1 00:00:00,000 --> 00:00:09,680 Welcome to From the Spectrum Podcast. This is a podcast about autism. It is my 2 00:00:09,680 --> 00:00:18,000 goal to explain what is autism. I intend to use a mixture of scientific literature, 3 00:00:18,000 --> 00:00:26,240 personal experience, and opinion. With opinion, I will explain why I feel the 4 00:00:26,240 --> 00:00:34,960 way I do and give examples. I will provide links to various references for each episode. 5 00:00:36,160 --> 00:00:41,280 For each episode, we will discuss various aspects of autism. 6 00:00:43,440 --> 00:00:50,960 For today's episode, we will discuss biological aspects implicating the excitation 7 00:00:50,960 --> 00:00:58,480 and inhibition balance. The EI balance is a worthy discussion with autism, 8 00:00:59,440 --> 00:01:09,280 and a lengthy discussion. Today's episode will be part one of a two-part series covering the EI 9 00:01:09,280 --> 00:01:20,240 balance. Notice not all of these topics of our biological mechanisms covered, or a cause 10 00:01:21,600 --> 00:01:32,240 of all cases of autism. Autism is a genetic patchwork, not one gene, and not all gene 11 00:01:32,240 --> 00:01:43,680 implications reach autistics in the same manner. The cause of all autistic phenotypes are unknown. 12 00:01:45,440 --> 00:01:53,200 I want to warn you, you need to know some literature, and even some literature I have 13 00:01:53,200 --> 00:02:02,400 shared on autism are attempts to create pharmacological help. This has concerns. 14 00:02:03,600 --> 00:02:11,280 This has concerns because of our medical paradigm, which likes and maybe even prefers 15 00:02:11,920 --> 00:02:18,640 prescriptions as the first line, as something that gets lots of financial backing. 16 00:02:18,640 --> 00:02:28,240 And it isn't hard to know why. I want you to understand autism, and I want you to make informed 17 00:02:28,240 --> 00:02:39,760 decisions. For the excitation and inhibition, we will discuss sensory, social, emotional, 18 00:02:39,760 --> 00:02:50,400 emotional, mnemonics, and some specific cell types, glutamate and GABA. We will cover cortical 19 00:02:50,400 --> 00:03:00,400 networks, memory, information processing, pattern learning, and plasticity. No, neuroplasticity, 20 00:03:00,400 --> 00:03:10,240 which is how we are shaped, shaped in our ways, our preferences, habits, comfort, and more. 21 00:03:11,520 --> 00:03:23,360 We will cover brain derived neutropic factor, or BDNF, and N-Methyldeaspartate, or NMDA, 22 00:03:23,360 --> 00:03:34,320 and AMPA. Now feel free to look up the long form scientific nomenclature of AMPA. It is long, 23 00:03:34,880 --> 00:03:43,600 and maybe not necessary for our discussion. However, those three receptors, or biological 24 00:03:43,600 --> 00:03:56,080 components, are excitation. We will also discuss neuromodulators and melanin. And we will also 25 00:03:56,080 --> 00:04:04,080 discuss certain brain regions, some of these we have mentioned before. With the EI balance, 26 00:04:04,080 --> 00:04:16,560 or imbalance, too much excitation creates a noisy brain. Think unstable cortex, lots of energy 27 00:04:16,560 --> 00:04:26,880 potential. Now imagine the EI balance. I will use balance, but it's basically an imbalance. 28 00:04:26,880 --> 00:04:36,640 Think about a C-cell. Excitation on one side, inhibition on the other side. 29 00:04:38,080 --> 00:04:48,160 Remember, excitation turns cells on, activates regions and systems. The cell is named glutamate. 30 00:04:48,160 --> 00:04:58,320 Inhibition turns regions and systems off, inactivates, or quiets things. This cell is called GABA. 31 00:04:58,320 --> 00:05:12,000 Glutamate is excitation, GABA is inhibition. This imbalance is either an increase in excitation, 32 00:05:12,000 --> 00:05:23,840 or a reduction in inhibition. This implicates perception, memory, cognition, and motor control. 33 00:05:25,760 --> 00:05:32,560 Think about stemming, think learning about a world around that seems chaotic and overwhelming, 34 00:05:32,560 --> 00:05:44,080 and our future preferences of what we are and who we are. You will hear cortical and subcortical. 35 00:05:44,960 --> 00:05:56,400 Cortical is the cortex. Think of what makes humans the superior species on earth. This is where our 36 00:05:56,400 --> 00:06:05,600 higher order functions occur, things like decision making and functioning and language and so forth. 