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Biomedical subjects

Donald C Hood

Publications and source records attributed to Donald C Hood.

At least 19 recordsLinked to original sources
PubMed2003

Multifocal visual evoked potential responses in glaucoma patients with unilateral hemifield defects.

PURPOSE: To determine whether the multifocal visual evoked potential (mfVEP) technique can detect damage to the visual system in the unaffected hemifields of patients with glaucoma and unilateral hemifield defects. DESIGN: Experimental study. METHODS: Monocular mfVEPs and achromatic automated perimetry (AAP) were obtained in both eyes of 16 patients with open-angle glaucoma and unilateral hemifield defects. The mfVEPs were obtained using a pattern-reversal dartboard array with 60 sectors; the entire display was 44.5 degrees in diameter. For each pair of mfVEP responses an interocular ratio of root-mean-square amplitude was calculated. These values were compared with the mean values obtained from 30 control subjects. Probability plots for MfVEP were derived. A cluster analysis was used to determine whether an mfVEP hemifield was normal or abnormal. RESULTS: Three of 60 (5.0%) mfVEP hemifields from control subjects had significant mfVEP deficits based upon a cluster of abnormal points. Significant mfVEP deficits were detected in the affected AAP hemifield in 15 of 16 (93.8%) glaucoma patients and in 6 of 16 patients in hemifields with apparently normal AAP. The percentage of hemifields with abnormal mfVEPs, but normal AAP, was significantly higher for the glaucoma patients than for the controls (37.5% vs 5.0%, P <.001, chi square).In glaucomatous eyes with achromatic visual fields defects limited to one hemifield, the mfVEP technique can detect evidence of glaucomatous damage in the unaffected hemifield.

Adult↗
PubMed2003

Electrophysiology.

Numerous electrophysiologic tests are available for use in the clinic. When properly recorded and analyzed, these tests provide important diagnostic and prognostic information about the site and nature of the disease process. If the results from these tests are combined with psychophysical findings (color vision, acuity, visual fields), their usefulness in defining disease can be further extended.

Electrophysiology↗
PubMed2003

Multifocal VEP and ganglion cell damage: applications and limitations for the study of glaucoma.

With the multifocal technique, visual evoked potentials (VEPs) can be recorded simultaneously from many regions of the visual field in a matter of minutes. Recently, the multifocal visual evoked potential technique (mfVEP) has generated considerable interest, especially among those seeking objective measures of glaucomatous damage. It is well accepted that significant ganglion cell damage can occur before functional deficits are detected with static automated achromatic perimetry, the "gold standard" for detecting and monitoring glaucomatous damage. In this article, we ask the following questions: What are the potential applications of the mfVEP technique? What are its limitations? To what extent will it replace or augment static automated achromatic perimetry? To answer these questions requires an understanding of the mfVEP technique, as well as techniques needed to relate its results to those of automated perimetry. describes how the mfVEP is elicited, recorded, derived and displayed. If both eyes of an individual are normal, then mfVEPs recorded for monocular stimulation of each eye are essentially identical. However, the amplitude and waveform of the mfVEP responses vary across individuals, as well as across the visual field within an individual. These variations in the normal mfVEPs are described in Section 3. In, these variations are related to cortical anatomy, and to the cortical sources contributing to the mfVEP. The mfVEP is predominantly generated in V1. Although there are undoubtedly extrastriate contributions, these contributions are probably smaller for the mfVEP than for the conventional VEP. The mfVEP is not a small version of the conventional VEP. To detect ganglion cell damage with the mfVEP requires methods for analyzing the responses and for displaying the results. In, a method for detecting ganglion cell damage is described. This method compares the monocular responses from the two eyes of an individual and produces a map of the defects. This map is in the form of a probability plot similar to the one used to display visual field defects measured with automated perimetry. Procedures are described for directly comparing these mfVEP probability plots to the probability plots for Humphrey visual fields (HVFs). The interocular mfVEP test described in will not be sensitive to bilateral damage. describes a test based upon monocular mfVEPs. The statistical basis of the monocular mfVEP test is relatively complex (see ). In any case, under many conditions the interocular test will be more sensitive and this is discussed in. summarizes a number of clinical applications of the mfVEP and concludes that the mfVEP has a place in the clinical management of glaucoma. To understand the limitations of the mfVEP, a signal-to-noise ratio (SNR) approach is described in. Using the techniques described in, the relationship between the amplitude of the mfVEP and the sensitivity loss of the HVF is discussed in. The evidence supports a simple model in which the amplitude of the signal portion, but not the noise portion, of the mfVEP response is proportional to HVF loss where HVF loss is expressed in linear, not dB, units. It is hypothesized that both the signal in the mfVEP, and the sensitivity of the HVF, are linearly related to ganglion cell loss. A theoretical approach, developed in, allows a direct comparison of the efficacy of the mfVEP and HVF in detecting glaucomatous damage. In short, when the mfVEP has a large SNR it will often be superior to the HVF in detecting damage. On the other hand, when the mfVEP has a small SNR, the HVF will probably be superior. summarizes the relative advantages of the HVF and the mfVEP. In summary, the mfVEP does have a place in the clinical management of glaucoma, although it is not likely to replace static automated achromatic perimetry in the near future. However, this is an evolving technology and the future will undoubtedly see major improvements in the mfVEP technique.

