WEBVTT 00:00:00.240 --> 00:00:03.500 I would like to take a moment and mention a pressing 00:00:03.500 --> 00:00:09.859 issue we are seeing in our modern world. And 00:00:09.859 --> 00:00:15.140 that is tech use and tech light. The data are 00:00:15.140 --> 00:00:19.600 impressive and concerning on isolated wavelengths 00:00:19.600 --> 00:00:25.320 of light, especially shorter wavelengths, which 00:00:25.320 --> 00:00:29.989 is blue light. For those that don't know, We 00:00:29.989 --> 00:00:33.649 have chromophores, which are special proteins 00:00:33.649 --> 00:00:39.429 that absorbs specific wavelengths of light. For 00:00:39.429 --> 00:00:43.429 blue light, the light that is LED light and tech 00:00:43.429 --> 00:00:49.649 light, that protein is called melanopsin. Melanopsin 00:00:49.649 --> 00:00:55.409 is responsible for our circadian biology, physiology, 00:00:55.710 --> 00:01:00.380 and cell functioning. hormone regulation, and 00:01:00.380 --> 00:01:06.480 even a connection to an area huge for mood. A 00:01:06.480 --> 00:01:10.439 consideration we should include is this protein 00:01:10.439 --> 00:01:16.120 was not even discovered until 1998. It seems 00:01:16.120 --> 00:01:20.900 important for us to understand how our biology 00:01:20.900 --> 00:01:25.680 uses the different wavelengths of light. for 00:01:25.680 --> 00:01:30.560 various aspects of our biology. This blue light 00:01:30.560 --> 00:01:35.640 chromophore is our master controller, our master 00:01:35.640 --> 00:01:40.319 clock. Remember circadian rhythm is a two -part 00:01:40.319 --> 00:01:47.239 process, two independent parts, light and dark. 00:01:48.079 --> 00:01:53.239 For a quick reference, see the 2017 Nobel Prize 00:01:53.239 --> 00:01:58.939 in Physiology medicine. But for now, I have something 00:01:58.939 --> 00:02:01.920 exciting. I want to introduce a product unlike 00:02:01.920 --> 00:02:06.799 any other product available. A highlight is the 00:02:06.799 --> 00:02:10.759 product from Daylight Computer Company created 00:02:10.759 --> 00:02:15.199 their product based on these factors. The Daylight 00:02:15.199 --> 00:02:20.759 Computer is completely blue light free. It has 00:02:20.759 --> 00:02:25.219 no flicker. Short wavelength flicker. is extremely 00:02:25.219 --> 00:02:29.020 harmful for our eyes and downstream biology. 00:02:30.080 --> 00:02:32.879 Light flicker is constantly turning our central 00:02:32.879 --> 00:02:37.860 nervous system on and off. Essentially it is 00:02:37.860 --> 00:02:41.099 like going to a light switch and repeatedly turning 00:02:41.099 --> 00:02:46.460 it on and off. The problem is blue light and 00:02:46.460 --> 00:02:51.680 LED light does this and it is so rapid You cannot 00:02:51.680 --> 00:02:56.500 even perceive this in real time. The daylight 00:02:56.500 --> 00:03:01.199 computer is the lowest stimulation and foremost 00:03:01.199 --> 00:03:06.240 for sensory sensitive users. It is no question 00:03:06.240 --> 00:03:10.419 that the alternative product, especially when 00:03:10.419 --> 00:03:15.240 used at night, do not address or consider this 00:03:15.240 --> 00:03:20.159 in their product. It is so toxic to human biology. 00:03:20.520 --> 00:03:25.379 Big tech corporations have patents on how their 00:03:25.379 --> 00:03:28.319 short wavelength implicate the human nervous 00:03:28.319 --> 00:03:34.120 system. And a bonus, despite daylight computer 00:03:34.120 --> 00:03:38.520 not having backlight, it is very functional for 00:03:38.520 --> 00:03:43.520 outdoor use. And of course, increased sunlight 00:03:43.520 --> 00:03:48.900 is always preferred. I am happy to offer a discount 00:03:48.900 --> 00:03:52.800 for the Daylight Computer. You can use the code 00:03:52.800 --> 00:03:59.900 Autism for a $25 off coupon. Again, use the code 00:03:59.900 --> 00:04:05.900 Autism and the discount code for $25 off. See 00:04:05.900 --> 00:04:09.039 the link in the show notes to Daylight Computer 00:04:09.039 --> 00:04:11.939 Company or just give it a quick search in your 00:04:11.939 --> 00:04:17.100 internet browser. Use the code Autism. for $25 00:04:17.100 --> 00:04:22.939 off. For today's episode, we will expand on the 00:04:22.939 --> 00:04:28.040 so -called Neuralation Time. Today, we will get 00:04:28.040 --> 00:04:32.879 into the process of brain development. We will 00:04:32.879 --> 00:04:36.620 talk briefly about maternal factors and biomarkers. 