37 00:06:06,880 --> 00:06:18,480 Subcortical is below the cortex, used for memory, emotion, pleasure, valence, or how we perceive 38 00:06:18,480 --> 00:06:29,840 our feelings. Evolutionary, subcortical areas are much older. Think reflexes. Think people being 39 00:06:29,840 --> 00:06:40,000 more impulsive or lacking emotional regulation. The cortical areas intends to quiet the emotions 40 00:06:40,000 --> 00:06:49,680 and feelings of the subcortical area. Let's quiet things so we can properly evaluate things. 41 00:06:51,680 --> 00:07:01,840 Remember, synaptic processes are where cells travel to connect and communicate. In the brain, 42 00:07:01,840 --> 00:07:12,000 areas become preferred. The more synaptic thickness or morphology exist at those connections. 43 00:07:13,440 --> 00:07:20,480 The brain and the nervous system passes things off to what is easiest for them. 44 00:07:20,480 --> 00:07:32,560 We are who we are for that reason. EI imbalance implicates synaptic and myelination functions. 45 00:07:33,680 --> 00:07:41,200 Remember myelin. Turns a gravel road into a paved road to improve the cells' travel. 46 00:07:42,960 --> 00:07:48,960 Subcortical areas and cortical areas communicate back and forth to each other. 47 00:07:48,960 --> 00:07:58,800 Ultimately, it wants to quiet the noise while considering survival functions. 48 00:07:59,840 --> 00:08:06,240 Now you can see, people with and without autism can have trouble with this. 49 00:08:07,200 --> 00:08:12,640 The EI imbalance is not just present in autism. 50 00:08:12,640 --> 00:08:24,480 Cortical areas are hypersensitive to sensations. These perceptual areas that allow the person 51 00:08:24,480 --> 00:08:31,280 to properly evaluate the sensations they are receiving from the outside world. 52 00:08:32,800 --> 00:08:38,960 This is all sensations, or some with autism have trouble with certain sensations 53 00:08:38,960 --> 00:08:48,880 and are better at others. GABA is crucial for sensory processing. 54 00:08:50,240 --> 00:08:57,360 A lack of GABA implicates downstream processing and quieting cognitive behaviors. 55 00:08:57,360 --> 00:09:07,840 GABA modulates the flow of information in the thalamus, a place that processes all sensations 56 00:09:09,040 --> 00:09:19,360 and helps modulate our attention. Now, we are talking about autism, which means we are born 57 00:09:19,360 --> 00:09:30,240 with it or it is developed early, likely on that critical period, that early stage of our 58 00:09:30,240 --> 00:09:40,160 critical development. If sensations are overwhelming or perceived as difficult at this time of the 59 00:09:40,160 --> 00:09:49,760 critical period, it implicates maturation of these processes, the process of developing. 60 00:09:50,960 --> 00:09:57,440 When exposed to challenging exposure, this closes the window of the critical period 61 00:09:58,240 --> 00:10:08,240 prematurely. In other words, our perception of the sensory going on implicates how long the 62 00:10:08,240 --> 00:10:16,400 critical period lasts. Some things to know, the critical period is an accelerated time, 63 00:10:17,280 --> 00:10:26,400 meaning lots of learning and understanding and development. GABA, which is inhibitory, 64 00:10:26,400 --> 00:10:34,640 remember GABA is inhibitory, GABA in the critical period is excitatory. 65 00:10:34,640 --> 00:10:44,400 Think about it. Perhaps the purpose is to not limit the processing of physical phenomena 66 00:10:44,400 --> 00:10:54,560 of the outside world. GABA turns or is created excitatory to accelerate that development period. 67 00:10:54,560 --> 00:11:04,160 Think about how easy it is for children to learn in this time, including multiple languages. 68 00:11:04,720 --> 00:11:12,480 Also, brain-derived, new tropic factor is the primary signaling source in the critical period. 69 00:11:14,080 --> 00:11:21,840 BDNF is powerful for the human brain. It's powerful because it regulates myelin. 70 00:11:21,840 --> 00:11:30,720 In autistic brains, data show larger brains in childhood. They are larger, in large part, 71 00:11:30,720 --> 00:11:43,520 because of myelination. BDNF also is a component of neuronal growth, neuroplasticity, learning and 72 00:11:43,520 --> 00:11:56,000 memory, which is essentially neuroplasticity. BDNF helps regulate glucose. BDNF are similar 73 00:11:56,000 --> 00:12:07,120 to insulin-like growth factors and act on survival genes. Therefore, BDNF are crucial 74 00:12:07,120 --> 00:12:19,760 for cell survival. Remember last episode, remember the rapamycin, the mTOR, discussion and autophagy. 