 So, it looks time to start, right? Everyone can hear me. I have the phone unplugged. I got the horse right here. His name is Paul Revere. Okay. First off, I want to talk about a little bit of biochemistry. People probably know about amino acids pretty well. Amino acids are pretty simple molecules with what's called the alpha carbon and attached to it is an amine or a nitrogen group and a carboxyl group and then a side chain. And unless the side chain is an H, you have four distinct bonds. These are covalent bonds, of course. The shared electronegativity by the way Pauling defined it. If you put your four fingers down on each hand and put your two hands together, you can touch your four fingertips together with corresponding fingers. If you try to lay your hand over your other hand, it won't work. You can't get a match up. Your left hand and your right hand are geometrically distinct. Now, if you imagine this, you can take a glove on your right hand and turn it inside out. It will become a left-handed glove and another little topological thing. You can just see it if you look at it. So anyway, if you put pure crystal, the geometrical enatomer or isomer into a solution and put polarized light through it, it will rotate the light in a certain direction. You can put the other symmetrically mirror image molecule, which is structurally identical except for the geometry. Orientation of the geometry being like an inverse tetrahedron. Then you'll get rotation in the opposite direction. Louis Pasteur discovered this. He had tartaric acid and it had crystallized. He was very observant and noticed that the crystals were opposite. Some of the crystals were one way and some another. He painstakingly separated them out and put them in solution and figured this out. I have a cat crying in the background. I don't know if you can hear it. Anyway, amino acids are quite important in life. You spend a lot of your time seeking them in your diet and you have 10 essential amino acids. The ones that we're going to be particularly interested in, you can classify them in different ways. We're going to be looking at aromatic and they're pretty hydrophobic, meaning they don't like water. They're more lipophilic or fat soluble and phenylalanine tryptophanes is interesting. It's precursor for serotonin and then tyrosine, which is not an essential amino acid but will be of interest. I wanted to introduce this way. Tyrosine has made me everything I am today. You, too. You couldn't live without it. It's phenylalanine. Let's start with that. It's in all kinds of things that are rich in protein. You can always get it from aspartame, aspartame, aspartame. It's called this commercial sweetener, which is a dimer of phenylalanine and aspartic acid. In your body, your enzymes break, hydrolyze these, too. I have it drawn here with a little arrow on the phenylalanine and the aspartic acid. If you peel off a water molecule and stick that nitrogen directly to the carbon that oxygen is on on the aspartic acid, you'll get aspartame. I really should learn to pronounce these sweeteners. There are people that can't take this. There's this enzyme. Phenylalanine is an essential amino acid. You can't synthesize it. You need it for proteins, but you can hydroxylase it. Hydroxylize it within hydroxylase, phenylalanine hydroxylase. If you look at the molecule on the right, at the very bottom, and I guess the para position is an hydroxyl group, which renders it just a little more soluble in water, but it's still lipophilic, and both these pass the blood-brain barrier easily. Lipophilic molecules tend to pass through the blood-brain barrier pretty easily. But anyway, there are people that have a disease called phenylketonuria. It's a genetic disease where they do not have a functioning of phenylalanine hydroxylase. If that's not detected really at birth, early in development, then they will build up toxic levels of phenylalanine and have mental retardation and brain damage from it. In the United States, and the number of countries test for this at birth, many countries don't. Aspartame is one of the things that has to be avoided by people with phenylketonuria. So there's that. Now, I'm just showing here again that you have L-tyrosine being synthesized here from L-phenylalanine. I don't want to get too much into these reactions, but just to have it related in your mind, the tyrosine is really quite important in production of catecholamines and thyroid hormones and melanin. Melanin is kind of interesting. Of course, you think of it as skin pigmentation, but you also have it in the central nervous system in a few places. And these aromatic molecules, like the phenyl group there on the tyrosine and the benzoyl group on the phenylalanine, they have what are called pi bonds. And because the resonation, you know, the molecules that can smear the distribution of the electrons that are shared over more configurations tend to be a little more stable. So these resonant molecules, aromatic molecules have resonance are very interesting. They absorb UV light. UV light is from 100 to 400 nanometers. And, you know, you think about UVA, UVB, UVC, I'll just tell you an easy way to remember it. If you think of like your four fingers, one to four, 100 to 400 nanometers. The UVA is the longest wavelength and therefore the lowest frequency and the lowest energy, it's the least damaging. And you absorb UVA and UVB quite well. Most of it gets blocked by the atmosphere, but think about 95% of UVA. But I think of UVA is like Newton, Newton's lifespan, Newton died at 84. 