Diagnostic Techniques, Ophthalmological↗
PubMed2003

Objective measurement of visual function in glaucoma.

Of the objective (electrophysiological), functional tests of glaucomatous damage, three hold the most promise. Some evidence suggests that the pattern electroretinogram, the photopic negative response of the electroretinogram, and the multifocal visual-evoked potential can detect early glaucomatous damage, damage that may be missed on static automated achromatic perimetry. However, in their current forms, these tests can supplement, but cannot replace, static automated achromatic perimetry. Further, the multifocal visual-evoked potential is the only one of these tests that supplies topographic information about local damage. In addition, we still lack a complete understanding of the relation between these tests and the underlying damage to ganglion cells. In this context, it has recently been suggested that the signal in the multifocal visual-evoked potential response may be linearly related to the loss of ganglion cells. Finally, more information is needed about these tests from longitudinal or prospective studies.

Electroretinography↗
PubMed2003

Detecting glaucomatous damage with multifocal visual evoked potentials: how can a monocular test work?

PURPOSE: To understand and improve the detection of glaucomatous damage with multifocal visual evoked potentials (mfVEP) obtained from single eyes. PATIENTS AND METHODS: Monocular mfVEP recordings were obtained from both eyes of 30 individuals with no known visual abnormalities. The 44.5 degrees -diameter display contained 60 sectors. Probability plots, analogous to the total deviation probability plot of the Humphrey Visual Field Analyzer, were created based on tests that compared each eye (monocular test), or the ratio of the responses from the 2 eyes (interocular test), to group norms. RESULTS: For the monocular test, the number of points exceeding the 5% confidence level was not distributed randomly among individuals or among field locations within an individual. Individuals with small signals (i.e., low signal-to-noise ratios [SNR]) showed too many "abnormal" points, while those with relatively large SNR values showed too few. Reasonably good specificity was obtained by defining an abnormality in terms of a cluster of significant points in the mfVEP probability plot. For the interocular test, the results were close to those expected by chance. CONCLUSIONS: Both monocular and interocular tests will be of value when testing glaucoma patients with the mfVEP technique. The interocular test is a more sensitive indicator of glaucomatous damage when a region when healthy has a large signal (SNR) and damage is largely unilateral, whereas the monocular test will be a more sensitive test when a region when healthy has a small signal (SNR). However, the statistics underlying monocular comparisons of mfVEPs are not simple. To obtain high specificity, criteria based on clusters of points need to be used and norms obtained for every laboratory.

Adult↗
PubMed2003

Conventional pattern-reversal VEPs are not equivalent to summed multifocal VEPs.