75 00:12:21,840 --> 00:12:29,920 BDNF is critical for metabolism. Remember the discussions on brain energy, how the brain 76 00:12:29,920 --> 00:12:40,560 changes blast-out energy. BDNF has a high affinity, meaning it loves the tyrosine-kines receptor. 77 00:12:41,840 --> 00:12:48,720 Something highlighted in research about neurodevelopmental conditions is that tyrosine 78 00:12:48,720 --> 00:13:00,480 receptor over expression of BDNF is shown in epilepsy. Remember they commentize with autism 79 00:13:00,480 --> 00:13:13,440 in epilepsy. So earlier I just mentioned tyrosine. Tyrosine makes dopamine, epinephrine, and nor 80 00:13:13,440 --> 00:13:24,160 epinephrine, which is essentially adrenaline, and it also makes melanin. Tyroxine, all more components 81 00:13:24,160 --> 00:13:34,320 of functioning and functioning with energy. Melanin and dopamine does much more than what you know 82 00:13:34,320 --> 00:13:44,160 in the human body. For melanin, you probably know about hair, eye, and skin color, which is mainly 83 00:13:44,160 --> 00:13:55,760 alpha-melanocyte-stimulating hormones, or AMSH, which is cleaved from POMP-C in the hypothalamus. 84 00:13:56,560 --> 00:14:03,840 I know, irrelevant information may be here for our discussion, but I am autistic and I love that 85 00:14:03,840 --> 00:14:13,760 topic. We're going to talk about some dark and deep melanin though, much different than the skin, 86 00:14:13,760 --> 00:14:23,200 hair, and eye color. We're going to talk about how melanin is used for energy and cells firing 87 00:14:23,200 --> 00:14:33,600 and functioning. Melanin comes from tyrosine. Tyrosine, like tryptophan from our last episode, 88 00:14:34,560 --> 00:14:49,200 is an aromatic amino acid, meaning it activates for UVB light, which is around 260 to 280 nanometer 89 00:14:49,200 --> 00:14:59,840 light. Starting in the eye, a source for many complications for autism. Think eye contact 90 00:15:00,480 --> 00:15:11,280 and looking inattentive and simply the eyes are a source of most of our sensations. We navigate the 91 00:15:11,280 --> 00:15:21,280 world in large part through the eyes. And think about development. Let's think about how the eyes 92 00:15:22,480 --> 00:15:33,520 help our downstream processes in development. Sunlight hits the eyes and regulates development. 93 00:15:33,520 --> 00:15:42,880 Physiology, neurotransmitters, remember the tyrosine and the tryptophan. So here we're talking about 94 00:15:43,680 --> 00:15:54,320 groups like monoamines and catecholamines, which are a group of neuromodulators lumped together 95 00:15:54,960 --> 00:16:02,560 based off of different functions. Now, the human body has about 40 days worth of catecholamines. 96 00:16:02,560 --> 00:16:11,280 These things are deletable and renewable. And without any chronic disease or lesion, 97 00:16:11,280 --> 00:16:19,040 we can always make more of these. But we can see, such as during the winter time, 98 00:16:19,040 --> 00:16:26,480 when the UV light is not as present, people's moods and the way we act and feel suffers. 99 00:16:26,480 --> 00:16:37,280 And that's because these aromatic amino acids require the UVB light range for activation. 100 00:16:38,640 --> 00:16:49,680 In addition, it helps development of the hormones and the energy, including metabolism. In contrast, 101 00:16:49,680 --> 00:17:00,000 modern light implicates those above, especially at the wrong time of day. 102 00:17:01,920 --> 00:17:14,880 Remember, autism was first observed in the late 1930s. So the 1930s is one to about one and a 103 00:17:14,880 --> 00:17:28,960 half generations after electricity and the power grid, 1893. Know this. I have to play a brief game 104 00:17:28,960 --> 00:17:36,880 of the tug of war with barbed wire here. As society is exposed to more artificial light, 105 00:17:36,880 --> 00:17:48,560 especially blue light, and we are less exposed to sunlight, diagnoses of autism increase. 106 00:17:49,520 --> 00:18:03,200 And this is a sharp increase. The light for the developing child is vast. Maybe everything. 107 00:18:03,200 --> 00:18:13,920 Remember, the brain and skin come from the same place and are connected through neuroectoderm. 