 200 years ago, it was pretty late that they got around to discovering EEG. It was discovered during, it wasn't recorded from a patient, just sitting in the patient, it was first discovered during a neurosurgery procedure. And it wasn't published until years and years later, which was 1929 by a guy named Hans Berger. And it got over to the United States within two or three years and they noticed pretty quickly that if you flashed a light at a patient and while they're recording their EEG, you could actually see the signal in the EEG from occipital scalp. So visually evoked potentials came out of EEG and similar to an ERG, retinitis pigmentosa was the disease that the ERGs were first applied to. Visually evoked potentials were first applied in neurology to verify optic neuritis and multiple sclerosis. Like ERGs, equipment to do it was not available commercially that you could buy until the early 60s for visually evoked potentials. I used one of the first, in the beginning, you had to have an EEG machine. So you had the write out from the EEG and then after that, so they used the EEG amplifiers. After that it went to an averaging machine to produce the visually evoked potentials. There was no programming it. There was no keyboard. There was nothing. It only did one thing and it had three buttons. Start, stop and print was all it was all I could do. So this is the south view of a northbound human and the sites indicated are the international 1020 system that's used in neurology based on measurements of the head, the nasium to the inion and the ears over the top of the head. All the placements are 10 and 20% measurements of that. So it's called the 1020 international electron system. You can get a visually evoked potential from anywhere on the back of the head. When I'm talking to patients, I'll put my hand on the back of the head and tell them, this is all visual and the middle's the middle. So the middle is the calcare and fissure, which is indicated by the OZ location, which is a 10% measurement of the back of the head from the inion that's the bump right here. So it's about three centimeters plus in an adult and a couple of centimeters in an infant. I don't measure the heads. I know about three centimeters. But EEG labs measure the head. The machines all come with measuring tapes. The most common electroplacements used are either the middle or 0102 or all three. Some labs think that they can lateralize pathology by recording from both hemispheres. Not, but they still do it, the majority of them. There is so much variation in the human occipital pole. And once you get off the surface, the poles start to reverse sometimes. You'll get false lateralization. So it looks like the left electrode is picking up pathology, but its origin is really the right side. But still there are labs that put an array all across the back of the head. Imaging, which tells you the lateralization, not that. So I routinely only record from OZ, the middle location. Inion, this is an example, I want to show you. This was recorded here by Jeffrey Anderson using a special functional MRI setup where he stimulated similar to the way we do clinically with a pattern that reversed at about three per second and looked at what are the hottest areas in a functional MRI with red being the hottest. Look how it jumps around, the hottest area jumps around depending on the slice level where it's only on one side at one slice, asymmetric most slices, deep below the cortical surface, other locations. So you can't depend on what you're getting from the surface. That's the downside of visual evo-potentials. The upside is anything that messes with the pathways after it exits the eye, to and including the cortex will affect it. And usually there's no confusion over what you're looking for. You know the child has meningitis. You know there's been trauma to the occipital pole. You know there's a pituitary tumor. And so it's not confusing. The visual evo-potential will quantify the delivery of flasher pattern information to the visual cortex. This is another one too complicated. This is a multifocal visual evo-potential showing how if you do use several electrodes on the back of the head, how you can get evo-potentials from an area of scanning. As I mentioned at the beginning, in fact most evo-potentials are extracted from EEG, whether it be auditory or visual or somatosensory. Have you ever seen cases where they do spinal cord monitoring like during rotations? They were exposed to that, like you did you in mid-school? Well they nowadays monitor somatosensory evo-potentials through most spinal surgeries. If you present a signal, whether it be a flash of light or a clicker in the ear or a peripheral stimulus to the median or tibial nerve, if you present any signal and then grab with a computer a set time period and grab a similar time period and you add them together over a period of not many presentations you get and evo-potentials because the background average is to near zero because it's random. The software, the computer program to do this was the second application of computers during World War II over 70 years ago. It was used to extract radar signals from jamming. So the random EEG is the jamming, the pattern, the person of views or the flash of light is the signal. I've lived through all of these, this is the generation of these. They visually evo-potentials started out using the grass, the most common is the grass brand in the United States of Strobe that they use for photic driving to try to induce seizures in EEG recording. So in the beginning