PURPOSE: To compare conventional pattern-reversal visual evoked potentials (cVEPs) with multifocal VEPs (mfVEPs). METHODS: mfVEPs and cVEPs were recorded during the same session in 12 normal subjects with an active electrode at Oz referenced to the inion (Oz-In) or to a midfrontal position, Fz (Oz-Fz). The mfVEP stimulus, a 60-sector dartboard, had a mean luminance of 100 cd/m(2) and a diameter of 42.2 degrees. The cVEP checkerboard stimulus subtended 21 degrees, had a mean luminance of 75 cd/m(2) and a contrast of 90%. Transient responses (2.5 Hz) were recorded for check sizes ranging from 12 to 50 minutes of arc (minarc). White cardboard masks were used to isolate upper and lower hemifields, within various field windows, for comparison with corresponding parts of the mfVEP. In a second experiment, VEPs were obtained using slowed m-sequences (8 and 16 video frames per m-step), as well as square-wave periodic reversals (2.4 Hz), for both the scaled dartboard display and an unscaled checkerboard display (check size of 50 minarc). RESULTS: The mfVEPs to fast m-sequence stimulation showed a strong polarity reversal between waveforms from the upper versus the lower hemifield. The cVEPs had larger amplitudes (approximately 3x) and longer implicit times (approximately 15-20 ms) and did not show the polarity reversal. Amplitude asymmetry between upper and lower hemifields was larger for cVEPs than for mfVEPs. As the stimulation rate was slowed, response amplitudes and implicit times of the major features increased, the upper versus lower polarity reversal was generally lost, and asymmetry of hemifield amplitudes grew. The same pattern of results was observed for scaled and unscaled spatial displays and for Oz-Fz and Oz-In signal derivations. CONCLUSIONS: Full-field cVEPs cannot be simply related to the sum of mfVEPs when each are recorded under their typical conditions. The stimulation rate has the largest influence on the differences between the two response types. The findings suggest that contributions from extrastriate sources are greater with the cVEP paradigm or the slowed mfVEP sequence than with the standard mfVEP paradigm.

Adult↗
PubMed2003

Cone and rod ERG phototransduction parameters in retinitis pigmentosa.

PURPOSE: To analyze cone and rod phototransduction parameters from ERG a-waves in patients with RP and to determine the relationships among these parameters, age, and mode of inheritance. METHODS: Sets of four white flashes (3.2-4.4 log scotopic troland [scot td-s]) were presented in the dark. The same stimuli were later presented against a rod-saturating background and the generated cone a-waves were subtracted from the dark-adapted responses to produce rod-only a-waves. The rod-only and cone a-waves were fit with computational models. RESULTS: Of 418 consecutive patients with retinitis pigmentosa (RP), cone a-waves were quantifiable in 136 (33%), whereas rod a-waves were quantifiable in 125 (30%). Cone R(max) (maximum response) and cone S (sensitivity) parameters were significantly below normal in all RP subgroups. Cone R(max) was lower in XlRP than in other forms of inheritance (P < 0.05). Cone S was abnormal in 77.9% of all patients with RP and in 96.8% of those with XlRP. More than 95% of the rod R(max) values were abnormal, whereas rod S was abnormal in 61.6% of these patients. CONCLUSIONS: The efficiency of cone phototransduction appears to be affected in all forms of RP, even in some patients in whom the sensitivity of rod phototransduction is normal. In this cross-sectional sample, there was no evidence that transduction efficiency decreased with increasing age of the patient. The X-linked mode of inheritance is associated with greater abnormalities in cone and rod photoreceptor function at a younger age compared with the other modes of inheritance.

Adolescent↗
PubMed2003

Regional variations in local contributions to the primate photopic flash ERG: revealed using the slow-sequence mfERG.