85 is the number, you remember from doing this, my memory here. 315 to 400 is UVA, 315 to 400 nanometers is UVA light. UVB is like Mozart 35 is when he died. Because the good die young, right? And especially the really smart ones and that's why I'm still alive. But let's see, 35 from 315 would be 280. I can do it faster than I can say it. So 280 nanometers to 315 is UVB and then UVC is below that and it's I think of it like a tortoise going from 100 to 180. So anyway, UV light is pretty significant in our existence. You think of all these aromatic resonating molecules that make up your code of life, the DNA. And the pigments essentially have a form, a shield against UV radiation that can damage your DNA. It's not perfect, but it's, you try going without it. I'll talk about that in a second. So anyway, this is an important molecule, this tyrosine. Nygro melanin was first noted in the 1930s and all these different species starts to occur after two to three years of age. And two places in the central nervous system, it's found substantia nigra, which is associated with Parkinson's when you get the parts compact to gets damaged. I just looked at in 1788 by unsurveiling and the locus ceruleus, which is not a dopamine site, but it's in the catecholamines. You know why catecholamines are called catecholamines? Catechol is a benzene with two adjacent hydroxyl groups on it. So catechol. So if you start to put on aliphatic chains with amides or nitrogen groups on them, they call them amines, catecholamines. So anyway, this isn't the slide I thought was going to be showing, but this is a very interesting point about neuro melanin. This is a little side journey here. But why would you have neuro melanin where the sun don't shine unless, you know, you're getting opened up? Basically, it's felt that it is possibly likely protective that it will give you protection against, like, I think it was periquette is one herbicide that's suspicious and its predecessor cyberquat cyberquat I think was, which was banned around 1975 in the United States. Was one of the toxins that could damage the substantia nigra. Neuro melanin is not the same as the myelin sheath. Myelin sheath there involves the surrounding of nerves by very flat cells that act as insulin and that act as insulators, not insulin. Keylation is, like, if you have a toxic metal, mercury, you put a keylating agent, which is something that bonds has two ionized groups on it that can grab the mercury atom on one end and the mercury atom on the other end and will tend then to go out the urinary track. Keylating agents like throwing somebody in with two hands a molecule in that has two hands that can grab the toxins and drag them out the urinary track. So, you know, in a word that's Yes, Phil, I think that's true. I think that there's a lot of Better living through chemistry that causes worse aging And So I'll let you Folks look at this on the PDF to go into it more. I just wanted to show a picture. One thing and you're thinking about the neural pathways that really came out in the 30s at the PAPAS Talking about neural circuits. Neural circuits, you have nuclei, which are lumps of cells That are basically gray matter. These cells look grayish and they have projections, which are fibers or groups of axons that Go to another nucleus or project to another site that they're going to modulate or influence and on it goes and there's from any one nucleus there's input and output and there are modulatory Inhibitory excitatory inputs And feedback and so you end up with loops that can be very complex but here this locus ceruleus has it if something kicks that on it kicks up the Norepinephrine release from the Peripheral nervous system and puts norepinephrine into sites in the cortex which is excitatory and Norepinephrine is a catecholamine and so it's coming from tyrosine which is related to Production of melanin so that's why you can have melanin neuro melanin showing up in the Locus ceruleus like substantia nigra. This is just a nice slide. It shows it's very well established pathways from tyrosine To L. Dopa to dopamine and norepinephrine and then epinephrine and Tyrosinase is a shoot off from tyrosine to produce Melon and I don't want to get off too much on melon and I just thought it was kind of interesting and it's a copper I know somebody out there likes Metal organo metal metallic bonds It's it's an interesting enzyme in that sense. It has copper in it as a cofactor But albinism can occur and at least 10% or so of the albinism is associated with Mutations in A familial based mutations rather than spontaneous mutations in the Lead to reduction of tyrosinase so that's another metabolic disease that can occur from based on genetics Now one of the interesting things to me is You know, you've got all your sugars and you're in Biochemistry just about our dextro. They have a dextro orientation in terms of endometrious and all your Amino acids are L. Levo and Why was that I don't know but there's a lot of interesting Speculation about it in literature and maybe someone here will get interested and do some deep research and ponder and Come up with some ideas as to refine why we have just L Orientation in our amino acids we couldn't use dextro amino acids and And dextro Oriented sugars Let's see someone if if the questions can be kept In the It's hard for me to talk and and look at private messages The rate limiting step Just like the rate limiting step to making Melanin is this tyrosinase rate limiting step is the Not the weak chain, but it's what determines the overall rate at which anything can be made, you know, if you got it's it's it's the It's the factory that causes the backup in the supply chain Or the shortage on the after this after the factory when you're waiting for deliveries So Tyros Tyrosin hydroxylase is the rate limiting step in Production of this chain of really important monoamines Like Eldopa and to epinephrine and Looking for markers associated with tyrosine hydroxylase is a good way to look for Monoamine neurotransmitting neurons in the central nervous system One of the things I'll mention by the way is in treatment of Parkinson's I'll talk about a little more Eldopa Can be given and that will perk them up for a time as long as they can utilize it because it depends on The having enough cells that can produce The dopamine from the Eldopa So It's it's one of the primary treatments for Parkinson's aside from and you know trying to put in new stem cells Okay I Talked too long. I'm sorry. I'm behind a little bit, but one of these things is not like the other Who can tell me is it left the Or right the over-the-counter Available ordinary commonly used medication or the One on the right which one is a controlled substance Anybody have any ideas? Okay, Phil thinks the natural stuff is left Well, it may not be natural. It's just at least it's just legal one of these is legal and the other one is Cooked in trailers Out in the desert Okay, boom