FUNCTIONAL NEUROLOGY ANATOMY AND CENTRAL NEUROLOGICAL PATHWAYS (MODULE ONE) Transcript Autonomics

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1 FUNCTIONAL NEUROLOGY ANATOMY AND CENTRAL NEUROLOGICAL PATHWAYS (MODULE ONE) Transcript Autonomics Presentation by Dr. Datis Kharrazian Okay, so let s get into Autonomics. So here s where we are in the big picture and the scheme of things throughout this module. So remember, the key thing with this module is that we re not actually going into deep treatment or into even going into all the depth that could be involved with each of the regions. But the goal is, after you leave this module, that you should be able to hear a history and know what area of the brain is involved, right? And then obviously there s a lot of clinical things to take away throughout the lectures, but that s the first goal that you want to be able to leave with after this course. So if you go through your notes, if you finish this course, you want to go through and go, What is seizure activity look like in each region of the brain? Is it cerebellar? Is it vestibular? Is this basal ganglionic? Is this inferior parietal? Is this frontal? And then get an idea of what those symptoms are, right? And once you know what those symptoms are associated with each region, then you can actually start playing the game. You can t play this game going right into treatment. You ve got to know what area s involved, and that s how you become good at what you need to do. Then we talked about the big picture, and the flow chart, and how these things go into those areas. Now, you re going to have people that have autonomic dysfunctions, or what we call autonomic dystonia, or dysautonomia, where the heart rate s all over the place, or they don t have proper digestion, or they have abnormal tearing, or they have different types of changes in their sympathetic responses and the pupil responses, they have anxiety for trivial reasons. That s all associated with the autonomic nervous system. So what I need to do is, I need to go over that and teach it to you. Now, if you re a neurology diplomate, I can tell you you learned it probably very limited. Because the way we ve learned it and taught it in the past, where they re taught to measure the reticulospinal tracts and mesencephalic reticular formation, how they integrate, is only isolated for instantaneous movement. It s not the connection through reticular pathways, it s not the connection through survival pathways, it s not the hypothalamic projections, and it s not necessarily even the limbic projections. So what I want to do is, I want to kind of add to that, and kind of go into more detail. So for those who are experienced, here s what you really need to do: We gave you, in the modules, to click onto the webpage with the modules, for each section, each topic, we gave you a bunch of research papers. If you re a neurology diplomate already, you need to go read all those, because you need to get up to date. That s how it works. Okay? So that s a section you really need to go through and read all the full papers so MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 1

2 you can understand the big concept here. And I m going to summarize it all for you in this presentation, and give you the key flow charts and diagrams, so it s easier to go through those concepts as well. So, the key concepts that I want to cover in my presentation is: understanding tonic versus phasic responses of the autonomic nervous system; understand central processing of autonomic nervous system; what happens in the brain with a sympathetic response; what happens in the brain with a parasympathetic response; understand the pathways for sympathetic responses; understand the pathways for parasympathetic responses; and then what happens when the brain is impaired, autonomically. Right? So those are the key concepts that I want to go through. Now, you guys have all seen these diagrams. You guys all have learned autonomic function before: sympathetic, parasympathetic. I don t need to really go through that with you. But what I want to go through with you is, what happens when someone comes in and they tell you that their heart rate s racing all over the place? What could be mechanisms why? Why would someone all of a sudden go see a move and get anxiety from it? Why does someone have a head injury and now they can t digest their food any more? Those are all the key things that I really want to focus on. So, you guys remember the parasympathetic system, and basically the way this works is, the cortex, the brain fires into the pontine areas of the brainstem, and you have all your parasympathetic nuclei there, and they have their effects. The key thing being the vagal goes all the way down to the gut, and you have all these visceral types of effects from the brainstem parasympathetic pathways. And then you have the sympathetic pathways, which involves the sympathetic chain, which then goes into releasing peripheral catecholamines, and having direct pre-and post-ganglionic connections to the viscera. You guys already all know that, right? It s not really something that we need to spend time with going over. So lets go over a clinical example to see where we need to go. A patient presents with chronic constipation. Her symptoms started a few weeks after a car accident five years ago. She also has ongoing difficulty with focus, attention, and concentration. So let s play this game. Let s start with the second sentence. She has ongoing difficulty with focus, attention, and concentration. What region is involved? Frontal. Perfect. Now, her symptoms started a few years ago after a car accident, and so we want to see how these symptoms developed over time, and remember, with post-traumatic brain injuries, you get a domino effect. The inflammatory consequence keeps happening and happening and happening, even after the injury. So a lot of times people will get a head injury and then have the recovery from the acute stage, and then they won t have symptoms for years later because the inflammatory cascade keeps going, right? So maybe they ve injured the frontal lobe in that area. Could that be a mechanism where they can cause constipation? Right, it can be. Because we have these brain-gut axis pathways, right? So we ll go over parasympathetic aspects, and some people, as they injure their brain and their brain becomes inefficient, for example, they can t fire into their vagus, so they can t produce enzymes, they can t digest, they can t get blood flow to the gut, and they get intestinal permeability. So we know that we have those types of mechanisms that take place with the brain. Now, how about this? Patient presents with chronic anxiety. Her resting heart rate fluctuates between 40 points. So if you look at her if you have her set up on a heart rate monitor, or a pulse-ox, and look at her heart rate over a minute, you see some people, the heart rate will be between 60, then it will be 62, and then 70, and then 100, and they re going all over the place. So they have abnormal heart rate variability. That s an autonomic or dysautonomia. Autonomic dystonia, dysautonomia. That is an issue. Those are MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 2