PURPOSE: To determine the variations with eccentricity of the primate photopic ERG and to separate contributions by different retinal cells by using intravitreal pharmacologic agents. METHODS: Slow-sequence multifocal (mf)ERGs were obtained from 19 anesthetized adult rhesus monkeys and 5 normal human subjects. Recordings in monkeys were obtained before and after injections of tetrodotoxin citrate (TTX) to block sodium-dependent spiking; TTX+N-methyl-D-aspartic acid (NMDA)+picrotoxin (PTX) or gamma-aminobutyric acid (GABA) to block all inner retinal activity; L-2 amino-4-phosphonobutyric acid (APB) to block the On-pathway; and cis-2, 3 piperidine dicarboxylic acid (PDA) to block the Off-pathway and the otherwise unblocked inner retinal activity. The stimulus consisted of 103 equal-sized hexagons within 17 degrees of the fovea; every 200 ms (15 frames), each hexagon had a 50% chance of remaining at 20 cd/m(2) or increasing briefly to 4.7 cd-s/m(2). Oscillatory potentials (OPs; 90-300 Hz) were extracted. RESULTS: The slow-sequence mfERG summed over the stimulated area looked similar to a standard photopic, full-field ERG, with a- and b-waves and OPs. OPs in the foveal and temporal retina were larger than in the nasal retina. This nasotemporal asymmetry was removed by TTX, and the OPs were eliminated, either by blocking inner retina activity or by blocking the On-pathway. The summed mfERG waveform, including OPs, was shaped mainly by the more peripheral retinal regions. The foveal b-wave peak occurred about 5 to 6 ms later than in the periphery, with the depolarizing peak of the On-pathway/bipolar contribution occurring earlier than the depolarizing peak of the Off contribution at all eccentricities. The a-wave was composed of a small photoreceptor contribution and postreceptoral portion originating from hyperpolarizing neurons. CONCLUSIONS: The variations in the primate photopic ERG with eccentricity are due to spike-driven oscillatory activity that is more prominent in central and temporal retina than in nasal retina and to the slower timing of all responses in the central, compared with the peripheral, retina. The full-field, photopic ERG most closely resembles the mfERG responses to stimulation of peripheral regions.

Adolescent↗
PubMed2002

Visual field defects and multifocal visual evoked potentials: evidence of a linear relationship.

OBJECTIVE: To determine the relationship between spatially localized multifocal visual evoked potentials (mfVEPs) and Humphrey visual fields (HVFs) in patients with unilateral field defects. METHODS: Humphrey visual fields and mfVEPs were obtained from 20 patients with unilateral field losses due to either ischemic optic neuropathy or glaucoma. Monocular mfVEPs were obtained for each eye. The amplitude of the mfVEP responses was calculated using root-mean-square and signal-noise ratio measures. Estimates of the HVF loss in the same regions of the field used for the mfVEP were obtained by interpolating the 24-2 HVF data. RESULTS: Monocular mfVEP amplitude decreased with HVF loss, although small mfVEP signals were not uniquely associated with poor fields. On average, the monocular mfVEP was indistinguishable from noise for field losses between -5 and -10 dB, and good monocular mfVEP amplitudes were never associated with extensive visual field loss. The interocular ratio of the mfVEP amplitudes correlated well with the difference between the HVF values of the 2 eyes, and this correlation improved with increased signal-noise ratio. CONCLUSIONS: The monocular and interocular results were consistent with a linear relationship between the amplitude of the signal portion of the mfVEP response and linear HVF loss. One way to produce this relationship would be if both the signal in the mfVEP and linear HVF loss were linearly related to the percentage of local ganglion cells lost. The clinical limitations of the mfVEP technique can be understood by taking the signal-noise ratio, and the linear model proposed herein, into consideration.

Adult↗
PubMed2002

Quantitative electroretinogram measures of phototransduction in cone and rod photoreceptors: normal aging, progression with disease, and test-retest variability.

