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00:00 | is going to be posted. Now at the slide that you have |
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00:08 | Actually from the very beginning from the beginning you look at the slide and |
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00:16 | said I'm going to show that slight you toward the end of the course |
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00:19 | at the end of the course. now when you look at the |
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00:23 | you understand a lot more than you when you first looked at it about |
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00:28 | months ago, you understand how neurons glia function on an individual unit |
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00:37 | You understand how membrane proteins and channels I on a tropic metal tropic, |
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00:44 | gated, chemically gated all of these that are happening in self. You |
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00:50 | how cells communicate to each other and these circuits. There are different subtypes |
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00:55 | cells and they produce their distinct patterns action potential and processing information and that |
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01:03 | circuits form larger networks and these larger then intertwined with other brain structures in |
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01:10 | brain and they form with you would a complete understanding whether it's a visual |
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01:19 | , auditor perception or the association of of these modalities together. So from |
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01:25 | single amino acids, two proteins, membranes to ions to neurotransmitters, signaling |
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01:34 | neuro transmission, gap junctions, networks, loads, all of them |
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01:41 | different functions and all of them having different reverberations or oscillations throughout the |
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01:49 | And this is going to be the subject for today. And in order |
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02:01 | understand brain rhythms. We have to about how to record those brain rhythms |
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02:07 | how we started understanding that those brain means something and this is the story |
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02:15 | the hologram. Sometimes the forest is interesting than the trees similarly were often |
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02:21 | concerned with the activities of single neurons with understanding the activity of a large |
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02:26 | of neurons. Okay that's interesting. ? Pick any sport you like? |
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02:35 | sport, soccer, football, you're interested in what that single player does |
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02:41 | more so importantly how the other players the team moved. And without that |
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02:48 | is no coherent activity in this network players that gets communicated against their |
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02:55 | So that's just a simple analogy. Eeg is a measurement of electrical activity |
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03:01 | the surface of the scalp that enables to glimpse the generalist activity of the |
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03:06 | cortex. So when we talk about . G. We're not talking about |
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03:10 | some spinal cord brain stem. We're about recording some cerebral cortex and from |
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03:16 | surface of the cerebral cortex. The of the V. G. Rely |
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03:21 | the work done by English physiologists, Cotton 1875 cotton made electrical recordings from |
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03:26 | surface of dog and rabbit brains using device sensitive to voltage. So you |
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03:33 | stuck electrodes and these recordings in the century. The human E. |
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03:38 | Was first described by Austrian psychiatrist hans in 19 29 who observed that waking |
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03:45 | sleeping in Giza distinctly different. And figure this figure below shows one of |
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03:51 | first published records taken from the head his 15 year old song Klaus. |
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03:57 | . The egg is used primarily to diagnose certain neurological conditions especially the seizures |
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04:03 | epilepsy and for research purposes notably to the stages of sleep and cognitive processes |
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04:10 | wakefulness. This is all about the of the brain functions of the |
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04:14 | And how can we understand the non . We talked about the imaging techniques |
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04:20 | scan MRI Fmri functional imaging. We about experimental techniques where you have to |
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04:27 | the dies on the surface of the or the tissue of all the sensitive |
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04:31 | calcium sensitive guys. But we want also measure activity non invasively specifically electrical |
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04:39 | that you can pick up non invasively the scalp. Oh so this is |
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04:50 | example of what you would call and . G. Helmet or E. |
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04:57 | . Cap. Where these electrodes are positioned have a certain positioning. Geodesic |
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05:07 | on the surface. It's a great the electrodes and each one of these |
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05:11 | will pick up the electrical activity from surface of the cortex that comes through |
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05:17 | skull through the scalp. Well compare activity in local regions and we'll tell |
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05:23 | about the brain rhythms or these oscillations what is happening in different distinct regions |
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05:28 | the brain in some instances where for you have either epilepsy uh focus or |
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05:38 | in the brain that keeps generating seizures that's really bad because that place in |
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05:44 | brain that keeps generating seizures is essentially up, it's short circuiting electrically. |
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05:50 | a massive inflammatory loud load in that . And it also is neuro degeneration |
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05:56 | to happen in that region. It will spread in the surrounding regions in |
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06:01 | perimeter of that main core issue. if you have to us growth. |
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06:08 | for example the most common tumor in brain is gliomas, big leo tumors |
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06:15 | form and now you have to cut tumor out of the brain. You |
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06:20 | to have neurosurgery. In that case will image the brain using FmRI FMRI |
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06:30 | that you already discuss and you will the location of the tumor. You |
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06:35 | then place an E. G. an individual to understand with. Around |
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06:41 | you are what you know is there's abnormal electrical activity through the eeg |
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06:48 | . You have to now open the and take or resect. It's called |
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06:55 | resection of brain tissue reset that tumor of the brain. The last step |
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07:01 | you will do is it will actually a grid after a lecture. This |
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07:05 | done intra operatively during the operation pre of the brain tissue. You place |
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07:12 | on the surface of the actual So now you have the skull open |
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07:17 | dura matters removed and now you're placing to pinpoint exactly with a lot more |
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07:25 | , spatial specificity. The area that that area tumor area seizure in the |
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07:32 | that are surrounding that do not in way affect major functions. If you |
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07:39 | on these areas, if you cut areas out. So using all of |
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07:43 | techniques then you can actually do neurosurgery cut out a piece of the brain |
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07:49 | . It's about 8-10 years of uh to become a neurosurgeon. So it's |
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07:54 | very very, very serious work. long surgeries. Uh neurosurgeons will work |
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08:01 | PhD and electro physiologists in the surgical room because electro physiologist neurophysiologist will be |
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08:10 | them with, especially brain surface or recordings intra operatively. So in this |
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08:20 | you actually have a lot of collaborations basic scientists, PhD who may be |
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08:25 | the rest of his time doing studies a mouse brain or right brain or |
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08:30 | like that. But spending a few every month working with neurosurgeons in helping |
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08:36 | understand and decode the electrical activity from electrodes. The more plasticity there is |
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08:45 | the brain. The earlier, during development of critical period of development you |
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08:51 | these surgeries, the more chances for recovery of the brain tissue and the |
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08:58 | chance there is for a significant loss function in older adults or older individuals |
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09:05 | and older individuals if you have if take a piece of the brain |
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09:11 | inevitably have some significant loss of function does not rebuild and regenerate itself because |
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09:17 | isn't that same amount of plasticity anymore the was following. Such significant trauma |
