T H E DIRECT CURRENT COMPONENT O F T H E ELECTRORETINOGRAM IN MAN

KAZUO KAWASAKI, M.D., AND JERRY H . ^

New York,

The direct current (d.c.) component of the electroretinogram (ERG) was first described by Brown and Wiesel1 from studies of the cat retina. It consisted of a positive on-response, a positive plateau maintained for the stimulus duration and a negative off-response. Han-itzsch and associates2 recorded a similar po­tential in three anesthetized human subjects.

A previous paper3 demonstrated close sim­ilarities between the threshold and spectral sensitivity of the human positive on- (b-wave), and negative off-responses. This may be construed to support the presence of a single steady potential as the basis of both the on- and off-responses.

This study confirms the presence of the d.c. potential in the human ERG and describes the effects of variation of stimulus intensity and adaptation level upon the potential. In­crement thresholds of the positive on- and negative off-responses were obtained and their similarity tends to confirm that both are due to the same mechanism.

METHOD

The tungsten sources for stimulus and adapting light, and the shutter to provide square wave stimulus were as previously described.8 Stimulus light entered one of the two input ends of a dichotomic (Y-shaped) glass fiber light guide. The adapting light was focused on the other input end. Heat fil­ters were placed in the path of stimulus and adapting light between the lamp and the glass fiber input end. The glass fibers carry-

From the Department of Ophthalmology, Cornell University Medical College, New York, New York. 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.

YUTAKA TSUCHIDA, M . D . , TACOBSON, M.D.

New York

ing the light from each source were mingled together at the output end. This was con­nected to the single input end of a second Y-shaped light guide. Half of the fibers of this light guide, carrying both stimulus and back­ground light, went to each of the two out­put ends. These output ends replaced the two incandescent lamps originally built in the upper portion of a Goldmann Weekers adaptometer sphere, and after being diffused by a sheet of white paper, they illuminated the white matte interior surface of the sphere. The stimulus and adapting light were essen­tially spread over the full field of vision. The distance between the center of the sphere and the cornea of the subject's eye was 27 cm. Stimulus duration was 0.74 second, ex­cept in one experiment (Fig. 2) , where it varied. Stimuli were repeated every two to 10 seconds, as specified.

Neutral density filters were used to con­trol the intensity of stimulus and adaptation. Intensity was represented in log10 units of filter density. Zero log unit corresponds to 5.4 X 10"3 lux at the surface of the subject eye.

The ERG was recorded with a low-vac­uum contact lens electrode (Medical Work­shop, Holland) which was referred to the combined earlobes, and amplified by a Grass 7P511 amplifier (time constant, 0.6 second). Eight to 20 responses were averaged by a Mnemotron CAT 400 computer, and dis­played on the computer oscilloscope. Re­sponses were measured from photographs of the oscilloscope tracings.

We (the authors) served as subjects, since our vision was normal except for mild my­opia. Tropicamide 1% (Mydriacyl) was used to induce mydriasis and cycloplegia. After the electrodes were attached, the subject was dark-adapted for 30 minutes, then placed his

244 AMERICAN JOURNAL OF OPHTHALMOLOGY FEBRUARY, 1972

0.7

S 1.0

l50yV

3 1.2

to

o

3.0

200pV 500 msec

Fig. 1 (Kawasaki, Tsuchida, and Jacobson). The ERG as a function of stimulus intensity. The bot­tom trace, which indicates stimulus "on" and "off," also shows the output waveform of square waves applied to amplifier input. This shows how a slow potential is deformed by the amplifier time constant. Judging from this frequency characteristic, the up­permost response (d.c. component) is almost con­stant in amplitude. The average was eight responses to stimuli delivered every two seconds with no adapting light. Upward deflection indicates positiv-ity of corneal electrode in this and all other figures.

head facing toward the adaptometer sphere, with the chin and forehead supported, and was light-adapted for five minutes to the level being studied.

Stimulus and adapting conditions for the measurement of subjective threshold were the same as those for ERG recording except that stimulus intensity was varied in 0.1 log steps, and no contact lens electrode was worn.

Separate studies indicated that the contact lens did not affect the subjective threshold more than 0.1 log unit. Subjective increment threshold (barely perceptible increase in

stimulus intensity at different levels of adaptation) were arithmetic means of several trials measured by increasing and decreasing stimulus intensity. All data are for white stimulus and white adapting light. The data illustrated are from a single subject (Y.T.). The results were verified with two addi­tional subjects.

RESULTS

The ERG response to our brightest full-field stimulus consisted of a large positive fa-wave, a plateau following the b-wave, and a small negative wave after the end of the stimulus (3.0, Fig. 1). With dimmer stimuli, the b-wave became smaller and broader, while the negative off-response was enlarged (1.5, 2.0, Fig. 1). With still dimmer stimuli, components of the response diminished at different rates. The b-wave was more greatly reduced, and its positive peak eliminated at a stimulus intensity of 0.7 log unit. Thus a positive plateau potential was disclosed (up­permost trace in Fig. 1).

This potential was observed in all nor­mal subjects tested who were sufficiently cooperative to provide a stable baseline. It was also confirmed in subjects under general anesthesia.