OBJECTIVES: To determine (1) reference values for cone and rod phototransduction variables derived from the a-wave of the electroretinogram, (2) their dependence on age, (3) the progression in cone and rod variables in patients with X-linked retinitis pigmentosa (XLRP), and (4) the test-retest variability in these a-wave measures compared with the variability in cone and rod b-wave measures. PARTICIPANTS: One hundred control subjects aged 5 to 75 years and 24 patients with XLRP aged 5 to 38 years. METHODS: High-intensity stimuli were used to elicit electroretinograms in the dark and in the presence of a rod-saturating background. Computer averaging and computer subtraction of cone components from mixed rod-cone responses were used to derive rod-only and cone a-waves. Rod and cone phototransduction variables were derived by computer fitting physiologically based computational models to the leading edges of a-wave ensembles. RESULTS: Phototransduction efficiency, as indexed by the sensitivity variable (S), decreased with age for cone and rod-only responses, whereas maximum cone and rod photoresponses (Rm(P3)) remained constant. In patients with XLRP tested annually for 4 years, Rm(P3) for rods and, to a lesser extent, cones declined with disease progression, whereas S remained stable. The test-retest variability in the a-wave Rm(P3) is lower than previously reported measures of the variability in b-wave peak-to-peak amplitude. CONCLUSION: The leading edge of the a-wave of the electroretinogram can be related to rod and cone phototransduction variables through quantitative models. Rm(P3), rather than S, should be the outcome measure of choice when using the a-wave to follow photoreceptor function in prospective studies and treatment trials.

Adolescent↗
PubMed2002

A method for comparing psychophysical and multifocal electroretinographic increment thresholds.

The multifocal electroretinogram (mfERG) has been commonly used as a method for obtaining objective visual fields. Although qualitative comparisons have been good, quantitative comparisons between the results from mfERG and the results from Humphrey Visual Field Analyser (HVFA) have found variable degrees of agreement depending upon the mfERG response parameter examined and/or the disease studied. Lack of agreement may be due to differences in methodology, differences in the sites of response generation, and/or differences derived from comparing suprathreshold versus threshold responses. In addition, the two procedures are performed at different levels of adaptation. We developed an approach for matching stimulus parameters and compared mfERG and psychophysical thresholds to assess the effects of technique and level of adaptation on the two responses. Psychophysical and mfERG thresholds were obtained as a function of the adaptation level (1.5-4.0 log td) and retinal location. The derived increment threshold-versus-intensity functions for both measures were fitted using the equation logT=logT(0)+log((A+A(0))/A(0))(n). We found that the values of A(0) for the mfERG data were one log unit higher than those for the psychophysical data. In addition, the value of the slope (n) for the mfERG data was shallower (0.8) than that of the psychophysical data (1.0). Predictions were made about comparisons of HVFA threshold and mfERG amplitude data in patients with retinal disease based upon a two-site model of adaptation. The data for some groups of patients could be best-fitted with a model of a disease acting at a site distal to all gain changes, whereas data from other patients were best fitted with a model of a disease acting at a site proximal to all retinal gain. The relationship between the Humphrey visual field threshold losses and mfERG amplitude reductions depends upon the site and mechanism of a particular disease process and the model of retinal gain assumed. In no case is a one-to-one relationship between the losses in the two measures predicted.

Adaptation, Ocular↗
PubMed2002

A signal-to-noise analysis of multifocal VEP responses: an objective definition for poor records.

Sixty local VEP records, called the multifocal VEP (mfVEP), can be obtained over a wide retinal area. From subject-to-subject, from day-to-day, and from location-to-location, these records can vary in quality presenting a challenge to quantitative analyses. Here three procedures are described for specifying the quality of mfVEP recordings in terms of signal-to-noise ratios. Monocular mfVEPs were recorded in two, 7-min runs. A '2-run signal-to-noise ratio' (2rSNR) was obtained as [RMS(RunA+RunB)]/[RMS(RunA-RunB)]-1, where RMS is the root-mean-square amplitude of the response over the period from 45 to 150 ms (signal window). Two 'noise-window signal-to-noise ratios' were obtained with the same numerator as the 2rSNR but with the denominators based upon the RMS of a signal-free window from 325 to 430 ms. In one case, inSNR, the denominator was the RMS of the record's noise window and in the other case, mnSNR, the denominator was the mean of the RMS amplitudes of all the signal-free noise windows for the subject. The SNRs were related to false-positive rates (i.e., detecting a signal when none was present) by recording mfVEPs with some of the sectors of the display occluded. In particular, the outer three rings (36 sectors) of the display were occluded so that only noise was recorded; false-positive rates for different values of SNR were calculated. The 2rSNR had the highest false-positive rate largely due to alpha in the records of some subjects. The mnSNR had a lower false-positive rate than did the inSNR because there was little correlation between the RMS of the noise in the signal-free window and the RMS of the noise within the signal window. Use of the mnSNR is recommended over the 2rSNR, especially where alpha contamination can not be eliminated. Ways to improve the SNR of the records are discussed.

