adaptation phenomenon affects not only the b-wave but also the OPs since the amplitude of the long latency OP4 will augment significantly, while its peak time will shorten with progressive light-adaptation (Lachapelle, 1987; Peachey, Alexander, Derlacki, Bobak & Fishman, 1991). Given the above, the flicker experiments reported above (Kojima & Zrenner, 1978; Nagata, 1963) were reinvestigated in fully light-adapted subjects to examine if the recently reported light-adaptation effect may have been contributory to their findings of a flicker-induced OP modification. Our results further accentuate the physiological differences between the short and long latency photopic OPs.
MATERIALS AND METHODS
The data was collected from a total of 18 normal subjects, aged 15-35 yr old, as part of a study on the intensity-coding property of OP 2 (Lachapelle, 1991). In order to limit the entire duration of the recording procedure, a complete set of data (Le. all flicker rates at all stimulus strengths) was not sought from the subjects. For the 8.9 cd m -2 sec stimulus, the 10 Hz data were obtained from 12 normal subjects and the 20 Hz
1851
1852
PIERRE LACHAPELLE
data from 7 subjects (of which 5 also yielded 10 Hz data). For the 0.89 cd m- 2 sec stimulus at 20 Hz, the data was collected from 7 subjects (out of which one generated data to the 8.9 cd m -2 sec stimulus at 10 and 20 Hz). Thus, only one subject generated a complete set of data. However, the flicker-induced OP modifications (at 10 and 20 Hz) were revealed by comparing (paired t-test) the flicker response peak times and amplitudes to those measured in the responses evoked from the same individual to the nonflickering stimuli (i.e. 0.5 Hz) of identical energy. All subjects underwent a complete ophthalmological examination to rule out possible retinal anomalies. The ERG protocol was explained in detail and all subjects agreed to participate. The subjects' pupils were fully dilated (cyc1opentolate HCl 1%, penylephrine HCl 10%) and the cornea anesthetized (proparacaine HCl 0.5%). A corneal contact lens (Medical Workshop Inc.) was used to record the signal with reference and ground electrodes placed on the forehead and earlobe respectively. The subjects were placed in front of a Ganzfeld of 45 cm in diameter, which housed the photostimulator strobe (Grass PS-22) and the rod saturating background light device (photopic background: 30 cd m- 2). The electroretinal signals were amplified 10,000 x (Grass P-511 preamplifiers) with a 100-1000 Hz bandwidth (3 dB of attenuation). Averages of 32 responses were performed online with a Tracor Northern NS-575 A signal analyzer. Hard copies of the waveforms were obtained with a Hewlett-Packard 7015B x-y plotter. To avoid the light-adaptation effect previously reported (Gouras & MacKay, 1989; Lachapelle, 1987; Peachey et al., 1989, 1991), the photopic OPs were recorded from fully light-adapted subjects who were not previously exposed to a darkadaptation period. The photopic oscillatory potentials were evoked to two strengths of stimulation as determined by the Grass PS-22 photostimulator relative intensity selector (i.e. 1-1 and 1-16). The strength of each selection, measured according to a method reported by Norden and Leach (1977), was of 0.89 cd m- 2 sec (Grass 1-1) and 8.9 cd m -2 sec (Grass 1-16). To avoid confusion, the flash stimuli will be reported in Grass PS-22 relative intensity units (i.e. 1-1 and 1-16). Three rates of presentation (0.5, 10 and 20 Hz) of the stimulus were used to evoke the retinal responses. The interval between consecutive flashes was determined by an interval generator
unit (WPI Instruments, Interval generator, Model 1830). It is well-known fact that gas discharge tubes, such as that which equips the Grass PS22 photostimulator, often see their light output reduced in proportion to the flicker rate used (Marmor, Arden, Nilsson & Zrenner, 1989). For example, according to the manufacturer's instruction manual (Grass Instrument Co., 1977), the effective output of an 1-16 stimulus delivered at 50 Hz is equivalent to that of an 1-8 stimulus delivered at 1 Hz, thus representing approximately a 0.3 log-unit attenuation in intensity. In order to ascertain that the reported flicker-induced OP modifications were solely due to the rate of presentation of the stimuli and had no intensity component, the effective output of the photostimulator was measured with a Minolta Flash Meter III. At 20 Hz, a stimulus of 1-16 setting is attenuated by less than 0.1 log-unit while a stimulus ofI-l setting is not affected. At 10 Hz, neither stimuli (1-16 and 1-1) are attenuated. According to previously published data (Lachapelle, 1991), a 0.1 log-unit of attenuation in the strength of the stimulus should have a negligible impact on the amplitude and peak time of the various OPs. The peak times of the OPs were measured from flash onset, while their respective amplitudes were measured from trough to peak.
