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BIOL 4315/6315 Neuroscience (18564/17642) - NEURO Lecture 21 BRAIN RYTHMS, EPILEPSY, and MEDICAL CANNABINOIDS I
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00:00 is going to be posted. Now at the slide that you have
00:08 Actually from the very beginning from the beginning you look at the slide and
00:16 said I'm going to show that slight you toward the end of the course
00:19 at the end of the course. now when you look at the
00:23 you understand a lot more than you when you first looked at it about
00:28 months ago, you understand how neurons glia function on an individual unit
00:37 You understand how membrane proteins and channels I on a tropic metal tropic,
00:44 gated, chemically gated all of these that are happening in self. You
00:50 how cells communicate to each other and these circuits. There are different subtypes
00:55 cells and they produce their distinct patterns action potential and processing information and that
01:03 circuits form larger networks and these larger then intertwined with other brain structures in
01:10 brain and they form with you would a complete understanding whether it's a visual
01:19 , auditor perception or the association of of these modalities together. So from
01:25 single amino acids, two proteins, membranes to ions to neurotransmitters, signaling
01:34 neuro transmission, gap junctions, networks, loads, all of them
01:41 different functions and all of them having different reverberations or oscillations throughout the
01:49 And this is going to be the subject for today. And in order
02:01 understand brain rhythms. We have to about how to record those brain rhythms
02:07 how we started understanding that those brain means something and this is the story
02:15 the hologram. Sometimes the forest is interesting than the trees similarly were often
02:21 concerned with the activities of single neurons with understanding the activity of a large
02:26 of neurons. Okay that's interesting. ? Pick any sport you like?
02:35 sport, soccer, football, you're interested in what that single player does
02:41 more so importantly how the other players the team moved. And without that
02:48 is no coherent activity in this network players that gets communicated against their
02:55 So that's just a simple analogy. Eeg is a measurement of electrical activity
03:01 the surface of the scalp that enables to glimpse the generalist activity of the
03:06 cortex. So when we talk about . G. We're not talking about
03:10 some spinal cord brain stem. We're about recording some cerebral cortex and from
03:16 surface of the cerebral cortex. The of the V. G. Rely
03:21 the work done by English physiologists, Cotton 1875 cotton made electrical recordings from
03:26 surface of dog and rabbit brains using device sensitive to voltage. So you
03:33 stuck electrodes and these recordings in the century. The human E.
03:38 Was first described by Austrian psychiatrist hans in 19 29 who observed that waking
03:45 sleeping in Giza distinctly different. And figure this figure below shows one of
03:51 first published records taken from the head his 15 year old song Klaus.
03:57 . The egg is used primarily to diagnose certain neurological conditions especially the seizures
04:03 epilepsy and for research purposes notably to the stages of sleep and cognitive processes
04:10 wakefulness. This is all about the of the brain functions of the
04:14 And how can we understand the non . We talked about the imaging techniques
04:20 scan MRI Fmri functional imaging. We about experimental techniques where you have to
04:27 the dies on the surface of the or the tissue of all the sensitive
04:31 calcium sensitive guys. But we want also measure activity non invasively specifically electrical
04:39 that you can pick up non invasively the scalp. Oh so this is
04:50 example of what you would call and . G. Helmet or E.
04:57 . Cap. Where these electrodes are positioned have a certain positioning. Geodesic
05:07 on the surface. It's a great the electrodes and each one of these
05:11 will pick up the electrical activity from surface of the cortex that comes through
05:17 skull through the scalp. Well compare activity in local regions and we'll tell
05:23 about the brain rhythms or these oscillations what is happening in different distinct regions
05:28 the brain in some instances where for you have either epilepsy uh focus or
05:38 in the brain that keeps generating seizures that's really bad because that place in
05:44 brain that keeps generating seizures is essentially up, it's short circuiting electrically.
05:50 a massive inflammatory loud load in that . And it also is neuro degeneration
05:56 to happen in that region. It will spread in the surrounding regions in
06:01 perimeter of that main core issue. if you have to us growth.
06:08 for example the most common tumor in brain is gliomas, big leo tumors
06:15 form and now you have to cut tumor out of the brain. You
06:20 to have neurosurgery. In that case will image the brain using FmRI FMRI
06:30 that you already discuss and you will the location of the tumor. You
06:35 then place an E. G. an individual to understand with. Around
06:41 you are what you know is there's abnormal electrical activity through the eeg
06:48 . You have to now open the and take or resect. It's called
06:55 resection of brain tissue reset that tumor of the brain. The last step
07:01 you will do is it will actually a grid after a lecture. This
07:05 done intra operatively during the operation pre of the brain tissue. You place
07:12 on the surface of the actual So now you have the skull open
07:17 dura matters removed and now you're placing to pinpoint exactly with a lot more
07:25 , spatial specificity. The area that that area tumor area seizure in the
07:32 that are surrounding that do not in way affect major functions. If you
07:39 on these areas, if you cut areas out. So using all of
07:43 techniques then you can actually do neurosurgery cut out a piece of the brain
07:49 . It's about 8-10 years of uh to become a neurosurgeon. So it's
07:54 very very, very serious work. long surgeries. Uh neurosurgeons will work
08:01 PhD and electro physiologists in the surgical room because electro physiologist neurophysiologist will be
08:10 them with, especially brain surface or recordings intra operatively. So in this
08:20 you actually have a lot of collaborations basic scientists, PhD who may be
08:25 the rest of his time doing studies a mouse brain or right brain or
08:30 like that. But spending a few every month working with neurosurgeons in helping
08:36 understand and decode the electrical activity from electrodes. The more plasticity there is
08:45 the brain. The earlier, during development of critical period of development you
08:51 these surgeries, the more chances for recovery of the brain tissue and the
08:58 chance there is for a significant loss function in older adults or older individuals
09:05 and older individuals if you have if take a piece of the brain
09:11 inevitably have some significant loss of function does not rebuild and regenerate itself because
09:17 isn't that same amount of plasticity anymore the was following. Such significant trauma