Adult↗
PubMed2002

Quantifying the benefits of additional channels of multifocal VEP recording.

For some individuals and for some locations, multifocal visual evoked potentials (mfVEP) may be too small or appear 'too noisy' to be reliably measured. By adding electrodes, especially electrodes placed lateral to the midline, and by recording with multiple channels, the amplitude of the signal can be increased in some field locations. However, the addition of electrodes involves certain costs; the set-up time is longer and the data analysis more time consuming and complex. The objective of this study was to assess the benefits of adding electrodes by quantifying these benefits using a signal-to-noise measure. In addition to the typical midline placement of electrodes, two electrodes were placed 1 cm above and 4 cm lateral to the inion on each side. This allowed for 3 channels of recording and 3 additional, derived channels. The mfVEPs were recorded with a 60 sector, pattern-reversing display presented to one eye. Two 7 min records were obtained from 14 individuals with no known visual problems. The two records were averaged and a signal-to-noise (SNR) measure was obtained for every response from all 6 channels. For each sector of the display and each subject, the benefits of additional electrodes were quantified by comparing the SNR from the traditional midline channel to the best SNR from amongst the 6 channels. The number of responses exceeding any given criterion SNR value was increased with the additional channels. For example, 79% of the responses for the typical midline channel exceeded a SNR of 0.6 (a false positive rate of about 2.5%) and this increased to 93% when the best SNR value was used. As expected, summing the mfVEP responses from contiguous sectors also increased the SNR values. Additional electrodes and multiple channels of recording substantially improve the quality of the mfVEP records and the SNR measure provides a useful metric for assessing these benefits.

Adult↗
PubMed2002

The multifocal visual evoked potential and cone-isolating stimuli: implications for L- to M-cone ratios and normalization.

Multifocal visual evoked potentials (mfVEP) were recorded with a pattern-reversing display that modulated only the long wavelength-sensitive (L) cones or only the middle wavelength-sensitive (M) cones. Outside the central 5.8 degrees (radius), the ratio of the amplitudes of the mfVEP responses to L- and M-cone modulation varied across the six subjects, ranging from 1.1 to 1.7. The responses from the central 1 degrees (radius) showed a substantially lower ratio, ranging from 0.8 to 1.1 (average of 0.9). The variation among individuals outside the central fovea is probably due to differences in the ratio of the L/M cone input to both magno- and parvocellular pathways. The substantially lower ratios for the central responses is consistent with an L/M cone ratio closer to 1.0 in the central 1 degrees and/or an adjustment in the gain of the L- versus M-cone contributions to the central parvocellular pathways. Taking into consideration evidence from other techniques, we believe it is unlikely that most individuals have a L/M cone ratio of 1.0 in the fovea. Instead, it appears that there is a change in gain before the mfVEP is generated in area 17.

Adolescent↗
PubMed2002

The multifocal electroretinogram (mfERG) and cone isolating stimuli: variation in L- and M-cone driven signals across the retina.