00:04:37.680 --> 00:04:42.639 My ask to you is this. To understand why autistics 00:04:42.639 --> 00:04:48.129 have so many comorbid conditions, mostly related 00:04:48.129 --> 00:04:52.610 in the medical conditions. Consider how and when 00:04:52.610 --> 00:04:57.290 the brain and body are created and connected 00:04:57.290 --> 00:05:04.189 in this time during embryogenesis. So some common 00:05:04.189 --> 00:05:08.310 maternal factors, some biomarkers, if you will. 00:05:09.750 --> 00:05:14.860 Tyrosine is a big one. Remember the risk of Hypothyroid. 00:05:15.939 --> 00:05:20.500 Many times, the mother will be put on a levothyroxine, 00:05:20.939 --> 00:05:26.220 maybe 50 to 200 micrograms daily dose. And this 00:05:26.220 --> 00:05:29.920 is usually taken in the morning. What's curious 00:05:29.920 --> 00:05:34.699 about this is you take this in the morning and 00:05:34.699 --> 00:05:37.939 you can only have water, no food, or other types 00:05:37.939 --> 00:05:42.680 of drink for 30 to 60 minutes. Now, if your metabolism 00:05:42.680 --> 00:05:45.680 is good, you can get by with just 30 minutes 00:05:45.680 --> 00:05:50.759 for the medicine to kick in. Essentially, what 00:05:50.759 --> 00:05:53.279 we are doing here with prescribing this medication 00:05:53.279 --> 00:05:58.100 is replacing the lack of sunlight we are getting 00:05:58.100 --> 00:06:02.660 during the day. Remember, tyrosine is an aromatic 00:06:02.660 --> 00:06:08.779 amino acid, and it absorbs strong, short wavelengths 00:06:08.779 --> 00:06:13.680 of light. Also related to the hypothyroidism, 00:06:14.500 --> 00:06:19.899 with the T3 and T4, iodine is often supplemented 00:06:19.899 --> 00:06:23.420 to mitigate the risk of autism. Iodine is the 00:06:23.420 --> 00:06:28.639 3 and 4 in the T3 and T4. Remember the Autism 00:06:28.639 --> 00:06:32.860 in Parkinson's episode. We cover T3 in good detail 00:06:32.860 --> 00:06:36.959 about its cellular roles, not just hormonal, 00:06:37.800 --> 00:06:43.300 but for the vast roles on the cell. Also, and 00:06:43.300 --> 00:06:46.060 similar to tyrosine, is tryptophan. Tryptophan 00:06:46.060 --> 00:06:50.620 is a huge one because of its roles in embryogenesis. 00:06:51.220 --> 00:06:54.139 We will get into that in more detail in a future 00:06:54.139 --> 00:07:00.040 episode with tryptophan, microtubules, and mitosis. 00:07:00.560 --> 00:07:07.060 Tryptophan here is vast. But remember, tryptophan 00:07:07.060 --> 00:07:10.879 is an aromatic amino acid as well. So it needs 00:07:10.879 --> 00:07:14.639 the sunlight. And we will get into on that episode 00:07:14.639 --> 00:07:20.540 about how indirect supplementation, maybe tryptophan 00:07:20.540 --> 00:07:23.060 from food is an example, doesn't really play 00:07:23.060 --> 00:07:28.579 into this. Also, the B9. We've covered B9 in 00:07:28.579 --> 00:07:32.519 the folate. That is a big biomarker and maternal 00:07:32.519 --> 00:07:40.160 risk factor. Remember this role with MTHFR. and 00:07:40.160 --> 00:07:45.660 methionine for the DNA methylation. Omega -3 00:07:45.660 --> 00:07:49.699 is a big supplemental factor to mitigate the 00:07:49.699 --> 00:07:52.220 risk of autism. Remember what we've talked about 00:07:52.220 --> 00:07:57.100 with DHA and how DHA is just vast for electrons, 00:07:57.180 --> 00:08:02.040 