09:24 the brain and Children, there is a procedure that's called hemispheric to me
09:29 the entire hemispheres removed. And that's one hemisphere is generating abnormal electrical
09:37 It's starting to burn tissue on one through corpus callosum is communicating that abnormal
09:44 of activity into the other hemisphere and now starting to burn the other hemispheres
09:49 order to save half of the You remove. This entire demonstrates down
09:53 smaller Children that have very very severe conditions like we mentioned epilepsy or uh
10:02 growth. And so when you place grid of electrodes on the surface,
10:07 one of these electrodes and comparing that to nearby electorate gives you a comparative
10:13 . So each one of these traces can think of as a is each
10:18 of these electors that's placed on the of the brain. And it will
10:22 up different rhythms. This is for an alfa rhythm. This is a
10:26 rhythm and we'll talk more about different of rhythms. This is a blinking
10:32 that it will pick up as So there's artifacts that happen and there
10:36 filtering and sorting that you have to and there's a lot of significant filtering
10:40 happens through the skull and through the . We need to pick up the
10:45 on the other side non invasively three . Recording that's uh to be able
10:54 older patients uh surgery. Not if cut out pieces of the cerebral cortex
11:04 you cut out the optical area of cerebral cortex. Now there's no recovery
11:10 function. What about areas are responsible ? It depends how strong the lesion
11:16 the cottage town. Yeah it depends significant there is the connectivity. Sometimes
11:23 not even the large area but it's connectivity that gets destroyed and now you're
11:29 large areas that would communicate through that those highways. So. Yeah
11:36 It's very good questions. Uh This the rhythms eyes closed. You have
11:43 alpha waves that have certain amplitude and eyes open to have the amplitude decrease
11:48 the frequency changes too. So alpha relaxed wakefulness beta. And intense mental
11:55 . And it's in frequency in hertz per second. How many oscillations are
12:00 picking up? Delta is drowsiness data driving this pathology during wakefulness but theta
12:07 fast gamma. And also ripples are rhythms that are very important for learning
12:13 memory. So what is what is ? What are these rhythms? Why
12:20 there what happens between 10 and What happens between 40 and up?
12:29 these rhythms? What do they They represent different state of being?
12:35 represent different behaviors? You're mentally intensely in the task or you're asleep and
12:41 brain rhythm changes? Okay so this patterns that stupid cop a sleeve drowsy
12:52 sleep pattern. They are different dominant that fall within these ranges of
13:00 In other words if you put the on and you record and recording your
13:04 and you try to make sense of that synchronized activity. Those are going
13:09 be the dominant rhythms that you will . So what are you picking up
13:14 activity when you're recording? E. . This is your E.
13:18 Electrode again that's sitting on top of scalp. Underneath. There is a
13:24 , there are three million Gs. there is a primary superficial layer one
13:31 the cerebral cortex, layer two, three, layer four, layer five
13:35 six going down. And if you anatomically the structure of the neocortex is
13:42 you have the tyrannical self projecting their dendrites all the way through the superficial
13:47 12. And so essentially when there activity in these local serpents around cells
13:54 . G. Is not picking up from a single cell, It's picking
13:58 activity from the circuits of cells that sitting underneath that particular electrode that is
14:04 one of the electrodes on the grid you can have 34, 800 something
14:09 go as many as several 100 electrodes the surface of the brain. If
14:14 want to be more specific special when cells are active there's gonna be charges
14:21 outside deep polarization, there's going to charge positive charge is coming inside and
14:27 going to be electric fields that get to electrical magnetic fields that get generated
14:34 they get filtered through all of these and the scalp and the scalp and
14:39 like a low pass filter and eventually that signal into the processing. So
14:47 like if you're looking at that uh of a network and if that activity
14:56 irregular activity that means that each south uh six cells depicted here is an
15:02 of this network. Each one of six cells is doing their own thing
15:07 of like when you look at the again let's use the analogy of the
15:13 , any of the team sports before game and warming up everybody's doing their
15:18 thing, they're kicking the ball. if you look there's no coherent activity
15:22 the team. So there's no synchrony no synchronized activity in the players and
15:28 all rushing forward defeating defending. Uh now if all of these neurons get
15:36 by stimulus stimulus all of these neurons the same and very strong input.
15:42 that input is repeated and now you neural transmission and communication and you also
15:49 gap junction transmission and with the help gap junction gap junctions and these common
15:56 inputs. What happens if you some coherent activity in the network or synchronized
16:04 will see that you can now pick a some eg recording that is meaningful
16:11 it's not to say that this E . Recording that is not synchronized is
16:15 meaningful because everything is like a history happens in the past in the brain
16:19 will determine something that happens in the . But this is one way to
16:24 about these dominant rhythms of the rhythms the south synchronized coherently and produced these
16:31 rhythms within the dominant frequencies. One my favorite neuroscience books are by Euribor
16:38 . I'm on the slide mouth that rhythms of the brain Jury Busacca and
16:42 left Oxford University Press. And we this uh circle of life. They
16:53 the circle of life and then the you can have certain phases in this
16:59 of life of birth. Life and . It's the concept that is prominent
17:05 permeates in science and philosophy in Um And it is quite often that
17:17 picture of nature emerges as being imbalanced both biological and religious interpretations. Philosophical
17:29 nature will balance things out. Let's an example of how we can pollute
17:37 earth in one region of the earth we can maybe upset the earth and
17:43 the earth is going to erupt the and kill half a billion people in
17:47 region that is polluting the earth. you could say maybe that's nature balancing
17:55 . I mean things like that happen ? But uh so if if it
18:04 all in the stable equilibrium then we keep it this way then there shouldn't
18:13 any environmental summits, electric cars, it drill, baby drill, Let's
18:22 it this way. Nature will take of them again, You know,
18:26 flood the coastal zone so there won't people here, they will, they
18:30 not need gas or die. But , that was the case. How
18:37 we get here in the first And that's kind of a question of
18:46 . How did we get here in first place? Everything was balanced and
18:50 we have a lot of parts of brain body, for example, is
18:54 of balance and consumes a lot of . It's a non linear system.
