| 00:00 | Recording progress. This is lecture 17 neuroscience and where we left off. |
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| 00:09 | last time was we were talking about disorders or movement disorders. And in |
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| 00:20 | , we discussed Parkinson's disease and we hunting. We saw that the structures |
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| 00:29 | different mechanisms of pathologies that determined and these two different neurological disorders. And |
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| 00:38 | talk about how there is programmed cell , how there is a necrotic cell |
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| 00:44 | also. And then we ended up this slide that talks about deep brain |
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| 00:54 | . And uh what it says is if these disorders such as Parkinson's |
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| 01:02 | it's so bad. The symptoms of disease are so bad with, with |
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| 01:09 | and other um symptoms that sometimes there's surgical lesion, a little surgery that |
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| 01:18 | being done in the areas that are by Parkinson's just as a reminder, |
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| 01:25 | is Parkinson's and having an effect on nigra particular. Now, if you |
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| 01:34 | do a brain resection, there is alternative that is called deep brain |
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| 01:41 | Uh Now we look at the whole of the treatments for Parkinson's disease. |
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| 01:52 | most common treatment for Parkinson's in the phase of the disease is L dopa |
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| 01:59 | you may recall dopa as a precursor dopamine. So again, when we're |
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| 02:09 | about Parkinson's disease, we're talking about loss of dopamine meg neons and |
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| 02:16 | you're supplying a precursor and that will mimic the activity of dopamine. And |
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| 02:26 | says that with time, the effects the drug usually diminish in new types |
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| 02:29 | abnormal and debilitating movements and dyskinesias may not being able to hold your gate |
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| 02:36 | stance. Numerous other drugs can be at this stage, but they're effective |
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| 02:42 | virus and they have side effects on own. And as early as 18 |
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| 02:49 | , uh British neurosurgeon, Victor Horsley started basically making lesions and surgical corrections |
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| 02:59 | these motor disorders. He was targeting cortex and the unfortunate thing is that |
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| 03:09 | because of the lack of knowledge in 80 eighties and maybe ethics also in |
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| 03:15 | these surgeries. Uh Doctor Horsley would the uncontrollable movement, but you would |
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| 03:25 | end up causing paralysis. A lot these patients, bleeding ability to move |
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| 03:31 | . So that wasn't so great. between 1940s and 70s, surgeons were |
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| 03:39 | these small lesions and glow thalamus pic and they could often improve the tremor |
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| 03:49 | in Parkinson's disease without inducing paralysis. now we're cutting slightly different parts of |
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| 03:55 | brain, making little lesions. in the late 60s, you have |
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| 04:00 | do and you have a backlash against types of ovary surgical treatments for Parkinson's |
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| 04:09 | also fell out of favor for a . Uh what are some of these |
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| 04:16 | that are not justified that are happening the 60s? And that's right frontal |
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| 04:26 | . So why they're justified because they're done in mentally ill patients. And |
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| 04:33 | procedure is really gruesome and not precise the knife is inserted through the nasal |
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| 04:43 | and the connections between the frontal lobe other parts of the brain are |
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| 04:48 | cut. So you can imagine the techniques in the sixties you're looking |
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| 04:54 | there's no F MRI, there's no C T s going on. You |
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| 05:00 | , you don't really know what you . It's just uh x-rays that you |
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| 05:04 | access to. So that falls out favor. There's a great movie called |
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| 05:11 | Flew Over the Cuckoo's Nest with uh Nicholson, famous actor who was very |
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| 05:18 | in that movie. And that movie about how people in the mental institutions |
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| 05:24 | undergo the lobotomy and they become So yeah, they're no longer |
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| 05:35 | They don't have aggression anymore, but don't have anything. They have no |
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| 05:40 | like that. And it's sad it's actually. So now we have development |
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| 05:49 | electrodes and electro physiology and electronics, seventies eighties and nineties. And so |
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| 05:54 | a possibility to instead of lesioning, the electrodes and stimulating that we also |
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| 06:00 | about plasticity. So when we talked long term plasticity and hippocampus and stimulation |
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| 06:06 | the shop for collateral. So we about the rate code. So that |
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| 06:10 | 1973, That's when it was published time. So we're starting to get |
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| 06:16 | hang down the seventies of what these can do that they can cause plastic |
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| 06:22 | , they can cause changes in activity some of these changes could be long |
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| 06:26 | changes. Therefore, there is a . Can we not imply that electrodes |
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| 06:33 | do these stimulations will cause long term in plasticity or neural cerp function in |
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| 06:41 | ? Uh Interestingly, it says the Greeks and the Egyptians were early advocates |
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| 06:45 | their power or electrical shocks. Their devices were electric yields and race. |
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| 06:51 | it was said that direct applications of a stimulating fish could help alleviate pain |
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| 06:56 | headache, hemorrhoids, god depression and sy. Uh so there is ancient |
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| 07:04 | of of electricity essentially for treatment of disorders. But electricity problem is charged |
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| 07:12 | nature. Uh We still use animals modern medicine. Leches are still being |
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| 07:18 | in modern medicine to, to help with drainage of blood and clearance of |
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| 07:25 | in certain conditions. So now, the modern use of deep brain stimulation |