I put pseudo pheron and kind of a rosy color there because it's a wussy Molecule nobody cares, right? It's Facetious and amphetamine and shaded red block letters This kind of Queenie out danger Yeah, it's a hydroxyl group, but it has to be a new right orientation of course But methamphetamine I've came across different statements about the original history of it the Amphetamines were discovered around 1888 or 87 I think and In 1919 or so Well, it's related to tyrosine But it really is comes from a fedron a fedron is a plant product I When I was on faculty at University of Pennsylvania I had a patient who bragged to me that her grandfather Had been she was older And her grandfather had gone to China and found Cooking meth is pretty simple chemistry compared to what chemistry really is It's anyway She come she bragged that her grandfather had brought a fedron back and popularized it He was he was basically the beginning of a fedron becoming used in the United States For Vasal constriction a fedron we used to spray a fedron Solution in the nasal cavity is common. I mean even now to Decongress the nose for examination Or if that with a little topical anesthesia if you're going to do Flexible fiber optic scope exam through nasal passage to look at the larynx or something So anyway a fedron Can be used to Make pseudo a fedron it's basically a sleight of hand by the chemical companies The difference between pseudo fedron and a fedron is It's an antimer you look at the orientation of the hydroxyl group there on the upper left It's toward you rather than away from you in a fedron and you can always look at this Benzo group Connected by a carbon there a carbon carbon to carbon bond as a It can rotate and it's planar. It's flat. That's a flat part of the molecule any rate The Pseudo fedron is chemically The number of month number of atoms is the same as a fedron. It's just the geometry is very slightly different and You take that off and add a methyl group You can make methamphetamine Okay, what happens with a normal Dopamine synapse I'm going to try to go through this without going real long First I wanted to talk a little bit about biochemistry and then about the synaptic level when I was in medical school so much of Neuro physiology was oriented towards synapses and axonal response the axon Nerve impulse and So Anyway, you have Down inside the Pre-synaptic Terminal you have tyrosine being converted to dopamine which is enclosed into double membrane vest vesicle and I think it's a vaso monoamine transport to is involved in Moving it to merge with the outer membrane to be released It's released into the synapse it stimulates Receptors on the post synaptic. I'm sorry I have a touch green and I waving my hand at it The post synaptic it's the purplish area and that kicks off a Response with depolarization down its axon in response to the dopamine and The dopamine and the synapse has to be dealt with some of its degraded by a monoamine oxidase the other is taken up by a dopamine transporter and DAT is the abbreviation you'll see and that gets taken back into the cell and the dopamine gets recycled and I guess on the right is just more about the Synthesis of dopamine from tyrosine. Oh, this is a synapse that's buggered up In a word what happens the principal thing that happens and similar for cocaine and meth amphetamine in Terms of blocking the DATs or dopamine transport molecules So they block both of those block trans reuptake of dopamine which serves to increase dopamine overstimulates the other cell the post synaptic cell and it gets stressed It gets oxidative stress and I Chronic damage can occur and in the Let's see I keep having notifications and stuff pop up in front of my screen the other thing that the meth does that the Cocaine does not do is it goes into the Pre-synaptic cell and causes more dopamine release and It tends to last longer than cocaine is what I understand although the half-life of in ingested Methamphetamine is Probably officially at three or four hours. I've read 12 hours and some sources So I'm not sure what to believe there But the effects seem to last longer than with cocaine and that goes for one of the things We'll talk about a psychosis that arises from use of methamphetamine that tends to last Longer than one would expect with something that gets cleared in three or four hours So one other thing that happens is the microglia which are supportive cells that look for Things that shouldn't be there they tend to get riled up and release cytokines and Damage cells and You do this for very long and you will start to kill off Or really severely damage the The synapse and the dopamine producing cells We'll talk about that a bit more as well but You do not want inflammation in your central nervous system if you want to keep thinking clearly into Whatever advanced years you're able to get Let's see I guess that's the main thing even get mitochondrial Stress here in the post-synaptic. I think that's kind of interesting. There's a lot more detail Endoplasmic reticulum stress a lot of oxidative species and highly reactive nitrogen species can occur that causes damage to Biochemical damage to the the cells so Speed is methamphetamine Speed has no cycle now speed that methamphetamine is this psychotropic drug and Sympathomimetic it acts like epinephrine to some degree Yeah, okay I Put the slide in basically to For anyone who wants to look at the PDF they can refer to it to Read about the points. I just made if they If anyone wishes That I sent out the note card and that is a link to the PDF for this talk I just posted right there So I'm gonna go on at this point, but yeah reactive oxygen species reactive nitrogen species occur mitochondrial Damage, which is really huge. I mean that's You need those guys Okay, let's go up above the cellular level to more of a system level talking about the brain and I thought it would be cool to talk about I guess McCain's Triune brain mech lean rather Triune brain which just reminded me so much of Star Trek and the Symbolic concepts of Star Trek. Yeah, that slide was for a barrigan this one, too. That's my McLean and Shatner's the only one living now But he rate He came out with this idea that you have the reptilian brain the limbic system