3 brain-related patterns, right? So you want to be able to identify those. When you see that, you know that there s something going on with autonomic nervous system function. And then, She also complains of arrhythmia, symptoms of disorientation and dizziness before anxiety attacks. So let s go into that a little bit more. She has disorientation and dizziness. What area of the brain? Disorientation and dizziness. Vestibulocerebellum pathways. Can vestibulocerebellum pathways cause anxiety? Well, we re going to go over the autonomic pathways, and Dr. Brock s going to go over the vestibular system with the greater detail going to autonomic pathways. And absolutely. So you would look at this and go, Okay. Her anxiety disorder may really be a vestibular disorder, just from the first two sentences, because she has anxiety she has dizziness before anxiety attacks. Because we know that the vestibular system fires into autonomic centers and limbic regions that can cause people to have anxiety to have this pattern of anxiety. So she may be thinking that her anxiety s cognitive where it s actually vestibular-based. You guys understand? So, you should understand the concept of going through, hearing the history, as you hear the history you can pretty much identify pathways, if you know your neuroanatomy. Right? That s the whole point of this course: neuroanatomy, functional neuroanatomy pathways. And so we re going to go over those regions with you in greater detail. So, as a basic level of understanding, you have what s called tonic and phasic, when you look at the nervous system. Tonic means you have steady action to potential firing at a constant frequency at rest. So we all have some degree of tonic-sympathetic activity, some degree of tonic-parasympathetic activity going on all the time. Right? And we need to have that so we have respiration, and we have blood flow, and we have circulation, and all those things. And then you have phasic responses, where something activates the autonomic centers. So a spike in resting action potential firing from presynaptic activity. So we want to really go into what pathways, like the vestibular system, that fires into autonomics, you get a phasic response. So all of a sudden they move their head to the right, and their heart rate goes up. So they had a phasic jump into it. So, some autonomic disorders have an abnormal tonic phase, so they re always in a sympathetic state, or they re always maybe in a parasympathetic state, typically more usually sympathetic. Or, they have a phasic response where something activates an autonomic response. Does that make sense? So you kind of, as a clinician, want to go, Huh. Are they always in a sympathetic drive? Or are there things that drive the sympathetic drive, are there movements, are there things in their history? So, on the previous case for example, when someone says they have disorientation and dizziness before an anxiety attack, then you re starting to think, Okay. This is the pathway that s causing a phasic response. Something s firing into that system and there s some degree of change, versus someone who had a traumatic brain injury, and their heart rate s never gone down since. Does that make sense? I mean, that s more of an ongoing tonic response that s there. So, there s a list for you of tonic activity, phasic activity. Just a nice review. It s all the papers all the references you ll see with papers you guys have in your module, notes, so if any of these diagrams are important for you, go ahead and really check those out and read them. So, when you look at the brain, here s what you have to first understand. And actually I m going to go into a bigger concept. So, what we ve been going through throughout this module is, we re teaching you first of all region-by-region function, and region-by-region symptoms of lesion and region-by-region symptoms of seizure activity. Okay? And that s a regional model. Then there s another model which is the hemisphericity model, where the right brain is involved in more things like hemineglect, and visuospatial orientation, and MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 3

4 left brain is involved with more things like language, and that s where you have more of a hemispheristic model. Then the next thing you have, instead of just regions and a hemispheristic model, is networks. So language is a network. Pain pathway, it s a network. So autonomics is a network, okay? You have multiple areas of integration that are working together to cause you to have proper respiration and heart rate and so forth, okay? Now, this is important because you can just have you don t have a lesion in just one part of your brain and now you don t have sympathetic function. You don t have a lesion just in one part of your brain and you lose parasympathetics. Does that make sense? Whereas you can have a lesion in your vestibular system, and then lose your balance altogether, okay? So when you re dealing with networks, it s there to be protective. The networks the pathways you need to survive are usually networks. So there s some room for error of the things that are involved. Now, what you see is, there s hypothalamic nuclei. The key ones for autonomics are paraventricular, dorsomedial, lateral hypothalamic areas; those are the key hypothalamic nuclei. And the hypothalamic nuclei are really important for us, is because they project ipsilaterally down the brainstem and spinal cord. And then as we look at areas of the brain that are involved, we have networks between the insula, which is where you have viscerosomatic processing, the anterior cingulate, which is what modulates your respiration and heart rate, and those types of autonomic survival functions. And then you go into areas of the periaqueductal gray, which coordinates pain, integration of different types of input come in and out of the brainstem. And these things all kind of work together, and they fire down to the brainstem nuclei that are parasympathetic, which have a parasympathetic effect, or they fire down to the spinal cord where you have