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| 07:32 | movement disorders began in the 80's and was uh experienced with lesions and noting |
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| 07:39 | promising effect of stimulation of the operating . Surgeons began it time and systematically |
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| 07:45 | with a high frequency stimulation P P could reduce abnormal movements over the long |
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| 07:50 | . So what happens is when you're a surgical resection of the brain |
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| 07:56 | you are typically uh your objective is slide, your objective is to cut |
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| 08:09 | small of a piece of the brain make as little of a leash as |
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| 08:14 | . Your objective is also to identify parts of the brain that is not |
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| 08:18 | affect other functions. So as a , you call a neurophysiologist, typically |
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| 08:24 | phd into the operating room and then the O R before the neurosurgeon that |
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| 08:30 | has opened the skull and tries to resect the piece of the brain. |
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| 08:34 | typical ask like physiologist, can we , run some tests and make sure |
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| 08:39 | I'm cutting off the, the ps as they were stimulating the this uh |
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| 08:46 | dysfunctions, they would stop the So I'm like, wait a |
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| 08:51 | maybe we can just stimulate instead you know, stimulating to find there |
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| 08:55 | cut it off, we can just leave the stimulating electrode and continue to |
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| 08:59 | it. And so now the USDA uh US FDA USDA is Department of |
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| 09:11 | is issue foods US FDA. Food drug administration is the body that controls |
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| 09:16 | of the medications. So all of pharmaceutical prescription medications that are in the |
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| 09:24 | that are federally controlled or controlled by federal agency FDA. So people would |
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| 09:29 | is this FDA approved or it's not approved FDA also approves medical devices. |
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| 09:35 | this would qualify not as a chemical , it would qualify as a medical |
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| 09:40 | as an implantable electrode medical device. the approach is to implant bilateral electrodes |
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| 09:50 | their tips and the subthalamic nucleate. uh you can use imaging techniques to |
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| 09:59 | but you implant the them the tips these electrodes in the correct location and |
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| 10:05 | have a generator that typically gets implanted the skin below the collarbone here. |
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| 10:15 | once you have the electrodes implanted, everybody has the same regime where the |
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| 10:21 | is gonna help them with their, their trailers. Somebody may need high |
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| 10:27 | , higher frequency, more repetitive others may need less uh of this |
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| 10:34 | frequency stimulation. So the most effective , at least, you know in |
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| 10:39 | book, uh 10 years old was and 30 to 180 Hertz. It |
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| 10:45 | is within this high frequency range. is, this does not resemble any |
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| 10:50 | neural type in the brain. How D BS work? So remember when |
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| 10:54 | looked at brain rhythms, we oh, there's this data or to |
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| 10:59 | Hertz, there's this gamma uh 40 this fast have my 80 Hertz. |
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| 11:04 | then we said there is these fast and there are like 306 100 |
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| 11:09 | And so this frequency 1 31 80 falls somewhere in between and one of |
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| 11:14 | frequencies that is not commonly found in brain with E E G recordings. |
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| 11:23 | how, how does it work? it's intense research. We don't exactly |
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| 11:28 | but stimulation may jam or suppress abnormal of firing if you have neurons that |
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| 11:34 | communicating with each other and they establish certain pattern of firing. What this |
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| 11:40 | stimulation does is it disrupts that firing by externally disrupting that firing pattern. |
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| 11:47 | could disrupt the synchrony and synchrony is needed to produce the repetitive movements |
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| 11:53 | or or jerks or traumas or so . This is usually repetitive activity, |
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| 11:58 | abnormal commands from basal ganglia that are that reply. So now it may |
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| 12:05 | release of neurotransmitters that modulate cells and may also vary with the brain structure |
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| 12:12 | stimulated. And it would not be if all of these effects are more |
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| 12:17 | important for the efficacy of D P who are several things that probably |
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| 12:22 | you're disrupting the firing, you're leasing . Uh and you are activating inhibitory |
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| 12:33 | that is suppressing this abnormal activity. deep brain stimulation is effective as it |
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| 12:40 | in controlling both hyperkinetic and hyperkinetic improve patients quality life. Uh |
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| 12:50 | the way that this works is that is a certain uh protocol that your |
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| 12:55 | works with you. So this is 110 Hertz repetitive and so on and |
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| 13:00 | sometimes the patient can actually control the or the little remote. So if |
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| 13:07 | getting tremors and the device is not in. They can actually uh turn |
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| 13:12 | on because it has connectivity underneath the . It still isn't a, you |
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| 13:16 | say it's, it's no longer an treatment. But what's interesting is that |
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| 13:23 | used in a range of psychiatric and conditions, major depression. So major |
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| 13:29 | depression and instances where pharmacological treatments do work, deep brain stimulation may be |
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| 13:35 | . O CD tourettes syndrome, epilepsy, tinnitus, oh my |
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| 13:41 | I have tinnitus. I would never of putting these things on my head |
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| 13:45 | my ear stimulating doing brain surgery. tinnitus chronic pain. Well, I |
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| 13:53 | , for some people, it can really, really horrible. You |
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| 13:55 | it doesn't mean that you're only stimulating brain structures that we're looking at |