19:01 you have this intimate relationship, these all food for thought. I don't
19:06 if I can make an exam question of this, but something for everybody
19:10 think about. I think that it's clear that we can tip the balance
19:14 nature, that it's a certain We are an active players in
19:19 One way or another, we can that balance. So this intimate relationship
19:24 space and time is packaged into the of space time, like Y.
19:29 . T. Dimensions, the oscillations synchronized activity in the south or oscillations
19:37 auditory signal oscillations and hair cells. can be conceived of as displayed in
19:44 of either space or tom the face of a sign of subtle harmonic oscillator
19:49 a circle, face plane. We walk the perimeter of the circle
19:56 twice or billions of times. And we always get back to groups.
20:02 always get back to our starting So the quote is what has
20:08 is what will be and what has done is what will be done.
20:11 there's nothing new under the sun. is the circle of life and I
20:16 in. This perimeter is measured by as a dislocation as an alternative to
20:24 . View of the universe is to periodicity is a series of sin
20:29 There's a circle. In fact, can take the circle and break it
20:33 into sine lines. So center for two. That's almost. But now
20:39 can walk along the troughs and peaks the line. We can walk peaks
20:47 Charles. This is panta rei. uh without ever returning to the starting
20:57 and these explosions are not always balance equal. Um or the media over
21:05 , I don't know the time. is a continuum of the cycle is
21:09 metric. The cycles are identical in and the start and end points of
21:13 cycles from an infinite path into seemingly universe. That's pretty cool just to
21:23 about stuff. So now we have rhythms in the brain and this activity
21:33 it just, it just walks this walk along like a sinus or it'll
21:40 along some axis of time and space because we have the electrodes. And
21:46 we're measuring activity in space and And you'll find a lot of similarities
21:52 rhythms and humans and monkeys, rabbits, rodents. In some
22:00 like algorithms will not be present in rabbit. So not all of the
22:06 will have the same rhythms, not of the same rhythms will be present
22:09 the same parts of the brain are the same parts of the brain.
22:14 have spindles and ripples and spindles and illustrate, especially in the case of
22:20 ripples. Some other they're interesting quality the circuits in the brain that they
22:27 sustain multiple rhythms at the same So it's just like the symphony
22:33 right? You can have the cello slow on top of that, you
22:39 have violins going really fast. So the same circuit and the orchestra is
22:48 these different rhythms at the same Sometimes they're resonant, sometimes they're
22:56 sometimes they're syncopated, Sometimes you would they're chaotic and their non synchronized.
23:05 now what you see here is these polarization, mostly deep polarization, sometimes
23:11 polarization is at a slower, So a slow ongoing rhythm in the
23:17 And on top of this slow rhythm , you have these very very fast
23:23 . There are ripples and those happen hundreds of hertz. So hundreds of
23:29 per second. Very fast rhythms. spindles and ripples are very important for
23:35 and mammals. Mhm. How these created. They created because from the
23:43 beginning of this course side uh talk you to think about neurons speaking different
23:52 of the same language producing different different frequencies of action potentials. And
23:58 have over 100 and 4800 and 50 setbacks of neurons. These dialects and
24:04 ability to produce fast firing versus slow will influence whether it's fast rhythm,
24:09 rhythms or somewhere in between excitation versus up. If it's all excitation there
24:16 be a lot of prolonged action potential . So but then inhibition kicks in
24:20 there's a control and there's a breakup these rhythms. You have neural transmission
24:29 you have gap junctions and it's not glutamate and gaba excitation and inhibition.
24:35 about serotonin? What about dopamine? they cause different rhythms? Yes.
24:42 now you're talking about what you've learned . The collections of these neurotransmitter systems
24:48 influencing actually ruth ethnicity and how if is upset with message as you'll see
24:54 apple Fc. And obviously there is in some of these systems glutamate
24:58 Gaba system, it's depression, serotonin and so on. Howard rhythms created
25:05 external entrainment. Those are the signals are coming at us. Those are
25:12 signals that we've been trained. We listen to herring in the water and
25:18 , we listen to human voices. our frequency range and how we preserve
25:24 and how we pay attention to there's certain range for auditory or visual.
25:31 it's external entrainment. It's also how does your car shape? That's your
25:38 entrainment or doesn't shape? Um Why many a solitary regimes? So you
25:47 these very slow regimes. The slowest that you can think of is your
25:52 cycle. You're super charismatic, See some light and starts producing prescription
25:58 that tell the rest of the Wake up, it's morning time.
26:03 the evening time lights are dimmed and charismatic. Nucleus tells the rest of
26:08 brain go to sleep and starts producing transcription factors. You have very slow
26:15 rhythms. You have a lot of rhythms that are even slower than
26:20 You have the cycles. Some monthly . You have in the brain rhythms
26:27 that are slow on the internal It's tens of seconds, few
26:36 21 oscillation per second delta, low fada 4 to 10 beta, 10
26:45 30. Gamma. 30 to 80 rhythm and ultra fast or ripples would
26:53 within this 200 to 600 rhythm, , Hz. Did you know that
27:00 circuits can oscillate at 600 cycles a . That's very impressive actually. You're
27:11 . So, Penton abu zaki why so many facility regions? Multiple
27:21 . You sleep with one rhythm awake a task that was a different
27:27 You have to be precise and You have to manipulate Circus must be
27:31 to play multiple rhythms depending on what demand is with the situation. External
27:37 and internal symbol in our if you slow and fast you have distinct levels
27:44 computation. Now you can take this and you can say it can break
27:49 up into these rhythms to represent different . There's some computation behind this,
27:56 maybe some mathematical system behind it. when you align these dominant rhythms here
28:03 you put it under Ellen, which supposed to be a church for
28:10 you take a log of the What you're seeing is that these dominant
28:17 delta theta, beta, gamma ultra fast, separated by a single
28:24 along this Ellen scale, log Uh So there is maybe a mathematical
28:32 to or at least there is a interpretation of what is happening in the
28:37 which is inevitably tied to what is happening external into stimulating. We're getting
28:44 . So our next topic is I've seen why epilepsy because epilepsy as
28:50 was described in E. G. . G. Would be used to
28:56 epilepsy to detect seizures and epilepsy is rhythmic brain disorder and one of the
29:04 diagnosis is using egg affects about one . So the incidents of new epilepsy
29:11 is high uh after birth and infancy then it decreases it has this almost
29:20 U shaped curve and it increases again 55 60 years of age, the
29:26 of epilepsy and seizures, There's many kinds of apple FC's so it's really
29:32 just epilepsy, but it's apple it's more common in developing countries.