this grass lamp was used, in fact, yes, here's the grass lamp and they haven't changed much for the last 60 years. In the beginning, this was used for the stimulus starting in neurology and then in early evo-potential recordings when they first got, you could buy a computer in the early 1960s and then started adding patterns to that flash, pattern reversal I'll talk about, pattern onset I'll talk about. So after the pattern flash they started putting patterns on top of the strobe, the same diameter as the strobe and then in the 1970s a neurologist at Queen Square in London, the National Institute for Neurology and Stroke in Great Britain came up with, I've met him, I've been to his lab, I've been back in the 70s and saw how he did it which was interesting. He took two Kodak projectors and put camera shutters in front of them and he had one slide that looked like this and then one slide that looked like this and by changing the camera shutters he induced this pattern reversal like I'm imitating here and he lined them up and back projected them onto a translucent plastic screen and that was the first application of pattern reversal which is now the worldwide standard. Why is it a standard? It has the less variability for the potential, the look of the potential it produces between individuals whereas a flash has a lot of variation between individuals. The normal pattern reversal visually of a potential, if I tested all of you they would all look like this unless you have some unknown pathology. You have a negative wave around 70-75 milliseconds, a big positive around 100 milliseconds and then a following negative around 145-150. This is about the maturation, you have a pretty good visually of a potential within six months in an infant even a pattern one and it improves up to about school age and by about age six or seven it doesn't change much until after 55 or 60. It's a very stable response. When the child is first born instead of it being a peak of around 100 which is the fourth dotted line the response will be out here and if you tested a child every six months or so until they got into school you would see this peak just march in like this so that by the time they were about seven it would be around 100 and stay there for the next 50 years or so. This shows the variation of take age seven that's about, there's about 20 people in each of these average age groups and look at the mean, there's not a significant statistical change until after 55. Like up to seven years old it varies a lot and after 60 when aging kicks in you get a lot of variance of a scattergram of that. So once you get into mid teens things tighten up pretty well until you get past 55 up to 60. So this is variation in aging and prior to that is variation in maturation, this is between a child that rides a bicycle at four or five versus one that can't ride a bicycle till they're seven or eight, a child that walks at eight months versus a child that walks at 14 months. So you get the greatest variation in the first five, six years and then again even a greater variation in aging after 60 or so. The pattern onset offset is gray screen, pattern pops out, goes back to gray screen. Any patient that has nystagmus for any reason at all the pattern reversal exacerbates their nystagmus. So you can't use it, you'll get no visual evoked potential. A degree had a patient a couple of years ago that was sent from California with the diagnosis of optic nerve disease based on their visual evoked potential. They had only used pattern reversal. So they were guaranteed this patient had nystagmus, they got no VEP. So they said, oh well they must have bad optic nerves but you just needed to use a different stimulus. Unfortunately most labs don't think this through. The technicians hook every patient up the same way and if you're lucky they even pay attention if they're watching. I've been in labs where once the tech pushes go they start texting their boyfriend. And then they look at everyone's file, oh the screen stopped. They don't even know if they're looking at the monitor or anything like that. And they do the same thing every patient regardless of they have nystagmus, they don't have nystagmus. Their vision is 2400 versus their vision is 2020. You've got to think those things through and apply the different stimuli to fit the patient. The pattern onset is also best for poor fixation, eye movement, lingering, deliberate defocusing and nystagmus. Adults really can't deliberately defocus. Children have plastic eyes, they can deliberately defocus. But adults usually can't but they can not cooperate. When I have a suspicious patient that's an empty cardboard box hit him on the head about the size of a shoe box and they're looking, they see early retirement and they come into the room like this and stuff like that. And then later you see them texting. And I've had patients look at, they'll look at the corner of the TV instead of at the center of the TV and stuff like that. This is upside down for the normal presentation but it shows those age groups of how the time slows with age a little bit. You can estimate acuity with visually vote potentials but you guys can do a better job. It looked like years ago a friend of mine named Sam Sokol invented back in the 70s that he presented pattern within cartoons. And just little babes in arms like this, they look at it and because the cartoon is random they get visually vote potentials from it. And you can estimate acuity by changing the check sizes within the pattern. As you know, everyone floats through, do these