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| 14:01 | Chronic pain, spinal pain, spinal the spinal nerve simulation would be |
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| 14:06 | quite uh beneficial Alzheimer's disease. Uh all of these protocols vary and you |
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| 14:14 | to really weigh the risks or weigh benefits over the long term harm. |
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| 14:21 | because it's once you have something implanted your brain, I mean, you |
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| 14:26 | it, but then it decreases the of infection, it increases uh build |
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| 14:31 | of glia around the electrodes in your *** tissue. And that isn't feeding |
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| 14:37 | other physiological liquidity along the electrode which so, you know, it's |
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| 14:44 | , it's, it's not that it's , yeah, let's just do it |
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| 14:47 | I don't, I don't feel well and there is a, as I |
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| 14:52 | , big stimulation. So there's a company here in uh does what is |
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| 15:02 | E N S therapy. And I just gonna not because I'm uh in |
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| 15:07 | way affiliated with them. But you see the Houston Methodist will use the |
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| 15:12 | N treatment which is Vegas Star And I think that the company is |
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| 15:21 | that's with, with or something like . So let's see what Methodist is |
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| 15:29 | because uh um or seizure diet. you can see medication, diet, |
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| 15:38 | cover rehabilitation. But worried about the implants still be if you're doing V |
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| 15:45 | si think it's not stimulation but they men in here. So I think |
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| 15:51 | the company that makes the in Um And medication was in advance or |
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| 16:02 | people having seizures is typically V ma simulation is for seizures. Drug resistant |
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| 16:11 | is diagnosed when a person tries two more prescribed medications without finding seizure. |
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| 16:16 | look into this in the next hour two. Also, people with drug |
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| 16:23 | other non treatment options like Vegas nerve therapy to maximize their seizure control and |
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| 16:30 | quality of life. So this is little device for vagus nerve stimulation. |
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| 16:35 | small device pulses through the vagus nerves of the brain. OK? It's |
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| 16:43 | out of 10 people report improvement to type of this position. And I'm |
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| 16:47 | advertising this company. I just want guys to know that these things are |
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| 16:51 | there. Uh uh and that they're and still, I would say not |
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| 16:59 | common but sometimes very effective form of treatment. Yeah, for the deep |
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| 17:09 | stimulation, does that restore them to movement or just less severe summer? |
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| 17:18 | I think that there is a, know, there's a tradeoff there again |
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| 17:22 | if you stimulate and certain protocols can almost like replicate like paralysis, |
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| 17:30 | stimulating the correct parameters in the and the correct location of the brain and |
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| 17:36 | post to operatively. It's not a that they may actually have to chest |
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| 17:40 | implants, electrodes that's again going back and to adjust and to see the |
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| 17:49 | . But I think that they have good methodology that about once they imply |
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| 17:53 | the stimulant to see if that they pick up the act activity, the |
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| 17:57 | activity to uh and then they know where it is. But you |
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| 18:03 | I mean, our brains are slightly and uh how we react to different |
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| 18:10 | is also very different. OK. this concludes our electron and major neurological |
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| 18:22 | . And the, the next lecture we're going to talk about I can |
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| 18:31 | up. So next, we're going start talking about epilepsy and we're gonna |
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| 18:38 | back to maybe some of the information we already described when we talked about |
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| 18:43 | rhythms. I, when we talked electro and the follows with E E |
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| 18:50 | . It was Austrian Psychiatrist Hans in who observed that waking and sleeping |
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| 18:55 | distinct with that uh And figure 191 one of his first published records taken |
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| 19:04 | the head of his 15 year old Claus. So nobody believes you, |
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| 19:10 | do it on your software, your members, prove it to everybody |
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| 19:14 | That's a very common theme. Uh invented the contrast for uh x-rays from |
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| 19:20 | they do like to expose the blood and nobody in the hospital believe |
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| 19:25 | So he called in the nurse, injected him. He like walk to |
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| 19:29 | x-ray with this contrast material and healed blood vessels after everybody is like, |
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| 19:35 | , maybe we'll try it, you . So an interesting story about Hans |
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| 19:40 | is that he is the father of . The guy that really invented the |
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| 19:47 | at least that education of E E for studying brain activity. Also the |
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| 19:52 | that contributed a lot to telepathy The story is quite interesting is that |
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| 20:00 | son here that described plow was 15 old, but his son was |
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| 20:05 | He once was stationed in the army he was some 100 or 200 miles |
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| 20:12 | from his father, Hans Beger and his uh sister. And that |
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| 20:19 | , the sister woke up crying, and ran to the father saying that |
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| 20:24 | something wrong. So now we're talking , you know, uh 19, |
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| 20:30 | 1920s, there's something wrong with with my brother. I just know |
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| 20:36 | something wrong and the father is like down, go to sleep, go |
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| 20:40 | to sleep, you know, and freaking out. There's no way something |
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| 20:44 | bad happened to him. She had with, I don't know. |
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| 20:50 | and so she said you have to to the telegraph office to uh put |