29:39 rates and childhood it's associated with Often if there's poor prenatal postnatal care
29:47 can increase the uh possibility of it occurs most often in young and
29:57 . The childhood epilepsy is typically caused by genetic disease of abnormality present
30:04 birth and elderly tend to acquire Annapolis a consequence of conditions such as uh
30:13 , tumors, stroke or other diseases we call comorbidities, comorbidities such as
30:21 disease. If you have Alzheimer's disease your 55 years old, you're upwards
30:27 60 times more likely to develop epilepsy seizures. If you have Alzheimer's disease
30:33 a certain age, you have a chance of having this co morbidity they're
30:37 comorbidities are trying to go kill Alzheimer's is trying to kill you and
30:44 is trying to kill you. So comorbidities, diabetes Annapolis sees color ability
30:50 both of them are trying to kill . So in this case you have
30:54 growth. Of course, do we . We discuss leo sis reactive fibrosis
31:00 tissue formation. So glial when it cleaning out damaging the brain, it
31:05 forming scar tissue just like you would in the skin, but that scar
31:10 and the brain means that there is proper communication, neural transmission can cause
31:15 significant problems damage the tissue, ruptured vessels or in grown blood vessels to
31:25 the tumor trauma such as traumatic brain , uh concussions, multiple concussions,
31:33 concussions can lead to epilepsy, genetic , metabolic dysfunction, viral bacterial
31:41 meningitis, which can be the bacterial viral, which is the brain infection
31:47 lead to epilepsy covid there is a small percentage of affecting and leading to
31:57 , vascular disease of micro vessels. abnormal micro vasculature, abnormal feeding of
32:07 nutrients and oxygen to brain regions and components toxins, chemicals. In many
32:13 the cause of epilepsy is not You guys remember this channel that's just
32:22 gated sodium channel. It has four , it has six trans membrane
32:29 It has the inner pore loop between five and a six S four serves
32:33 voltage sensor, beautiful channel. Remember comprised of all of these different sequences
32:39 amino acids. And so this is same channel as an example of the
32:47 common genetic mutations that lead to epilepsy sodium potassium and calcium channels in this
32:53 is an illustration of sodium channel. everywhere you see along these sub units
32:58 these trans membrane segments, a red in that channel will result in sME
33:07 , which stands for severe my chronic of infancy. It's intractable or untreatable
33:14 deadly and over 20% of Children epilepsy literally die at night in their sleep
33:23 . You see these green mutations in same channel. You will have guests
33:29 stands for generalized epilepsy with febrile We'll talk about generalized epilepsy in the
33:35 febrile seizures are the heat induced, thermally induced seizures. And in
33:41 febrile seizures are quite common when they an infection and the temperature goes up
33:47 and they start having what is called febrile seizure and you may take them
33:50 the emergency room and they may never it again. But if you have
33:57 seizures, if you have epilepsy and are very susceptible to febrile seizures,
34:03 small increases in body temperature and even temperature and provoke seizures constantly. And
34:11 Children that have jeffs gaps, types seizures and their parents are looking forward
34:18 colder months and cooler climates because it affect how many seizures the kids would
34:24 having a day or a week, on requirement. Um you can alter
34:33 functions of sodium channels, they may longer in the excitatory cells and too
34:39 sodium coming in, there's gonna be much of glutamate release. Maybe there's
34:44 mutation and the inhibitory south and sodium and we know that there are mutations
34:49 then there's not enough of sodium coming de polarize inhibitory south. So there
34:54 enough inhibition. So this is kind the general themes. But there's other
35:01 in potassium channels calcium channels that can to many different forms of epilepsy.
35:06 I'm using here sodium channel we're familiar to discuss those two types of epilepsy
35:13 general Apple etc. On a gross of things. If you think about
35:18 . G. Recordings, what is what is the peak the keepers deep
35:23 ? What is the trough? The ? Is the hyper polarization? So
35:28 means there is excitation for deep There is inhibition, hyper polarization.
35:34 most of our brains, they are walking along this plank, this blue
35:41 sitting on the triangle here and this is shifting and swinging as we walk
35:48 it, not only up and down sideways too. And then Apple
35:55 One of the easy ways to explain start thinking about you about pathologists is
36:01 that is referred to excitation and emission . What happens if this plank is
36:09 ? If there is too much there's too much excitatory activity, There's
36:16 enough inhibit their activity. So there's much of the excitation And now what
36:24 want to do is using therapy, want to rebalance it. So you
36:28 to rebalance excitation and inhibition And most the cases most of the anti what
36:34 called anti epileptic drugs are really anticonvulsant because there's no drug that will cure
36:38 epilepsy so far. But in some seizures and epilepsy is with certain drugs
36:44 go away and it partly is maybe part of the developmental process to you
36:51 want to dampen glutamate. So you're starting to think about, okay,
36:55 are the therapy strategies? What have learned about excitation inhibition? What if
37:00 plank is imbalanced? What do I to care about? I need to
37:05 about synaptic transmission. I need to about enzymes and synthesized gabba and vitamin
37:10 need to care about transport, particular . I need to care about member
37:17 transport of these neurotransmitters back. If need more Gabba transported back, all
37:22 these strategies become part of your a call kind of a therapeutic approach
37:28 the disease. So you have to types of seizures that distinguish generalist
37:39 roses, partial seizures and generalized seizures have loss of consciousness. Uh type
37:48 the generalized seizures. Grand mal and mall. They're both generalized seizures because
37:54 both grandma and the gym, all lose consciousness grandma is occurs with the
38:04 . That is described as an aura means an individual feels or suspect as
38:11 as a good feeling. Something is or about to begin alexander, the
38:16 said that his aura was so fantastic gave him such incredible visions that he
38:21 want to trade his apple apps Uh for not having that or
38:28 So there's some interesting activity in the that is happening or preceding seizure
38:34 That individual sense the best of detecting that will happen in humans or dogs
38:42 are specifically trained for that that can their owner about two minutes before seizure
38:48 happened the symptoms and learning about So grandma, you have lots of
38:55 . Then you, when you think the typical seizure upwards, you heard
38:59 somebody's on the floor, they're shaking jerking. The phone is coming out
39:04 their mouths. That's what you think epilepsy and seizure and tonic clonic.
