There is also a tendency for a gender difference in the mfOP response amplitude [20]. Using a cone-isolating technique based on the silent substitution method [21], stimuli were set up that modulated activity of either the long-wavelength sensitive cone (L cone) alone or the middle-wavelength sensitive cone (M cone) alone. The summed amplitudes from the two cone types (L + M) tend to be higher, and the ratio of the amplitudes of L:M, corresponding to the cone ratio, is slightly lower for female than for male observers. One reason for this difference may lie in a direct effect of sex hormones on Na+-K+ adenosine triphosphatase (ATPase) activity and K+ and Ca+ channel function [22]. A gender difference has also been reported in mfOP recordings from monkeys. Cynomolgus females have higher amplitudes (extracted from mfERG recordings) than males in both firstand second-order kernel analysis [23], as in humans. However, these authors additionally showed that the gender difference is species dependent: Rhesus females give significantly lower mfOPs than males in both kernels.

DISEASE-RELATED CHANGES

The evidence outlined indicates that mfOPs arise in the inner retina, and that both rods and cones are active in their generation. Further information about the origins of the mfOPs can be sought in recordings from patients suffering from diseases with a known pathogenesis. Conversely, mfOPs can be a useful tool in the clinic to detect a dysfunction of the inner retinal layer.

Origins of Single Potentials

Although in some cases all mfOPs are altered to a greater or lesser degree in response to disease or other processes, there are instances when pronounced differences occur in the behavior of the individual potentials.

Dichromats

About 8% of the male population suffers from a color vision deficit arising from alterations in the genes on the X chromosome, which encode the opsins, the cone photopigments responsible for the absorption of photons. A small group of them are the single-gene dichromats, found in about 2–3% of the male population; the single-gene protanopes have lost the function of the long-wavelength sensitive (L) cone and the single-gene deuteranopes that of the middle-wavelength sensitive (M) cone. As mentioned, we set up stimuli, which modulated activity in only one class of photoreceptor (either the L or M cone), and tested them in ten normal control subjects, two protanopes, and two deuteranopes [24]. In Fig. 3 we show the average response waveform of the traces of all 61 hexagons for one control subject aged 20 years (dashed lines), for a single-gene protanope aged 29 years (thick continuous lines), and for a single-gene deuteranope aged 25 years (thin continuous line). The first-order traces are shown in the upper panel, the second-order kernel in the lower panel. The upper traces in each panel show the results from all three subjects to the black-and-white stimulus. Here, there is little difference between the control traces and those of the dichromats. The lower traces in each panel show a comparison of the results of the control subject to L-cone stimulation with those of the deuteranope (left) and of M-cone stimulation in the control with those of the protanope (right). In the first-order

Protanopes and Deuteranopes

First order kernel

control

protanope Black-white stimulus deuteranope

Second order kernel

Black-white stimulus

1 nV/deg2

10 msec

Fig. 3. Black-white and L- and M-cone-driven multifocal oscillatory potential (mfOP) traces, from one control subject aged 20 years (dashed lines), one protanope aged 29 years (thick continuous line), and one deuteranope aged 25 years (thin continuous line) summed over all 61 hexagons. The first-order kernel is shown in the upper panel, the second-order (first-slice) kernel in the lower panel. The traces obtained from black-white stimulation (upper traces of each panel) are similar for all three subjects and show two major peaks in the first-order and three major peaks in the second-order kernel response. In contrast, stimulating a single cone class (either L or M cones) produces only the first potential in the first-order kernel and the second potential in the second order.

kernel, all subjects show only one potential around 22–23ms. The second-order kernel traces are again similar, showing evidence of only a much-reduced second potential and the hint of a first potential for the L-cone stimulation. The dichromats showed no response to modulation of the missing receptor type. The control results to stimulation of only