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| 20:57 | , put a telegram, you have go and send a telegram check on |
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| 21:04 | on the stations a couple of 100 away. And so they send this |
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| 21:10 | and you get a response saying that morning when the sister woke up, |
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| 21:15 | fell off the horse and suffered a severe injury to, he got knocked |
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| 21:20 | unconscious and had severe injury, although wasn't deadly, but it was gonna |
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| 21:25 | him some long time to recover. was the response that came. And |
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| 21:29 | how Hans Beger who was looking for electrical physiological changes became interested in telepathy |
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| 21:38 | really pushed forward the, the signs the same person that uh e for |
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| 21:46 | recordings. When you do these you typically have a cap and we |
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| 21:50 | about that these caps will have a electrodes if this is on the of |
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| 21:54 | scalp. And this group of electrodes vary from two electrodes. We need |
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| 22:02 | least two because you're comparing one electrode another electrode activity, one electron to |
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| 22:06 | electrode, but you can have 120 you can have 200 52. And |
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| 22:15 | all very much depends. Now, about this, if you have two |
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| 22:20 | connectivity, how much precisely is spatial gonna determine left or right, maybe |
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| 22:26 | it, but not front, not , not for. So to this |
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| 22:31 | when E G recordings are done and are very lucky we live in |
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| 22:36 | you know, this magnificent uh medical , the largest in the world. |
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| 22:41 | you'll have all of the electrodes on hand that you want to and the |
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| 22:46 | E G caps really fast processing lower because you're acquiring information from 100 and |
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| 22:52 | channels at the same time. That's lot of data that needs to be |
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| 22:56 | digitally in a very fast way. Imagine yourself in rural India where you're |
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| 23:06 | if the nearest E G cap is hours away from you and it may |
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| 23:12 | 12 to 24 electrons and you may to wait two weeks in line to |
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| 23:17 | that cap on you so that the would be able to do your |
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| 23:21 | So it really is resource what you access to. Uh and and the |
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| 23:28 | electrodes you have more precisely you can where problems arising. So some of |
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| 23:35 | recordings, as you can see each of these comparison electro of the year |
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| 23:40 | 1 to 22 to 33 to 44 five and so on E G |
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| 23:46 | Once again, it's taking the activity the various surface of the skull uh |
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| 23:53 | the scalp and the activity is coming the parameter cells. So uh this |
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| 24:02 | here underneath it has to involve hundreds not thousands of cells in order for |
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| 24:11 | electrode to pick up a signal, means you have to have a really |
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| 24:19 | amount of synchronism. Look at the brain development uh brain recordings here. |
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| 24:23 | is algorithm then this is blank This is beta rhythm as the subject |
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| 24:30 | awakened by the reporting size that indicated first few seconds show normal alpha which |
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| 24:37 | frequencies of 13 and the largest tal halfway through the report subject open his |
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| 24:43 | signal by the large artifacts and alpha here with the pre beta rhythms. |
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| 24:51 | this is normally the E G and see normal RTH that you get at |
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| 24:55 | cop. Uh But that is also indication of the synchronization of thousands of |
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| 25:01 | producing these rhythms in awake or a state, so to speak. So |
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| 25:08 | generate E E G signals, if have this irregular activity, which indicates |
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| 25:16 | there are six cells on the circuit and they're kind of doing their own |
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| 25:20 | , they're receiving different inputs and they're oxygen controls at different times. And |
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| 25:25 | you look at the sub E E there doesn't seem to be one repetitive |
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| 25:29 | frequency at which these neurons are But once these neurons get synchronized, |
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| 25:36 | was by the common input. For , you're jolting the shop of the |
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| 25:40 | and the hippocampus. And that means activating hundreds of para cells and you |
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| 25:45 | actively synchronizing them with a very strong during input. If these neurons get |
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| 25:52 | and they depolarize and hyperpolarize at the time. So they're synchronized in time |
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| 25:57 | when you look at the sum of G, you will now see a |
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| 26:00 | clear dominant frequency and pattern here address . So these rhythms that we have |
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| 26:08 | we discussed algorithm spindle and rhyth and ripple rhythms, spindles and ripples are |
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| 26:16 | , very important for learning. So we're talking about alpha and beta and |
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| 26:21 | best description we can give here to rhythm is a subject is uh uh |
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| 26:31 | subject is awake and quiet. Uh then beta rhythm is what the algorithms |
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| 26:38 | suppressed here. But if you look these other rhythms, spindles and |
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| 26:44 | we talked about how individual dominant rhythm represent distinct behavior, potentially mental uh |
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| 26:54 | processing capabilities. And what's interesting is you record algorithms and humans, |
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| 27:02 | cats, goose, sorry, a , maybe we should give a trace |
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| 27:09 | Easter, the rabbit. And then have rodents spindles everywhere and the spindles |
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| 27:17 | really interesting rhythm and it even has one is referred to K complex this |
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| 27:23 | one of the distinguishing features. This is a spindle rhythm, a K |
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| 27:27 | . And typically, it has this large kind of a a synchronized activity |
