ISOLATION O F FASTER COMPONENTS IN T H E ELECTRORETINOGRAM AND VISUALLY EVOKED RESPONSE IN MAN

YUTAKA TSUCHIDA, M.D., KAZUO KAWASAKI, M.D., KAZUMASA FUJIMURA, M.D., AND JERRY H. JACOBSON, M.D.

New York, New York

The electroretinogram (ERG) response evoked in man by intense illumination pre­sents a series of oscillatory potentials super­imposed on the b-wave.1"2 These oscillatory potentials are of clinical importance,3 since in the presence of certain diseases they are reduced or disappear prior to some changes of the a- and b-waves.

Measurement of the amplitude of the os­cillatory potential is difficult, since the con­figuration of the oscillatory potential is af­fected by the inclination of the b-wave. To delineate the oscillatory potential clearly, short amplifier time constant recording (for example, 0.01 second) has been recom­mended.4 In this range of amplifier time con­stant, the a- and b-waves are still too large to isolate the ocillatory potentials.

It was demonstrated that rhythmic wave­lets are superimposed on the human visually evoked response (VER) produced by in­tense illumination.6'6 These VER wavelets are small and much distorted by slow compo­nents, making clear identification difficult.

The purpose of the investigation reported here was to isolate the oscillatory potentials and VER wavelets by eliminating the slow components of the ERG and VER with band pass filters.

METHOD

The stimulus light was obtained from a tungsten lamp, passed through a series of heat and neutral density filters, and brought to a focus at a magnetic shutter. Square-wave flashes were delivered from the shut­ter, driven by an electronic pulse generator.

This study was supported by Public Health Service Grant EY 00264 from the National Eye Institute, and by a grant from the Samuel Bronfman Foun­dation.

Reprint requests to Jerry H. Jacobson, M.D., 215 Rensselaer Avenue, Ogdensburg, New York 13669.

The adapting light was provided by another tungsten lamp, also controlled by a series of heat and neutral density filters.

Stimulus and adapting lights were focused on each of the two input ends of a dichotomic (Y-shaped) glass fiber light guide. The glass fibers carrying the light from each source were mingled together at the output end (7 mm in diameter), which was held 2 cm from the cornea of the subject's eye. The maximum stimulus light intensity was 3.1 X 10s mL (7.1 X 105 scotopic trolands, pupil diameter 7.5 mm) and that of the adapting light in­tensity 1.9 X 103 mL (4.4 X 105 scotopic tro­lands). Neutral density filters were inter­posed in the light path to decrease the lum­inance. The maximum stimulus intensity (3.1 X 103 mL) is designated as 0.0 log™ unit, and the maximum adapting intensity (1.9 X 103

mL) , therefore, corresponds to —0.2 log units.

The ERG was detected with a low-vacuum contact lens electrode being referred to the combined earlobes. The VER was detected bipolarly from disk electrodes (Grass, 8 mm in diameter) placed on the inion and 5 cm anterior to the inion in the midline. Upward deflection indicates positivity of the corneal electrode for ERG and negativity of the electrode placed on the inion for VER.

The ERG and VER were led to a Grass EEG amplifier (7P511). After amplification (amplifer time constant, 0.25 second; high-frequency response, 1 kc), the signals were filtered by Krohn-Hite 330 MR band pass filter to exclude high and low frequency components. Attenuation slopes of this filter were 24 db per octave on either side of the pass band. When rectangular potential changes are fed into the band pass filter, they exhibit "ringing." The absence of stimu­lus artifacts and of early receptor potentials

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in this experiment exclude distortion due to the ringing. The amplitude of the filtered wave was linear to that of the input wave when its frequency was within the range of the pass band. Decrease of the peak latency of the oscillatory potential was not more than 3.0 msec, when the lower limit of the pass band was set at 80 Hz. Responses were averaged by a Mnemotron CAT 400 com­puter.