That the small negative wave after the end of the stimulus was indeed the off-response, is proven by the experiment illustrated in Figure 2. The small negative wave occurred. with constant latency after the end of the stimulus when stimulus duration was varied. The negative off-response, unlike the posi­tive off-response with high threshold,4 was not significantly diminished by decreasing the stimulus duration to 100 msec (Fig. 2) .

The responses to full-field stimulus of vary­ing intensity are shown at several levels of full field adaptation (Fig. 3). Our previous paper3 has shown that the threshold of the human negative off-response is as low as that of the initial positive on-response in the ab­sence of adapting light. It can be seen (Fig. 3) that this is also the case at varying levels of light adaptation. The amplitudes of the

VOL. 73, NO. 2 ELECTRORETINOGRAM COMPONENTS 245

Fig. 2 (Kawasaki, Tsuchida, and Jacobson). Changes in the ERG with changes in duration of stimulus. Duration of responses follows stimulus duration linearly, unless stimulus is very short. Stimulus mark below each trace shows output waveform of square wave passed through the CR-coupled amplifier. There was an average of eight responses to stimuli delivered every two seconds; stimulus intensity was 1.0 log units; there was no adapting light. Amplitudes differ among responses to stimuli of different duration. This is probably partly due to change in adaptation level induced by repetitive stimuli of different duration.

77771r

positive on- and negative off-responses in­creased approximately linearly to log stimulus intensity throughout the entire range of light adaptation tested (Figs. 4 and 5). A stimulus intensity was, however, usually reached beyond which the negative off-response was diminished at each adaptation level except the brightest one ( Fig. 5 ) . The diminution of the negative off-response at high stimulus intensity occurred also in other than full-field stimulation3 and in single flash (non-repetitive) stimulation.1·5

The minimum stimulus intensity required to evoke the positive on- and negative off-re­sponses of constant amplitude (10 μ ν ) at various levels of adaptation (increment threshold) is shown in Figures 4 and 5. The thresholds (10 μ ν ) of both positive on- and negative off-responses were unaffected by adapting light up to about 102'7 times the asbsolute subjective threshold (Fig. 6) . For adaptation levels above this plateau, the in­crement threshold of the positive on- and negative off-responses increased, obeying Weber's law—i.e., one log unit increase in adaptation level ( I ) increased the threshold (ΔΙ) about one log unit, with a slope of 1.0 on the same logarithmic scale of abscissa and Ordinate (Fig. 6) . The curves for the posi­tive on- and negative off-responses approxi­mated each other over the entire range of ad­aptation tested.

The curves for the ERG thresholds were

200 pV

5 0 0 msec

steeper than a slope of 1.0 at the adaptation levels between 2.3 and 2.8 log units (Fig. 6) . This might be partly clue to light-adapting effect of stimulation, since the stimulus was repetitive.

The subjective threshold was unaffected within one log unit from the absolute thresh­old, and then increased, following Weber's law (Fig. 6) .

The ERG threshold (10 μ ν ) was 2.4 log units higher than the subjective threshold in the dark or at low levels of light adaptation,

246 AMERICAN JOURNAL OF OPHTHALMOLOGY FEBRUARY, 1972

200 μν

1-3 1.8 22 Log. Adapting Light Intensity

2.8

300r

200-

L100-

Fig. 4 (Kawasaki, Tsuchida, and Jacobson). Amplitude of the positive on-response (onset of d.c. com­ponent and b-wave) plotted against log» stimulus intensity at six adaptation levels. Numbers attached to the curves indicate logm adapting light intensity. Data are the same as for Figure 3.

VOL. 73, NO. 2 ELECTRORETINOGRAM COMPONENTS 247

Fig. 3 (Kawasaki, Tsuchida, and Jacobson). Responses to full-field stimuli of varying intensity at six levels of full-field adaptation. The d.c. component is shown at low stimulus intensity with no, or dim, adapting light. Average of 10 responses to stimuli delivered every 10 seconds. Stimulus light was increased in 0.5 log step from sub-threshold level. Responses in the dark (left column) were first recorded after initial dark adaptation of 30 minutes. Then recordings in brighter adaptation were made. A five-minute interval in the dark was allowed between recordings at different adaptation levels. Then the eye was light-adapted for five-minutes to the level being studied before the beginning of recording.

and only 0.5 log unit higher in light adapta­tion above 0.8 log unit ( Fig. 6) .

DISCUSSION

The positive plateau potential described here in the human resembles the d.c. compo­nent of the cat in the following respects: Both are revealed by weak stimulus and have a positive waveform sustained during the stimulus (Figs. 1-3).1·2'6·7 The amplitudes of

both responses increase approximately lin­early to log stimulus intensity up to a limit at various levels of adaptation, when they are measured as the amplitude of the decay phase (negative off-response) (Fig. 5).8 The decay (negative off-response) of both re­sponses attained maximum amplitude at moderate stimulus intensity—a very dim or bright light evoked only a small deflection (Figs. 1 and 3).2·5'6 The latencies of the on-

1.0 2.0 Log 10 Stimulus Intensity

ao

Fig. 5 (Kawasaki, Tsuchida, and Jacobson). Amplitude of the negative off-response plotted against logio stimulus intensity at six adaptation levels. Numbers attached to the curves indicate logio adapting light in­tensity. Recording conditions were same as those described in Figure 3, except that this figure was plotted from records with higher amplification.

