In this study, we investigated the contrast response properties of the VEP in a group of patients with RP within the framework of the MC and PC pathways. The spatial characteristics of the VEP response to luminance modulation were similar in the patients with RP and the control subjects
(Fig. 1) . The mean spatial response functions of the two groups peaked at the same angular check size, but the response amplitude of the patients was reduced overall. A similar finding of a reduced amplitude but equivalent spatial scaling was reported for the pattern-reversal VEP in patients with RP.
31
There were no systematic differences between the VEP responses of the subjects to luminance increments and decrements
(Fig. 1) , although asymmetries for increments and decrements have been reported previously for the VEP of visually normal subjects.
30 However, the stimulus conditions used in the present study were probably not optimal for observing such asymmetries. Amplitude differences in the response to increments and decrements were reported to be most evident at intermediate temporal frequencies (∼3–10 Hz) and with large (>100 minutes) and small (<10 minutes) check sizes.
30 In comparison, the temporal frequency used for the spatial response functions in the present study was 11.2 Hz, and the check size used for the contrast response functions was 11.4 minutes.
The patients’ contrast response functions showed primarily a reduction in
R max for both chromatic and luminance modulation
(Figs. 2 3) . Further, the ratios of the
R max values of the patients versus controls were approximately equivalent for chromatic modulation and luminance modulation at a temporal frequency of 5.6 Hz
(Table 2) . This result is consistent with a previous psychophysical study of spatial contrast sensitivity in patients with RP, as measured with steady-pedestal and pulsed-pedestal paradigms that target the MC and PC pathways, respectively.
21 In that study, patients’ deficits in contrast sensitivity were equivalent for both paradigms. The VEP results indicate further that the decreased psychophysical contrast sensitivity of the patients with RP is probably the result of a change in response scaling rather than a change in contrast scaling. Still to be determined is why patients with RP showed equivalent losses of spatial contrast sensitivity under conditions that targeted the two pathways,
21 but showed a greater deficit under conditions that favored the MC pathway when contrast discrimination was evaluated,
22 using equivalent stimulus durations.
The fact that the patients with RP showed a decreased
R max for chromatic modulation, which emphasizes the PC pathway, is in agreement with a previous psychophysical study of contrast discrimination in patients with RP.
22 In that study, increment threshold functions for contrast discrimination within the pulsed-pedestal paradigm, which favors the PC pathway, were fit with a quantitative model (see equation 3 in Ref.
19 ) to derive the characteristics of the contrast response function. The discrimination thresholds of the patients with RP were better fit by a decreased
R max than by an increased σ. The decreased
R max for chromatic modulation is also in agreement with a previous psychophysical study that estimated the contrast response of the cone system in patients with RP using a probe-on-flash technique,
32 which favors the PC pathway. A psychophysical analysis of the contrast response function for the MC pathway has not been made in patients with RP, because a pedestal-Δ-pedestal paradigm is necessary,
19 and the task is difficult even for visually normal subjects to perform.
The patients with RP in the present study showed a greater VEP response deficit at the higher temporal frequency of luminance modulation
(Fig. 3) . This finding is consistent with the increased time constant of temporal integration that was observed psychophysically in patients with RP under conditions that emphasized the MC pathway.
23 That is, an increased time constant of temporal integration corresponds to a lower corner frequency of the temporal response function (i.e., frequency at which the sensitivity has decreased by 3 dB).
33
It seems unlikely that this VEP deficit at such a relatively low temporal frequency is due to a response abnormality at the level of the cone photoreceptors, given that cone photoreceptors normally can respond at temporal frequencies up to 100 Hz.
34 It is also unlikely that the substantially greater amplitude reduction in the VEP at 11.2 Hz represents disease occurring within the early retina, because the focal ERGs of patients with RP show only a small amplitude loss compared to normal at this temporal frequency.
35 36 Instead, it is more likely that the temporal frequency deficits observed psychophysically and in the VEP response represent the impact of cone photoreceptor degeneration on contrast processing within the MC pathway. For example, there is evidence that the spatiotemporal integration properties of cortical cells are related to the level of synaptic background activity.
37 A reduced synaptic input, owing to a loss of cone photoreceptor signals, would decrease input conductance, which in turn would increase the effective time constant of the cells and act as a low-pass temporal filter.
37
The control subjects showed a relative phase advance with increasing contrast at both temporal frequencies of luminance modulation
(Fig. 4) , as reported previously.
25 This was also the case for the patients with RP. This phase advance is consistent with a nonlinear gain control mechanism, as has been described for neurons within the MC pathway.
38 Further, there was a phase advance between the VEP responses to temporal frequencies of 5.6 and 11.2 Hz in both groups. A similar phase advance between these two temporal frequencies is observed in the full-field flicker ERG,
39 which suggests that it originates at an early retinal level. It is unlikely, however, that the phase lag observed at 11.2 Hz in the VEP of the patients with RP compared with normal is due to an abnormality at the same retinal level, because the phase of the focal ERG is normal in patients with RP whose visual acuities are within the range of those included in the present study.
35 36 The relative phase lag of the patients’ luminance-modulation VEP at 11.2 Hz more likely represents a difference in VEP response latency, which would produce the type of frequency-dependent phase shift observed in
Figure 4 .
Given the overlap of response properties that may exist between the MC and PC processing streams,
40 the VEP procedures used in this study may not generate responses that are entirely selective for the MC and PC pathways. However, the contrast response functions of the control subjects for chromatic and luminance modulation had the characteristics expected from electrophysiological studies of the MC and PC pathways,
17 and the functions corresponded to VEP responses reported previously under equivalent testing conditions.
25 In addition, there was consistency between the results obtained for the VEP and those obtained psychophysically in patients with RP, as discussed earlier.
In summary, the patients with RP in this study showed VEP contrast response functions for chromatic and luminance modulation that were characterized predominantly by a decrease in
R max, which corresponds to an overall reduction in response amplitude. The decrease in
R max was essentially equivalent for chromatic and luminance modulation at a temporal frequency of 5.6 Hz, indicating equivalent response deficits for the PC and MC pathways. However, there was a substantial reduction in VEP amplitude at a temporal frequency of 11.2 Hz under the same adapting conditions, indicating a marked impairment of function within the MC pathway. The results are in agreement with a previous conclusion that the relative functional impairment within MC and PC processing streams in patients with RP depends on the nature of the stimuli and testing protocols that are used to evaluate these functional deficits.
21