Multifocal electroretinograms (mfERG) were recorded from 38 normal trichromats with a pattern-reversing display that modulated only their long-wavelength sensitive (L) or only their middle-wavelength sensitive (M) cones at equal cone contrasts and average quantal catches. The display consisted of scaled, 103 hexagonal elements, subtending 84 degrees x 75 degrees of visual angle. Typically, the amplitude of the L-cone driven signal was greater than that for the M-cone driven one at all retinal eccentricities, but large differences were found among observers. These values correlated with L- to M-cone ratios obtained psychophysically in the same observers using 2 degrees (dia.) heterochromatic flicker photometry. Interestingly, the L- to M-cone driven amplitude ratios differed between the central and peripheral retina. For the central fovea (5 degrees dia.), the mean ratio was 1.4 +/- 0.6 (for the N1P1 component), whereas for the annular ring centered at 40 degrees in the periphery, it was 2.3 +/- 2.0. The mean P1 latency of the summed M-cone driven mfERG (28.0 +/- 2.6 ms) was significantly advanced relative to the L-cone driven signal (29.0 +/- 1.9 ms), but the mean N1 latencies were similar (15.6 +/- 1.7 ms and 16.2 +/- 1.3 ms, respectively). The P1 latency difference between the L- and M-cone driven waveforms was not found in the central 5 degrees (dia.) of the retina. However, it increased with retinal eccentricity. The regional differences in the amplitudes and latencies of the L- and M-cone driven mfERG signals can be related to variations in the L- to M-cone ratios and/or the receptor to bipolar gain factors that depend on eccentricity.

Adult↗
PubMed2002

Retinal origins of the primate multifocal ERG: implications for the human response.

PURPOSE: To better understand the cellular contributions to the human multifocal ERG (mfERG), rhesus monkey and human mfERGs were recorded using the same stimulus conditions. The monkey mfERGs were recorded before and after injections of pharmacologic agents known to selectively block activity of particular cells and circuits in the retina. METHODS: Photopic mfERGs were recorded with Dawson-Trick-Litzkow (DTL) fiber electrodes from 16 eyes of 10 anesthetized adult rhesus monkeys (Macaca mulatta) and from 4 normal humans. The display consisted of 103 equal-sized hexagons within 17 degrees of the fovea. Monkey mfERGs were obtained before and after inner retinal responses were suppressed with intravitreal injections of tetrodotoxin (TTX), TTX+N-methyl-D-aspartic acid (NMDA), TTX+NMDA with the gamma-aminobutyric acid (GABA(A&C)) antagonist picrotoxin (PTX), or the inhibitory amino acid GABA and after L-2 amino-4-phosphonobutyric acid (APB) to block signal transmission to ON-bipolar cells. Finally, a combination of APB and cis-2,3 piperidine dicarboxylic acid (PDA) was used to isolate the contributions from the cone photoreceptors. RESULTS: TTX, which blocks sodium-based action potentials, removes a large contribution from the monkey's mfERG, but it does not remove all inner retinal influences. After administration of TTX, the mfERG is further modified by the addition of NMDA. TTX+NMDA, TTX+NMDA+PTX, or GABA alone have similar effects, suggesting that, at the concentrations used, they are largely removing the inner retinal contributions. After removing the inner retinal influences, the monkey's mfERG is mainly composed of ON- and OFF-bipolar contributions, as revealed after APB and PDA were injected. The leading edge of the first negative potential (N1) is largely shaped by the initial hyperpolarization of the OFF-bipolar cells. The photoreceptors also contribute to the leading edge of N1, but this contribution is small, except in the central 6 degrees. The depolarization of the ON-bipolars and the recovery of the OFF-bipolars contribute to the leading edge of the major positive component (P1), with the recovery of the ON-bipolars being the dominant influence on the trailing edge. The waveform of the human mfERG most closely resembles the rhesus monkey's mfERG after administration of TTX. CONCLUSIONS: The monkey's mfERG is shaped by large contributions from ON- and OFF-bipolar cells, combined with both spiking and nonspiking inner retinal contributions, and a small contribution from the photoreceptors. In comparison, the human mfERG resembles the monkey's mfERG after reduction of inner retinal contributions. Based on the pharmacologic dissection of the monkey's mfERG, a model of the waveform of the human mfERG is proposed. This model suggests that the waveform can be understood as a combination of overlapping ON- and OFF-bipolar cell contributions combined with smaller contributions from inner retina and photoreceptors.

Action Potentials↗