39:10 is what it's called, tonic clonic . This could be a tonic
39:14 rigidity of muscles and attention and literally like turning the hands and the
39:21 and getting it stuck. It's really . Or it could be spasms and
39:27 , which is what you would if somebody is jerking or twitching on
39:30 floor having a fit. There's another term procedures as a fit.
39:37 not like a, you know, fit, but in this case,
39:42 physiological and emotional psycho, physiological, , psychological and following that there is
39:49 to the depression, recovery phase mental because during generalized seizure you have to
39:56 generalized seizures, grandma's within half an , otherwise they start burning brain circuits
40:01 they start killing you and making your down so you have to stop them
40:06 half an hour. And if you a seizure that lasts for minutes or
40:13 when people recover from their seizures, are absolutely exhausted mentally, physically and
40:18 lot of times there's this political depression there is no signal, not much
40:24 in the brain tune. So as you've shaken up and activated all the
40:31 and the circuits and burning them up now they're silent for a while.
40:35 need to recover in this post natal stage absence, seizures that are more
40:40 than Children are also generalized seizures and don't have a tonic clonic component at
40:46 . So here is the type of seizure that you would say, what's
40:50 on with the skin, just staring space and that's exactly what happens you're
40:55 with your child and then all of sudden they would turn their head and
40:59 blank stare in space during the awake The start of nowhere and then
41:06 out about 10 seconds later and they , were you talking to me about
41:12 ? You know? And yeah, don't remember what happened. So seizures
41:18 but different types of seizures can have motor component. You can have a
41:22 seizure or simple partial seizure of complex seizures. Simple partial is that means
41:28 it is in one area of the . Complex partial is you have focal
41:35 impaired awareness with the focal onset means starts in one spot in the brain
41:42 you have generalized seizures, you have of solano cortical circuits to remember this
41:47 , thalamus, the cortex, cortical cortical thalamic through these circuits,
41:52 generalize the seizures and this is where lose the consciousness focal seizures or simple
41:59 seizures. For example, if you seizure activity in the motor cortex,
42:04 can actually have a tonic clonic component you can become completely consciously aware of
42:12 tonic clonic component in your leg and really painful and annoying, you can't
42:17 it. So again, when you about appearances of seizures don't think
42:23 Somebody has fallen on the ground has out of their mouth and not having
42:28 so called fit. It's really a different array of all sorts of
42:34 Annapolis is frontal lobe seizure so often as freaking out and screaming and swearing
42:42 throwing things and then coming out of and saying what's going on, what
42:45 I do? And they record of activity. Really massive of normal activity
42:51 the frontal cortex. The brain structures are very susceptible to epilepsy and
42:58 Hippocampus and neocortex. You think about functions encoding of memory, retrieval of
43:07 . It's a part of the limbic , emotional processing, semantic memory,
43:15 , so that part of the brain wiped out. A lot of these
43:18 are getting wiped out. Neocortex. depends where in neocortex, that seizure
43:24 originating from where the focus is of seizure, whether it's in the left
43:29 , right hemisphere exhibit alone, temporal the most common seizures. Apple,
43:35 see, sorry, I'm for a revolution. Uh huh. Mhm.
43:49 structure is also hippocampus, neocortex are only susceptible to damage rappel, of
43:54 seizures. Alzheimer's disease. Schizophrenia also affect these regions. This is a
44:00 in a that has a cap in there's an aura, the feeling that
44:06 is about to happen and then you can see that activity starts between
44:12 , It looks like 16 and 13 and then spreads to another five electrodes
44:19 then in be the person who is having a seizure and then see that
44:24 has now spread. We call this march. It marches through the brain
44:30 the circus, it becomes generalist. if you have repeated seizures you would
44:36 neuro degeneration. This is in the and if the campus will also be
44:41 degenerated and other neurological conditions such as and other parts of the brain will
44:47 a new journal neuro degenerated and other . Parkinson's disease will be dope and
44:52 degeneration. Alzheimer's disease. You will call an urgent neurons are leon but
44:59 are important and susceptible parts of the . There's something in these circuits that
45:04 and can sustain these abnormal levels of . Not in the peripheral circuits,
45:09 words. Yes. Oh, euro can occur in different parts of the
45:18 depending on what the condition is or type of absolute top epilepsy it
45:23 Yeah. The most common one is lobe epilepsy and hippocampus is located behind
45:29 the temporal lobe if you may and why it is also one of the
45:34 acceptable structures in the brain but it occur other places to damage. So
45:41 talk about this balance again in the approaches and most of the therapeutic approaches
45:47 a policies to boost inhibition through Galba . So Gabba will boost inhibition.