under anesthesia. All you have to do is work with the anesthesiologists and tell them to get them, I tell them to make them as light as they're comfortable. And my lines are that and anything short of setting up works for me. Not yet a good visually vote potential if under surgical depth anesthesia because you get a flat line to EEG. I use these goggles who are going to be switching to a little handheld thing that they took on the Micronesia trip when they come back that we can produce any colors with. These goggles just have red LEDs inside. As I mentioned at the first the classic initial application was through neurology was to confirm and look at the progression of optic neuritis and multiple sclerosis patients. What happens is, what is the purpose of myelin on the neuron? Speed, speed. So if you get plaques on the myelin on the optic nerve neurons, you're going to get slowing. The classic patient, there are no absolutes in the universe, the classic patients which would just be one out of 100 or 200 would be, one nerve is still completely normal, the top one in this case, the right, and the left is slowed, usually not this dramatically. The classic, not sure they're MS patient, the slowing is usually only 10, 12, 15 milliseconds at the most. So one eye will be right around 100 in a peak time and thousands of a second. The eye with the episodes of optic neuritis will be 110 or 12 or 14 or something like that. But sometimes both are affected at the same time. No absolutes. Over time, when enough myelin is lost in one of the optic nerve pathways, you'll also start to lose amplitude. And if you would follow a patient from that first 110 milliseconds or so and test them every year or so for the next 20 years, you would just watch it march out like 115, 120, 125, 130, 140, 150, and then when they're like really debilitated and they're in a wheelchair, it's 106, 106 keeps going, and then after the first decade or so, the amplitude starts coming down too as more and more of the optic neurons and the nerve are affected. So it's a way to quantify the degree. Also, the effect will be more dramatic during, if you catch them during an episode. When they say they can't see anything, it's like looking through a veil. Another optic neuritis patient. Both nerves affected, but the left barely 112, the other 120. Just running through, different looking, every individual. A patient, is there a reason we see so many neurofibromatosis type 1 here? I see a lot. I mean like almost like MS patients. The best way to quantify neurofibromatosis effects on the optic nerve, unlike what the MRI people think, it's not the MRI. The MRI sure will show you the size, but it tells you almost nothing about the degree of function and the effect on the optic nerve pathway. If you look at a neurofibromatosis patient visually of a potential, you can't tell it from a multiple-storosis optic neuritis patient. They look similar. The initial issue is slowing. I can't, I'm sure there's one, but I've tested hundreds through the years and they all, even if they don't develop the gliomas, have slowing of the optic nerve pathways by about school age. So this is a sad case. This is an initial VEP of an NF1. This is three years later. These are gliomas growing on the optic nerve pathways. This is four years later. This is the worst case scenarios, although the very worst case scenarios is they'll lose an eye because they'll have malignant gliomas. I'm going to run through some different kinds of patients to give you examples of the application of visually evoked potentials. Cerebral palsy with pale nerves and orbital mass. Let's see, I think I have a follow-up on this here. There you go. Sometimes you can get no, the top, the right, you'll get no visually evoked potential with a large mass before it's removed or sometimes in trauma cases. You'll get no visually evoked potential. This is after decompression. It starts to come back a little. Look at the top. Again, look at the just no visually evoked potential. The right eye, those two traces at the top start to come back. Do I have a further? No, neuroblastoma, ambitol, nerve toxicity. Also, it looks just like MS. Here's the slowing. Once you get it past about 110, 112, that's two standard deviations. Slowing, the slide doesn't go out far enough, but anything. Halfway, past halfway between the fourth and fifth eye to the line is this, the middle here is 112, that's two standard deviations. It's not going to go in a cardi syndrome. We occasionally see these in exams under anesthesia. Usually it's one eye only with nerve affected. Vocal VE visually evoked potentials similar to multifocal electroretanograms give you more potentials that can be more discriminating in detecting the degree of pathology. Our system is roughly similar to this one, except in, in the patients, most patients view them like this for other manufacturers, ours is inside. They use a different kind of stimulus than the multifocal electroretanogram. This uses a dark board stimulus like so. This was also invented by Eric Sutter, the guy that invented multifocal electroretanograms. And everybody copied his stimulus like they copied his multifocal ERG stimulus. So normal visually evoked, visually evoked multifocal, visually evoked potentials from each eye superimposed. Starting out with an episode of severe acute optic neuritis in the right multifocal. During severe, you off, during the episode, you often lose a lot of amplitude. So that they're, can't tell very well, but the lower, the lower line is the right that's red. And then, let's