RESULTS The number, amplitude and peak time of the various OPs that compose the human photopic response vary with the strength of the stimulus. As shown at Fig. 1, in response to a threshold stimulus (tracing 1) one major retinal OP (i.e. OP 2 ) is evoked. A stimulus 1 log-unit brighter shortens the peak time and increases the amplitude of OP 2 , adds OP3 and OP4 , and further accentuates OPs , OP6 and OP7 which were previously reported to signal the activation of the ganglion cells and/or the optic nerve (Lachapelle, 1990). This study will concentrate on the effect of a flicker stimulus on OP 2 , OP 3 and OP4 • The threshold difference illustrated in Fig. 1 also offers the opportunity to study flicker-induced OP 2 modification at two different strengths of stimulation, namely Grass 1-1 and 1-16. In Fig. 2 are illustrated the photopic OPs tracings evoked from three normal subjects (tracings 1,2; 3,4; 5,6) to a stimulus of 0.89 cd m- 2 sec (Grass 1-1) delivered at 0.5 Hz
1853
The effect of a slow flicker
~
2
2
1~
24Vn 2
3
~
2
3~
2
20msec
Fig. I. Representative recordings of human photopic oscillatory potentials evoked to flash stimuli of 0.89 cd m -2 sec (tracing I) and 8.9 cd m- 2 sec (tracing 2), delivered at 0.5 Hz. Brighter stimuli adds new OPs (of longer latency) to the threshold response (i.e. OP2 ). Vertical arrow indicates flash onset. Open arrow head (tracing I) points at what is believed to be remnants of OP3 and OP4 •
(tracings 1,3,5) and 20 Hz (tracings 2,4,6). Data on peak time and amplitude are reported in Table 1. An increase in the flicker rate from 0.5 to 20 Hz slightly (but significantly: Table 1) augments the amplitude and peak time of OP 2 without adding new OPs to the response. Interestingly, while at 0.5 Hz OP, notch (preceding OP 2 ascending limb) is usually difficult to recognize, it becomes more obvious (tracings 2,6) with the 20 Hz stimulus making it possible to better identify the small OP, whose origin and significance remains obscure. As shown at Fig. 2, there is some intersubject variability in the magnitude of the effect. For example, the OP 2 amplitude increment is only of 8.3% for the first subject (tracings 1,2) while it is of 54% of the last one (tracings 5,6). The latter variability could be partly explained by the threshold nature of the resulting stimulus when one considers that the energy of the flash was only of 0.89 cd m- 2 sec and combined to a rod saturating background of 30 cd m - 2. However, there was no variability in the polarity of the effect since all subjects tested (N = 7) had their OP 2 amplified (range 6-63%) and delayed (range 0.6-3.3 msec) by the 20 Hz stimulus. In contrast, a slightly different picture emerges when the 8.9 cd m -2 sec (Grass 1-16) stimulus is used. Representative examples obtained from three subjects (A-e) are shown in
2
6~ 40msec
Fig. 2. The effect of a flickering stimulus on the photopic OPs evoked to a 0.89 cd m -2 sec stimulus delivered at 0.5 Hz (tracings 1,3,5) and 20 Hz (tracings 2,4,6). The data illustrated were obtained from three normal subjects (tracings 1,2; 3,4; 5,6) different from those illustrated in Figs 3 or 4. As previously reported elsewhere (Lachapelle et aI., 1990b; Lachapelle, 1991) OP2 is the major OP evoked at this threshold stimulus. Vertical arrows indicate flash onset.