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09:24 | the brain and Children, there is a procedure that's called hemispheric to me |
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09:29 | the entire hemispheres removed. And that's one hemisphere is generating abnormal electrical |
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09:37 | It's starting to burn tissue on one through corpus callosum is communicating that abnormal |
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09:44 | of activity into the other hemisphere and now starting to burn the other hemispheres |
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09:49 | order to save half of the You remove. This entire demonstrates down |
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09:53 | smaller Children that have very very severe conditions like we mentioned epilepsy or uh |
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10:02 | growth. And so when you place grid of electrodes on the surface, |
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10:07 | one of these electrodes and comparing that to nearby electorate gives you a comparative |
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10:13 | . So each one of these traces can think of as a is each |
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10:18 | of these electors that's placed on the of the brain. And it will |
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10:22 | up different rhythms. This is for an alfa rhythm. This is a |
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10:26 | rhythm and we'll talk more about different of rhythms. This is a blinking |
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10:32 | that it will pick up as So there's artifacts that happen and there |
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10:36 | filtering and sorting that you have to and there's a lot of significant filtering |
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10:40 | happens through the skull and through the . We need to pick up the |
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10:45 | on the other side non invasively three . Recording that's uh to be able |
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10:54 | older patients uh surgery. Not if cut out pieces of the cerebral cortex |
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11:04 | you cut out the optical area of cerebral cortex. Now there's no recovery |
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11:10 | function. What about areas are responsible ? It depends how strong the lesion |
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11:16 | the cottage town. Yeah it depends significant there is the connectivity. Sometimes |
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11:23 | not even the large area but it's connectivity that gets destroyed and now you're |
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11:29 | large areas that would communicate through that those highways. So. Yeah |
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11:36 | It's very good questions. Uh This the rhythms eyes closed. You have |
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11:43 | alpha waves that have certain amplitude and eyes open to have the amplitude decrease |
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11:48 | the frequency changes too. So alpha relaxed wakefulness beta. And intense mental |
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11:55 | . And it's in frequency in hertz per second. How many oscillations are |
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12:00 | picking up? Delta is drowsiness data driving this pathology during wakefulness but theta |
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12:07 | fast gamma. And also ripples are rhythms that are very important for learning |
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12:13 | memory. So what is what is ? What are these rhythms? Why |
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12:20 | there what happens between 10 and What happens between 40 and up? |
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12:29 | these rhythms? What do they They represent different state of being? |
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12:35 | represent different behaviors? You're mentally intensely in the task or you're asleep and |
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12:41 | brain rhythm changes? Okay so this patterns that stupid cop a sleeve drowsy |
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12:52 | sleep pattern. They are different dominant that fall within these ranges of |
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13:00 | In other words if you put the on and you record and recording your |
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13:04 | and you try to make sense of that synchronized activity. Those are going |
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13:09 | be the dominant rhythms that you will . So what are you picking up |
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13:14 | activity when you're recording? E. . This is your E. |
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13:18 | Electrode again that's sitting on top of scalp. Underneath. There is a |
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13:24 | , there are three million Gs. there is a primary superficial layer one |
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13:31 | the cerebral cortex, layer two, three, layer four, layer five |
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13:35 | six going down. And if you anatomically the structure of the neocortex is |
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13:42 | you have the tyrannical self projecting their dendrites all the way through the superficial |
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13:47 | 12. And so essentially when there activity in these local serpents around cells |
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13:54 | . G. Is not picking up from a single cell, It's picking |
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13:58 | activity from the circuits of cells that sitting underneath that particular electrode that is |
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14:04 | one of the electrodes on the grid you can have 34, 800 something |
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14:09 | go as many as several 100 electrodes the surface of the brain. If |
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14:14 | want to be more specific special when cells are active there's gonna be charges |
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14:21 | outside deep polarization, there's going to charge positive charge is coming inside and |
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14:27 | going to be electric fields that get to electrical magnetic fields that get generated |
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14:34 | they get filtered through all of these and the scalp and the scalp and |
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14:39 | like a low pass filter and eventually that signal into the processing. So |
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14:47 | like if you're looking at that uh of a network and if that activity |
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14:56 | irregular activity that means that each south uh six cells depicted here is an |
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15:02 | of this network. Each one of six cells is doing their own thing |
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15:07 | of like when you look at the again let's use the analogy of the |
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15:13 | , any of the team sports before game and warming up everybody's doing their |
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15:18 | thing, they're kicking the ball. if you look there's no coherent activity |
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15:22 | the team. So there's no synchrony no synchronized activity in the players and |
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15:28 | all rushing forward defeating defending. Uh now if all of these neurons get |
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15:36 | by stimulus stimulus all of these neurons the same and very strong input. |
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15:42 | that input is repeated and now you neural transmission and communication and you also |
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15:49 | gap junction transmission and with the help gap junction gap junctions and these common |
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15:56 | inputs. What happens if you some coherent activity in the network or synchronized |
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16:04 | will see that you can now pick a some eg recording that is meaningful |
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16:11 | it's not to say that this E . Recording that is not synchronized is |
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16:15 | meaningful because everything is like a history happens in the past in the brain |
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16:19 | will determine something that happens in the . But this is one way to |
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16:24 | about these dominant rhythms of the rhythms the south synchronized coherently and produced these |
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16:31 | rhythms within the dominant frequencies. One my favorite neuroscience books are by Euribor |
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16:38 | . I'm on the slide mouth that rhythms of the brain Jury Busacca and |
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16:42 | left Oxford University Press. And we this uh circle of life. They |
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16:53 | the circle of life and then the you can have certain phases in this |
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16:59 | of life of birth. Life and . It's the concept that is prominent |
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17:05 | permeates in science and philosophy in Um And it is quite often that |
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17:17 | picture of nature emerges as being imbalanced both biological and religious interpretations. Philosophical |
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17:29 | nature will balance things out. Let's an example of how we can pollute |
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17:37 | earth in one region of the earth we can maybe upset the earth and |
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17:43 | the earth is going to erupt the and kill half a billion people in |
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17:47 | region that is polluting the earth. you could say maybe that's nature balancing |
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17:55 | . I mean things like that happen ? But uh so if if it |
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18:04 | all in the stable equilibrium then we keep it this way then there shouldn't |
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18:13 | any environmental summits, electric cars, it drill, baby drill, Let's |
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18:22 | it this way. Nature will take of them again, You know, |
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18:26 | flood the coastal zone so there won't people here, they will, they |
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18:30 | not need gas or die. But , that was the case. How |