the intermediolateral cell column, which creates a sympathetic response. Now, the intermediolateral cell column is where is the area of the spinal cord that fires into the sympathetic chain, which causes a sympathetic response. At the spinal cord level itself, it s always firing. It always reflexively has to fire so you have some degree of vascular tone, some degree of blood flow and constriction in your peripheral regions, okay? And the brain projections tend to they can activate it, but they mostly inhibit it. Okay? So as a general concept, here s just something to think about. General concept. As you lose brain, you get ipsilateral increase in parasympa,,, increase in sympathetic, and less para I m sorry, you get increased sympathetic tone, and less parasympathetic tone, okay? Now, before we get into those concepts, let s talk about integration itself. So, let s talk about the insular cortex. So, the insular cortex, if you guys see this diagram, this is really a good illustration. So you go in here and you see these forceps; they re pulling up the frontal parietal areas, they re pulling away the temporal area, and right behind the temporal lobe you have this insular cortex. Right? It s the insulated area of the brain. It s hidden, okay? And this insular cortex integrates visceral pain, temperature sensation, and if we go to this diagram, it kind of summarizes the key function. The insular carries the visceromotor function, controlling sympathetic and parasympathetic outputs via relays in the lateral hypothalamus. So input comes in from viscera, from muscle, skin, respiratory effects, through face pathways; goes to the thalamus, goes to the insula, and it starts to integrate what kind of autonomic effects you re having in the gut. Okay? If you have an emotional response, and then you feel something like a gut response or something, that visceral response, that s the insular cortex. Okay? MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 4

5 Then you have the anterior cingulate autonomic integration areas, and these are really involved with blood pressure, heart rate, emotions, impulse control, autonomic changes. And this is really where, when you think of things and you change your heart rate, when you think of things and you calm down, when you do things like mindful meditation you have people that do meditation and they control the heart rate this is all anterior cingulate. Okay? So for some people that have abnormal autonomic functions, they can do things like deep breathing and mindful meditation. Those things increase plasticity in their anterior cingulate areas. Okay? Now, when you look at how these systems all integrate together, you have the prefrontal cortex, which involves your emotions, your personality, what s going on in your life, who you are, the drama of your life, right? That can change your heart rate, that can change your autonomic function, that can change your visceral function, right? as you go through the day. You have inputs coming in from your viscera through insular cortex, you have inputs coming in from the periaqueductal gray area modulating things like sympathetic inputs and pain modulation, you have fear, anxiety, aggression coming in through limbic areas like the amygdala, and they re all integrating together throughout the brain. And then the final common pathway for these is the hypothalamus which then has projections down the brainstem and then down into the spinal cord, which we ll go into. Now, this is a great paper you guys have in your module notes, published in the Journal of Neuroscience, and they re looking at brain activity. And look at all these things firing together with the sympathetic response. Look at you even see here: the cerebellum is involved with sympathetic responses. So different areas throughout the frontal cortex, the insula, the limbic areas are all firing during a sympathetic response, as fas as integration. So remember, there s not one region in the brain that just controls sympathetic; it s a network. And look at parasympathetic. Now you see these different regions of the brain firing, and then take a look at them both together. On the very top you have sympathetic integration pathways firing, you have parasympathetic integration firing. So there s a network of things firing all the time. So as far as your brain function goes, you have all these different types of inputs that are ascending into the brain through sensory pathways. All the different types of inputs through your viscera, through your skin, pathways to your prefrontal cortex, motions, thoughts, limbic system: they re all integrating in your hypothalamus, but all that integration that eventually ends up in your hypothalamus is involved with all these different regions of the brain that are working together, so you have a bilateral, simultaneous, active response to control autonomics throughout the brain. That s why you can have a brain injury cause some time of autonomic dysfunction, or you can also have no specific region of the brain involved if you have an injury cause total loss of autonomics altogether. Okay? So, this then, that paper they then go on and show things like mood, mood changes, cognition, somatosensory overlap, and you can see the different regions of the brain, the medial prefrontal areas, you can see those in the cingulate, the insular areas, the anterior insulate. So just mood disorders, or just thinking about things, changes your insular, which is your visceral areas of your brain, integration areas, your limbic regions, and those things all have an impact on autonomics. So, this is a great review paper of what s actually happening in the autonomic networks of the brain. And what you see here is, it doesn t follow the region-by-region lesion model. This isn t a like, you get a motor strip lesion in the homunculus in the foot distribution and now you have spasticity. It s not that model, you understand? It s just a complete network model. Okay. MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 5