108 00:18:15,120 --> 00:18:26,480 The skin is the largest endocrine organ in the entire body. It's a solar panel for the energy hog 109 00:18:26,480 --> 00:18:38,800 that is our brain. Those aren't my words, but they are accurate words. Now back to melanin. 110 00:18:40,560 --> 00:18:50,880 In the eye, melanin comes from the retinopigment epithelium, or RPE for short. It provides dark 111 00:18:50,880 --> 00:19:00,480 pigments for the light receptors in the retina. Also, melanopsin, which regulates all 112 00:19:01,200 --> 00:19:09,600 non-image forming processes with physiology and hormones and such, that is done by a 113 00:19:09,600 --> 00:19:21,360 monosynaptic connection, which is bizarre in our biology. Monosynaptic means a direct connection, 114 00:19:22,160 --> 00:19:30,160 and this spaces out from the back of the eye to the midbrain and the hypothalamus. It's a long 115 00:19:30,160 --> 00:19:45,680 connection. In the hypothalamus, there's a nuclei called supracrasmatic nucleus, or SCN for short. 116 00:19:48,320 --> 00:19:56,960 The hypothalamus is subcortical and a place where endocrine processes meet cellular processes, 117 00:19:56,960 --> 00:20:05,120 so they can orchestrate together in perfect synchrony to carry out the biological processes 118 00:20:05,120 --> 00:20:16,800 in perfect concert. The SCN controls this. The SCN is the master clock of our biology. 119 00:20:16,800 --> 00:20:28,240 All cells, all tissues, and organs start with the master clock before those things take flight 120 00:20:29,600 --> 00:20:38,000 and work, become active. There's a clock at the beginning of the process. That has to be 121 00:20:38,000 --> 00:20:48,560 in sync. That needs to be in sync. Melanin and melanopsin are all over the brain. 122 00:20:50,240 --> 00:21:01,200 It's important. Melanopsin was first discovered in the human eye in the retina in 1998 by Iggy 123 00:21:01,200 --> 00:21:10,160 Provincio, and then critical discoveries in retinal ganglion cells during the next six, seven, 124 00:21:10,160 --> 00:21:17,840 eight years or so. Melanopsin is still being discovered across the human body, including 125 00:21:17,840 --> 00:21:31,200 in the brain, no fewer than about 30 regions in the brain in 2017 and 2018 or so, so not long ago. 126 00:21:32,080 --> 00:21:41,600 This presents lots of curiosity and concern. The biggest concern is most, indeed most, 127 00:21:41,600 --> 00:21:53,920 of artificial light is blue light. I'm talking about LED, tech screens, TV, that's blue light. 128 00:21:55,200 --> 00:22:05,680 Light, like incandescent, is mostly red. Candles and fireplaces are mostly red and infrared. 129 00:22:05,680 --> 00:22:16,720 In short, those longer wavelengths, red and infrared, they have less harm to the human 130 00:22:16,720 --> 00:22:30,560 biology. There's less photonic energy. Furthermore, why modern light is so critical to melanopsin, 131 00:22:30,560 --> 00:22:44,640 melanopsin activates for 480, about 460 to 480 nanometer light. That's blue light. So anytime 132 00:22:44,640 --> 00:22:52,160 you have blue light exposed to the human body, it's implicating melanopsin somehow. 133 00:22:52,160 --> 00:23:02,480 Evolutionary, we want that blue light because when we're outside, most of the light we see, 134 00:23:03,280 --> 00:23:14,480 most of the color we see, is blue. Okay, why is this a topic? It is most certainly a topic 135 00:23:14,480 --> 00:23:24,000 because of the implication to brain development at all stages of human life, from embryo to the 136 00:23:24,000 --> 00:23:35,280 other end in older adults. And this covers from autism to neurocognitive or degenerative diseases, 137 00:23:35,280 --> 00:23:45,440 like Alzheimer's and the dementias and so forth. All of these conditions are new in the medical 138 00:23:45,440 --> 00:23:54,880 world. Melanin and melanopsin implicates all the things we covered with the synaptic development, 139 00:23:54,880 --> 00:24:08,960 migration, cellular health, and so forth, including the neuroplasticity. Remember, becoming what we are 140 00:24:09,840 --> 00:24:17,680 and continuously becoming what we are through changing from habits and learning. This is a 141 00:24:17,680 --> 00:24:29,520 continuous process. Neuroplasticity doesn't stop. Implications in melanin and pom-C possibly 142 00:24:29,520 --> 00:24:38,160 allows sensory cells to shift based on how it is perceiving the outside world, the outside 143 00:24:38,160 --> 00:24:48,800 environment. Melanin dysfunction can also implicate cortical communication and connection. 