and the neocortex You know the limbic system was what was called the rhombin Cephalon at the the Rhine and Cephalon Rhombin Cephalon is like the ponds and Below the midbrain the ponds and the medulla oblin cata Yeah, the nose brain and and he thought that was like you're looking at rats or lower mammals They've got a huge nose brain and that was what were They were the best subjects for study and so They figured That was how they sorted out stimuli and such and then McLean started to think I think that there's a fear or motion aspect of this and It's kind of started to evolve to the limbic system and that was still not So commonly said it was said by some and others seemed to be wary of it wary of it when I was in medical school Over the past 50 years great deals come a long ways There's another little picture that shows the idea of this You got the squash up here and The limbic system is not just this middle portion and it's just too simple and These systems don't operate independently It's not like you got a reptile, you know, you can't blame your bad deeds on That's the reptile in me, you know It's all integrated and I put a little neural glossary here just for Anyone that's interested again this will be in the PDF Particularly we're going to be interested in talking about nucleus is any cluster of neurons and they're like modular areas of the Of the of the forebrain and midbrain some and Even some in the hindbrain there's some clusters of cells and they project Excuse me axons to other nuclei So they interact they feed back they talked to each other Did I make a big jump oh Well, thank you. Thanks. Thank you Mike So I Will leave this for people to come back to to refer to in a sense the forebrain and the mid The forebrain refers to the dian cephalon and telencephalon the telencephalon It's like this rebrum and basal ganglia and the dian cephalon is the through brain Which is particularly in my thinking the thalamus, which is a relay center for everything that goes down the spinal cord and it Kind of balances a lot of stuff out the midbrain is below the hypothalamus and thalamus and It's a small area really the forebrain is The cerebrum is related to the first two ventricles. You have a left and right large cavity in the Port ventricles they are full of cerebral spinal fluid and it's secreted inside of them they perk percolates down through a little duct into a third ventricle which is Basically the ventricle of the thalamus and hypothalamus and then it trickle late it Percolates down to a fourth ventricle which is a little cavity in the Raman cephalon or brainstem ponds and I Wondered about why they called it ramen cephalon and because There are like raw eight rum beers Which are swellings that Form embryologically that become the ramen cephalon So it's related to a term they used in embryology and That term was first used in 1895 apparently Rum as something as a rhomboid is like a parallelogram or four-sided equal sides, I think Uh Can be doesn't have to be right angled all right There are Four dopaminergic pathways and I use this slide a couple times in this talk This also shows cerebellum is also at the level of the ponds in fact the ponds has this bundle of fibers that goes across In front of it that relate to the cerebellum and a vermus in the center Between its hemispheres Cerebellum means little brain. It's not very interesting to neurologists. It's Except You get a lot more bang for your buck buck with lesions in the spinal cord than you do with dealing with things in this cerebellum Uh, cerebellum is never interested Your science as much as how we think but these Listed on the left here, especially the mesocortical and especially meso olympic pathways Are of interest. These are all dopaminergic pathways. Those are the only dopaminergic pathways in No, and that's not right. They are the four major ones that Might want to put in your brain the meso olympic Relates to the ventral tegmental area in the Mesencephalon Oh, I went on to the next slide and you can read it there and I Don't mention that here in this but I give a little description of what are involved in these pathways the ones a nycosterial is Substantia nigra which is considered part of the basal ganglia. I'll tell you in a minute what the basal ganglia are and it projects to other basal ganglia and That's of course where you get Parkinson's when you have loss of cells or loss of dopamine production in those cells the meso olympic and mesocortical have a lot to do with motion and how you activate your body and Have a emotional movement a motor a volant volitional movement and a Response to emotion and emotions and feelings in general are Including fear are in this and memory especially episodic memory the There again, I want you to think of Loops or circuits like the papas circuit for the limbic system which involves the hippocampal formation and The amygdala and the amygdala is Right in front of the body of the hippocampus. I have better pictures for that in a minute and singulate gyrus So Okay, here's your hippocampus Hippocampus comes from the term for seahorse and so now you can see why this Curve thing here is the tail up is actually What's called the fornix or arch? and It's also closely related to the olfactory system In the very front of the body here at the top left of the hippocampus is Where you would find amygdala which is Part of where you get fear That's that's thought of with fear, but I'm gonna tell you a story about that in a minute for I do let me just tell you about I used to deal Over my time I did a couple of operations and with in combination with neurosurgeons most of them involved sinus disease frontal sinus disease where the Sinus disease have destroyed the posterior bony plate of the sinus and he wrote it into the frontal lobe area Anterior cranial fossa and so I would do surgery in combination And cooperation with a neurosurgeon But this is olfactory bulb. It's the first of 12 cranial nerves It is the one that goes right into your brain right into your cerebrum. It doesn't go to your midbrain or Brainstem, it's the It's less than five percent. Maybe it's a few percent of your brain Function is and involves the olfactory Perception per se whereas it's maybe 40 percent in a rat But you can