6 Now, let s go into a clinical case example. A child with autism suffers from bed wetting, poor digestion, floating stools, and rage attacks. His parents have done extensive heavy metal chelation and placed the child on numerous vitamin protocols. Nothing has helped. Why do you think? Well, where is the brain integration protocol? Okay, so let s go through this step by step. Bedwetting. So, the brain has what are called micturition centers. It has some in the medial frontal areas, and it has some in the pons areas. When they re not working, you have abnormal tone of bladder, and usually get bed wetting. Poor digestion. What controls digestion. Vagus. Floating stools. Why would you have floating stools? Because you re not digesting. Can t digest your fats. Rage attacks. What area of the brain s causing rage attacks? Limbic areas, amygdala areas. So when you re looking at this, you re going, Wow. These are you know some autonomic phenomena are coming out here. Micturition centers are not working well, their vagal system isn t integrating, and their amygdala is firing too high. Does that make sense? So then you do your exam, and go, Hey, how do I what s firing into these pathways abnormally, what s not inhibiting these pathways? And that s the initial thought process you want to go through. But right now, the key thing for you is to be able to identify, hear a symptom, and go, What area of the brain is involved? Everybody with me? So, a lot of these unfortunate cases of developmental delays or autism have significant autonomic dysfunctions. And when people don t understand brain, they re trying to use supplements for all their digestion issues, but it s actually brain-vagal responses, they re looking at them having rage attacks, and they just think, Well, that must be you know something in their eating that s causing that. And it could have a contributing factor, but it could just be the brain firing too high from different reasons altogether that are neurogenic based instead of metabolic. Now, the key thing is that all these different areas of the brain, through the insular cortex, the anterior cingulate, periaqueductal gray, the amygdala, they re all working together as a network, and they all end up going to the hypothalamus, where that s processed, and then you have hypothalamic projections down the brainstem and down the spinal cord that are ipsilateral. Okay? So I put a little summary diagram for you. So here s the big picture of how this works. You have the ventromedial prefrontal cortex, which is your limbic regions, the reticular system, the insular cortex, the brainstem, the anterior cingulate, the periaqueductal gray, the amygdala. They are all integrating like that functional MRI you guys saw, with all those areas lighting up. They re all working and integrating together. They fire into the hypothalamus, the hypothalamus processes all that information out, and then you have output. The most critical survival areas of the brain are midline deep and protected by other structures. Okay? So you will obviously see autonomics is way, way, way deep in there. All of that layer of other tissues to get destroyed before that one gets destroyed, because you have to have that function to be alive, right? Now, when you look at the outputs of the hypothalamus, there s, you know, three main mechanisms where we re looking at just metabolic issues, like glucose, metabolism, sodium osmolarity function, and all that stuff, right? I m not going to get into those in this presentation. What I want to get into is the autonomic effects from the hypothalamic projections, the neurogenic model of hypothalamic activity of autonomics. Okay? So, the hypothalamus projections. So once the hypothalamus processes everything, It has an impact on sympathetic responses, visceral effects, parasympathetic responses, and we have four main neurological MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 6

7 I m not talking about the pituitary pathways for endocrine modulation; we re just going talk about neurological canalized projections that take place. So we have the hypothalamospinal tract, that has direct activation of the intermediolateral cell column, involved with sympathetic responses; we have the projection from the hypothalamus called the medial forebrain bundle, and it fires into the ventral tegmentum, the nucleus accumbens that s your reward dopamine system; and then you have pathways to the dorsal longitudinal fasciculus and the mammilotegmental tract, which regulate parasympathetics and visceral function. So things like digestion, saliva production, enzyme production in the gut, tearing. They re going through these dorsal longitudinal fasciculus pathways. Everybody with me? Okay. So, here is a great diagram of the circuitry. So, here you have the hypothalamus and remember, these are ipsilateral pathways, okay? So, you have hypothalamic integration. Here you can see the medial forebrain bundle going all the way down through autonomic centers throughout the brainstem. Here you can see the dorsal longitudinal fasciculus going down. And these are primarily involved with parasympathetic types of reactions. And then you have the hypothalamospinal tract, and you can see it projecting down to the intermediolateral portion of the spinal cord, firing to the sympathetic chain, which is involved with a sympathetic response. Here s even a better picture. And this is a picture that illustrates both of them. So, here you have areas of the brain, paraventricular lateral hypothalamic areas up here, and you have projections through parasympathetic pathways to the parasympathetic nuclei, like the Edinger-Westphal nuclei, or superior salivatory nuclei, inferior salivatory nuclei, dorsal motor, vagal. Those are all your parasympathetics, right? So your hypothalamus is going to project through these projections to parasympathetic nuclei, so you have tearing, you have saliva production, you have digestion, right? You have enzyme production in the gut, that s pretty straightforward. Then you have other projections of the hypothalamospinal tract, which go all the way down through the intermediolateral cell column, that fires into the sympathetic chain, fires into the adrenal medulla, to release epinephrine and norepinephrine. You guys with me? Okay. So let s talk about the sympathetic response first. So, when you look at the hypothalamic response, this is the pathway you want to cover first. You guys okay? Just here: hypothalamospinal tract, intermediolateral cell column projection, sympathetic response. And then we ll cover the dorsal longitudinal fasciculus and the mammilotegmental spinal tract later. I m not going to get into the ventral dopaminergic reward system; I just want to get into sympathetics and parasympathetics with you today. So let s talk about the hypothalamic projections. Okay. So basically, these hypothalamic projections are ipsilateral, they come down through the brainstem, down the spinal cord, fire into the intermediolateral cell column, go up to the sympathetic chain, and then go with vasculature to end tissue, organs, or to the adrenal medulla, where you have catecholamine responses. So, you guys have all seen these diagrams of these pathways, projections of the hypothalamus to the sympathetic centers. Those are