Fig. 3 where responses evoked to a 0.5 Hz flicker (columns A-e, tracing 1) are compared to those evoked to a 10 Hz (columns A-e, tracing 2). Data on peak time and amplitude are reported in Table 2. The most striking 10 Hz flickerinduced modification is the significant reduction (average reduction: 72.4 ± 16.5%) in the amplitude of OP3 , a feature seen in all the subjects tested (range: 30-100%). This dramatic Table I. The effect of a 20 Hz flicker on the peak time (in msec ± I SD) and amplitude (in Jl.V ± I SD) of OP2 evoked to a 0.89 cd m- 2 sec stimulus; statistical analysis was performed with a two-tailed paired Student's t-test (t); d.f. = degrees of freedom (N = 7) OP2 Amp 0.5Hz 20Hz t (dJ.)
PT
16.90 ± 3.70 19.30 ± 0.43 22.60 ± 6.98 21.15 ± 0.83 -3.11 -5.83 (6) P < 0.05
(6)
P 0.05
27.6 ± 0.9 26.95 ± J.I 2.748 (6) P 0.05) from the 19.22 ± 0.5 msec measured for an OP2 evoked to a stimulus of 0.89 cd m- 2 sec delivered at 0.5 Hz (Table 1). Secondly, while a reduction in the energy of the stimulus progressively abolishes OP4 and OP3 (Lachapelle, 1991) as shown in Fig. 1, OP4 is not significantly modified (amplitude and peak time) by the flicker stimulus. Finally, the fact that brighter and dimmer flickering stimuli differently affect the amplitude of OP2 rule out
the possibility that the reported findings are mostly reflecting an energy-response function. In summary, the results presented in this study further confirm that each photopic OP is electrophysiologically different from the other. The flicker data further accentuates the physiological difference between the short and intermediate latency OP2 and OP3 with the long latency OP4 , in support of previous observations obtained with various methodological approaches (Kojima & Zrenner, 1978; Lachapelle, 1987; Lachapelle et al., 1983; Wachtmeister, 1980, 1981a, b). Acknowledgements-Supported by a grant-in-aid from the McGill University-Montreal Children's Hospital Research Institute, and the Medical Research Council of Canada (MA-8649). This is publication number 91006 from the McGill University-Montreal Children's Hospital Research Institute.
REFERENCES Anderson, C. M., Troelstra, A. & Garcia, C. A. (1979). Quantitative evaluation of photopic ERG waveforms. Investigative Ophthalmology and Visual Science, 18, 26-43. Denny, N., Frumkes, T. E. & Goldberg, S. H. (1990). Comparison of summatory and suppressive rod-cone interaction. Clinical Vision Sciences, 5, 27-36. Gouras, P. & MacKay, C. J. (1989). Growth in amplitude of the human cone electroretinogram with light-adaptation. Investigative Ophthalmology and Visual Science, 30, 625-630. Grass Instrument Co. (1977). Models PS22 and PS23 photostimulators instruction manual. Quincy, Mass.: Grass Instrument Co. Kojima, M. & Zrenner, E. (1978). Off-components in response to brief light flashes in the oscillatory potential of the human electroretinogram. Albrecht von Graefes Archiv fiir Klinische Experimentelle Ophthalmologie, 206, 107-120. Lachapelle, P. (1987). Analysis of the photopic electroretinogram recorded before and after dark adaptation. Canadian Journal of Ophthalmology, 22, 354-361. Lachapelle, P. (1990). A possible contribution of the optic nerve to the photopic oscillatory potentials. Clinical Vision Sciences, 5, 421-426. Lachapelle, P. (1991). Evidence for an intensity-coding oscillatory potential in the human electroretinogram. Vision Research, 31, 767-774. Lachapelle, P., Litde, J. M. & Polomeno, R. C. (1983). The photopic electroretinogram in congenital stationary night blindness with myopia. Investigative Ophthalmology and Visual Science, 24, 442-450. Lachapelle, P., Benoit, J., Little, J. M. & Faubert, J. (1990a). The diagnostic use of the second oscillatory potential in clinical electroretinography. Documenta Ophthalmologica, 73, 327-336. Lachapelle, P., Benoit, J., Blain, L., Guite, P. & Roy, M.-S. (1990b). The oscillatory potentials in response to stimuli of photopic intensities delivered in dark-adaptation: An explanation for the conditioning flash effect. Vision Research, 30, 503-513.