see how much later. Two months later, it recovers the amplitude, but the slowing, the slowing almost always is maintained once a person has a significant episode of optic neuritis. And then three months after recovery, some of the times you've been recovering in part of the field, the lower field, you can see them match up pretty well on the lower field. Ischemic optic neuropathy, back again to that, highlights the area affected where you can see the difference between the two hemis, two eyes. The rest of them are superimposed pretty well in this ischemic attack. It maps within the optic nerve affected nerve pathways. Optic nerve glioma. So what I'd like to get out of this is that you can use it to quantify anything that has to do with the optic nerve pathways, whether it be something like birth anoxia, near-death, surviving near-death drowning, pituitary tumors. I test patients pre and post pituitary tumor removal, anything that messes with it. And again, there's even more information on the web vision site. Back to, there we go. Top right for you to start. Here. Or over, I guess maybe to your left. Top left. Top left. Oh, top left. This one? Keep going. This is from current slide. The play button. One more. The play button? Yeah. Traditionally, for the previous 60 years or so, a German piece of apparatus called the Goldman Weekers dark adeptometer was used for determining dark adaptation. It's the Creole monster in a Goldman Weekers dark adeptometer. Very German. Very solid. It had, it was just indestructible. It was a great thing. It had a built-in weighted calibrated. It had a rotating disc. It reminds me of the tracking of walk-in coolers that measures the temperature. It had only electronic parts. It was that disc rotating based on time. And the light. Other than that, it didn't have anything else that could fail. What the patient viewed inside was a stripe and a fixation point. Your best night vision is about 10 degrees off of center, which would be your fist at arm's length if you looked at the middle of the handout. It's your best. So you ask the patient to just look at the little red light, which wasn't an LED because the machine was old. It was just a little red light. And then you would turn off the white in the stripes to zero and slowly turn it up and it blinked to about once per second. And when they can first see the stripe, and then you pulled a little trigger and it punched a hole in that rotating drum. That's really neat. And I think the Germans would come up with it. And you could control rotating the stripe so that you would ask them which way the stripe orientation, because bad patients will guess. There's two different. Because of having rods and cones, when you dark adapt a person over time, you will get cone response or pathological response. This is congenital stationary night blindness with myopia up there. And the normal person will dark adapt about three logs a thousand fold, because rods are three logs more sensitive than cones depending on the color. Three or more logs more sensitive. So this is what you got out of that machine, this rotating drum on time and you'd punch holes in it and then in the end you'd put it on an X-ray light box and connect the dots with the pan. The concept of rods versus cones and separating the two is similar as in electroratnograms. The peak for rods combined is about 505 to 510 nanometer bluish-green. And all the cones combined is about a 560 nanometer, 555, 560 nanometer yellow, tennis ball yellow. So you can do the same kind of dark adaptation using blue dots and red dots to produce two different This phenomena of the little bit of a break here about seven minutes out is called, I don't know why it's called the cone break. I call it the rod break, but it's when the rods really kick in. They call it the cone break. I guess it means breaking away from the cones. I don't know who named it. So you can test people separately like this. And this is the way it's done now with LEDs in Gonsfeld's. So now they're done in a Gonsfeld that can produce any color. The patient has a button to push like they're doing a Humphrey visual field and asks to push the button if they see any flash. And the program alternates a red or a blue really dim flash. And the program knows if the patient doesn't push it to make it a little bit brighter, if they do push it make it a little bit dimmer so that over a period of 30 minutes or an hour, depending on how long you want to test their dark adaptation, it produces two curves. So the red light curve gives you this for the cones. The blue light gives you this curve for the rods. As you can see, most people are about 90, 95 percent there within 20 minutes. You're just there 15, 20 minutes and there's very little improvement after that. If you put a person in really complete darkness, not the approximation we have in the rooms here where we try to make them completely dark, people will improve actually for about 45 minutes if your measurements are sensitive enough. And there are labs in the world that test for 45 minutes or an hour. We did a study here once that they wanted an hour. I mean, just tedious. They wanted poor patients to pay attention to push this button for an hour. This is a patient of Bernstein's that had a little small intestine and prior to vitamin A therapy, they had no dark adaptation. Just stayed up there all the way across and then this is after vitamin A therapy for two months and then four months and got down into not the best possible normal range but into normal range. That's Dale. Dale and I