hypothalamospinal tracts. Okay. Now, here s what you let me make this very simple. Your sympathetic system is firing for different reasons, all at the same time, at different regions. At the spinal cord level, you have your intermediolateral cell column firing on its own, reflexogenically. As input comes in through the spinal cord, like movement, posterior column stimulation, you have some type of sympathetic tone at all times. So the intermediolateral cell column is just firing on its own. You have pathways from your hypothalamus that are keeping some degree of tonic sympathetic tone all the time, through hypothalamospinal pathways. Then you have pathways that are involved with your emotions, through the limbic regions. Let s talk about those first. So the ventromedial prefrontal cortex is the area of your brain involved with your emotions that impacts autonomics. Let s talk about that first. So the area of your brain involved with emotional MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 7

8 cognitive thought process that can change your heart rate. So you think about something that stresses you out, whatever that could be. Maybe it s an IRS audit, maybe it s something, a test if you re a student. If you think about that and it stresses you out, that s your ventromedial prefrontal cortex that s involved with those types of functions, okay? Now, normally, if it s healthy and working adequately and there s no trauma to it, then as it does its job, this is what you get: You get a parasympathetic response, increase in parasympathetic response, and you lower sympathetic activity. So if your life is cool, everything s standing around, before you even do anything you should have some higher degree of parasympathetic activity than sympathetic. It s normal for you to think about something stressful and have your sympathetics go up. That s a normal response. Do you guys understand that? Think about something stressful that makes you engage and have to do something, like studying for a test, and your stress hormones go up that is normal. Okay? So the ability to have normal responses through cognitive function is also ventromedial prefrontal cortex. Now, the key issue, though, is at a regular and guys, that s the difference between tonic and phasic. So if you have to all of a sudden increase your stress demands because you think about something that makes you have to do something that s stressful to you, a normal phasic response is, you activate this part of the brain through your limbic system, and it changes your sympathetic tone as it normally should do it. At a resting cognitive emotional healthy state, your limbic regions, your prefrontal medioventral prefrontal areas should have higher parasympathetic tone and lower sympathetic tone. So let s say it in a different way. What would happen if you injured, or have degeneration, or lack of activity of your ventromedial prefrontal cortex? Then you have the opposite effect. You have less parasympathetics and more sympathetics. So the general theme you ll see as you to go different regions is, when the brain is injured, when the brain is degenerating, the brain is compromised, you lose parasympathetic tone and you get increased sympathetics. Just the general tone as we go through each different pathway here. Okay? So, activation of the ventromedial prefrontal cortex increases parasympathetic activity an decreases sympathetic activity. And this is a great paper you guys can read. Our results show that ventromedial prefrontal cortex has no major influence on autonomic modulation at rest during non-emotional physical stimulation. The paradoxical heart rate and blood pressure response in VMPFC-R patients suggest hemispheric specialization for VMPFC interaction with predominant parasympathetic activation by the left, but sympathetic inhibition by the right. So, now they also know that these autonomic centers have a hemispheristic response as well. So here s a summary. The left ventromedial prefrontal cortex activates parasympathetic activation, the right ventromedial prefrontal cortex activates sympathetic inhibition. Now, let s talk about this for a second. What would happen if you injured your left what would happen with your sympathetic tone if you injured your left? If you lost your parasympathetic activation, then you would have what? Greater sympathetic. It s like a seesaw effect. If you lose your right ventromedial prefrontal cortex which normally activates sympathetic inhibition, what would happen to your sympathetic tone? So does it matter if you injure your left or injure your right? You get increased sympathetic tone. The common theme you ll see is, the brain gets injured in its regions, you get increased sympathetic tone. Okay? This is a reference paper I m going to go over. Now, here s how the key region is. The key region that activates your spinal cord sympathetic response is the rostral ventrolateral medulla. It s in the lower medulla. So what you guys are seeing in this diagram is the lateral hypothalamus and paraventricular hypothalamus firing into this. Now, let me explain a couple of things. The pre when you look at the ventromedial prefrontal cortex, that s involved with your emotional response to autonomics. They talk about this at rest, but here s MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 8

9 the thing: When do you not have emotions firing? When are you not thinking at cognitive? So there s some degree of ventromedial prefrontal cortex impacting autonomics all the time. Are you guys with me? And then there s hypothalamic control of your autonomics through your paraventricular hypothalamus, lateral hypothalamus, at any ongoing basis, to make sure you have healthy heart rate and respiration. So you have a couple things here. You have hypothalamic involvement at any given time at rest, for your sympathetic tone, and you have your ventromedial prefrontal cortex that s involved with your thoughts and emotions throughout your day, all controlling your autonomic tone. Okay? Now, if it s going to fire into the intermediolateral cell column, the pathway in the spinal cord that fires sympathetics, it goes through this rostral ventrolateral medulla area, and then that fires down to the sympathetic system, and you get a sympathetic response. This is going to be important for us, because we re going to talk about all the other things that fire into this area. Okay? Let me recap one more time. Hypothalamus has a projection, your limbic system has a projection to your sympathetic centers. At any given time, while you re asleep, while you re unconscious, while you re in different brainwave activity, your hypothalamus is