The effect of a slow flicker Marmor, M. F., Arden, G. B., Nilsson, S. E. G. & Zrenner, E. (1989). Standard for clinical electroretinography. Archives of Ophthalmology, 107, 816-819. Miyake, Y., Horiguchi, M., Ota 1. & Takabayashl, A. (1988). Adaptional change in cone-medIated electroretinogram in human and carp. Neuroscience Research (Suppl.), 8, SI-SI3. Nagata, M. (1963). Studies on the photopic ERG of the human retina. Japanese Journal of Ophthalmology, 7, 96-124. Norden, L. C. & Leach, N. E. (1977) Calibration of the ERG stimulus. Documenta Ophthalmologica Proceedings Series, 13, 393-403. Peachey, N. S., Alexander, K. R, Fishman, G. A. & Derlacki, D. J. (1989). Properties of the human cone system electroretinogram dunng light adaptation. Applied Optics, 28, 1145-1150. Peachey, N. S., Alexander, K. R., DeriackI, D. J., Bobak. P. & Fishman, G. A. (1991). Effects of light adaptation on the response characteristics of human oscillatory
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potentials. Electroencephalography and Clinical Neurophysiology, 78, 27-34. Wachtmeister, L. (1972). On the oscillatory potentials of the human electroretinogram in light and dark adaptation. Acta Ophthalmologica (Suppl.), 116, 5-32. Wachtmeister, L. (1980). Further studies of the chemical sensitivity of the oscillatory potentials of the electroretinogram (ERG). Acta Ophthalmologica, 58, 712-725. Wachtmeister, L. (198Ia). Further studies of the chemical sensitivity of the oscillatory potentials of the electroretinogram (ERG}-II. Glutamate-aspartate- and dopamine antagonists. Acta Ophthalmologica, 59, 247-258. Wachtmeister, L. (l98Ib). Further studies of the chemical sensitivity of the oscillatory potentials of the electroretinogram (ERG}-III. Some n amino acids and ethanol. Acta Ophthalmologica, 59, 609-619. Winkler, B. S. (1972). Analysis of the rabbit's electroretinogram following unilateral transection of the optic nerve. Experimental Eye Research, 13, 227-235.