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| 27:32 | the form of cave complex. And will find it again across different |
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| 27:37 | So not just that rhythm but also K complex within the spin ripples are |
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| 27:42 | fastest uh oscillations. And they can from uh 2, 300 to 600 |
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| 27:52 | . And these are very important, spindles of the ripples or some of |
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| 27:57 | faster rhythms that are very important for in them. Now, you can |
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| 28:05 | go back to this information here that have in the supportive class literature that |
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| 28:23 | discusses, discusses that. And also look at this figure which is underneath |
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| 28:34 | that you have bad gerbil rat And you can see that there's |
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| 28:46 | a little bit of variation, let's a human, the or rhythm, |
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| 28:53 | slower than the dominant beta rhythm in guinea pig or the hamster. So |
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| 28:59 | are slow slide, slight variations. is actually here is as a function |
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| 29:09 | the brain weight. So you have frequency and as the brain weight |
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| 29:16 | So the brain wave for each E rhythm across species known how little the |
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| 29:23 | of the E G rhythms vary despite vast range of brain sizes. And |
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| 29:29 | because right of a mouse is only 23 centimeters, two centimeters, maybe |
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| 29:39 | is £3.5 but we still have the of these circuits still to produce all |
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| 29:45 | these different dominant frequencies that are gonna a that is quite remarkable. Uh |
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| 29:55 | when you talk about synchronous activity or of synchronous activity, one of them |
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| 30:05 | be illustrated here and I basically have descriptions. So we can either go |
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| 30:11 | into the um power point or PDF , or here, But there's two |
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| 30:16 | that you typically synchronize the audience uh you synchronize. In this case, |
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| 30:22 | performers, if you have Six people , 1, 2, 3, |
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| 30:29 | , 5, 6, they're playing trumpet or trombone. And if they're |
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| 30:35 | on their own, they're like warming . It's all the synchronized, that's |
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| 30:40 | sort of like the, when you to uh orchestra and they're check, |
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| 30:45 | their tuning and everything sounds all over place and then the conductor stands up |
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| 30:50 | waves the magic wand and then everybody synchronizes and produces the sound at the |
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| 30:56 | time. So this is the Something is making the pace the conductor |
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| 31:02 | and his stick is setting the Oh The 2nd mechanism is more subtle |
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| 31:12 | here the timing and the synchrony arises this collective behavior in the cortical neurons |
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| 31:22 | . So it's this is instead of conductor and symphony here, this is |
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| 31:26 | likens to jam session. So synchronized are jamming, but it's coming from |
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| 31:33 | their around there's nobody directing the band them to the jam session, uh |
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| 31:42 | connections, of course synapses and uh we have is we have oscillations. |
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| 31:56 | let's look at these oscillations here we here, constant active excitatory input that |
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| 32:04 | activating, excitatory solve and that is inhibitory solve. So when you have |
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| 32:11 | input is on top of the it's constantly firing the excitement cell, |
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| 32:17 | you say, well, we should the constant firing of action potentials. |
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| 32:21 | doesn't because when this gets activated, first have excitation and until you produce |
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| 32:27 | the excitatory cell, the number of potentials. But then excitatory cell goes |
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| 32:33 | . So it's not 1-1, it's following the pace of the constant Exci |
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| 32:40 | . And that's because you get a feedback loop and you have the inhibitory |
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| 32:45 | firing. And therefore the excitatory cell inhibited, firing. An excitatory cell |
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| 32:51 | inhibited. Oh So one excited So one of the up on the |
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| 32:59 | , as long as there's a constant her drive, which does not have |
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| 33:03 | be rhythmic onto an E cell activity tend to trade back and forth between |
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| 33:10 | two neurons while activity cycled through the will generate the pattern of firing show |
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| 33:16 | the dashed box. OK. So can have uh a repetitive firing. |
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| 33:26 | that repetitive firing actually sets out two rhythms in the input cells that you're |
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| 33:33 | with that repetitive firing. Now, look at this diagram in 9 |
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| 33:41 | Under certain conditions, the lambic neurons generate very rhythmic action potential discharges. |
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| 33:49 | . And this constant firing or up down we refer to as oscillation. |
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| 33:55 | how did a lot of parents Some volumic cells have a particular set |
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| 34:01 | voltage gated ion channels that allow each to generate very rhythmic self-sustaining discharge patterns |
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| 34:08 | when there is no external input in cells. So the rhythmic activity of |
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| 34:14 | thalamic pacemaker neuron then becomes synchronized with other thalamic cells via hand clapping kind |
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| 34:22 | collected interaction. So, clapping synchronization what uh performance is finish. People |
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| 34:30 | clapping. At first thing you hear clapping and then everybody at the end |
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| 34:34 | clapping synchronized, right? So this a different way. Visual neurons can |
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| 34:40 | to the rhythm of the group or clapping forms of the rhythm of the |
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| 34:46 | . Then these rhythms have passed on cortex. Remember very strong thalamic cortical |
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| 34:52 | , exciting cortical cells and then a small group of centralized thalamic cells acting |
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| 34:59 | the bandleader can compel a much larger of cortical cells acting as the band |