The pupil was dilated with 1% tropicam-ide and accommodation was paralyzed. The authors, whose eyes were normal except for mild myopia, served as normal subjects.

RESULTS

Figure 1 shows the effect of the band pass filter on the ERG. Stimulus intensity was 0.0 log unit, and 100 responses were averaged. The lower limit of the pass band was in­creased up to 200 Hz, while the upper limit was kept constant at 1000 Hz. We labeled the individual oscillatory potentials Oi, 0 2 , 0 3 , 0 4 , and 0 5 in the conventional way. Figure 2 is the graphic representation of Figure 1.

Fig. 1 (Tsuchida, Kawasaki, Fujimura, and Ja­cobson). Effects of band pass filter on the ERG. The lower limit of the pass band increased, while the upper limit kept constant at 1000 Hz. Stimulus intensity 0.0 log unit. Stimulus duration, 100 msec. Stimulus frequency 0.5 Hz. Average of 100 re­sponses. Positivity of corneal electrode, upward.

200pVr

150pV-

ΙΟΌμν-

50μν

ΟμΥ1-'

200-

Fig. 2 (Tsuchida, Kawasaki, Fujimura, and Jacobson). Effects of the pass band on the amplitude of a-wave and oscillatory potentials.

848 AMERICAN JOURNAL OF OPHTHALMOLOGY MAY, 1973

The amplitude of Oi was measured from the bottom of the a-wave, and those of 0 2 , 0 3 , 0 4 , and 0 5 from the preceding negative trough as illustrated.

As the lower limit of the pass band in­creased, the amplitude of the a-wave decreased sharply and disappeared at 70 Hz. The ampli­tude of Oi increased up to 20 Hz, and then decreased and disappeared at 100 Hz. The amplitudes of 0 2 , 0 3 , O4, and 0 5 were not as sharply decreased as Oi and were present at 100 Hz. The oscillatory potentials were easily seen on a flat baseline. When the low pass band was set higher than 100 Hz, the first de­

flection of the ERG was corneal negative and its peak corresponded to the trough between Oi and 0 2 . Greater increase of the low pass band caused gradual diminution of the re­sponse, but oscillations were still discernible at 180 Hz.

Figure 3 shows the effect of stimulus in­tensity on the ERG. Column A was obtained with band pass of 100-200 Hz. Columns B and C were obtained without a band pass filter; amplifier time constants were 0.003 and 0.25 seconds, respectively. The threshold of the oscillatory potentials was —4.5 to —4.0 log units in Column A, and —2.5 or —2.0 log

Fig. 3 (Tsuchida, Kawasaki, Fujimura, and Jacobson). Effects of stimulus intensity on the ERG. Column A was obtained with band pass filter of 100-200 Hz. Columns B and C were obtained without band pass filter; their amplifier time constants were 0.003 and 0.25 sec, respectively. Stimulus duration, 125 msec. Stimulus frequency, 0.5 Hz. Average of 200 responses. Positivity of corneal electrode, upward.

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units in Column B or C, respectively. Ampli­tudes of oscillatory potentials gradually in­creased as stimulus intensity increased.

Figure 4 shows the effect of band pass fil­tering on the VER in three normal subjects. Stimulus intensity was 0.0 log unit, and 500 responses were averaged. The lower limit of the pass band was increased to 160 Hz, while the upper limit was kept constant at 200 Hz. As the lower limit of the pass band in­creased, slow components were gradually eliminated and fast components were dis­closed on the flat baseline. These rhythmic wavelets were prominent when the lower limit of the pass band was 60-100 Hz. The latency of the rhythmic wavelets of the VER was about 36 msec. Further increase of the low pass band level diminished the rhythmic wavelet amplitudes.

Figure 5 shows the effect of stimulus in­tensity on the VER, obtained with a band pass filter of 80-140 Hz. The threshold of the rhythmic wavelets of the VER was about - 5 . 0 to - 4 . 0 units.