Copyright
0042-6989/91 53.00 + 0.00 Pergamon Press pic
© 1991
THE EFFECT OF A SLOW FLICKER ON THE HUMAN PHOTOPIC OSCILLATORY POTENTIALS PIERRE LACHAPELLE
Department of Ophthalmology, McGill University and Montreal Children's Hospital, Montreal, Canada H3H IP3 (ReceIVed 19 November 1990; in reVIsed form 4 February 1991)
Abstract-Flicker-induced modifications of the human photopic oscillatory potentials (OPs) were investigated with the use of flash stimuli of 0.89 and 8.9 cd m- 2 sec in strength. When the dimmest stimulus is used, increasing the rate of presentation from 0.5 to 20 Hz augments the amplitude and peak time of OP2 • For a brighter stimulus, the 10 Hz flicker significantly reduces the amplitude of OP2 and OPJ , increases the peak time of OP2 and reduces that of OP4 • The 20 Hz flicker increases the peak time and reduces the amplitude of OP 2 and completely abolishes OP J , while it has no significant impact on the amplitude and timing of OP4 • The data presented support the claim that each OP making the photopic response represent independent electrophysiological entities. Oscillatory potentials
Electroretmogram
Photopic
INTRODUCTION
Few studies have specifically examined the oscillatory potentials evoked to a flicker stimulus. Anderson, Troelstra and Garcia (1979) compared the waveforms of human ERG signals evoked to a singie flash and to a 24 Hz stimulus. Although no specific reference is made to the OPs, their illustration (their Fig. 1) clearly shows that two OPs are seen on the ascending limb of the b-wave of the single flash ERG, while none are seen on the 24 Hz b-wave. Similarly, Winkler (1972) showed in rabbits that, for a flicker rate of 10 flashes/sec, the resulting b-wave was without OPs on its ascending limb. Analysis of the flicker-evoked retinal potentials with the use of an OP specific recording bandwidth was also performed by Nagata (1963), and more recently by Kojima and Zrenner (1978). They showed that, with a progressive increase in the flicker rate, there is an increase in the peak time of the short latency OPs and, at the same time, a shortening in the timing of the long latency OPs. Interestingly, both studies made use of a similar methodological approach where the retina was first darkadapted, and light-adaptation was progressively obtained by using the flickering stimulus. It is now well documented that following a period of dark-adaptation, the retina needs to be light-adapted for at least 10 min before photopic signals of maximal amplitudes are
Flicker
Intensity
Retina
Human
obtained (Gouras & MacKay, 1989; Lachapelle, 1987; Miyake, Horiguchi, Ota & Takabayashi, 1988; Peachey, Alexander, Fishman & Derlacki, 1989). This light-adaptation phenomenon affects not only the b-wave but also the OPs since the amplitude of the long latency OP4 will augment significantly, while its peak time will shorten with progressive light-adaptation (Lachapelle, 1987; Peachey, Alexander, Derlacki, Bobak & Fishman, 1991). Given the above, the flicker experiments reported above (Kojima & Zrenner, 1978; Nagata, 1963) were reinvestigated in fully light-adapted subjects to examine if the recently reported light-adaptation effect may have been contributory to their findings of a flicker-induced OP modification. Our results further accentuate the physiological differences between the short and long latency photopic OPs.
MATERIALS AND METHODS
The data was collected from a total of 18 normal subjects, aged 15-35 yr old, as part of a study on the intensity-coding property of OP 2 (Lachapelle, 1991). In order to limit the entire duration of the recording procedure, a complete set of data (Le. all flicker rates at all stimulus strengths) was not sought from the subjects. For the 8.9 cd m -2 sec stimulus, the 10 Hz data were obtained from 12 normal subjects and the 20 Hz
1851
1852
PIERRE LACHAPELLE