144 00:24:50,560 --> 00:24:59,520 Kids in developmental stages have broken processes in their skin, their eyes, and circulatory system, 145 00:24:59,520 --> 00:25:07,680 which features the heart, blood vessels, and blood, making indifference to the outside sensations 146 00:25:08,320 --> 00:25:20,400 and complications. Now we covered in criteria B some of these symptoms. Additionally, our modern light 147 00:25:20,400 --> 00:25:31,440 implicates this melanopsin protein and downstream distal connections because all opsin have a weak 148 00:25:31,440 --> 00:25:46,960 covalent bond to vitamin A or 11 cis retinal and blue light wavelength breaks this bond. It destroys 149 00:25:46,960 --> 00:25:57,440 the blood vessels and this regulates plasticity and connections, including, certainly, including 150 00:25:58,080 --> 00:26:09,760 complicating excitatory and inhibitory processes. Melanin is the screen. Sunlight is the light 151 00:26:09,760 --> 00:26:18,720 beam and the sun is the projector and every piece of that three-step process must function properly 152 00:26:18,720 --> 00:26:33,040 to organize our biology properly. Anything broken or time delayed presents chaos and just like that, 153 00:26:33,040 --> 00:26:41,200 just like the warning earlier, the broken processes upstream can manifest differently downstream, 154 00:26:42,000 --> 00:26:51,360 meaning there are many genetic implications to autism, but those same genetic implications 155 00:26:51,360 --> 00:27:00,640 are also seen in other disorders and conditions like OCD, TICS, Tourette's, schizophrenia, 156 00:27:00,640 --> 00:27:11,200 focal epilepsy, Vret syndrome, fragile X syndrome, and so forth. In other words, as we have problems 157 00:27:11,200 --> 00:27:20,560 upstream in our biological processes, by the time we get downstream, they present differently. It 158 00:27:20,560 --> 00:27:31,120 manifests differently. It can look different as the process unfolds. This explains the spectrum. 159 00:27:31,120 --> 00:27:40,400 This explains why there are many inconsistencies with autism and a lot of unknown factors. 160 00:27:40,400 --> 00:27:53,920 I know we covered a lot of biology here, a lot of areas, but understand humans evolved under the sun 161 00:27:54,800 --> 00:28:04,880 and the sun was the primary light source. Today we have many light sources. We also have photo 162 00:28:04,880 --> 00:28:13,040 receptors all over our body and the photo receptors in our biology that we have evolved 163 00:28:13,040 --> 00:28:25,040 to become are implicated today. Recently things have changed. Our world and our environments 164 00:28:25,040 --> 00:28:38,080 have changed. We cannot understand autism unless we understand these areas and the purpose of these 165 00:28:38,080 --> 00:28:49,760 areas. And I'm talking about our biology. Despite melanopsin being discovered in 1998, 166 00:28:49,760 --> 00:29:01,200 it predates humans. In other words, it is a crucial part of many species biology and development. 167 00:29:02,560 --> 00:29:10,800 Before humans evolved on earth, other species, and that's not limited to just mammals, 168 00:29:10,800 --> 00:29:22,080 have had melanopsin. Lastly, think about all of our new modern diseases such as autism, 169 00:29:22,960 --> 00:29:32,480 diabetes, both type 1 and 2, obesity, all the recent new cancers and the rates of cancer, 170 00:29:32,480 --> 00:29:42,560 and all of these new neurodegenerative conditions, all of these aging diseases that are just increasing 171 00:29:43,360 --> 00:29:54,480 too quickly. Everything I just named are increasing much too quickly. I don't understand why we don't 172 00:29:54,480 --> 00:30:08,320 look someplace else. Think about all the cardiovascular diseases. Melanopsin is in tissues. Our environment 173 00:30:08,320 --> 00:30:19,440 is changing and so is our biology. If you would like to contact me, you can reach me by email 174 00:30:19,440 --> 00:30:31,120 at info.fromthespectrumatgmail.com. And thank you for listening to part one of a two-part series 175 00:30:31,120 --> 00:30:40,560 covering the excitation and inhibition. And most importantly, thank you for listening to From the 176 00:30:40,560 --> 00:30:50,560 Spectrum podcast.