always going. Your paraventricular nucleus, your lateral hypothalamus, is going to have some degree of sympathetic-parasympathetic control going through. If it s sympathetic control, these areas of the hypothalamus fire down to the rostral ventrolateral medulla, and that fires into sympathetic centers of the spinal cord, the IML, and you get a sympathetic tone. For thought, cognitive process, where you re conscious, being a human being living through life, your ventromedial prefrontal cortex is firing to these same areas of the brain. Do you guys understand? Okay. Now, as it fires into the sympathetic tone, you get it changed. Now, I want to show you guys a different region here. A different illustration. This is the best flow chart that kind of summarizes everything. So here you have your medial prefrontal cortex, involves limbic regions. PL and IL are limbic regions. Okay? These limbic regions fire down and they can activate parasympathetic centers, or they can fire down and activate the rostral ventrolateral medulla, and have an effect. You can also have sympathetics fire into the midbrain reticular formation, called the cuneiform nucleus, that also causes sympathetic tone. I m going to break that down for you guys slower; I just want you to see the big picture first. Okay? And this is the diagram that we ll reference here in a second. Now, here s the interesting thing. There s the caudal ventrolateral medulla, which can inhibit the rostral ventrolateral medulla to change sympathetic tone if it s being activated by hypothalamic pathways. I don t want to get into too many loops I m sorry! But this is how it works. I ve got to go over it. So, here s an illustration where we have the medial prefrontal cortex firing into the lateral hypothalamus. That can inhibit. So when you see a solid line, that s excitation, and then when you see this, this is inhibition. So you could have your lateral hypothalamus inhibit your rostral ventrolateral medial areas, and you have sympathetic inhibition. You can also have your pathways in your frontal cortex, or your hypothalamus, activate the caudal ventrolateral hypothalamus, which then inhibits the rostral ventrolateral medulla, which then causes sympathetic inhibition. All you need to do is, you need to look at this diagram a few times, and there s going to be some part of you have to look back and kind of make sense of it for your own sake. Okay? Are you guys there, I hope? Okay. Now, what I m trying to show Here s a summary of this. Here s what this means in the summary phase. Your brain autonomics, your thought processes, your hypothalamus, can either excite or inhibit your sympathetic tone as it needs to. If you think about something stressful, a normal response is for your brain to fire down to your rostral ventrolateral medulla, and then basically increase your sympathetic tone. I MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 9

10 need to go do this right now. I don t want to do it. And you get all stressed out. That s a normal autonomic response. You should be able to do that, okay? You can t activate that, you can t get things done. At the same time, you can go, Hey! Let s say you re a student. I have a final tomorrow! Arh! Now again, normal to have a sympathetic tone to get your brain working, focus, but then you go, Oh no no, it s okay. It s all good. I can take a deep breath, relax, it s fine. Then you activate the areas of your brain, your lateral hypothalamus, to then inhibit that area, and then you calm down. Does that make sense? Okay. Now, you have a pathway independent of your hypothalamic projections in your midbrain, called the cuneiform nuclei. It s in the midbrain reticular formation. This area can be activated unrelated to your hypothalamus, unrelated to your limbic regions, just by different types of stimulation. And when you activate this cuneiform nucleus, it fires right into this rostral ventrolateral medulla, which fires down into the IML and causes sympathetic response. So you have a survival sympathetic system in the midbrain, okay? Which is activated by the vestibular system by quickly visual targets going in your visual field, by high-pitched sound, that then activates a sympathetic response. Are you guys with me? Okay. So you have reflexive sympathetic responses for survival, you have hypothalamic sympathetic tone on a given time, and then you have limbic activation of sympathetic centers. Everyone okay with that? What I want to do is, I want to go over this. I want to go over your midbrain survival reticular reflexive sympathetic response. Okay? So meaning this: If something s going to come in and attack you, you should immediately be able to go into sympathetic tone without having to think about it right away, right? Now, this all happens in the midbrain. If you guys remember, in the midbrain reticular formation, your reticular activating system, what s the job of it? The job of it is to get you alert right away, right? It s what causes you to wake up when you re sleeping, it causes alertness. So the way it causes the method in which it causes alertness is, it fires the sympathetic centers, the catecholamine centers, floods your brain with catecholamine so you become alert and focused, has the peripheral effect, raises your heart rate, right? Dilates your pupils so you can see everything, so you can survive. Okay? Now, this pathway through your sympathetic inputs could happen through vestibular input. If you re falling, what do you have to all of a sudden do? Increase your heart rate, get alert, and not fall. Sound that s really abrupt and loud that comes in, or something quickly comes into your visual field, like something trying to attack you or eat you, has a reflexive response in the midbrain areas, to have a sympathetic tone change. Increase in sympathetic tone. Painful stimuli increases sympathetic tone. Are you guys with me so far? This is unrelated to hypothalamic projections coming down, unrelated to thought-emotion limbic projections coming down. This is all at the midbrain by itself. Okay? So if you guys see the midbrain here, you have the periaqueductal gray, which we talked about yesterday, wit pain inhibition, and then you have this area called the colliculus, and you have a superior and inferior colliculus where light and sound come in, in a general fashion. If you guys remember Dr. Brock, he was talking about embryology, and you have telencephalon, and mesencephalon, and rhombencephalon, that all differentiate? Well, mesencephalon never differentiates. So it s all kind of connected together. So it s a phylogenetic homologue that s all connected together, so when you fire one area, you fire the others. Now, the midbrain, many neuroanatomists feel, is an area of your brain where you have survival responses, and it directly fires into your sympathetics. This is going to be really important to understand, because it can change how some people come in with symptoms of dysautonomia. So your superior colliculus, which is a part of your brain, a posterior part of the midbrain called the tectum, that quickly monitors and fires when something quickly comes in. So if something quickly comes in, it could be what? Could be something attacking you. MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 10