Figure 6 shows the effect of light adapta­tion on the ERG and VER. ERG and VER were recorded simultaneously. With no back­ground light, four oscillatory potentials and six VER wavelets were observed. As the level of light adaptation increased, the os­cillatory potentials and VER wavelets grad­ually disappeared, those with longer latency being first to be lost. With light adaptation of —0.7 log units, only one oscillatory po­tential and two VER wavelets were record­able. At our maximum light adaptation (—0.2 log units), both oscillatory potentials and VER wavelets vanished.

DISCUSSION

Intense illumination has, heretofore, been required to produce the oscillatory potential. The use of band pass filtering permits re­cording of the oscillatory potential with lower levels of stimuli (Fig. 3) .

Several workers7"9 have used band pass filtering to record the rhythmic wavelets of the human and animal ERG. Dawson and

Stewart7 called these wavelets fast retinal potential (FRP) and distinguished them from the oscillatory potential. The difference between these potentials seems to be only in threshold. However, the higher threshold of the oscillatory potential noted in the conven­tional ERG might be attributable to conceal­ment by the b-wave. From our data (Figs. 1-3), we conclude the F R P and the oscillatory potential are identical under our recording conditions.

The corneal positive peaks of the oscilla­tory potentials have been labeled Oi-05. Simonsen,10 Usami,11 and Algvere12 mea­sured the amplitude of the oscillatory po­tential perpendicularly from corneal positive peak to the line which combined two neigh­boring negative troughs. Recently, Brunette and Desrochers13 considered the oscillatory potentials negative potentials, although they did not discuss the reason.

In this experiment, as the lower limit of the pass band increased, Oi disappeared at 100 Hz, while 0 2 - 0 5 were definitely record­able up to 180 Hz. The different frequency characteristic of Oi leads us to propose the following explanation. Oscillatory potentials are approximately sinusoidal waves. Their first phase starts with a corneal negative-going deflection. Therefore, Oi is not an ac­tive component, but is a passive deflection which is composed of the interaction between the b-wave and the corneal negative first de­flection of the oscillatory potential. If this is the case, the corneal negative trough be­tween Oi and 0 2 should be considered the first peak of the oscillatory potential.

Cobb and Dawson5 found a series of rhythmic wavelets superimposed on the slow waves of the human VER. They stated that their numbers were from 4 to 7 and their pe­riod was between 8 and 11 msec, corre­sponding closely with the period of the oscil­latory potential in the ERG. Yokoyama, Taniguchi, and Yonekura6 confirmed the same wavelets in the human VER and dis­cussed the relationship to the oscillatory po­tential.

850 AMERICAN JOURNAL OF OPHTHALMOLOGY MAY, 1973

Fig. 4 (Tsuchida, Kawasaki, Fujimura, and Jacobson). Effects of band pass filter on the VER in three normal subjects. The lower limit of the pass band increased, while the upper limit remained constant at 200 Hz. Stimulus intensity, 0.0 log unit. Stimulus duration, 150 msec. Stimulus frequency, 3.0 Hz. Average of 500 responses. Negativity of the electrode placed on the inion, upward.

VOL. 75, NO. 5 ISOLATION OF ERG AND VER RESPONSES

Using the band filter in this study, it seems that there is a similar period for the oscillatory potential of the ERG and VER wavelets (Figs. 1 and 4) . The threshold of the VER wavelets (Fig. 5) was close to that of the oscillatory potential (Fig. 3) . In the light adaptation study on simultaneously re­corded ERG and VER (Fig. 6) , the oscilla­tory potential and VER wavelets showed similar changes. These findings seem to fa­vor the assumption that the oscillatory poten­tials in the ERG are conveyed to the brain.