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18:37 | we get here in the first And that's kind of a question of |
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18:46 | . How did we get here in first place? Everything was balanced and |
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18:50 | we have a lot of parts of brain body, for example, is |
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18:54 | of balance and consumes a lot of . It's a non linear system. |
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19:01 | you have this intimate relationship, these all food for thought. I don't |
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19:06 | if I can make an exam question of this, but something for everybody |
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19:10 | think about. I think that it's clear that we can tip the balance |
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19:14 | nature, that it's a certain We are an active players in |
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19:19 | One way or another, we can that balance. So this intimate relationship |
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19:24 | space and time is packaged into the of space time, like Y. |
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19:29 | . T. Dimensions, the oscillations synchronized activity in the south or oscillations |
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19:37 | auditory signal oscillations and hair cells. can be conceived of as displayed in |
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19:44 | of either space or tom the face of a sign of subtle harmonic oscillator |
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19:49 | a circle, face plane. We walk the perimeter of the circle |
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19:56 | twice or billions of times. And we always get back to groups. |
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20:02 | always get back to our starting So the quote is what has |
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20:08 | is what will be and what has done is what will be done. |
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20:11 | there's nothing new under the sun. is the circle of life and I |
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20:16 | in. This perimeter is measured by as a dislocation as an alternative to |
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20:24 | . View of the universe is to periodicity is a series of sin |
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20:29 | There's a circle. In fact, can take the circle and break it |
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20:33 | into sine lines. So center for two. That's almost. But now |
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20:39 | can walk along the troughs and peaks the line. We can walk peaks |
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20:47 | Charles. This is panta rei. uh without ever returning to the starting |
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20:57 | and these explosions are not always balance equal. Um or the media over |
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21:05 | , I don't know the time. is a continuum of the cycle is |
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21:09 | metric. The cycles are identical in and the start and end points of |
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21:13 | cycles from an infinite path into seemingly universe. That's pretty cool just to |
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21:23 | about stuff. So now we have rhythms in the brain and this activity |
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21:33 | it just, it just walks this walk along like a sinus or it'll |
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21:40 | along some axis of time and space because we have the electrodes. And |
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21:46 | we're measuring activity in space and And you'll find a lot of similarities |
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21:52 | rhythms and humans and monkeys, rabbits, rodents. In some |
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22:00 | like algorithms will not be present in rabbit. So not all of the |
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22:06 | will have the same rhythms, not of the same rhythms will be present |
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22:09 | the same parts of the brain are the same parts of the brain. |
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22:14 | have spindles and ripples and spindles and illustrate, especially in the case of |
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22:20 | ripples. Some other they're interesting quality the circuits in the brain that they |
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22:27 | sustain multiple rhythms at the same So it's just like the symphony |
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22:33 | right? You can have the cello slow on top of that, you |
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22:39 | have violins going really fast. So the same circuit and the orchestra is |
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22:48 | these different rhythms at the same Sometimes they're resonant, sometimes they're |
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22:56 | sometimes they're syncopated, Sometimes you would they're chaotic and their non synchronized. |
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23:05 | now what you see here is these polarization, mostly deep polarization, sometimes |
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23:11 | polarization is at a slower, So a slow ongoing rhythm in the |
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23:17 | And on top of this slow rhythm , you have these very very fast |
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23:23 | . There are ripples and those happen hundreds of hertz. So hundreds of |
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23:29 | per second. Very fast rhythms. spindles and ripples are very important for |
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23:35 | and mammals. Mhm. How these created. They created because from the |
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23:43 | beginning of this course side uh talk you to think about neurons speaking different |
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23:52 | of the same language producing different different frequencies of action potentials. And |
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23:58 | have over 100 and 4800 and 50 setbacks of neurons. These dialects and |
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24:04 | ability to produce fast firing versus slow will influence whether it's fast rhythm, |
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24:09 | rhythms or somewhere in between excitation versus up. If it's all excitation there |
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24:16 | be a lot of prolonged action potential . So but then inhibition kicks in |
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24:20 | there's a control and there's a breakup these rhythms. You have neural transmission |
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24:29 | you have gap junctions and it's not glutamate and gaba excitation and inhibition. |
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24:35 | about serotonin? What about dopamine? they cause different rhythms? Yes. |
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24:42 | now you're talking about what you've learned . The collections of these neurotransmitter systems |
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24:48 | influencing actually ruth ethnicity and how if is upset with message as you'll see |
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24:54 | apple Fc. And obviously there is in some of these systems glutamate |
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24:58 | Gaba system, it's depression, serotonin and so on. Howard rhythms created |
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25:05 | external entrainment. Those are the signals are coming at us. Those are |
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25:12 | signals that we've been trained. We listen to herring in the water and |
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25:18 | , we listen to human voices. our frequency range and how we preserve |
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25:24 | and how we pay attention to there's certain range for auditory or visual. |
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25:31 | it's external entrainment. It's also how does your car shape? That's your |
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25:38 | entrainment or doesn't shape? Um Why many a solitary regimes? So you |
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25:47 | these very slow regimes. The slowest that you can think of is your |
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25:52 | cycle. You're super charismatic, See some light and starts producing prescription |
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25:58 | that tell the rest of the Wake up, it's morning time. |
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26:03 | the evening time lights are dimmed and charismatic. Nucleus tells the rest of |
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26:08 | brain go to sleep and starts producing transcription factors. You have very slow |
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26:15 | rhythms. You have a lot of rhythms that are even slower than |
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26:20 | You have the cycles. Some monthly . You have in the brain rhythms |
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26:27 | that are slow on the internal It's tens of seconds, few |
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26:36 | 21 oscillation per second delta, low fada 4 to 10 beta, 10 |
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26:45 | 30. Gamma. 30 to 80 rhythm and ultra fast or ripples would |
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26:53 | within this 200 to 600 rhythm, , Hz. Did you know that |
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27:00 | circuits can oscillate at 600 cycles a . That's very impressive actually. You're |
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27:11 | . So, Penton abu zaki why so many facility regions? Multiple |
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27:21 | . You sleep with one rhythm awake a task that was a different |
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27:27 | You have to be precise and You have to manipulate Circus must be |
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27:31 | to play multiple rhythms depending on what demand is with the situation. External |
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27:37 | and internal symbol in our if you slow and fast you have distinct levels |
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27:44 | computation. Now you can take this and you can say it can break |
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27:49 | up into these rhythms to represent different . There's some computation behind this, |
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27:56 | maybe some mathematical system behind it. when you align these dominant rhythms here |
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28:03 | you put it under Ellen, which supposed to be a church for |