11 So, there s projections right from the superior colliculus to the cuneiform nucleus, which is the midbrain reticular formation, which then fires down to the IML and causes sympathetic response. Do you guys understand that? How would you test this with a patient? You put a heart rate monitor on them, like a pulse-ox or something, and then just, like, you can take a pin light and start flashing it. And if the heart rate goes up, that system is firing too high. Right? Or you can, like, you can literally put a heart rate monitor on him, and then turn off the lights, on, tch tch tch tch tch, and then look at the resting heart rate, and see some of these people will spike ten points, fifteen points, right away. And now you just find the cause of their anxiety disorder. You understand? Okay. Now, when people have superior colliculus pathways firing too high into autonomic centers, this is what they tell you causes them stress, causes them anxiety: flashing lights, objects moving quickly in their visual fields, bright lights, quick screen changes in movies, rapid conversion of eyes. So you can literally go to a patient and go, Hey, look at my finger, and you go whoo, whoo, and they go, Arrr. They get anxiety from it. Crowded, busy locations where things are moving in and out of their fields; that s telling you, if they re getting anxiety from that, this autonomic reflexogenic sympathetic area of the midbrain is activated. Okay? Now, you ll have patients tell you, I can t Some people, they can only watch black-and-white movies. Why? There s not these screen changes. Some people will tell you they can t handle action movies. Why? Because the screen changes are so fast, there s all these stress things happening, you know, things come in at the movie screen really quickly, and they get anxiety from it. That s letting you know that that superior colliculus is firing aggressively into the cuneiform areas, causing sympathetic activation. Does that make sense to you guys? And what kind of things if the patient has that, how can you make their life easier? Hey, I want you to avoid flashing lights. I want you to avoid being in environments where things are moving too quickly, or a crowded areas. Maybe you should wear some sunglasses. You can literally go into your office with a patient and just turn off the office light, and they go, Oh, I feel better. And you can even ask patients that. Hey, how do you feel? Oh, I feel okay. Let me turn the lights off for a second. How do you feel now? Oh, I feel more relaxed. Okay, cool. You just found out their superior colliculus is firing into their sympathetic centers. You guys with me? Okay. Now, here s a clinical case example. A patient states they feel overstimulated when they are in crowded places. The patient states that looking at your carpet pattern gives her feelings of anxiety. What are you guys thinking? Well, you think that there s some autonomic response happening, right? Through the collicular pathways. Now, here s another example. Patient complains of tearing when stimulated with a pin light. Light stimulation also leads to headaches and racing heart rate. So, light stimulation s going to hit the visual pathways, which then fires to the tectum, which then fires to autonomic centers, so this is firing too much; they can have anxiety from just a pin light test, for example. You guys understand? Okay. And that could be the test you do. Just test the heart rate monitor, and then turn the lights on and off, or do a pin light, and if you see that firing too much, then you re understanding their dysautonomia mechanism. Okay? Now, look at this case scenario: Her gain demonstrates a wide-stance gait. What area of the brain would you think is involved? Cerebellum. So let s start putting this together. Light stimulation leads to headaches and racing heart rate. What does that tell you? Superior colliculus is firing into the midbrain reticular formation, or the cuneiform area, and she has a wide-stance gait. So now you go, Hey, is there a cerebellar connection between her autonomics? And there is. We ll go over that. But as you start learning how to piece the history together from the symptoms, then you start to localize the region. Remember the flowchart from yesterday. You can t go any further clinically unless you can pick MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 11

12 this stuff up from the history. That s why this is such an important module for us. We had people, like, tell us: Hey, we re not going to come to Module 1 because I already know neuroanatomy. We re like, It s not about knowing, memorizing neuroanatomy, it s about understanding how these are clinical, functional pathways. Okay? Anyways. Now, then you have the inferior colliculus, so if you guys ever look at the brain, the mi dbrain, you have a superior colliculus on top, an inferior colliculus below. Cranial 3 s by the superior colliculus, cranial 4 s by the inferior colliculus, to those little bumps in back. When you take the brain and look at the brainstem, you see those four little bumps. Those are the colliculi. Okay? So, the inferior colliculi s where loud sound comes in. You could take How would you test the inferior colliculus with the patient? And if this pathway s going to You could put them on a heart rate monitor and just go like this [claps]. If the heart rate races up, you ve got an inferior colliculus firing into those centers way too aggressively. Okay? So they tell you sharp-pitched sounds, sudden sounds, cause their anxiety. You guys, if you hear a person telling you that stimulus causes their anxiety disorder, their anxiety disorder is neurogenic. It s not chemical. It s not metabolic. Most chronic anxiety disorders are neurogenic. It s not because they just need, like, GABA support. Those things can take the edge off, but there s usually deeper models. Okay, so, let s talk about this. Patient complains of freezing hands and feet with daily headaches that are only relieved by turning off the lights and closing her eyes. What did she just tell