SUMMARY

Eliminating slow components by the use of band pass filtering, the oscillatory poten­tial of the electroretinograms and the rhyth­mic wavelets of the visually evoked response

Fig. 6 (Tsuchida, Kawasaki, Fujimura, and Ja-cobson). ERG and VER as a function of adapting light intensity. ERG and VER were recorded simul­taneously. Amplifier time constant, 0.25 sec. Stimu­lus intensity, —1.0 log units. Stimulus duration, 150 msec. Stimulus frequency, 2.0 Hz. Average of 500 responses. Upward deflection indicates positivity of the corneal electrode for ERG and negativity of the electrode placed on the inion for VER.

were recorded selectively. Close similarity exists in the frequency, threshold, and light adaptation effect between the oscillatory po­tential and the wavelets of the visually evoked response. These results suggest the hypothesis that the oscillatory potential of the electroretinogram in man begins with a corneal negative-going deflection.

Fig. 5 (Tsuchida, Kawasaki, Fujimura, and Ja-cobson). Effects of stimulus intensity on the VER in a normal subject with band pass filter of 80-140 Hz. Stimulus duration, 150 msec. Stimulus fre­quency, 3.0 Hz. Average of 500 responses. Negativ­ity of the electrode placed on the inion, upward.

REFERENCES

1. Cobb, W. A., and Morton, H. B. : A new com­ponent of the human electroretinogram. J. Physiol. 123:36, 1954.

2. Bornschein, H., and Goodman, G. : Studies of the a-wave in the human electroretinogram. Arch. Ophth. 58:431,1957.

3. Yonemura, D., Tsuzuki, K., and Aoki, T.:

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Clinical importance of the oscillatory potential in the human ERG. Acta Ophth. 70(Suppl.) : 115, 1962.

4. Yonemura, D. : The oscillatory potential of the electroretinogram. Acta Soc. Ophth. Jap. 66:1566, 1962.

5. Cobb, W. A., and Dawson, G. D. : The latency and form in man of the occipital potentials evoked by bright flashes. J. Physiol. 152:108, 1960.

6. Yokoyama, M., Taniguchi, M., and Yonekura, Y. : The "on" rhythm in the visual evoked response (VER). Jap. J. Clin. Ophth. 20:563, 1966.

7. Dawson, W. W., and Stewart, H. L. : Signals within the electroretinogram. Vis. Res. 8:1265, 1968.

8. Adams, C. K., and Dawson, W. W. : Fast reti­

nal potential luminosity functions. Vis. Res. 11 : 1135, 1971.

9. Kozak, W. M. : Electroretinogram and spike activity in mammalian retina. Vis. Res. 11 (Suppl.) :1, 1971.

10. Simonsen, S. E. : Electroretinographic study of diabetics. Preliminary report. Acta Ophth. 43 : 841, 1965.

11. Usami, E. : Studies on the method of mea­surement of oscillatory potential on ERG. Acta Soc. Ophth. Jap. 70:84, 1966.

12. Algvere, P. : Electroretinographic studies on posterior uveitis. Acta Ophth. 45 :299, 1967.

13. Brunette, J. R., and Desrochers, R. : Oscilla­tory potentials : A clinical study in diabetics. Canad. J. Ophth. 5:373, 1970.

OPHTHALMIC MINIATURE

The elimination of the N I H training programs will save the govern­ment about $160 million per year. Yet the proposed budget for fiscal 1974 allots some $80 billion for defense, and of this, $7.4 billion is earmarked for research and development. (Incidentally, eight new F-14 fighter air­craft will cost $160 million.) . . . Elimination of the NIH training pro­grams will remove an incentive that directs young physicians into over-populated scientific careers and away from the requirements of medical practice—and medical educators cannot deny this disadvantageous effect of the training programs. Yet, in the pursuit of national security, exces­sive production of military equipment, much of which becomes obsolete before it is ever used, is tolerated as insurance against the unforeseen. Question: Should the number of medical scientists be determined by minimum peacetime needs, or should an allowance be made for the multi­ple possible emergencies the country may face ?

F. J. Ingelfinger New Eng. J. Med.

288:580, 1973