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28:10 | you take a log of the What you're seeing is that these dominant |
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28:17 | delta theta, beta, gamma ultra fast, separated by a single |
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28:24 | along this Ellen scale, log Uh So there is maybe a mathematical |
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28:32 | to or at least there is a interpretation of what is happening in the |
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28:37 | which is inevitably tied to what is happening external into stimulating. We're getting |
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28:44 | . So our next topic is I've seen why epilepsy because epilepsy as |
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28:50 | was described in E. G. . G. Would be used to |
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28:56 | epilepsy to detect seizures and epilepsy is rhythmic brain disorder and one of the |
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29:04 | diagnosis is using egg affects about one . So the incidents of new epilepsy |
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29:11 | is high uh after birth and infancy then it decreases it has this almost |
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29:20 | U shaped curve and it increases again 55 60 years of age, the |
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29:26 | of epilepsy and seizures, There's many kinds of apple FC's so it's really |
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29:32 | just epilepsy, but it's apple it's more common in developing countries. |
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29:39 | rates and childhood it's associated with Often if there's poor prenatal postnatal care |
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29:47 | can increase the uh possibility of it occurs most often in young and |
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29:57 | . The childhood epilepsy is typically caused by genetic disease of abnormality present |
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30:04 | birth and elderly tend to acquire Annapolis a consequence of conditions such as uh |
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30:13 | , tumors, stroke or other diseases we call comorbidities, comorbidities such as |
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30:21 | disease. If you have Alzheimer's disease your 55 years old, you're upwards |
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30:27 | 60 times more likely to develop epilepsy seizures. If you have Alzheimer's disease |
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30:33 | a certain age, you have a chance of having this co morbidity they're |
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30:37 | comorbidities are trying to go kill Alzheimer's is trying to kill you and |
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30:44 | is trying to kill you. So comorbidities, diabetes Annapolis sees color ability |
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30:50 | both of them are trying to kill . So in this case you have |
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30:54 | growth. Of course, do we . We discuss leo sis reactive fibrosis |
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31:00 | tissue formation. So glial when it cleaning out damaging the brain, it |
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31:05 | forming scar tissue just like you would in the skin, but that scar |
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31:10 | and the brain means that there is proper communication, neural transmission can cause |
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31:15 | significant problems damage the tissue, ruptured vessels or in grown blood vessels to |
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31:25 | the tumor trauma such as traumatic brain , uh concussions, multiple concussions, |
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31:33 | concussions can lead to epilepsy, genetic , metabolic dysfunction, viral bacterial |
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31:41 | meningitis, which can be the bacterial viral, which is the brain infection |
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31:47 | lead to epilepsy covid there is a small percentage of affecting and leading to |
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31:57 | , vascular disease of micro vessels. abnormal micro vasculature, abnormal feeding of |
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32:07 | nutrients and oxygen to brain regions and components toxins, chemicals. In many |
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32:13 | the cause of epilepsy is not You guys remember this channel that's just |
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32:22 | gated sodium channel. It has four , it has six trans membrane |
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32:29 | It has the inner pore loop between five and a six S four serves |
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32:33 | voltage sensor, beautiful channel. Remember comprised of all of these different sequences |
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32:39 | amino acids. And so this is same channel as an example of the |
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32:47 | common genetic mutations that lead to epilepsy sodium potassium and calcium channels in this |
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32:53 | is an illustration of sodium channel. everywhere you see along these sub units |
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32:58 | these trans membrane segments, a red in that channel will result in sME |
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33:07 | , which stands for severe my chronic of infancy. It's intractable or untreatable |
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33:14 | deadly and over 20% of Children epilepsy literally die at night in their sleep |
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33:23 | . You see these green mutations in same channel. You will have guests |
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33:29 | stands for generalized epilepsy with febrile We'll talk about generalized epilepsy in the |
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33:35 | febrile seizures are the heat induced, thermally induced seizures. And in |
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33:41 | febrile seizures are quite common when they an infection and the temperature goes up |
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33:47 | and they start having what is called febrile seizure and you may take them |
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33:50 | the emergency room and they may never it again. But if you have |
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33:57 | seizures, if you have epilepsy and are very susceptible to febrile seizures, |
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34:03 | small increases in body temperature and even temperature and provoke seizures constantly. And |
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34:11 | Children that have jeffs gaps, types seizures and their parents are looking forward |
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34:18 | colder months and cooler climates because it affect how many seizures the kids would |
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34:24 | having a day or a week, on requirement. Um you can alter |
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34:33 | functions of sodium channels, they may longer in the excitatory cells and too |
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34:39 | sodium coming in, there's gonna be much of glutamate release. Maybe there's |
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34:44 | mutation and the inhibitory south and sodium and we know that there are mutations |
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34:49 | then there's not enough of sodium coming de polarize inhibitory south. So there |
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34:54 | enough inhibition. So this is kind the general themes. But there's other |
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35:01 | in potassium channels calcium channels that can to many different forms of epilepsy. |
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35:06 | I'm using here sodium channel we're familiar to discuss those two types of epilepsy |
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35:13 | general Apple etc. On a gross of things. If you think about |
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35:18 | . G. Recordings, what is what is the peak the keepers deep |
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35:23 | ? What is the trough? The ? Is the hyper polarization? So |
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35:28 | means there is excitation for deep There is inhibition, hyper polarization. |
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35:34 | most of our brains, they are walking along this plank, this blue |
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35:41 | sitting on the triangle here and this is shifting and swinging as we walk |
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35:48 | it, not only up and down sideways too. And then Apple |
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35:55 | One of the easy ways to explain start thinking about you about pathologists is |
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36:01 | that is referred to excitation and emission . What happens if this plank is |
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36:09 | ? If there is too much there's too much excitatory activity, There's |
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36:16 | enough inhibit their activity. So there's much of the excitation And now what |
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36:24 | want to do is using therapy, want to rebalance it. So you |
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36:28 | to rebalance excitation and inhibition And most the cases most of the anti what |
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36:34 | called anti epileptic drugs are really anticonvulsant because there's no drug that will cure |
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36:38 | epilepsy so far. But in some seizures and epilepsy is with certain drugs |
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36:44 | go away and it partly is maybe part of the developmental process to you |
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36:51 | want to dampen glutamate. So you're starting to think about, okay, |
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36:55 | are the therapy strategies? What have learned about excitation inhibition? What if |
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37:00 | plank is imbalanced? What do I to care about? I need to |
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37:05 | about synaptic transmission. I need to about enzymes and synthesized gabba and vitamin |
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37:10 | need to care about transport, particular . I need to care about member |
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37:17 | transport of these neurotransmitters back. If need more Gabba transported back, all |
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37:22 | these strategies become part of your a call kind of a therapeutic approach |
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37:28 | the disease. So you have to types of seizures that distinguish generalist |