45:55 barbiturates. Gabba busy stands for The guys have been so classical anticonvulsant
46:05 and boosting inhibition. What else wants gather receptor? Oh that's a
46:12 All right. So what do you think binding of Gaba makes Gaba feel
46:20 of a similar to ethanol. Benzodiazepines necessarily bind the same way. The
46:29 is intoxication and for Children, benzodiazepines have significant side effects or any epilepsy
46:39 but it's also causing a drunk like . But glutamate and glare. Let's
46:50 back to the subject matter that neurons glia dramaturgical signaling or the balance of
46:57 is very much dependent on Julia and synthesis and when there is too much
47:03 the activation of glia there is reactive sis there is overproduction of glutamate and
47:09 release of glutamate Biglia. So now is actually boosting this excitatory tone and
47:16 excitatory and talents because glee is very involved in the control of the excitation
47:24 most of the therapeutic approaches are still gaba receptors but now think about all
47:31 the cool things you've learned about Can you target vesicles. Can you
47:36 vesicles binding. Can you degrade What happens if you do great blue
47:43 make, do you go brain dead and you're all inhibited mount stop So
47:49 of these different things? Yes. . An M. D. A
47:58 and glutamate receptor inhibitors now that there's not antagonists are not used. The
48:03 is that all of these drugs, of the things are pills that you
48:07 , they will have a systemic Now the systemic effect. And if
48:11 have a focal problem where you have mutation in one circuit, you're now
48:16 that systemic effects of the drugs and future drugs will really get have to
48:21 more specific to glutamate vesicles versus vegetable serotonin vesicles versus dopamine and so
48:30 . Huh? So but this is of the things we need to think
48:35 . And when we think about epilepsy start actually talking about cannabis and cannabinoids
48:40 the reason why because you learned about endocannabinoid system and cannabis contains Fido can
48:47 . So you learned an undercover avenue . You produce your own cannabinoids inside
48:51 body to a rocket. Donald glycerol . G. And then and a
48:58 and cannabis plants that are phyto cannabinoids get produced in these try combs,
49:05 translucent protrusions on the female cannabis flowers they're synthesized here together with the aromatic
49:14 ins and that's the smell of cannabis comes through the olfactory system in the
49:20 of different Turpin's that you'll find in tri cones? So cannabinoids, phyto
49:28 and endocannabinoid will act through cannabinoid And you already know that this retrograde
49:35 of endocannabinoid will target CB one receptor is located preseason optically on neurons.
49:42 two CB one receptor will control both release of glutamate and gaba. So
49:47 is a really attractive system and balancing and in condition to CB one
49:52 And uh and phyto cannabinoids. CB receptors although they are also found in
49:58 neurons are predominantly expressed them. Wheel and CB two receptors are dominant in
50:04 micro glial cells that control and influence of the functions of the microbe leah
50:09 pro inflammatory cytokine release and CB two control inflammation and control this pro inflammatory
50:17 release by microglia Activation of CB one neurons will cut off calcium influx and
50:25 control again whether glutamate gaba release. an attractive system to work with them
50:31 contaminate our system. And why do talk about Canada's and epilepsy? Because
50:36 hundreds of years people have seen for of years actually epilepsy have been treated
50:42 cannabis. Uh This is uh William dr William O'Shaughnessy, a medical
50:50 brilliant physician also brilliant inventor. He working in India playing telegraphs, working
50:58 the uh british government uh and he a court physician also. And when
51:07 was in India he discovered indian hemp or ganja known in India and he
51:15 multiple applications of India and how that were using locally including the production of
51:25 milk preparation called bang or cannabis flowers mixed together and smushed together with cream
51:32 milk. And it is drawn during of the biggest religious festivals in
51:39 And so he observed all of this he took indian him back with him
51:46 he started looking at how to So he took cannabis flower uh and
51:55 used ethanol and he extracted those try and he prepared these extracts that are
52:02 also as a hashish. Hashish is a different drugs from marijuana or from
52:07 . It's actually translucent try counts that been separated from the plant and
52:13 So this is from 1843. It's case of infantile convulsions that they're interesting
52:21 of this disease has recently occurred in private practice. The particulars of which
52:25 have the permission of the family to in this paper on the seventh I've
52:32 dr Nicholson and consultation and despairing of cure from the help. It was
52:37 to intermittent. It's used to apply mustard poultices to the gas stream and
52:41 give a dose of castor oil and . The child however rapidly became worse
52:47 the two p.m. At a tonic spasm in which lasted without intermission until half
52:53 six p.m. So this child started having having some treatment and it's not helping
53:03 has four hour long seizures. The back was tried without solution to the
53:09 . So called bath cold helmet will used to stop of normal brain activity
53:14 be used to quiet too low temperature the signaling in the brain overall
53:21 Okay, so they tried to give full doctor didn't work. The help
53:26 therefore again resorted to and the dose 30 drops equal to 1.5 grains of
53:31 resin was given at once. Immediately this dose was given, the limbs
53:38 , the little patient fellas fast asleep so continue for 13 hours. So
53:45 gave this child some hashish in the of the drops in the oil.
53:50 the child has now passed out for hours while asleep. She was evidently
53:54 the peculiar influence of the drug. was high because when you extract the
54:01 combs to extract cannabinoids and the dominant , the THC and CBD and indian
54:09 contained more THC and CBD actually. THC tetrahydrocannabinol is the major fighter.
54:16 and CBD is cannabidiol, the second phenomenon. So on eight October at
54:23 AM there was a severe fit. from this hour to 10 at 9:25
54:28 occurred. The child is suffering and and 30 drops of this tincture were
54:34 them. 30 drop doses was now a struggle between the disease and the
54:39 , but the 10 p.m. She was , narco ties high and from that
54:43 north it returned from the three following , there was considerable gripping and on
54:49 large doses of almond oil, several dark green lumps of hemp resin were
54:55 , which gave effectual relief. The is now December 17 and the enjoyment
55:01 robust health and has regained her natural and happy appearance. In reviewing this
55:08 , several of their remarkable circumstances present . First, we find three drops
55:12 1/20 of the grain causing profound narcotics subsequently defined 130 drops daily required to
55:20 the same effect. Three drops, drops. The severity of the symptoms
55:31 doubtless must be taken chiefly into account endeavoring to explain the circumstance. So
55:39 is he doing here? He's talking some very interesting concepts. First of
55:43 , it's the same concepts that are . Now when we're talking about medical
55:47 and medical marijuana, medical cannabis is things don't help. So people resort
55:56 extractions to supplements to nutraceuticals to And this was very, very popular
56:03 this country all throughout the beginning of century, all over the pharmacies.