get tumors off this bulb and it has the bulb has processing and such but Asthesioneuroblastomas which grow down into nasal cavity and are destructive and That's a that's one that I've dealt with with combined procedures with neurosurgeons Those are Stimulating cases you keep awake quite easily and You have this cribiform area in the roof of the up ethmoid where Little perforators come through and those are your olfactory endings. Those are basically pure brain Looking down. That's like like an open retina there at any rate this feeds right into Structures associated with the limbic system the uncus down here on the right is Cortex right over amygdala and the head of the hippocampus And then you have primary olfactory epithelium and it projects up into Some of the cortex as well. I Thought this was a good slide. It shows the right Well, it's actually the patients you're looking at the base of the brain and the bottom of the It's not a patient the bottom of this human brain and so this Is the left olfactory bulb? It's been removed on the right side Which is on your left and it's marked as olfactory sulcus at at any rate You see how small it is compared to the overall structure You can see down at the bottom is the ponds. That's what is related to the cerebellum and its functions and mammary bodies are important in the limbic system and Part of the pepe's circuit As well and you have mammalothalamic tracts the ponds is at the bottom medulla is below out of the picture It's not shown These are just above the ponds there are two little Bumps in the mid-dine Right adjacent to each other and in front of it is like if you put your fingers in a V That's the optic chiasm The optic nerve crosses and the pituitary gland comes out in close relation to the optic chiasm too, but at any rate the memory bodies are Part of the thalamus and important in the limbic system and Let's see I guess that's about all the temporal lobes are on the left and right here Think of put your arms with your fists to your sides like in a karate stance down down to your sides and think of those those are like your temporal lobes and It's kind of in that position your brain is folded so your temporal lobes come round and forward and There's uncus you can see uncus marked out there just if you look at where the mammary body is down there and the center about the bottom 25% of the picture just to the right and left is uncus and that's over that's cortex over the hippocampus This is from an old book That was made its classic Netter he just did such fabulous pictures showing the hippocampus and fornix the hippocampus is a temporal lobe structure and Starts out in the temporal lobe and swings around and with the fornix and the amygdala or to Nuclei that on each side and the temporal lobes that are just at the head of the hippocampus the amygdala this is Place where you process fear now as I read this One thing and I've heard it's discussed Like if you get rats and you put electrodes in the front and the back of the amygdala if they're in a safe place like a Nice warm cozy Place with food and water and soft light no scary things and no predators then The amygdala seems to act as more of a pleasure center But if they're in a Rat hell, you know where there's a lot of fear things that could cause them stress then the front of the amygdala shoots a lot of Impulses neural impulses in the back can as well so the amygdala can Adjust its function based on what's going on It's not purely fear. It's not that simple it's also a site where aggression can be located and It's some of sexual behavior comes from that and one wonders if the aggression associated with the amygdala and sexual function associated with the amygdala It's mixed up in some guys so that they think that sexual activity has violence and Harm involved It's an interesting question This is looking at from the brain split down the center from front to back Vertically and you can see underneath the Temporal lobe frontal lobe to your right. I would have anterior I wrote in there and the singulate gyrus is part of the And it's even more than just singulate gyrus It's and they now say prefrontal cortex and that includes singular gyrus singulate gyrus But that's some of the processing of the limbic system limbic system is not just It's part of this cerebrum deep cerebrum and So Okay, thing I liked most about this picture. It's midline, but it shows this corpus callosum and Basically the hippocampus Fornix runs below it but the corpus callosum is a band of associative neural fibers running from the left to the right hemisphere and in some people that's Doesn't form or it can be divided neuro-surgically and interesting things happen, but Also You see here they show the pituitary hanging down there like a grape Right in the center in front of the temporal lobe If you can see that Go from the center at the bottom straight up and you'll see this light gray thing on a Dibular stalk that's the pituitary gland and it is controlled by the hypothalamus which Does two things it does a lot for the autonomic nervous system and it has a neuro ectocrine function it sends It creates hormones that go in a portal system a Little circulation specialized circulation between the hypothalamus and the pituitary gland to stimulate the Receptor cells in the pituitary gland to create thyroid hormone cortical corticosteroids and Hypothalamus is really busy maintaining the Homeostasis You also have I mentioned locus ceruleus with the parasympathetic nervous system The One point I've come across is that all these structures in the limbic system particularly and in the thalamus are competing to Control the hypothalamus. They're all talking to each other and they're all talking to hypothalamus and they're all trying to talk down every other Nucleus and get their message into the hypothalamus to tell it what to do and it gets weighed out and That's how you deal with stress and all kinds of stuff. Okay, limbic system. These are the main parts of it. I Thought this was a nice slide for it the reason why it's important is Is Because I still don't well there's in This is the Circuitry for emotions like limbic think of the bottom bunch of stuff is the hippocampal formation and Look how it tracks it from the hippocampus