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37:39 | roses, partial seizures and generalized seizures have loss of consciousness. Uh type |
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37:48 | the generalized seizures. Grand mal and mall. They're both generalized seizures because |
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37:54 | both grandma and the gym, all lose consciousness grandma is occurs with the |
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38:04 | . That is described as an aura means an individual feels or suspect as |
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38:11 | as a good feeling. Something is or about to begin alexander, the |
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38:16 | said that his aura was so fantastic gave him such incredible visions that he |
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38:21 | want to trade his apple apps Uh for not having that or |
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38:28 | So there's some interesting activity in the that is happening or preceding seizure |
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38:34 | That individual sense the best of detecting that will happen in humans or dogs |
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38:42 | are specifically trained for that that can their owner about two minutes before seizure |
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38:48 | happened the symptoms and learning about So grandma, you have lots of |
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38:55 | . Then you, when you think the typical seizure upwards, you heard |
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38:59 | somebody's on the floor, they're shaking jerking. The phone is coming out |
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39:04 | their mouths. That's what you think epilepsy and seizure and tonic clonic. |
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39:10 | is what it's called, tonic clonic . This could be a tonic |
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39:14 | rigidity of muscles and attention and literally like turning the hands and the |
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39:21 | and getting it stuck. It's really . Or it could be spasms and |
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39:27 | , which is what you would if somebody is jerking or twitching on |
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39:30 | floor having a fit. There's another term procedures as a fit. |
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39:37 | not like a, you know, fit, but in this case, |
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39:42 | physiological and emotional psycho, physiological, , psychological and following that there is |
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39:49 | to the depression, recovery phase mental because during generalized seizure you have to |
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39:56 | generalized seizures, grandma's within half an , otherwise they start burning brain circuits |
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40:01 | they start killing you and making your down so you have to stop them |
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40:06 | half an hour. And if you a seizure that lasts for minutes or |
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40:13 | when people recover from their seizures, are absolutely exhausted mentally, physically and |
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40:18 | lot of times there's this political depression there is no signal, not much |
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40:24 | in the brain tune. So as you've shaken up and activated all the |
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40:31 | and the circuits and burning them up now they're silent for a while. |
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40:35 | need to recover in this post natal stage absence, seizures that are more |
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40:40 | than Children are also generalized seizures and don't have a tonic clonic component at |
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40:46 | . So here is the type of seizure that you would say, what's |
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40:50 | on with the skin, just staring space and that's exactly what happens you're |
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40:55 | with your child and then all of sudden they would turn their head and |
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40:59 | blank stare in space during the awake The start of nowhere and then |
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41:06 | out about 10 seconds later and they , were you talking to me about |
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41:12 | ? You know? And yeah, don't remember what happened. So seizures |
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41:18 | but different types of seizures can have motor component. You can have a |
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41:22 | seizure or simple partial seizure of complex seizures. Simple partial is that means |
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41:28 | it is in one area of the . Complex partial is you have focal |
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41:35 | impaired awareness with the focal onset means starts in one spot in the brain |
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41:42 | you have generalized seizures, you have of solano cortical circuits to remember this |
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41:47 | , thalamus, the cortex, cortical cortical thalamic through these circuits, |
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41:52 | generalize the seizures and this is where lose the consciousness focal seizures or simple |
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41:59 | seizures. For example, if you seizure activity in the motor cortex, |
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42:04 | can actually have a tonic clonic component you can become completely consciously aware of |
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42:12 | tonic clonic component in your leg and really painful and annoying, you can't |
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42:17 | it. So again, when you about appearances of seizures don't think |
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42:23 | Somebody has fallen on the ground has out of their mouth and not having |
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42:28 | so called fit. It's really a different array of all sorts of |
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42:34 | Annapolis is frontal lobe seizure so often as freaking out and screaming and swearing |
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42:42 | throwing things and then coming out of and saying what's going on, what |
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42:45 | I do? And they record of activity. Really massive of normal activity |
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42:51 | the frontal cortex. The brain structures are very susceptible to epilepsy and |
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42:58 | Hippocampus and neocortex. You think about functions encoding of memory, retrieval of |
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43:07 | . It's a part of the limbic , emotional processing, semantic memory, |
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43:15 | , so that part of the brain wiped out. A lot of these |
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43:18 | are getting wiped out. Neocortex. depends where in neocortex, that seizure |
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43:24 | originating from where the focus is of seizure, whether it's in the left |
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43:29 | , right hemisphere exhibit alone, temporal the most common seizures. Apple, |
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43:35 | see, sorry, I'm for a revolution. Uh huh. Mhm. |
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43:49 | structure is also hippocampus, neocortex are only susceptible to damage rappel, of |
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43:54 | seizures. Alzheimer's disease. Schizophrenia also affect these regions. This is a |
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44:00 | in a that has a cap in there's an aura, the feeling that |
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44:06 | is about to happen and then you can see that activity starts between |
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44:12 | , It looks like 16 and 13 and then spreads to another five electrodes |
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44:19 | then in be the person who is having a seizure and then see that |
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44:24 | has now spread. We call this march. It marches through the brain |
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44:30 | the circus, it becomes generalist. if you have repeated seizures you would |
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44:36 | neuro degeneration. This is in the and if the campus will also be |
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44:41 | degenerated and other neurological conditions such as and other parts of the brain will |
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44:47 | a new journal neuro degenerated and other . Parkinson's disease will be dope and |
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44:52 | degeneration. Alzheimer's disease. You will call an urgent neurons are leon but |
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44:59 | are important and susceptible parts of the . There's something in these circuits that |
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45:04 | and can sustain these abnormal levels of . Not in the peripheral circuits, |
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45:09 | words. Yes. Oh, euro can occur in different parts of the |
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45:18 | depending on what the condition is or type of absolute top epilepsy it |
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45:23 | Yeah. The most common one is lobe epilepsy and hippocampus is located behind |
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45:29 | the temporal lobe if you may and why it is also one of the |
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45:34 | acceptable structures in the brain but it occur other places to damage. So |
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45:41 | talk about this balance again in the approaches and most of the therapeutic approaches |
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45:47 | a policies to boost inhibition through Galba . So Gabba will boost inhibition. |
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45:55 | barbiturates. Gabba busy stands for The guys have been so classical anticonvulsant |
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46:05 | and boosting inhibition. What else wants gather receptor? Oh that's a |
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46:12 | All right. So what do you think binding of Gaba makes Gaba feel |
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46:20 | of a similar to ethanol. Benzodiazepines necessarily bind the same way. The |
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46:29 | is intoxication and for Children, benzodiazepines have significant side effects or any epilepsy |