248 AMERICAN JOURNAL OF OPHTHALMOLOGY FEBRUARY, 1972

< 2

3 o

I. c « ε s υ c

σ> o

- * positive on-response ( b-wave)

-a negative off-response

ΙΟμΥ criterion

-1 -

- 2 -

dark x / -L2

Log Adapting Light Intensity ( | )

Fig. 6 (Kawasaki, Tsuchida, and Jacobson). Stimulus intensity (ordinate) required for ERG responses of 10 μ ν amplitude and for subjective light perception at different adaptation levels (abscissa). Note the almost exact fit of increment thresholds of the positive on- and negative off-response. Full-field presenta­tion of stimulus and adapting light was employed for electroretinographic and psychophysical measure­ments. Ordinate and abscissa are in the same units. Data was derived from that shown in Figures 4 and 5.

response (time from stimulus onset to the beginning of the on-response) and off-re­sponse (time from end of stimulus to the be­ginning of the off-response) of the human positive plateau potential are about 60 msec when isolated at low stimulus intensity (Fig. 1). This value is comparable to that of the cat d.c. component.6 For these reasons we feel justified in referring to it as the human d.c. potential.

We have no evidence that the dc compo­nent and the b-wave are separately generated in man, as is asserted to be the case in the cat.1-8

Studies under general anesthesia and cylcoplegia that were employed rule out the

possibility of this potential being a product of eyeball motion or ciliary activity.

The present study reveals that the incre­ment thresholds (10 μ ν criterion) of the positive on- and negative off-responses are almost exactly the same, and that they follow Weber's law in the same range of adapting intensity (Fig. 6). Our previous paper3 shows that the positive on- and nega­tive off-responses have the same spectral sensitivity which approximately fits the Com-mision Internationale d'Éclairage9 (CLE.) scotopic sensitivity in the absence of adapt­ing light. The close similarities between the positive on- and negative off-responses make it likely that these two responses are

VOL. 73, NO. 2 ELECTRORETINOGRAM COMPONENTS 249

due to a common ERG component, the onset and decay of which constitute the positive on- and negative off-responses, respectively. The most likely candidate for this compo­nent underlying the positive on- and negative off-responses is the d.c. component.

Full-field stimulation was employed in this study, in order to eliminate effects of stray light so that the ERG increment threshold could be determined. Full-field stimulation, however, was not essential to recording of the d.c. component. It was also revealed by decreasing the intensity of other than full-field stimuli subtending 20 degrees in visual angle.

The human d.c. component was obtained by decreasing stimulus intensity in the dark or low levels of light adaptation (left two col­umns in Fig. 3). It was not obtained in high levels of light adaptation in which a nega­tive-going wave immediately after the peak of positive on-response prevented the devel­opment of the positive plateau of the dc com­ponent (right column in Fig. 3) . This is due to a negative potential which is sustained during an intense stimulus and is more re­sistant to light adaptation than the d.c. com­ponent.

SUMMARY

In subjects responding to low-intensity stimuli in dark adaptation or low levels of light adaptation, the electroretinogram that

is obtained consists of a positive qn-response (b-wave), a negative off-response, and a pla­teau of positive potential between the two, lasting for the duration of the stimulus. The plateau was not observed with brighter stim­uli or at higher levels of light adaptation.

In the range of adaptation levels at which the plateau, or direct current component, was detected, increment thresholds of b-wave and negative off-responses were almost identical and followed Weber's law.

REFERENCES 1. Brown, K. T., and Wiesel, T. N. : Analysis of

the intraretinal electroretinogram in the intact cat eye. J. Physiol. 158:229, 1961.

2. Hanitzsch, R., Hommer, K., and Bornschein, H. : Der Nachweis langsamer Potentiale im men­schlichen ERG. Vision Res. 6:24S, 1966.

3. Kawasaki, K., Tsuchida, Y., and Jacobson, J. H. : Positive and negative deflections in the off re­sponse of the human electroretinogram. Am. J. Ophth. 72:367, 1971.

4. Nagata, M. : Studies on the photopic ERG of the human retina. Jap. J. Ophth. 7:96, 1963.

5. Schweitzer, N. M. J., and Troelstra, A. : An end effect in the human ERG. Ophthalmologica 145:119, 1963.

6. Brown, K. T. : The electroretinogram : Its components and their origins. Vision Res. 8:633, 1968.

7. Steinberg, R. H. : Comparison of the intrareti­nal b-wave and d. c. component in the area centralis of cat retina. Vision Res. 9:317, 1969.

8. Steinberg, R. H. : High-intensity effects on slow potentials and ganglion cell activity in the area centralis of cat retina. Vision Res. 9:333, 1969.

9. International Commission on Illumination : 1951 C.I.E. Scotopic luminosity function for young eyes. J. Opt. Soc. Am. 41:734, 1951.