have been friends for 40 years. Dale is now a woman in San Francisco. Dale is a type, the classic type one kind of albino. He's a sax player in San Francisco. And I have permission to use his photo. In fact, it's pinned on my office. I have it that I can use his photo for anything. Albinos eyes get a lot more light into them. So he told me a story from here. He told me a story of hiking at dusk up Mill Creek Canyon. So by the time they got up wherever they were going, it was completely dark. And there's very little light up there because you're pretty far away from the city lights. And he and his friends said, let's race back to the car. Well, his night vision is so much better because his eyes let more light in that to him, it was just like dusk bell. And he could run back and the other guys were running into tree lamps. He showed up the car and about 10 minutes later, the first guy showed up and he had cuts on his face and stuff like that from falling off the tree. I'm running into things. I don't know if I have it here, but they gave me an idea of doing a study. So I studied their dark adaptation and they are better. I mean, even because you test people, normal people, you test them dilated, but they still have some pigment in their eyes. But let's see what do I have. These are panagal, bainos type. These are two different kinds of albinos. Those that have some pigment, those that don't have any pigment. And almost all of them were at the very best of a normal person you'd ever test or a half a log or a log or a log. What time is it? 741. Contrast sensitivity is another way to measure optic nerve function. There are particular channels, neurons, that are sensitive to contrast sensitivity. What is contrast sensitivity? These are the guy who invented contrast sensitivity as a perceptual test and was the one that visually both potentials based on contrast sensitivity was a guy named David Martin Regan. And this was the original Regan charts. So you would test a patient on this chart for their acuity, like you were testing for acuity normally. And then you would test them on this chart, how well do they do, how many lines do they get on this chart. And then, take my word for it, it's not very good in here. If we had a darkened room, this is another level of contrast sensitivity. And there's another one but it's too light in here. And then this was the scoring chart and everybody does poorer on each success contrast sensitivity chart. The question is how much poorer do you do? So the scoring was, most of you would score that you could read 10 of the 10, 20, 20, 15 line and then at 9% you might drop a little bit. But if you drop greater than the dotted line, that's pathological. It agrees almost completely with degree of optic neuritis, for example. The results of this fit with the visually potential results you get was slowing of the optic nerve. And I think there are some, I know there are some studies, they have a different system on the fourth floor in that study room, in the clinic or off of plastics there. There's some study that's using them, using a different version than the Regan studies. So what you get in pathology would be the person would drop, the person that dropped that dramatically, the dark lines when you get. And sometimes they can only do the first one. When you go to the really dim ones they don't get anything at all. That's what contrast sensitivity is. The end is near. You're going to live, it's going to be close. As you're all aware there are three kinds of color receptors plus rods. A really good source you want to pursue this further if you have any reason you have to is also web vision. A guy has like a 40 page chapter on color vision in there. Oh I love the mantis shrimp. They have, I forget how many do I have it here. 16 types of color receptors including UV and polarized light. Do you know the mantis shrimp? The mantis shrimp that has the acceleration of a 22 caliber bullet for killing prey. 22 caliber bullet. One of his little clubs here. You have to use super high film to catch it. Give you an example of where we are. Creatures that have this extent. They're not number one. There are animals that have even more receptors and UV and infrared and polarized light receptors. These are the three kinds of receptors and they're approximate peak colors in real approximate colors that I picked. If you combine them all together you end up with tennis ball yellow. Here's some more realistic colors that we've worked with. So we have the cones in the eye that are receptors and then sent on to the lateral geniculate. There are plus minus cells that fire that are red, green versus and yellow, blue cells that's processing so that it's cleaned up a lot before it gets to the visual cortex. Again, the same if you lump them all together and they have the various sorting that you see in neuro for detecting color problems. Then you have the sensitivity difference between all of your cones as a group versus rods and there's at least three logs difference in their sensitivity. Ishihara plates. Test for red, green color blindness. Sample. It's misspelled. Farnsworth. There's two versions. There's the 15 and 100 which isn't really 100. I think it's 88. It's called the 100. I don't know why it's called the 100. It looks like this. So the patient is given them mixed up and there to put them in sequence of color. It's like a rainbow. Ishihara plates. Again, picking things out of dots, triangles, squares, paths. Those are the most common ones used in ophthalmology. You lose. You win. See you next week.