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46:39 | but it's also causing a drunk like . But glutamate and glare. Let's |
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46:50 | back to the subject matter that neurons glia dramaturgical signaling or the balance of |
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46:57 | is very much dependent on Julia and synthesis and when there is too much |
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47:03 | the activation of glia there is reactive sis there is overproduction of glutamate and |
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47:09 | release of glutamate Biglia. So now is actually boosting this excitatory tone and |
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47:16 | excitatory and talents because glee is very involved in the control of the excitation |
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47:24 | most of the therapeutic approaches are still gaba receptors but now think about all |
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47:31 | the cool things you've learned about Can you target vesicles. Can you |
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47:36 | vesicles binding. Can you degrade What happens if you do great blue |
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47:43 | make, do you go brain dead and you're all inhibited mount stop So |
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47:49 | of these different things? Yes. . An M. D. A |
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47:58 | and glutamate receptor inhibitors now that there's not antagonists are not used. The |
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48:03 | is that all of these drugs, of the things are pills that you |
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48:07 | , they will have a systemic Now the systemic effect. And if |
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48:11 | have a focal problem where you have mutation in one circuit, you're now |
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48:16 | that systemic effects of the drugs and future drugs will really get have to |
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48:21 | more specific to glutamate vesicles versus vegetable serotonin vesicles versus dopamine and so |
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48:30 | . Huh? So but this is of the things we need to think |
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48:35 | . And when we think about epilepsy start actually talking about cannabis and cannabinoids |
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48:40 | the reason why because you learned about endocannabinoid system and cannabis contains Fido can |
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48:47 | . So you learned an undercover avenue . You produce your own cannabinoids inside |
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48:51 | body to a rocket. Donald glycerol . G. And then and a |
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48:58 | and cannabis plants that are phyto cannabinoids get produced in these try combs, |
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49:05 | translucent protrusions on the female cannabis flowers they're synthesized here together with the aromatic |
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49:14 | ins and that's the smell of cannabis comes through the olfactory system in the |
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49:20 | of different Turpin's that you'll find in tri cones? So cannabinoids, phyto |
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49:28 | and endocannabinoid will act through cannabinoid And you already know that this retrograde |
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49:35 | of endocannabinoid will target CB one receptor is located preseason optically on neurons. |
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49:42 | two CB one receptor will control both release of glutamate and gaba. So |
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49:47 | is a really attractive system and balancing and in condition to CB one |
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49:52 | And uh and phyto cannabinoids. CB receptors although they are also found in |
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49:58 | neurons are predominantly expressed them. Wheel and CB two receptors are dominant in |
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50:04 | micro glial cells that control and influence of the functions of the microbe leah |
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50:09 | pro inflammatory cytokine release and CB two control inflammation and control this pro inflammatory |
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50:17 | release by microglia Activation of CB one neurons will cut off calcium influx and |
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50:25 | control again whether glutamate gaba release. an attractive system to work with them |
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50:31 | contaminate our system. And why do talk about Canada's and epilepsy? Because |
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50:36 | hundreds of years people have seen for of years actually epilepsy have been treated |
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50:42 | cannabis. Uh This is uh William dr William O'Shaughnessy, a medical |
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50:50 | brilliant physician also brilliant inventor. He working in India playing telegraphs, working |
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50:58 | the uh british government uh and he a court physician also. And when |
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51:07 | was in India he discovered indian hemp or ganja known in India and he |
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51:15 | multiple applications of India and how that were using locally including the production of |
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51:25 | milk preparation called bang or cannabis flowers mixed together and smushed together with cream |
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51:32 | milk. And it is drawn during of the biggest religious festivals in |
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51:39 | And so he observed all of this he took indian him back with him |
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51:46 | he started looking at how to So he took cannabis flower uh and |
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51:55 | used ethanol and he extracted those try and he prepared these extracts that are |
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52:02 | also as a hashish. Hashish is a different drugs from marijuana or from |
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52:07 | . It's actually translucent try counts that been separated from the plant and |
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52:13 | So this is from 1843. It's case of infantile convulsions that they're interesting |
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52:21 | of this disease has recently occurred in private practice. The particulars of which |
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52:25 | have the permission of the family to in this paper on the seventh I've |
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52:32 | dr Nicholson and consultation and despairing of cure from the help. It was |
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52:37 | to intermittent. It's used to apply mustard poultices to the gas stream and |
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52:41 | give a dose of castor oil and . The child however rapidly became worse |
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52:47 | the two p.m. At a tonic spasm in which lasted without intermission until half |
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52:53 | six p.m. So this child started having having some treatment and it's not helping |
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53:03 | has four hour long seizures. The back was tried without solution to the |
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53:09 | . So called bath cold helmet will used to stop of normal brain activity |
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53:14 | be used to quiet too low temperature the signaling in the brain overall |
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53:21 | Okay, so they tried to give full doctor didn't work. The help |
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53:26 | therefore again resorted to and the dose 30 drops equal to 1.5 grains of |
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53:31 | resin was given at once. Immediately this dose was given, the limbs |
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53:38 | , the little patient fellas fast asleep so continue for 13 hours. So |
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53:45 | gave this child some hashish in the of the drops in the oil. |
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53:50 | the child has now passed out for hours while asleep. She was evidently |
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53:54 | the peculiar influence of the drug. was high because when you extract the |
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54:01 | combs to extract cannabinoids and the dominant , the THC and CBD and indian |
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54:09 | contained more THC and CBD actually. THC tetrahydrocannabinol is the major fighter. |
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54:16 | and CBD is cannabidiol, the second phenomenon. So on eight October at |
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54:23 | AM there was a severe fit. from this hour to 10 at 9:25 |
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54:28 | occurred. The child is suffering and and 30 drops of this tincture were |
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54:34 | them. 30 drop doses was now a struggle between the disease and the |
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54:39 | , but the 10 p.m. She was , narco ties high and from that |
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54:43 | north it returned from the three following , there was considerable gripping and on |
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54:49 | large doses of almond oil, several dark green lumps of hemp resin were |
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54:55 | , which gave effectual relief. The is now December 17 and the enjoyment |
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55:01 | robust health and has regained her natural and happy appearance. In reviewing this |
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55:08 | , several of their remarkable circumstances present . First, we find three drops |
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55:12 | 1/20 of the grain causing profound narcotics subsequently defined 130 drops daily required to |
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55:20 | the same effect. Three drops, drops. The severity of the symptoms |
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55:31 | doubtless must be taken chiefly into account endeavoring to explain the circumstance. So |
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55:39 | is he doing here? He's talking some very interesting concepts. First of |
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55:43 | , it's the same concepts that are . Now when we're talking about medical |
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55:47 | and medical marijuana, medical cannabis is things don't help. So people resort |