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| 35:07 | the thalamic beats. Now, this an example in in 9 12, |
|
| 35:12 | here it also 9 11. So is single stimulus, you produced a |
|
| 35:18 | stimulus and and this is an example sleeve stain. This is intracellular |
|
| 35:27 | So these are action potentials, this no potential this is temporal scale in |
|
| 35:31 | water of milliseconds. And here you a short pulse here, a hyper |
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| 35:40 | pulse. And what that hyper polarizing does pulse only happens once it sets |
|
| 35:50 | this bursting, repetitive firing, bursting and the themselves. So a single |
|
| 35:58 | in this hyper polarizing stimulus turns on gated sodium voltage gated channels, not |
|
| 36:04 | channels, voltage gated channels, reduce , put down channels and they have |
|
| 36:08 | kinetics polarize again. But this is one. So this is two of |
|
| 36:15 | bursts. What a bursts typically referred is a depolarization that has a number |
|
| 36:22 | action potentials on top of that So these are normal bursts, the |
|
| 36:29 | cortical bursts and this is the So how can the brain basically continue |
|
| 36:34 | oscillation? And that is because of certain structure of voltage gated channels in |
|
| 36:40 | thalamic cells of these base maker lamic and these styles and have such a |
|
| 36:47 | cortex. So if these thalamic cells going through bursting activity, cortical cells |
|
| 36:51 | also not responding to this bursting And in this case, this would |
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| 36:56 | a rhythm for sleep. So it no external stimuli while you're sleeping. |
|
| 37:03 | the sleep rhythm continues. And that because of certain properties, electrophysiological channel |
|
| 37:09 | of certain cells and their connectivity, ability of certain cells to have pacemaker |
|
| 37:16 | qualities dependent on their membrane channel uh . So if you have this rhythm |
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| 37:25 | the thalamus that is produced here, rhythm in the thalamus is also going |
|
| 37:30 | drive the rhythm cortex. And in thalamus, you have uh excitatory |
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| 37:38 | These are the relay cells that will projecting into the cortex. But in |
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| 37:43 | thalamus, as you recall, you have inhibitory cells. So this is |
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| 37:50 | example where you can have an apparent input stimulation going on the bo |
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| 37:58 | The sell is excited excites inhibition and what happens? It hyper polarizes and |
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| 38:07 | hyper polarization turns on voltage gated zum that uh voltage gated channels that produce |
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| 38:15 | burst of activity again and through this communication, right, this is negative |
|
| 38:22 | communication through inhibition, you get this activity. So just one stimulus and |
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| 38:30 | have a burst followed by inhibition. this is excitatory cell and inhibitory cell |
|
| 38:39 | fired like this inhibiting the this is stimulus of the, the R could |
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| 38:52 | , we have many pacemakers in our and our brains and our systems. |
|
| 39:00 | So now let's uh just discussed this I wanted to remind you this thalamic |
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| 39:12 | and also the laic reticular nucleus that have over the that there is also |
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| 39:17 | inhibitor loop that is forming here that influence the laic activity, it can |
|
| 39:24 | and bursting activity in the S. uh E E G and when we |
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| 39:34 | these recordings of different rhythms, we're E E G and what we discuss |
|
| 39:41 | limitation of E E G is that only will pick up star activity and |
|
| 39:48 | will only they got killed their activity the bone, a low pass and |
|
| 39:58 | from the surface, what if that is deep? The So we talked |
|
| 40:04 | how you can do pet uh uh . And also pet imaging is better |
|
| 40:11 | the surface changes, surface a anatomical changes for F MRI is better |
|
| 40:20 | deep imaging. Uh And in both , it's metabolism, its blood, |
|
| 40:27 | glucose. If we're imaging or we're that's imaging. But uh remember those |
|
| 40:37 | not correspond to electrical activity Of corresponds electrical activity. When we talked about |
|
| 40:44 | neuroscience sym techniques, both of sensitive that tracked 1-1 with number of potential |
|
| 40:50 | action potentials. These do not. what if we won't need to address |
|
| 40:56 | ? We're limited to E G on surface. But there's also M E |
|
| 41:02 | or magnetoencephalography. And this is a that is receiving an M E G |
|
| 41:14 | . Magnetic signals are generated by neurons the brain that detected by an array |
|
| 41:19 | 150. In this case, highly magnetic detectors. The researchers use the |
|
| 41:28 | to calculate the location of the sources neural activity. So you can see |
|
| 41:33 | image here and you can see that locating activity deep within different areas of |
|
| 41:41 | brain here, you're not recording electrical , you're picking up magnetic changes because |
|
| 41:53 | . When electricity changes, the charger its electromagnetic fields that get generated and |
|
| 41:59 | activity can get picked up. And M E G s have a potential |
|
| 42:05 | reveal the electrical activity deep inside and uh improved the localization of whatever problem |
|
| 42:18 | trying to localize. In this uh seizures or epilepsy, the source |
|
| 42:22 | that. So once again, if are undergoing clinical diagnosis of epilepsy or |
|
| 42:29 | , you are most likely gonna undergo experimental sort of our techniques or investigational |
|
| 42:39 | . E E G is a very way to diagnose epilepsy and seizures. |
|
| 42:52 | is a little bit more about the cortical network. So this is another |
|
| 43:01 | . This is the somatic sensory cortex that doesn't matter where you are because |
|
| 43:06 | connectivity, the thalamus cortex cortex, thalamus, this rhythmicity can be found |
|
| 43:11 | different nuclei and different uh different cortices what you have in being the normal |
|
| 43:19 | conditions, sensory signals from uh relayed in this uh tonic firing. And |
|
| 43:29 | during a the form of this predominant instead of tonic firing becomes burst |
|
| 43:37 | So these are, these are some the terms that are also reported tonic |
|
| 43:41 | burst firing, burst firing typically indicates synchronization of cells. And that and |
|
| 43:52 | you can see for example, in tray here below. So first of |
|
| 43:57 | , you have an interesting uh channel . T type calcium channels that are |
|
| 44:06 | in part for this rhythmic activity in powers. Uh Now, in this |
|
| 44:13 | , you actually have an epileptic rat in D. And our upper panel |
|
| 44:21 | , this trace is an E E recording and lower panel is intracellular |
|
| 44:30 | In the reticular theon neurons, the neurons surround the follows. And what |
|
| 44:38 | can see that now that tonic neuronal , tonic neuronal firing, this is |
|
| 44:44 | neuronal firing in one uh does not to spikes or does not correspond to |
|
| 44:53 | uh trace of deity and changes that pick up at the level of aging |
|
| 45:00 | burst firing produces a very clear dip , which means that in burst |
|
| 45:08 | it correlates closely with the E E trays during spike wave discharge. So |
|
| 45:14 | are some of the physiological things that happening in epilepsy and seizures. You're |
|
| 45:20 | this abnormal repetitive activity, sometimes you need one stimulus for it to continue |
|
| 45:25 | a long time. And when you bursting activity, that also indicates synchronized |
|
| 45:32 | , sometimes it's normal, but a of times if you record normal brain |
|
| 45:36 | , you will not see these uh we call uh spike wave discharges. |
|
| 45:42 | you would not see this bursting like and synchronized activity that you would be |
|
| 45:47 | to detect an epileptic uh uh epilepsy . Is that abnormal E E G |
|
| 45:55 | just while they're having a seizure? is it abnormal at other times? |
|
| 46:00 | maybe not quite. So, it's necessarily that it's abnormal, it's that |
|