56:10 else is he talking about? He talking about dozing. I'm giving this
56:15 , I'm giving this much. I'm this much. He doesn't know what
56:18 doing. He's dozing THC most likely a little bit of CBD in that
56:24 because we know what these plants contain 100 years ago in India through other
56:29 research. What else is he His first thing three drops was enough
56:36 get somebody high. First time around then to maintain that state and to
56:44 the state of Seizure Free stayed. now 130 drops. So it's
56:52 it's not just dozing, it's also or first what is called first pass
56:57 when people use cannabis, marijuana or edible or whatever. First time can
57:04 strong. The fact okay, that with everything. First cigarette alcohol drop
57:10 have an intoxicating substance, But this quite significant that habituation 1843. So
57:18 already have systems set up dozing from or hashish to treat Children with
57:26 We come back to it at the of the 20th century, there is
57:29 ban on cannabis. We don't understand . We come back The 20th century
57:36 we start talking about CBD and CBD is economic ill. There's a
57:42 of charlotte figure. Unfortunately she passed charlotte figi and her parents moved to
57:47 in order to start consuming cannabis that both THC and CBD. It helped
57:53 and it helped them their scientific literature shows that helped a lot of
57:57 Wean off benzodiazepines and then you have say, well wait a second and
58:03 kids are high. So okay, there are Benzodiazepines, they're drunk.
58:08 don't know what is your preference? state would you can actually function
58:15 Not even a preference. What state you function? Some people will say
58:20 so people will say that, you , depends on the physiology,
58:24 Gupta brought these arguments into daylight about years ago through a series of well
58:30 where he was skeptical, didn't believe medical cannabis, you know, whatever
58:34 tale house. One person to see effect. Let's discard it. And
58:38 he traveled and not charlotte figi and these parents putting this weird green substances
58:44 and their kids mouse. And why you do it? Because nothing else
58:48 . And this actually help and it help and it helps beyond the placebo
58:53 . It's not well studied. It's clinically FDA approved but it's a system
58:59 exists actually these all of the articles even the ham strain that contained high
59:05 levels was called after charlotte's web. there's interesting progression of Canada dial enriched
59:13 use in pediatric treatment resistant epilepsy. resistant means that these kids do not
59:20 anymore. You can give them we can make them drunk. So
59:23 either drunk falling to the ground or having seizures. So there was a
59:30 for alternatives. What we know is medical pharmaceuticals have been around since
59:39 So what William motions. Didn't know the use of high performance liquid chromatography
59:45 allows you to isolate individual Active ingredients active botanical chemicals from the plant preparations
59:53 these HBoc Collins 1960 for Rafael Meshulam , THC tetrahydrocannabinol describes it uh correct
60:06 and he gives it to monkeys in labs that it's a brilliant movie.
60:11 should watch it. It's called the . And Youtube. Raphael Meshulam goes
60:15 a police station in Israel and confiscates from police. The first scientists and
60:21 last scientists ever do it. He the hashish from the police station,
60:26 it to his lap and extracts THC he says, okay, I'm going
60:31 give this to the monkeys in the and some monkeys fall asleep. They
60:35 rouse him, others to somewhat So he says, okay, I'm
60:39 take you home, give it to wife and we're gonna make a chocolate
60:44 . And I'm gonna invite some prominent and friends is gonna be eight of
60:48 I think. And 10 mg of he took from the lab the isolated
60:54 of cake. So they had dinner then they had cake and after the
60:59 a couple of them started joking and a good time and a personal laughing
61:04 or third person just staying in space one of them is having a massive
61:08 attack feeling like she's going to And this is what we still know
61:15 effects of THC or effects of cannabis marijuana and different individuals. It agrees
61:20 some individuals, causes massive side effects august and uh and it doesn't kind
61:28 a uh impede with with others, it can affect others in a
61:33 very powerful way. There's a level addiction of THC in cannabis is one
61:38 11 to get addicted. But when talk about medical cannabis as a medical
61:44 were kind of a weighing that harm in benefits versus uh the negative effects
61:52 Canada has. But from that knowledge , pharmaceutical companies synthesized Delta nine THC
62:01 the lab in 19 eighties. It the nominal an abalone 1980 synthetic THC
62:07 that's used an appetite stimulant, anti or anti vomiting, often was used
62:13 chemotherapy. The people that like these very much they're still around. And
62:19 we talk about th seeds, Delta THC, you will see there's a
62:23 debate now in the state of texas Delta eight THC. And if you
62:27 to some coffee shops or even gas , you'll see CBD and Delta eight
62:32 solve here, Delta. And as eight THC, it doesn't come from
62:36 plant, it's actually synthesized from But all of these synthetic medications have
62:41 Delta nine THC point being, we know if Delta eight THC has any
62:47 beneficial effects. It's a huge market . Nonetheless. Uh plant based
62:56 Plant the right medications, the same now come into life into 21st century
63:03 of all, it's the Tvx, is 1 to 1 THC to
63:07 It's a buccal spray, cheek spray fast absorption through the cheek. It's
63:12 for anti spasmodic and pain In multiple . It's available in over 25
63:18 but not in the United States. not approved by the FDA in the
63:22 States. I don't know why would originally produced by a UK company.