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55:56 | extractions to supplements to nutraceuticals to And this was very, very popular |
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56:03 | this country all throughout the beginning of century, all over the pharmacies. |
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56:10 | else is he talking about? He talking about dozing. I'm giving this |
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56:15 | , I'm giving this much. I'm this much. He doesn't know what |
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56:18 | doing. He's dozing THC most likely a little bit of CBD in that |
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56:24 | because we know what these plants contain 100 years ago in India through other |
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56:29 | research. What else is he His first thing three drops was enough |
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56:36 | get somebody high. First time around then to maintain that state and to |
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56:44 | the state of Seizure Free stayed. now 130 drops. So it's |
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56:52 | it's not just dozing, it's also or first what is called first pass |
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56:57 | when people use cannabis, marijuana or edible or whatever. First time can |
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57:04 | strong. The fact okay, that with everything. First cigarette alcohol drop |
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57:10 | have an intoxicating substance, But this quite significant that habituation 1843. So |
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57:18 | already have systems set up dozing from or hashish to treat Children with |
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57:26 | We come back to it at the of the 20th century, there is |
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57:29 | ban on cannabis. We don't understand . We come back The 20th century |
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57:36 | we start talking about CBD and CBD is economic ill. There's a |
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57:42 | of charlotte figure. Unfortunately she passed charlotte figi and her parents moved to |
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57:47 | in order to start consuming cannabis that both THC and CBD. It helped |
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57:53 | and it helped them their scientific literature shows that helped a lot of |
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57:57 | Wean off benzodiazepines and then you have say, well wait a second and |
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58:03 | kids are high. So okay, there are Benzodiazepines, they're drunk. |
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58:08 | don't know what is your preference? state would you can actually function |
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58:15 | Not even a preference. What state you function? Some people will say |
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58:20 | so people will say that, you , depends on the physiology, |
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58:24 | Gupta brought these arguments into daylight about years ago through a series of well |
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58:30 | where he was skeptical, didn't believe medical cannabis, you know, whatever |
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58:34 | tale house. One person to see effect. Let's discard it. And |
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58:38 | he traveled and not charlotte figi and these parents putting this weird green substances |
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58:44 | and their kids mouse. And why you do it? Because nothing else |
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58:48 | . And this actually help and it help and it helps beyond the placebo |
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58:53 | . It's not well studied. It's clinically FDA approved but it's a system |
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58:59 | exists actually these all of the articles even the ham strain that contained high |
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59:05 | levels was called after charlotte's web. there's interesting progression of Canada dial enriched |
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59:13 | use in pediatric treatment resistant epilepsy. resistant means that these kids do not |
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59:20 | anymore. You can give them we can make them drunk. So |
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59:23 | either drunk falling to the ground or having seizures. So there was a |
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59:30 | for alternatives. What we know is medical pharmaceuticals have been around since |
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59:39 | So what William motions. Didn't know the use of high performance liquid chromatography |
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59:45 | allows you to isolate individual Active ingredients active botanical chemicals from the plant preparations |
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|
59:53 | these HBoc Collins 1960 for Rafael Meshulam , THC tetrahydrocannabinol describes it uh correct |
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|
60:06 | and he gives it to monkeys in labs that it's a brilliant movie. |
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|
60:11 | should watch it. It's called the . And Youtube. Raphael Meshulam goes |
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60:15 | a police station in Israel and confiscates from police. The first scientists and |
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60:21 | last scientists ever do it. He the hashish from the police station, |
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60:26 | it to his lap and extracts THC he says, okay, I'm going |
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60:31 | give this to the monkeys in the and some monkeys fall asleep. They |
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60:35 | rouse him, others to somewhat So he says, okay, I'm |
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60:39 | take you home, give it to wife and we're gonna make a chocolate |
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60:44 | . And I'm gonna invite some prominent and friends is gonna be eight of |
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60:48 | I think. And 10 mg of he took from the lab the isolated |
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60:54 | of cake. So they had dinner then they had cake and after the |
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60:59 | a couple of them started joking and a good time and a personal laughing |
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61:04 | or third person just staying in space one of them is having a massive |
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61:08 | attack feeling like she's going to And this is what we still know |
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|
61:15 | effects of THC or effects of cannabis marijuana and different individuals. It agrees |
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|
61:20 | some individuals, causes massive side effects august and uh and it doesn't kind |
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61:28 | a uh impede with with others, it can affect others in a |
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61:33 | very powerful way. There's a level addiction of THC in cannabis is one |
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61:38 | 11 to get addicted. But when talk about medical cannabis as a medical |
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61:44 | were kind of a weighing that harm in benefits versus uh the negative effects |
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61:52 | Canada has. But from that knowledge , pharmaceutical companies synthesized Delta nine THC |
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62:01 | the lab in 19 eighties. It the nominal an abalone 1980 synthetic THC |
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62:07 | that's used an appetite stimulant, anti or anti vomiting, often was used |
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62:13 | chemotherapy. The people that like these very much they're still around. And |
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62:19 | we talk about th seeds, Delta THC, you will see there's a |
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62:23 | debate now in the state of texas Delta eight THC. And if you |
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62:27 | to some coffee shops or even gas , you'll see CBD and Delta eight |
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62:32 | solve here, Delta. And as eight THC, it doesn't come from |
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62:36 | plant, it's actually synthesized from But all of these synthetic medications have |
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62:41 | Delta nine THC point being, we know if Delta eight THC has any |
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62:47 | beneficial effects. It's a huge market . Nonetheless. Uh plant based |
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62:56 | Plant the right medications, the same now come into life into 21st century |
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63:03 | of all, it's the Tvx, is 1 to 1 THC to |
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63:07 | It's a buccal spray, cheek spray fast absorption through the cheek. It's |
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63:12 | for anti spasmodic and pain In multiple . It's available in over 25 |
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63:18 | but not in the United States. not approved by the FDA in the |
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63:22 | States. I don't know why would originally produced by a UK company. |
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63:29 | is now approved in the United States another prescription pharmaceutical called it The |
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63:34 | Which is 10% CBD oral solution drops its anticonvulsant for dr Dr Syndrome is |
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63:43 | name for severe market on a couple 70 rinsing. So, a mutation |
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63:47 | the sodium channel that yourself and let's started epilepsy is a lot of these |
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63:52 | have also infantile spasms of spazz Matic . And we're talking about when I |
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63:57 | telling about O'Shaughnessy as well. this is now approved CBD 10% CBD |
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64:04 | . So you'll say, okay, is this a proven what is in |
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64:09 | gas station? It's also 10% What's the difference? Well, the |
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64:17 | is that on a federal level, preparations with CBD, you can find |
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64:24 | a Walgreens and CVS. That's your . What's in Walgreens and CVS that's |
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64:29 | approved. It's creams and topical for of CBD FDA is now sorting out |