| 46:06 | such a limiting technique. And if don't even an epileptic patient, if |
|
| 46:12 | not having a seizure, and you're a four hour reporting of E E |
|
| 46:15 | and the seizure never comes about. doctor, neurologist may not be able |
|
| 46:20 | tell the source or location of the . So a lot of it is |
|
| 46:25 | uh for diagnose purposes, people may to spend a week with E G |
|
| 46:33 | for two nights to see if they're having seizures at night versus the daytime |
|
| 46:40 | . Uh And one clear indication would before you see seizure activity is an |
|
| 46:50 | brain would have these spike wave That's sort of all like if you |
|
| 46:55 | it on, you don't see seizure , but you see periodically these synchronized |
|
| 47:02 | which we call spike waves that will neurologists something here is not right. |
|
| 47:08 | I didn't record seizure activity, but picked up these synchronized bursts that are |
|
| 47:14 | spike wave or inter spike sometimes because just that this kind of behavior would |
|
| 47:21 | happening in between the seizures and it typically increase before or after seizure |
|
| 47:30 | So it gives neurologists the flu. ? I didn't pick up the seizure |
|
| 47:35 | I picked up the spike wave, have to do further tests and it's |
|
| 47:40 | that the person has abnormal secreting. the person is a, especially if |
|
| 47:47 | committed saying that they're having seizures, know, because each person's description of |
|
| 47:51 | they're having and their level of education be very different. No, and |
|
| 47:58 | seizure of parents, this is a can range from generalized to clonic. |
|
| 48:05 | person foaming out of their mouth and all of the muscles and spasms to |
|
| 48:14 | an emotional outcry. And that is a frontal lobe seizure. So we |
|
| 48:20 | this emotional kind of aggressive outcry and the person we need to work |
|
| 48:25 | . Did I do that just Or absent seizures and young Children where |
|
| 48:31 | just go blind for about five So there's no motor component, there's |
|
| 48:36 | tonic clotting, there's no falling over stare, but they're not conscious during |
|
| 48:41 | period. It's actually a generalized form seizure. So we'll, we'll, |
|
| 48:46 | get into some of these details, or partial uh generalized seizures uh about |
|
| 48:54 | actually. So when we are talking these, the cortical signals, remember |
|
| 48:59 | we have a, a homo cortical , we look at the visional inputs |
|
| 49:03 | into layer four, we have intracortical , 2, 3 to deep layers |
|
| 49:09 | , 3. And then we have laic outputs and these loops, they |
|
| 49:15 | rhythmic activity. The cortical loops are important, generating this rhythmic activity that |
|
| 49:20 | talking about asci activity because we produce lot of tasks like, you |
|
| 49:25 | I'm waving my hand now, you , I have to have my neurosis |
|
| 49:30 | at certain frequency, not a much frequency, not a much lower |
|
| 49:34 | And my motor command center is to this right. So um and then |
|
| 49:44 | input coming into thalamus, thalamus controlling influencing uh cortex, cortex, putting |
|
| 49:51 | the output. But these loops are strong that you can have a |
|
| 49:59 | a channel pathology, you can have pathology and these rhythms now that are |
|
| 50:07 | your normal rhythms to produce synchronized repetitive activity turn into a normal rhythms |
|
| 50:18 | you can't stop repetitive activity. you are in some sort of a |
|
| 50:22 | disorder or potentially a seizure like state has a motor component. So, |
|
| 50:33 | yeah. Well, let's see. thing we're gonna talk about is incidence |
|
| 50:39 | epilepsy. Prevalence of epilepsy by age where you look. Typically it's about |
|
| 50:48 | of the population that suffers from There's some variability in this percentage of |
|
| 50:56 | that suffer from epilepsy. If you look in certain countries, they have |
|
| 51:03 | to 2% in other countries, about . Some of it is because of |
|
| 51:08 | reporting, some of it could be when we looked at some of these |
|
| 51:13 | differences in neurological disorders in the United , we said we look at these |
|
| 51:17 | , you know, that's a stroke , that's a uh motor disorders kind |
|
| 51:22 | a state. Well, uh if look across the world, different countries |
|
| 51:32 | different standards for reporting for amassing the . And then if you look, |
|
| 51:42 | , certain countries and cultures have certain and foods that either predisposes them to |
|
| 51:53 | more disease and not necessarily epilepsy. cardiac sort of stuff like that, |
|
| 51:59 | you could talk about uh obesity or that contain actis in them that have |
|
| 52:08 | to do with weight but has something do with inflammation, with circulation of |
|
| 52:15 | molecules, their precursors. So there this kind of a like AAA street |
|
| 52:23 | if you may that maybe population of has less incidences of epilepsy. And |
|
| 52:33 | because uh the diet contains a lot curriculum that has very potent anti inflam |
|
| 52:43 | and also has some anti seasonal So some of us like in the |
|
| 52:48 | cultures may consume curry or car cumin , you know, on occasion when |
|
| 52:56 | go get Indian food or you Thai food or whatnot. But in |
|
| 53:02 | cultures, it's a part of daily that's different. So then it almost |
|
| 53:08 | like when people buy turmeric as a or curcumin as a supplement, there's |
|
| 53:13 | lot of turmeric in at, at Indian cuisine as well. |
|
| 53:19 | you know, if you consume something times a day, it's almost like |
|
| 53:23 | taking a certain supplement that they have properties unintended that are good or sometimes |
|
| 53:31 | un attempted. The fact. If look at this uh curve here of |
|
| 53:38 | currents of epilepsy based on age, can see that the highest peak for |
|
| 53:45 | is in the very early childhood And then it's in this U curve |
|
| 53:51 | it peaks again in the very aging . So why, why is |
|
| 54:03 | Are there differences between what people get different uh epilepsies? It's not just |
|
| 54:11 | disease, it's many different diseases. , if you're talking about childhood |
|
| 54:16 | it could be a lot of genetic related epilepsies that emerge early on during |
|
| 54:23 | development. Uh later in life, can have causes of epilepsy from traumatic |
|
| 54:29 | injury or accidents that may be And then why is it later? |
|
| 54:35 | why more incidences about war inflammation, of brain plasticity, uh stress death |
|
| 54:48 | neurons, uh death of inhibition or of inhibition that allows a normal synchrony |
|
| 54:54 | excitation. Uh These are some of questions that we don't always uh |
|
| 55:01 | paras scientists don't have any answers to is more common in developing countries. |
|
| 55:07 | I use the example of India, example, which is a developing |
|
| 55:11 | especially with less rates of epilepsy, rates of untreated child with epilepsy, |
|
| 55:17 | and poor pre post natal care that contribute to higher rates. Um it |
|
| 55:24 | mostly young Children and elderly childhood epilepsy usually congenital, I think in general |
|
| 55:33 | genetics genes. So cause by genes sometimes by abnormality that could be present |
|
| 55:40 | birth. But most of the things we look at, they have a |
|
| 55:44 | component. A mutation of the And when we talked about the |
|
| 55:51 | channels or sub channels, they're collections strings of ao acids struck together twisted |
|
| 56:00 | in three dimensions to make this So you'll see that some of these |
|
| 56:05 | can affect just a few amino but affecting a few amino acids can |
|
| 56:10 | change the function of the channel that to a neurological disorder of severe one |
|
| 56:16 | epilepsy, uh elderly. So acquired of epilepsy versus congener acquired epilepsy, |
|
| 56:26 | , tumors. Alzheimer's disease inflammation, stress potentially uh which causes chronic inflammation |
|
| 56:35 | your brain. Uh lack of maybe or synthesis of neurotransmission. All |
|
| 56:41 | these things are, you know, good when you start eating it, |
|
| 56:45 | is more a symptom of disease than disease itself. Uh And you cannot |
|
| 56:52 | it's epilepsy. It's really the correct tumor. That's why I wanted to |
|
| 57:01 | that lecture because tumors as they start , they typically glial tumors or typically |
|
| 57:09 | tumors that this process. Remember, gliosis, we going on fire and |
|
| 57:19 | tissue formation because that Mya around the of the injury around the tumor. |
|
| 57:26 | you have scars forming and the scars blood cells now become a a complication |
|
| 57:34 | they impede with normal communication, not the tumor itself but the scars that |