63:29 is now approved in the United States another prescription pharmaceutical called it The
63:34 Which is 10% CBD oral solution drops its anticonvulsant for dr Dr Syndrome is
63:43 name for severe market on a couple 70 rinsing. So, a mutation
63:47 the sodium channel that yourself and let's started epilepsy is a lot of these
63:52 have also infantile spasms of spazz Matic . And we're talking about when I
63:57 telling about O'Shaughnessy as well. this is now approved CBD 10% CBD
64:04 . So you'll say, okay, is this a proven what is in
64:09 gas station? It's also 10% What's the difference? Well, the
64:17 is that on a federal level, preparations with CBD, you can find
64:24 a Walgreens and CVS. That's your . What's in Walgreens and CVS that's
64:29 approved. It's creams and topical for of CBD FDA is now sorting out
64:35 rules, but now you can find of CBD everywhere for years Now,
64:40 oil. CBD hemp oil and that's federally legal in the oil itself because
64:46 federal illegal. And the cramp is type of cannabis that doesn't produce much
64:53 can be used for both nutritional and and industrial purposes. Uh, so
65:01 so what is the difference? So I be dialing the dialects 10% oral
65:07 has been tested to clinical trials. a system for it. It's being
65:12 , safety and efficacy studies. You get prescription. We're going to consult
65:17 will tell you how to use it to use it. The alternative is
65:22 to the gas station, help storm to somebody that doesn't know as much
65:27 you guys will know after taking this and say, okay, help me
65:32 this. And they'll start telling you and you'll be like, I do
65:37 experiment once in a while, you , people, it's like, you
65:40 , everything will heal you, you , it will heal you, you
65:44 walk again, you will see you know, just Everything is
65:48 But I'm not saying that this is now. I'm just saying that we
65:52 know, we may have 10% preparations the market. Actually that I myself
65:57 a as a consumer would prefer because 10% of the dialogues contains ethanol contains
66:04 seed oil and some kind of a flavor. And that's not for
66:08 Since a consumer, I would go 10% CBD oil and hemp seed oil
66:13 this is what the plant is, is what I want to consume.
66:16 want sesame seed oil or ethanol. don't want that, you know.
66:21 what am I saying? I'm saying there's very limited supply of pharmaceutical approved
66:26 . There's only one And there's probably brands of Em CBD products that have
66:33 concentrations but they're not approved. They're studied. It's just you're just self
66:40 it to yourself basically. What is ? Dangerous? Not that much CBD
66:46 be bad for your liver if you're out of drugs. But other than
66:50 it's not intoxicating. It's not Delta eight THC which is sold illegally
66:57 regulated. It's it can get you high cause that peculiar effect. Uh
67:07 . What systems do we have? actually have medical and recreational it's also
67:14 use system, the differences in medical . Children can get medical Canada's and
67:19 cannabinoids and recreational Children do not get . They're pharmaceuticals. National international
67:27 Sativex, synthetic THC. And also . There are THC so prescription insurance
67:35 , doctor supervision then there's National Medical systems in Germany prescription supervision, you
67:43 buy it in the national level. is cannabis plant flower not a
67:49 not a picture of a flower like and a container that you buy in
67:59 . Uh There's state cannabis programs. States texas has what is called texas
68:06 use program. It's very rapidly growing . As of late about 13,000 patients
68:14 probably be a million patients in the 23 years and there is uh an
68:21 of massachusetts. State medical Canada's I use that because massachusetts also has
68:28 adult use program. So what is difference? If you have medical patient
68:32 to dispensary versus a Iraq uh go to dispensary. The difference is
68:41 in tax. In Massachusetts. State still do not provide insurance subsidies for
68:47 cannibals. The state of Texas, regulators decided that medical cannabis is good
68:53 over 150 conditions. If you ask in the FADA, if you ask
69:00 in the building that startles out. , I only know that it helps
69:04 this, this and this, but from 150 conditions. But the reality
69:09 that these systems could exist And they're , some people will say, you
69:16 , there's a lot of information on that you can get to See.
69:21 horrible. Why would you do You know, I get all of
69:23 fishing information on Facebook cannot find it , cannot find on YouTube cannot find
69:28 from the guys in the store. don't want to pay $25 a book
69:32 find two paragraphs. And the subject . I go to a post.
69:37 that subject matter is, you 200 comments with gear and links and
69:43 and that, wow, it's incredible . And this is actually how I
69:46 my decision. Do I make my about how flat the way I don't
69:52 , I don't but position yourself in situation. Your child is having seizures
69:59 . You don't understand much about silence neurologist appointment is three months from
70:06 You're observing your child dwindling away, in front of your eyes. What
70:12 after your appointment with a neurologist? long is the appointment with a
70:17 You guys see a specialist, anybody element 20 minutes next appointment 3 -
70:25 months. Lucky you live in you can get it in 2-3
70:29 Maybe. What if you live in middle of nowhere, about six months
70:34 then you have to travel someplace 34 . So then you start reading in
70:40 and the facebook groups, what parents doing, what other parents are doing
70:44 sometimes you find solutions and sometimes it things worse. You know, I'm
70:49 gonna judge, I'm just gonna put out there that all of these things
70:53 as far as recreational program, it's taxation, You have state cannabis
70:58 recreational massachusetts California or colorado New Uh, I don't know how many
71:07 now, Maybe in 25 or 30 . I don't count most of them
71:12 both programs and you have recreational national , which is problems specifically. So
71:20 you go in Canada, you in , the province of Quebec, you're
71:26 uh Montreal. Then you go to dispensary and it's a government run shop
71:34 is open at 10 am and closes five PM. There you go to
71:40 british Columbia. It's consumption lounges open midnight. So it's each province and
71:48 private. So each province regulates it now, you know a lot.
71:55 this is the last slide when we back, we're gonna come back and
71:58 about the endocannabinoid system. Because I understanding these things, what cannabis is
72:04 synthetic cannabinoids is for pharmaceutical medications are these elements interact within the cannabinoid
72:11 What are some of the key And the fact that in my view
72:16 endocannabinoid system is going to be one the major major already is becoming a
72:25 development target for many different drives. is a reason why people 150 conditions
72:32 200 conditions seek cannabis and get help cannabis. What is that reason?
72:40 don't know. So let's try to what that reason is. Is there
72:45 common thread between diseases? Of course is, the brain is in flames
72:51 Alzheimer's disease. The brain is in and epilepsy information. Could this be
72:57 common thread why cannabinoids? Endocannabinoid system such a powerful effect on many
73:04 So we'll look into that. Next , It will be online and you'll
73:09 an email from me uh sometime tomorrow that. Thanks for being here
73:15 And I will see you online. Sorry for holding you up a little
73:21 .
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