you? When she decreases her light stimulation, there s a change in her probably in her autonomic tone. Testing the patient s hearing perception with a tuning fork induces a startle reaction. That s the other thing you ll see when the tectum is firing too high. You ll, like, want to check their hearing with a tuning fork. You put it next to their ear and they have a startle response and the heart rate goes up. You ll have some people like, if you just clap next to them, they ll be freaked out for a few minutes, which is immediately diagnostic to you. Everybody with me so far? Okay. So, those are the superior and inferior colliculus pathways going into this reflexogenic center. You guys, it has nothing to do with your ventral your periventricular nucleus hypothalamic projections, doesn t have to do with your lateral hypothalamus projections, doesn t have to do with your ventromedial frontal projections. This is an immediately reflexogenic sound-light activation of sympathetic centers which is theoretically survival-based. Right? Something loud, something quickly moving in, something flashings, something coming in abruptly towards your field, has a reflex to your autonomic centers. Okay. Then you have the periaqueductal gray area, which is pain. So if you get pinched, what happens to your pupils? They dilate, right? So, there s projections right from the periaqueductal gray to the cuneiform areas, which makes you alert. So all of a sudden you re being stabbed, or something s poking you, your heart rate should go up and you should be able to get away from it very quickly. Those are all part of this midbrain sympathetic response. And then cognitive processes, like things that are stressful, can fire into these areas and activate the sympathetic tone, and so can cerebellar projections. Remember Dr. Brock talking about the dentatorubral projections? Well, vestibular inputs fire right into this cuneiform nucleus, because if you re all of a sudden falling, what do you need to do? You ve got to respond to that, get your heart rate up, get catecholaminedriven so you can get out of it. Okay? So something coming quickly into your visual field, superior colliculus; sharp, abrupt noise, inferior colliculus; sense of falling, pain, and thought processes all fire to this midbrain cuneiform nucleus, which then causes a sympathetic response. MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 12

13 Now, how would you tell if the vestibular system is involved with heart rate changes? Or autonomic effects? You can put them on a heart rate monitor, you can put them on a swivel chair and just go doot doot doot, look at the heart rate. If it jumps up, you re having this projection from the dentatorubral projection, the vestibular pathways, into this. Or you can take an optokinetic tape, which makes the patient feel like they re moving, that red-and-white strip, just do that a couple times. If the heart rate goes up, you have activation from vestibular system to the sympathetic area. Which means what? Which means, you guys, there s a vestibular disorder that s causing their autonomic imbalances, causing them to have anxiety, or increased heart rate, or poor gut function, or whatever the increased sympathetic tone could be. You guys okay with this so far? Okay. This is a good paper if you guys want to look at vestibulospinal sympathetic responses. You guys have it in your Module 1. Okay. So at the end of the day, these are all the inputs that are firing into the midbrain, causing a sympathetic response. Now remember, embryologically, this is all the tissue hasn t differentiated. So when you fire one, you fire all of it. So if you have light, sound stimulation, pain, abnormal quick movement, you immediately get a sympathetic response, reflexively. But some people have way too much activity here. Now, what would cause a person to have too much activity here? Why would someone all of a sudden have an increased tectum response? Why would they be sensitive to sound or sensitive to light, or sensitive to quick-flashing things, or Something s causing this whole midbrain area to fire too much. Okay? The most common cause is a vestibular cerebellar disorder, which Dr. Brock is going to go into later today. So here s the thing: Your cerebellar outputs, vestibular cerebellar outputs, they activate this cuneiform area of the midbrain, and that causes increased activation of the intermediolateral cell column and the sympathetic chain; you get epinephrine, norepinephrine changes, and you change the heart rate, and you can get anxiety, and you get metabolic rate changes. At the same time, you guys, the cerebellum projects through the brachium pontis, to the pontine areas where you have the vagus, and it controls vagal tone. And if you don t have enough activity there, you can get nausea. So a lot of times when the cerebellar system is dysfunctioning, especially this Purkinje inhibition, or this Purkinje surround inhibition pathway Dr. Brock just went over, you can have abnormal gating of cerebellar inputs from the environment, from muscle spindle Golgi tendon vestibular inputs, that should be gated, that aren t gated. There s abnormal projections to these midbrain areas, abnormal projections to the pons areas, and you get dysautonomias. Okay? Let me put it to you a different way. If you see someone that has the heart rate change with sound, heart rate change with flashing objects, heart rate change with conversions, heart rate change with movement, you probably have a vestibular cerebellar disorder that s firing into these autonomic centers. You should always go to that first. Okay? And, you guys, the thing that usually fixes this for most people is just visual fixation. Alright? You just have them visually fixate, and do some head movements like this, and then you check the heart rate again with sound or light, and it immediately dampens it. That causes frontal pontine cerebellar Purkinje inhibition activation, this whole system starts to calm down. But we ll cover that and other strategies as we get into more treatment modules later. Okay. Now here s the thing. When you have the sympathetic centers fire, what does that do to your blood sugar levels? When your epinephrine, norepinephrine levels go up, what does that do to your heart rate? What does that do to your energy expenditure? It makes you burn up your glucose. So when you burn up your glucose, you immediately become what? Hypoglycemic. When you become hypoglycemic, your blood sugar drops. How do you get your blood sugar back up? Your lateral hypothalamus fires into your MODULE ONE TRANSCRIPT AUTONOMICS Copyright 2016 FUNCTIONAL NEUROLOGY SEMINARS LP Page 13