runs up the fornix to these mammary bodies And they have mammalothalamic tracts and the anterior thalamic nuclei It's actually called an area because there's three nuclei talk to the cingulate gyrus and Tell it what it's doing and Then there's feedback To the hippocampus and it's all this is important in an emotion and and processing of emotion and Memory especially episodic memory or explicit memory On the other hand basal ganglia, which you think of putamen called eight a migtula is that kind of fear nucleus I talked about But Down there with the hippocampus and the temporal lobe These are collectively called the stria striatum and They are kind of a processor for Executive function interacts they these interact with the prefrontal cortex a lot these are deep nuclei in the brain that interact with the frontal cortex to decide What to do what how to weigh something out and what action to take or not to take and If you play piano, this is where implicit memory is in these basal ganglia and in synapses that form there, that's you you can Implicit memory means memories without a condense Consolidating event necessarily it's maybe by you know experience that gets incorporated and by repetition as opposed to The explicit episodic memory that's associated especially with emotional Things that happen Okay, all this leads to nucleus accumens, which is kind of major reward Center in the brain the ventral tegmental areas that those are dopamine dopaminergic neurons and they send Information to the I said to amygdala, but also I'm I think it does but I Meant to write I was going to emphasize here nucleus accumens Nucleus accumens is really part of the basal ganglia close in with the cold eight and the putamen and The ventral tegmental area is the target of Methamphetamine and you get methamphetamine in there it starts sending out dopamine and It's it's it's a dopamine producing Nucleus and it's dopaminergic neurons go to limbic and cortical areas and They get a cheap reward they get a feeling of I've achieved something without doing anything I Put this slide in just to show these Caudate and putamen basal ganglia Globus Palatis as isn't there it is. Yeah, it is indicated there It's not functionally related so much to the caudate and putamen, but it's one of the basal ganglia Here's another slide you can see the gray there and there's internal capsule if you look there's just a streak kind of going diagonally where that this idea of lenticulophore Lynn Lentiform nucleus is kind of our cake. It's Putamen and and Caudate together I just messed up my view if I hit the wrong Okay Just quickly again because I think Parkinson's is one of the interesting things about Methamphetamine that people don't talk about as much as they should Parkinson's was first described by James Parkinson and I couldn't find a Picture of him and that's because they weren't taking photographs back then Pictures that were incorrectly or erroneously attributed to him look scary So I could see why they would cause people to shake if they saw that face but in any rate he had a small series of patients plus some people on the street and I think in London and He distinguished between people with trimmer at rest, which is typical of Parkinson's versus tremors with motion, which is Like Essential trimmer Tourette's is quite different Tourette's is it's Parkinson's Tourette's I don't think is closely related to Parkinson's at all Parkinson's is What's it's got a complex of Symptoms they get Parkinsonian faces where they basically don't show expression They can't get going they can't keep going and they can't stop They can't control motor function. They even have trouble swallowing. They start to have Perceptual hallucinatory effects it eventually On the other hand, I think of Tourette's I had a patient Who had Tourette's once and I was writing a prescription back when we wrote prescriptions and She took a swing at me and I heard the wish The swoosh as it went by my ear. She just did crazy stuff that that's a little different Anyway, I thought he was Interesting thing to point out One of the things I wanted to impress upon you is that methamphetamine methamphetamine users are almost twice as much likely to have Parkinson's develop as people who never used it You don't want to burn out your equipment and I Before I leave the system thing. I want to impress upon you that Methamphetamine like cocaine now cocaine Kind of have an interesting common history or parallel history coca was derived and presented to Europeans really came of interest in the 19 1800s and I guess There was a wine Produced Vin marina then marina that was wine and coke cocaine there was about two grams of cocaine per ounce of wine and This was sold by this Gentleman Perkinson maybe in United States as a Beverage To help you as it basically he touted it as a an aphrodisiac to help your sexual organs rejuvenate and the sort of thing so It was popular and then like 17 I'm sorry 1885 after the Bad compromise and the Hays administration and they allowed Jim Crow to resume in the South They had a temperance law in Georgia where they forbade the sale of alcohol and So this Perkinson Had to take his Wine and cocaine mixture and do something he replaced the wine with sugar and Coca-Cola and So I Think he could have gone to another state, but they're still in Georgia And just lately after they passed new Jim Crow laws they came out said those aren't very nice but Cocaine was Eventually controlled in 1914 there was a Harrison bill That Regulated production and distribution and sale of opiates and coca products and Basically it was influenced by people like Halstead who was a top surgeon in the United States that Who was very famous at Johns Hopkins when I was in Training and I did general surgery for a few years everybody talked about Halstead and he was a Hero and Meanwhile some of his writings he was a cokehead himself he injected cocaine and Was addicted to it so was Freud and others And in fact that that drink I mentioned with the coke on the wine I think that Thomas Edison and Ulysses S. Grant thought it was just great thought it was very stimulating Of course Grant was known to be an alcoholic and Edison liked to experiment but In any way Halstead wrote about Timid