|
| 57:38 | around the tumor, uh damaged the necrosis killing of the cells, |
|
| 57:46 | vessel ruptures lack of oxygen, lack nutrient supply, causing further, the |
|
| 57:52 | of their trial was a traumatic brain , Concussions, repeated concussions, penetrated |
|
| 58:01 | brain injury. Interesting thing with traumatic injuries. Uh this is one of |
|
| 58:07 | signature traumas, traumatic brain injury from latest wars in Iraq where because of |
|
| 58:16 | improvised explosive devices, such about 20% soldiers that were injured came back with |
|
| 58:23 | brain injuries. But the interesting thing was noted is that not all of |
|
| 58:28 | developed seizures or epilepsy immediately. And delay, a lot of times is |
|
| 58:35 | to as a latent period during that period. So if you suffer a |
|
| 58:40 | to your head or two blows to head, you recover. But that |
|
| 58:44 | mean that your brain has recovered fully it's functioning normally. But slowly you |
|
| 58:49 | a build up of inflammatory cytokines that unregulated or scarring tissue. And this |
|
| 58:58 | period can last a couple of weeks a decade. So the soldiers that |
|
| 59:05 | back and they were a little bit . And then two years later, |
|
| 59:08 | having 23 seizures a day. This what happened to me. So like |
|
| 59:13 | that, that happened two years The seizure first genetics and we'll talk |
|
| 59:20 | genetic mutations, sodium channels, one the common sides for uh what we |
|
| 59:28 | opathy or genetic abnormal mutations, the , metabolic dysfunction, mitochondria A T |
|
| 59:35 | production, um infections to viral bacterial infections, meningitis, cod in |
|
| 59:45 | cases, this has led to repetitive . Uh meningitis can lead to repetitive |
|
| 59:53 | and develops too vascular disease, So we have this forms of |
|
| 60:04 | Alzheimer's disease that we've discussed. But also have this micro vessel disease and |
|
| 60:08 | of a very interesting emergence and quite form of dementia. Also, it's |
|
| 60:14 | the constriction of your blood vessels that getting older a lot of times or |
|
| 60:18 | you have some sort of a uh vessel circulatory condition. Um and these |
|
| 60:25 | vessels uh now are properly delivering the and oxygen causing aosis or necrosis of |
|
| 60:33 | and leading to seizures and environmental chemical environmental. Some people have uh audio |
|
| 60:46 | and a lot sounds will cause Uh quite common to have warnings on |
|
| 60:55 | Gamers stations and games that this game a lot of strobing activity and changes |
|
| 61:03 | light. And there's a warning that have uh neurological conditions that you should |
|
| 61:10 | consult your physician before you play this game. So some people have the |
|
| 61:15 | lines and then let's say have that that occurred once from stroke lines. |
|
| 61:21 | would mean that you should have one you have back. So you have |
|
| 61:24 | have multiple seizures started down diagnosed with . Um In fact, the most |
|
| 61:31 | type of seizure is in young it's called feb seizures. A lot |
|
| 61:36 | kids that have fever will have a and maybe even two, sometimes over |
|
| 61:42 | span of a few years. It mean they have epilepsy, they overheat |
|
| 61:46 | . And during overheating hyperthermia, the synchrony changes, synchronizer kicks in. |
|
| 61:55 | you should stop that seizure as soon possible. Little kids that if they |
|
| 61:59 | 104°F, they can't take them to the right away to tell them to put |
|
| 62:03 | in the eyes bath, literally hold eyes back because you got to bring |
|
| 62:08 | the temperature. You know, it's gonna affect their organs internally as much |
|
| 62:14 | rise to temperature. It's gonna start neurons, they're very sensitive to temperature |
|
| 62:20 | . So all of these things are . Uh many cases causes the level |
|
| 62:28 | so spontaneous or sporadic. Sometimes it's happens in the older person's even know |
|
| 62:36 | it happens when the person is having shoes and having to see a neurologist |
|
| 62:42 | the dino. Uh let's see, off with these. Yeah, let's |
|
| 62:51 | very briefly discuss the channel off with . This is a trans membrane organization |
|
| 62:57 | sodium channels. So this is called sodium channels. And you have 1234 |
|
| 63:06 | in these channels and each one of subunits has six trans membrane segments. |
|
| 63:14 | four is the voltage sensing segment So this is the segment that will |
|
| 63:19 | activated by changing voltage. And then the five and six, you have |
|
| 63:25 | poor loop. That's where sub units in and form a poor loop. |
|
| 63:30 | that poor loop is a selectivity So that this channel is selectively per |
|
| 63:37 | to just so you know, other and then there's some uh uh nitrous |
|
| 63:45 | uh end here or box cell to , then you have modulatory, this |
|
| 63:53 | the inactivation part of the channel or gate that they discussed. I think |
|
| 64:01 | didn't but can now. And this a diagram. It is also from |
|
| 64:07 | supporting light materials here. So you read in more detail if you |
|
| 64:12 | This is a diagram that basically shows bot sodium channel. And everywhere you |
|
| 64:21 | a red dot They can view mutation along this channel and red. And |
|
| 64:29 | you have this red dog, you're likely going to have SME I which |
|
| 64:35 | for severe by boing apple through infancy syndrome. And we'll talk some more |
|
| 64:43 | Dr Dr Dr or severe mylo So severe means bad my clonic. |
|
| 64:54 | means it has a component of uh seizures, clonic, counting clonic mylo |
|
| 65:02 | epilepsy. It's epilepsy, infancy. means you get it as a little |
|
| 65:08 | . That's an infant. That's one epilepsy and the symptoms of seizure show |
|
| 65:14 | . So it's not just one mutation that one channel. If you fall |
|
| 65:19 | between one of these body mutations or I along the channel, you can |
|
| 65:24 | SME I if you have a mutation where there's a green dot You will |
|
| 65:32 | generalized epilepsy with deep seizures. Generalized will get in a little bit partial |
|
| 65:41 | epilepsy, generalized epilepsy. If you consciousness, febrile seizures, sometimes febrile |
|
| 65:49 | plots. So that means that that in this mutation makes the person febrile |
|
| 65:56 | . This heat induced seizures, some induced seizures. These are the seizures |
|
| 66:01 | little kids would have when they have fever. They will go into the |
|
| 66:06 | common type of seizure in Children is seizure or he do seizure doesn't mean |
|
| 66:12 | . But in the Children that will up having one of these mutations along |
|
| 66:17 | channel, al sodium channel, they end up being hyper sensitive to |
|
| 66:24 | And if their body temperature goes up 38.5 cmade, 37 is physiological. |
|
| 66:33 | fever is in the 40 C. for some of these Children or even |
|
| 66:39 | , a small rise in temperature and start having ses in fact, Children |
|
| 66:46 | have severe Microtic s of infancy will have seizures just like generalized eps of |
|
| 66:52 | seizures plus. And another interesting thing a lot of parents of these Children |
|
| 66:59 | say thank God the winter is here there is really a potential correlation with |
|
| 67:06 | ambient outside temperature, hot climates. these Children, with these potatoes having |
|
| 67:13 | seizures during hot times of the The parents are grateful when the when |
|
| 67:19 | cooler months come. So they see reduction in seizures. So there's some |
|
| 67:25 | factors that can still affect even And uh if you have a predisposition |
|
| 67:30 | you have this mutation. Uh So are the two most important gaps, |
|
| 67:39 | level of c seizures plus and severe mutations of gene sodium channel tassin channel |
|
| 67:49 | channel. This is an example of channel. It doesn't mean that this |
|
| 67:55 | the only channel that is implicated in . This is only one of |
|
| 67:59 | but you can actually have different mutations channel, different mutations of the channel |
|
| 68:07 | can lead also these different forms of , uh different forms. So they |
|
| 68:13 | not be sme I or gas but they would still be uh considered |
|
| 68:19 | form of. Oh OK. So we come back, we're gonna talk |
|
| 68:25 | about excitation and addition mechanisms. Review about the circuits of the genesis, |
|
| 68:33 | about models of seizures. And I what I'm missing here is an updated |
|
| 68:38 | of kind of a distinction between partial generalized seizures. Um So I'll try |
|
| 68:45 | prepare that for fun. To enjoy . Thank you very much and enjoy |
|
| 68:54 | rest of the week. I'll see guys on |
|