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64:35 | rules, but now you can find of CBD everywhere for years Now, |
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64:40 | oil. CBD hemp oil and that's federally legal in the oil itself because |
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64:46 | federal illegal. And the cramp is type of cannabis that doesn't produce much |
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64:53 | can be used for both nutritional and and industrial purposes. Uh, so |
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65:01 | so what is the difference? So I be dialing the dialects 10% oral |
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65:07 | has been tested to clinical trials. a system for it. It's being |
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65:12 | , safety and efficacy studies. You get prescription. We're going to consult |
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65:17 | will tell you how to use it to use it. The alternative is |
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65:22 | to the gas station, help storm to somebody that doesn't know as much |
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65:27 | you guys will know after taking this and say, okay, help me |
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65:32 | this. And they'll start telling you and you'll be like, I do |
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65:37 | experiment once in a while, you , people, it's like, you |
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65:40 | , everything will heal you, you , it will heal you, you |
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65:44 | walk again, you will see you know, just Everything is |
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65:48 | But I'm not saying that this is now. I'm just saying that we |
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65:52 | know, we may have 10% preparations the market. Actually that I myself |
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65:57 | a as a consumer would prefer because 10% of the dialogues contains ethanol contains |
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66:04 | seed oil and some kind of a flavor. And that's not for |
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66:08 | Since a consumer, I would go 10% CBD oil and hemp seed oil |
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66:13 | this is what the plant is, is what I want to consume. |
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66:16 | want sesame seed oil or ethanol. don't want that, you know. |
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66:21 | what am I saying? I'm saying there's very limited supply of pharmaceutical approved |
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66:26 | . There's only one And there's probably brands of Em CBD products that have |
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66:33 | concentrations but they're not approved. They're studied. It's just you're just self |
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66:40 | it to yourself basically. What is ? Dangerous? Not that much CBD |
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66:46 | be bad for your liver if you're out of drugs. But other than |
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66:50 | it's not intoxicating. It's not Delta eight THC which is sold illegally |
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66:57 | regulated. It's it can get you high cause that peculiar effect. Uh |
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67:07 | . What systems do we have? actually have medical and recreational it's also |
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67:14 | use system, the differences in medical . Children can get medical Canada's and |
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67:19 | cannabinoids and recreational Children do not get . They're pharmaceuticals. National international |
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67:27 | Sativex, synthetic THC. And also . There are THC so prescription insurance |
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67:35 | , doctor supervision then there's National Medical systems in Germany prescription supervision, you |
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67:43 | buy it in the national level. is cannabis plant flower not a |
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67:49 | not a picture of a flower like and a container that you buy in |
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67:59 | . Uh There's state cannabis programs. States texas has what is called texas |
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68:06 | use program. It's very rapidly growing . As of late about 13,000 patients |
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68:14 | probably be a million patients in the 23 years and there is uh an |
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68:21 | of massachusetts. State medical Canada's I use that because massachusetts also has |
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68:28 | adult use program. So what is difference? If you have medical patient |
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68:32 | to dispensary versus a Iraq uh go to dispensary. The difference is |
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68:41 | in tax. In Massachusetts. State still do not provide insurance subsidies for |
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68:47 | cannibals. The state of Texas, regulators decided that medical cannabis is good |
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68:53 | over 150 conditions. If you ask in the FADA, if you ask |
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69:00 | in the building that startles out. , I only know that it helps |
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69:04 | this, this and this, but from 150 conditions. But the reality |
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69:09 | that these systems could exist And they're , some people will say, you |
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69:16 | , there's a lot of information on that you can get to See. |
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69:21 | horrible. Why would you do You know, I get all of |
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69:23 | fishing information on Facebook cannot find it , cannot find on YouTube cannot find |
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69:28 | from the guys in the store. don't want to pay $25 a book |
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69:32 | find two paragraphs. And the subject . I go to a post. |
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69:37 | that subject matter is, you 200 comments with gear and links and |
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69:43 | and that, wow, it's incredible . And this is actually how I |
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69:46 | my decision. Do I make my about how flat the way I don't |
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69:52 | , I don't but position yourself in situation. Your child is having seizures |
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69:59 | . You don't understand much about silence neurologist appointment is three months from |
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70:06 | You're observing your child dwindling away, in front of your eyes. What |
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70:12 | after your appointment with a neurologist? long is the appointment with a |
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70:17 | You guys see a specialist, anybody element 20 minutes next appointment 3 - |
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70:25 | months. Lucky you live in you can get it in 2-3 |
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70:29 | Maybe. What if you live in middle of nowhere, about six months |
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70:34 | then you have to travel someplace 34 . So then you start reading in |
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70:40 | and the facebook groups, what parents doing, what other parents are doing |
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70:44 | sometimes you find solutions and sometimes it things worse. You know, I'm |
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70:49 | gonna judge, I'm just gonna put out there that all of these things |
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70:53 | as far as recreational program, it's taxation, You have state cannabis |
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70:58 | recreational massachusetts California or colorado New Uh, I don't know how many |
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71:07 | now, Maybe in 25 or 30 . I don't count most of them |
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71:12 | both programs and you have recreational national , which is problems specifically. So |
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71:20 | you go in Canada, you in , the province of Quebec, you're |
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71:26 | uh Montreal. Then you go to dispensary and it's a government run shop |
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71:34 | is open at 10 am and closes five PM. There you go to |
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71:40 | british Columbia. It's consumption lounges open midnight. So it's each province and |
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71:48 | private. So each province regulates it now, you know a lot. |
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71:55 | this is the last slide when we back, we're gonna come back and |
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71:58 | about the endocannabinoid system. Because I understanding these things, what cannabis is |
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72:04 | synthetic cannabinoids is for pharmaceutical medications are these elements interact within the cannabinoid |
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72:11 | What are some of the key And the fact that in my view |
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72:16 | endocannabinoid system is going to be one the major major already is becoming a |
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72:25 | development target for many different drives. is a reason why people 150 conditions |
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72:32 | 200 conditions seek cannabis and get help cannabis. What is that reason? |
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72:40 | don't know. So let's try to what that reason is. Is there |
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72:45 | common thread between diseases? Of course is, the brain is in flames |
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72:51 | Alzheimer's disease. The brain is in and epilepsy information. Could this be |
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72:57 | common thread why cannabinoids? Endocannabinoid system such a powerful effect on many |
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73:04 | So we'll look into that. Next , It will be online and you'll |
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73:09 | an email from me uh sometime tomorrow that. Thanks for being here |
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73:15 | And I will see you online. Sorry for holding you up a little |
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73:21 | . |
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