Negroes becoming unmanageable and because they become Fiends for dope or doper fiends and become a constant menace to the community so There was Concern about Cocaine fiends among the Negroes And so that was America See what Jack Johnson the boxer was up against and So in 1914 they passed that bill to regulate it and cocaine kind of disappeared from the scene until the 70s when the Sex drugs and rock and roll scene really Caught on I remember when LSD was not illegal and methamphetamine was not illegal methamphetamine was first Regulated in the United States in 1970 and When I was in college, I knew a lot of people that were doing decks and speed and things and a lot of other drugs and I I Was I feel so lucky when I was about 14 to 15 I was I Discovered I didn't feel like I had much going for me. I wasn't well to do and I Didn't have Impressive clothing my all my clothes were from my cousin and Which Got me made fun of at times because they didn't fit great and they were worn but I Was in Mathematics classes and we had linear equations multiple linear equations like in for unknowns and They said you got to write this down and I tried I discovered I could look at it on the board and solve it without writing it down and I got a rush out of that kind of a reward in my brain out of that and I Sometimes the math teachers like me and sometimes they didn't I would return in stuff with no derivations Or if I use derivations, they didn't like my derivations Because they sometimes one of them told me they didn't know calculus and I was using calculus which I had taught myself but one summer and I was so afraid that's all I had I was so afraid if I lost that I wouldn't I would be nothing and so I was really protective of my brain function and all this time and I never drank much and I got drunk once in my life and I Never did drugs. I Drank coffee and I did smoke for a time but I Quit that when I was young and This stuff caused this brain damage, but a rate it's an increasing problem since The Well the finish up with the cocaine in the 80s I guess they started cutting cutting corners and Cutting cocaine for distribution illegally with baking soda and things and they would heat it and it make cracking sounds And so they called it crack cocaine and they said that's more addictive. Well It was cheaper. It was so it became more popular than ever ten ten bucks and you could get a hit of crack cocaine and you had in Philadelphia you had Teenage girls and some teenage boys selling their bodies For a ten bucks To get another hit of crack cocaine. It's just really form of slavery What happens with these things, but it's causes deaths and methamphetamine overdoses are a dangerous thing and Most recently the Native Americans are In the United States are suffering the most with that I think people that are poor and desperate and don't have much to be happy about You take something like this and it makes you feel Invincible makes you feel like you've won Or that you're going to win it one of the big things about this is anticipation So what happens if you take? Amphetamine side effects Some of these are the same if you take a lot you get high levels of serotonin as well But you can end up with a heart attack comas and Paranoia paranoia is a big thing with this One of the problems and here's where I want to talk a little bit just just a couple more minutes about the socio Medical aspects of of methamphetamine use it becomes a community. There is a paranoia associated there's also paranoia associated with cocaine and violence Was something that's associated with cocaine use, you know about Supposedly 90% of people they're using cocaine or just recreational use. They're not using it heavy But they're not habitual But that 10% they'll start using it a little more frequently They'll start during the week and then they'll start daily and then they'll binge they'll go days They will stop eating. They'll stop sleeping. They lose their job. They lose their family So they get really down and out and they're a mess and the only thing that makes them feel good is more Methamphetamine there's stories like a Woman she's and but it's a problem. There's a methamphetamine crosses the placenta as well as the blood brain barrier So it gets to the baby, but a woman that This is not at all in common. I was pregnant, but using methamphetamine quite a lot After the baby was born the family was there to see the new baby and uggling and oggling and She felt nothing She felt nothing It couldn't compare to what she felt when she got meth So it's a tough problem is really no cure for this They get into a community where you're either in or you're out If you're not a if you're even an occasional user of meth, you're out They they don't trust it, you know anybody that's not a heavy user and they can see that they're heavy users Yeah, it destroys the teeth and the people that are heavy users they'll start with proxies and where they grind and crush their teeth and fracture them and Necolect dental hygiene as well and Long-term heavy use can lead to psychosis among other things death as well, but the psychosis can last for over a day and sometimes longer and I Was going to talk more about history by only to go on and on I Put the slide in for people that are interested These are three interesting articles about how governments exploited their young Mostly men, but now it's men and women, but Methamphetamine is not used the same way now In in militaries at least in the United States But the Germans it was it was an over-the-counter medication of methamphetamine available in Germany during World War two Hitler was a meth freak It was used in soldiers to keep them going and when the war is over What then they're screwed up? so there's a there's a lot to a lot of hypocrisy and a lot to Be concerned about here One last picture You look at these you can do this with PET scans or specialized MRI scans And these commercials I'm making fun of I'm sorry Yeah, there we are Too far They didn't work. They were pretty striking. This is this is your brain. This is your brain on Bad memes this is your brain on Drugs Okay, that's pretty striking somebody. It doesn't use drugs or someone that does they think that's lame And One of the things I wanted to