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Maximally Specific Hypothesis - University of Auckland

Note, then, that whether an imperative is hypothetical or categorical is, in a sense, a function of how it’s meant.

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Finding Maximally Specific Hypothesis: ..

According to Ohm’s law in electricity, when an electrical current flows through a resistor, a gradient of electrical potential is formed that equals the product of multiplying the magnitude of the current by that of the resistance. By applying this law, we can derive the relationships between the currents, IA and IB (Fig. 3a), the resistances of the ocular tissues and the measurements of potential differences. Figure 3b shows an equivalent electrical circuit of the eye (Rodieck, 1973). A light stimulus elicits an extracellular current (source I) that divide into two pathways; one flowing through the retina (local pathway, IA in Fig. 3a) and the other through extra-retinal and -ocular tissues (remote pathway, IB in Fig. 3a). Each tissue (e.g. retina, vitreous, sclera, choroid, pigment epithelium) is represented in figure 3b by an electrical resistor. According to Ohms’ law, the potential difference between two points is independent of the pathway through which the current is flowing. Therefore, the voltage difference between points A and B can be calculated for the local or remote pathways.

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This type of analysis can also help in understanding the site of disorder. Any disorder that is localized to the photoreceptors and does not involve more proximal sites will be expressed in abnormal a-wave amplitude but normal b-wave to a-wave ratio. In contrast, a defect in signal transmission in the outer plexiform layer will show abnormal b-wave to a-wave ratio but the amplitudes of the ERG waves may even increase. This is illustrated in figure 24 for two cases. In this figure, the b-wave to a-wave ratio is plotted in a different manner. The a-wave is used as the independent variable and is used together with the normal b-wave to a-wave ratio (of Fig. 23) to derive the expected b-wave. Then, the ratio of the measured b-wave to the expected b-wave tells us about signal transmission in the OPL. In figure 24, the mean (+/- s.d) of the b-wave ratios for 20 volunteers with normal vision is plotted as a function of the a-wave amplitude. The data from normal subjects that were recorded in another two laboratories (red and blue symbols) fall well within the normal range of my laboratory. The b-wave ratios of a patient with high myopia and of a patient suffering from congenital stationary night blindness (CSNB) are compared to the normal range. The patient with high myopia is characterized by subnormal ERG responses due to the reduced function of the photoreceptors. However, the b-wave ratio is normal indicating normal signal transmission. The CSNB patient is characterized by subnormal b-wave ratio in agreement with the known defect in synaptic transmission from rods to bipolar cells.

Finding a Maximally Specific Hypothesis 68.

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In order to derive the relationship between P3 and time for the entire ERG range, very bright flashes that saturate the photoreceptors (i.e. shut down the ‘dark’ current completely) are needed (Fig. 25A). As can be seen in these ERG records, the a-wave saturates for the 2 brightest light stimuli. Time of analysis is limited to the period before b-wave intrusion, as shown by the two dashed vertical lines (Fig. 25A). Application of eq. (3) to these ERG data is shown in figure 25B. The data points are the amplitude measurements of the ERG responses and the continuous curves are the fitted model. The fit of the theoretical curves to the actual data is quite good for the first 25ms of the ERG responses. Longer intervals cannot be compared because the positive P-II component starts to develop and to affect the ERG recordings.

ERG analysis that is based only upon amplitude measurements may lead to erroneous conclusions if the pupil is not maximally dilated. Furthermore, exchange of information between laboratories that use different recordings conditions has always been problematical. One way to circumvent this difficulty is to compare a series of ERG responses for the relationship between the a-wave and the b-wave (Perlman, 1983). This analysis is based upon our understanding of retinal physiology and the origin of the ERG waves. If the a-wave reflects activity in the photoreceptors and the b-wave originates from post-synaptic neurons, than normal signal transmission in the distal retina will be expressed in normal relationship between the b-wave and the a-wave. Such analysis can also be used to compare ERG data between laboratories as shown in figure 23. The figure was constructed from ERG data of 20 volunteers with normal vision who were tested in the dark-adapted state with light stimuli of different intensities. The relationship between the b- and a-waves was derived for each subject and the normal mean (continuous line) and range (+/- s.d., dashed lines) are shown in the figure. ERG data from two other laboratories that use different corneal electrodes and different light sources are shown (red dots, blue triangles). The data points from these laboratories fall within our normal range indicating normal retinal function.

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However, we have to remember that the magnitude of the different resistances and more so, the relationships between them can also affect the ERG that is measured with extra-ocular electrodes. The division of the current originating from the light-induced retinal activity into the local and remote pathways depends upon the relative resistances of the two pathways. From Equation (1), we can derive the following relationship

If someone tells you to do something, but then backs off upon finding out that you don’t have objectives that would be advanced by doing that thing, then the imperative is hypothetical.

Newman EA, Odette LL. Model of electroretinogram b-wave generation: a test of the K+ hypothesis. J Neurophysiol. 1984;51:164–182. []
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The most common ERG response from a human, that is elicited with full field (Ganzfeld) flash of light, contains the a-wave and the b-wave as shown in figure 21. The amplitude of the a-wave is measured from a baseline that is monitored prior to the light stimulus, to the trough of the negative wave. Since the b-wave reflects the sum of the negative P-III component and the positive P-II component, its amplitude is measured from the trough of the a-wave to the peak of the b-wave. The temporal properties of the ERG response are usually defined by the time-to-peak (implicit time) of the b-wave, and are measured from stimulus onset to the peak of the b-wave (Lb in Fig. 21). In some laboratories the time-to-peak of the a-wave is also measured (La in Fig. 21). These ERG parameters change with intensity of the light stimulus (Fig. 17) and with the state of adaptation (Fig. 16) as we have seen earlier.

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In order to reveal the fast flicker of the rod signals, special care is needed for recording conditions. Under regular recording conditions of the ophthalmic clinic, it can be accepted that rod-mediated electrical signals can follow flickering stimuli up to 15Hz. Therefore, it is customary to apply bright light stimuli at a frequency of 30Hz in order to isolate the cone system from the rod system. The responsiveness of the cone system and its ability to follow fast flickering stimuli depend upon the level of ambient illumination as shown in figure 20 (Peachey et al., 1992). In this figure, ERG recording was performed from one subject using 31.3Hz flicker of constant intensity while changing the level of ambient illumination. The responses are of larger amplitude and are characterized by faster rise times as the irradiance of the adapting field is raised. This observation is consistent with the notion that the cone system is suppressed in the dark-adapted state and that light adaptation removes this inhibitory action. However, using scotopically matched backgrounds indicates that mechanisms intrinsic to the cone system itself are also involved (Peachey et al., 1992).

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Therefore, light stimuli of different spectral content can elicit ERG responses that are dominated by one or the other systems as shown in figure 19. These ERG responses were recorded in a volunteer in the dark-adapted state using dim blue or bright red light stimuli. The blue stimulus elicits a slow positive ERG of the more sensitive rod system (A). The red light stimulus produces an ERG response composed of two parts; a fast wave peaking around 30ms and a slow wave peaking at 100ms (B). This ERG is a combination of rod and cone contributions with the cone-mediated response being of fast kinetics and the rod-mediated response of slow time-to-peak. The fast cone-mediated ERG is sometimes referred to as the x-wave (Bornschein et al., 1957; Berson and Howard, 1971). The two light stimuli were balanced to produce equal rod excitation as evidenced by the equality in the slow ERG component (Fig. 19C). With this procedure, cone-mediated function can be isolated from the large amplitude rod ERG and allows analysis of cone vs rod system in the dark-adapted state.

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