data from 7 subjects (of which 5 also yielded 10 Hz data). For the 0.89 cd m- 2 sec stimulus at 20 Hz, the data was collected from 7 subjects (out of which one generated data to the 8.9 cd m -2 sec stimulus at 10 and 20 Hz). Thus, only one subject generated a complete set of data. However, the flicker-induced OP modifications (at 10 and 20 Hz) were revealed by comparing (paired t-test) the flicker response peak times and amplitudes to those measured in the responses evoked from the same individual to the nonflickering stimuli (i.e. 0.5 Hz) of identical energy. All subjects underwent a complete ophthalmological examination to rule out possible retinal anomalies. The ERG protocol was explained in detail and all subjects agreed to participate. The subjects' pupils were fully dilated (cyc1opentolate HCl 1%, penylephrine HCl 10%) and the cornea anesthetized (proparacaine HCl 0.5%). A corneal contact lens (Medical Workshop Inc.) was used to record the signal with reference and ground electrodes placed on the forehead and earlobe respectively. The subjects were placed in front of a Ganzfeld of 45 cm in diameter, which housed the photostimulator strobe (Grass PS-22) and the rod saturating background light device (photopic background: 30 cd m- 2). The electroretinal signals were amplified 10,000 x (Grass P-511 preamplifiers) with a 100-1000 Hz bandwidth (3 dB of attenuation). Averages of 32 responses were performed online with a Tracor Northern NS-575 A signal analyzer. Hard copies of the waveforms were obtained with a Hewlett-Packard 7015B x-y plotter. To avoid the light-adaptation effect previously reported (Gouras & MacKay, 1989; Lachapelle, 1987; Peachey et al., 1989, 1991), the photopic OPs were recorded from fully light-adapted subjects who were not previously exposed to a darkadaptation period. The photopic oscillatory potentials were evoked to two strengths of stimulation as determined by the Grass PS-22 photostimulator relative intensity selector (i.e. 1-1 and 1-16). The strength of each selection, measured according to a method reported by Norden and Leach (1977), was of 0.89 cd m- 2 sec (Grass 1-1) and 8.9 cd m -2 sec (Grass 1-16). To avoid confusion, the flash stimuli will be reported in Grass PS-22 relative intensity units (i.e. 1-1 and 1-16). Three rates of presentation (0.5, 10 and 20 Hz) of the stimulus were used to evoke the retinal responses. The interval between consecutive flashes was determined by an interval generator
unit (WPI Instruments, Interval generator, Model 1830). It is well-known fact that gas discharge tubes, such as that which equips the Grass PS22 photostimulator, often see their light output reduced in proportion to the flicker rate used (Marmor, Arden, Nilsson & Zrenner, 1989). For example, according to the manufacturer's instruction manual (Grass Instrument Co., 1977), the effective output of an 1-16 stimulus delivered at 50 Hz is equivalent to that of an 1-8 stimulus delivered at 1 Hz, thus representing approximately a 0.3 log-unit attenuation in intensity. In order to ascertain that the reported flicker-induced OP modifications were solely due to the rate of presentation of the stimuli and had no intensity component, the effective output of the photostimulator was measured with a Minolta Flash Meter III. At 20 Hz, a stimulus of 1-16 setting is attenuated by less than 0.1 log-unit while a stimulus ofI-l setting is not affected. At 10 Hz, neither stimuli (1-16 and 1-1) are attenuated. According to previously published data (Lachapelle, 1991), a 0.1 log-unit of attenuation in the strength of the stimulus should have a negligible impact on the amplitude and peak time of the various OPs. The peak times of the OPs were measured from flash onset, while their respective amplitudes were measured from trough to peak.
RESULTS The number, amplitude and peak time of the various OPs that compose the human photopic response vary with the strength of the stimulus. As shown at Fig. 1, in response to a threshold stimulus (tracing 1) one major retinal OP (i.e. OP 2 ) is evoked. A stimulus 1 log-unit brighter shortens the peak time and increases the amplitude of OP 2 , adds OP3 and OP4 , and further accentuates OPs , OP6 and OP7 which were previously reported to signal the activation of the ganglion cells and/or the optic nerve (Lachapelle, 1990). This study will concentrate on the effect of a flicker stimulus on OP 2 , OP 3 and OP4 • The threshold difference illustrated in Fig. 1 also offers the opportunity to study flicker-induced OP 2 modification at two different strengths of stimulation, namely Grass 1-1 and 1-16. In Fig. 2 are illustrated the photopic OPs tracings evoked from three normal subjects (tracings 1,2; 3,4; 5,6) to a stimulus of 0.89 cd m- 2 sec (Grass 1-1) delivered at 0.5 Hz
1853
The effect of a slow flicker
~
2
2
1~
24Vn 2
3
~
2
3~
2
20msec