make a point of here lastly is that People that do these things cause Changes in the physiology of their of their brain. Dang it. Sorry They lose dopamine function and The healthy brain is to the left and in the upper left-hand corner and the Person who's been a heavy abuser of dope? Methamphetamine is on the right and you see a lot less Dopamine activity and that can last at least 36 months and I think there's some literature That suggests there are permanent changes. So I know just say no is an easy It's gonna take more than a village to make people quit. They need a lot of support acceptance and That's about it, thank you Della Delia I say things always mispronounce things so Any questions Do you want to read stuff? That's really cool and one of the things I enjoyed the most in medical school was neuroanatomy and It's really been refined we had a Stodgy Older woman who taught neuroanatomy and she had published and was very dry and would only show cold Diagrammatic anatomy and then we had labs Examining brains and brain areas and we also did histology and There was it was frustrating for me because it was so much stuff and I was what in the world There's all this stuff too. How does it interact? You almost need artificial intelligence to understand the brain There's so much Going on between areas. I went over a little bit. I appreciate everyone sitting in Through this and thank you to everyone Was there a question Steven? I missed it. I'm sorry. Thank you Phil. Thanks for coming synergy. Thank you day Thank you, Manuela. Thank you max Okay, there's a new approach to dealing with epidemics of addiction to Think of it as an epidemic of an infectious agent. How much do you think that approach will help? Well, I think it is a disease this is like a disease and Approaching it by punitive legalistic And Archaic Schemes is fraught with failure and it's gonna I Psychiatry and psychology are As as applied Sciences are Really lacking in the psychiatry if they Have anything for which they can't just give a medication say that's it then it's a Lot of work and the things that are easier Kind of take precedence But it's it's gonna take big social Structural changes and in the way People are dealt with and the support they get if they're stuck on meth The other thing is meth is causes toxic waste sites it you go stay in a motel room You may be staying a place which has toxins and Dangerous chemicals As residues in the air or on the surfaces that were used for cooking meth There's all this mobile Meth labs and things like this. It's not really hard to make and I refused and Expressively did not talk about how it's synthesized as I don't think anyone needs to know that really But yeah, I think society needs to needs to regard it as a disease You know you look at the brain and so little of what we do is a Tributable to free will or if any or They put a person in jail because they're migtala screwed up Basically, I mean it's really Striking You have to deal with people by their actions if they're danger to others But it's one of the reasons I really don't accept the death penalty. I hope I gave a reasonable answer to that Oh, yeah, the Stephen Danes of Montana was complaining that They used to have homegrown meth in Montana now it's coming from the cartels in Mexico like it's suddenly Mexico's fault What a jerk Thank You Shaila. I was thinking this exactly Phil what politician brains look like I think about like that many of them about like that Egg on the left in the middle with the pepper on it kind of a lot of coagulated protein And a fat glob in the center called the yoke. Yeah, meth labs are very dangerous and They don't take precautions they're dealing with I mean with flammable and volatile agents and Getting chemicals from all kinds of places that then they just Put in the garbage It's not being disposed of properly and things aren't being cleaned down properly and They're not trained or oriented towards safety. Yeah, especially when it turns brown Phil Nitrogliss ready to make it home The brown stuff you got to really walk easy And the fumes are coming off of it Thank You barricade Thanks, Stephen. I've never seen breaking bed. I saw an excerpt of it, but I'm not sure where I saw the excerpt but and I know that actor Not personally but sorry max. Oh, I had one last thing. I'll tell anyone who's here that's still interested How to increase your own dopamine levels Naturally, so for those who are still here if you want to jack up your dopamine levels exercise walking walking is great for making new synapses and It'll jack up your dopamine naturally nature nature is a good way to Improve natural pleasure responses nutrition is important good nutrition healthy nutrition meditation which like Shiloh does that would I Think and naturally increase Gratitude and attitude have a good attitude about life Think positively look for positive aspects to life and the things that work for you again, I was like I Could have come out a lot of ways and again. I just feel so lucky. I was I Kind of got stoned on learning stuff. I got a rush out of learning stuff and It was like a drug thing for me. So learning a new thing was gave me Sense of gratification. Yeah, it's a great thing. Isn't it max? So being grateful for what works for you and You know sticking to it goal achievement setting yourself a goal something doable and then do it and then Of course dopamine is also involved in the anticipation of a goal because it's part of how the brain Learns. Oh did I do this before how did I do this and how did I get that and now day? How do I do it again? It's sort of the old is it still there? And is it does it still feel good type of thing and Finally go out and make some happy memories and dwelling on happy memories if you can Choosing the memories you dwell on or Is better than dwelling on negative memories, so that's all I got Yes dopamine is really important in learning. Oh, thank you. Once again, I'm posting my PDF for anyone that would like to download it and Or have access to it and Does that think there was good diagrams overall? Only had one place where I would have edited it a little differently if I were to do it over Thanks everyone for coming. I really appreciate your attention and interest. See you Phil