Fig. I. Representative recordings of human photopic oscillatory potentials evoked to flash stimuli of 0.89 cd m -2 sec (tracing I) and 8.9 cd m- 2 sec (tracing 2), delivered at 0.5 Hz. Brighter stimuli adds new OPs (of longer latency) to the threshold response (i.e. OP2 ). Vertical arrow indicates flash onset. Open arrow head (tracing I) points at what is believed to be remnants of OP3 and OP4 •
(tracings 1,3,5) and 20 Hz (tracings 2,4,6). Data on peak time and amplitude are reported in Table 1. An increase in the flicker rate from 0.5 to 20 Hz slightly (but significantly: Table 1) augments the amplitude and peak time of OP 2 without adding new OPs to the response. Interestingly, while at 0.5 Hz OP, notch (preceding OP 2 ascending limb) is usually difficult to recognize, it becomes more obvious (tracings 2,6) with the 20 Hz stimulus making it possible to better identify the small OP, whose origin and significance remains obscure. As shown at Fig. 2, there is some intersubject variability in the magnitude of the effect. For example, the OP 2 amplitude increment is only of 8.3% for the first subject (tracings 1,2) while it is of 54% of the last one (tracings 5,6). The latter variability could be partly explained by the threshold nature of the resulting stimulus when one considers that the energy of the flash was only of 0.89 cd m- 2 sec and combined to a rod saturating background of 30 cd m - 2. However, there was no variability in the polarity of the effect since all subjects tested (N = 7) had their OP 2 amplified (range 6-63%) and delayed (range 0.6-3.3 msec) by the 20 Hz stimulus. In contrast, a slightly different picture emerges when the 8.9 cd m -2 sec (Grass 1-16) stimulus is used. Representative examples obtained from three subjects (A-e) are shown in
2
6~ 40msec
Fig. 2. The effect of a flickering stimulus on the photopic OPs evoked to a 0.89 cd m -2 sec stimulus delivered at 0.5 Hz (tracings 1,3,5) and 20 Hz (tracings 2,4,6). The data illustrated were obtained from three normal subjects (tracings 1,2; 3,4; 5,6) different from those illustrated in Figs 3 or 4. As previously reported elsewhere (Lachapelle et aI., 1990b; Lachapelle, 1991) OP2 is the major OP evoked at this threshold stimulus. Vertical arrows indicate flash onset.
Fig. 3 where responses evoked to a 0.5 Hz flicker (columns A-e, tracing 1) are compared to those evoked to a 10 Hz (columns A-e, tracing 2). Data on peak time and amplitude are reported in Table 2. The most striking 10 Hz flickerinduced modification is the significant reduction (average reduction: 72.4 ± 16.5%) in the amplitude of OP3 , a feature seen in all the subjects tested (range: 30-100%). This dramatic Table I. The effect of a 20 Hz flicker on the peak time (in msec ± I SD) and amplitude (in Jl.V ± I SD) of OP2 evoked to a 0.89 cd m- 2 sec stimulus; statistical analysis was performed with a two-tailed paired Student's t-test (t); d.f. = degrees of freedom (N = 7) OP2 Amp 0.5Hz 20Hz t (dJ.)
PT
16.90 ± 3.70 19.30 ± 0.43 22.60 ± 6.98 21.15 ± 0.83 -3.11 -5.83 (6) P < 0.05
(6)
P 0.05
27.6 ± 0.9 26.95 ± J.I 2.748 (6) P 0.05) from the 19.22 ± 0.5 msec measured for an OP2 evoked to a stimulus of 0.89 cd m- 2 sec delivered at 0.5 Hz (Table 1). Secondly, while a reduction in the energy of the stimulus progressively abolishes OP4 and OP3 (Lachapelle, 1991) as shown in Fig. 1, OP4 is not significantly modified (amplitude and peak time) by the flicker stimulus. Finally, the fact that brighter and dimmer flickering stimuli differently affect the amplitude of OP2 rule out
the possibility that the reported findings are mostly reflecting an energy-response function. In summary, the results presented in this study further confirm that each photopic OP is electrophysiologically different from the other. The flicker data further accentuates the physiological difference between the short and intermediate latency OP2 and OP3 with the long latency OP4 , in support of previous observations obtained with various methodological approaches (Kojima & Zrenner, 1978; Lachapelle, 1987; Lachapelle et al., 1983; Wachtmeister, 1980, 1981a, b). Acknowledgements-Supported by a grant-in-aid from the McGill University-Montreal Children's Hospital Research Institute, and the Medical Research Council of Canada (MA-8649). This is publication number 91006 from the McGill University-Montreal Children's Hospital Research Institute.
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