moving electrons through the body. Vitamin D 00:08:02.040 --> 00:08:08.639 is an easy one. And gestational diabetes. We 00:08:08.639 --> 00:08:12.360 will get into that on a different episode even 00:08:12.360 --> 00:08:16.019 about how the growth hormones and excessive maternal 00:08:16.019 --> 00:08:20.420 insulin -like growth factors or the placenta 00:08:20.420 --> 00:08:25.139 growth can signal over -stimulate cell division 00:08:25.139 --> 00:08:28.980 in the embryo in this timeline that we are fitting 00:08:28.980 --> 00:08:34.340 right now. So sticking with this theme, some 00:08:34.340 --> 00:08:38.620 common environmental insults and toxins. but 00:08:38.620 --> 00:08:42.700 remember autism predates these findings these 00:08:42.700 --> 00:08:45.639 were not problems back in the canner kids and 00:08:45.639 --> 00:08:49.159 asperger kids and all the way up through the 00:08:49.159 --> 00:08:53.820 60s 70s 80s 90s and so forth these are all kind 00:08:53.820 --> 00:09:00.120 of new there's pollution glyphosate aluminum 00:09:00.120 --> 00:09:05.419 the bpa is a big one very concerning mercury 00:09:05.419 --> 00:09:10.129 of course Just see the episodes from Nicole Rincon 00:09:10.129 --> 00:09:16.129 and Christian Lyaw for a full review on some 00:09:16.129 --> 00:09:20.070 of these environmental insults and toxins. So 00:09:20.070 --> 00:09:23.669 during embryogenesis, and we are creating the 00:09:23.669 --> 00:09:28.850 brain here, remember the four cell types, proencephalon, 00:09:29.830 --> 00:09:34.710 mesencephalon, ROM encephalon, and then the fourth 00:09:34.710 --> 00:09:40.029 one, the spinal cord. Okay. So this happens early 00:09:40.029 --> 00:09:43.269 in embryonic development, specifically during 00:09:43.269 --> 00:09:46.490 the process of neurolation, when the neural tube 00:09:46.490 --> 00:09:49.450 forms and begins to differentiate into the primary 00:09:49.450 --> 00:09:53.190 brain, vesicles. These three structures, the 00:09:53.190 --> 00:09:57.649 proencephalon, mesencephalon, and rhombencephalon, 00:09:58.710 --> 00:10:01.549 are the first major divisions for the brain. 00:10:01.809 --> 00:10:04.769 And this appears around the third to fourth week 00:10:04.769 --> 00:10:09.289 of the embryonic stage. approximately 21 to 28 00:10:09.289 --> 00:10:14.950 days. So the proencephalon is responsible for 00:10:14.950 --> 00:10:18.750 the forebrain. This begins to form around day 00:10:18.750 --> 00:10:24.110 22 or 23 as the neural tube closes and expands 00:10:24.110 --> 00:10:28.649 at the anterior, so the front end. And by the 00:10:28.649 --> 00:10:31.570 end of the fourth week, the proencephalon differentiates. 00:10:31.870 --> 00:10:35.029 So it further divides. It becomes a larger complex. 00:10:35.519 --> 00:10:39.539 So it differentiates into two secondary vesicles. 00:10:40.440 --> 00:10:43.860 And we are creating the brain here. The first 00:10:43.860 --> 00:10:48.240 vesicle is the telencephalon, which will become 00:10:48.240 --> 00:10:52.700 the cerebral hemispheres. So very vast for humans. 00:10:53.799 --> 00:10:57.460 And the second vesicle is this diencephalon. 00:10:57.759 --> 00:11:00.519 And this will form the thalamus, that sensory 00:11:00.519 --> 00:11:03.539 relay station. We've talked about the thalamus 00:11:03.539 --> 00:11:08.269 in great detail. If you want to understand sensory 00:11:08.269 --> 00:11:11.549 perception processes, you must understand the 00:11:11.549 --> 00:11:16.990 thalamus. It also forms the hypothalamus, the 00:11:16.990 --> 00:11:20.669 little nuclei that is responsible for our hormone. 00:11:21.669 --> 00:11:25.789 It combines the brain and body through the hormonal 00:11:25.789 --> 00:11:30.409 system. The diencephalon are also responsible 00:11:30.409 --> 00:11:34.590 for some eye development and the epithalamus. 00:11:38.520 --> 00:11:41.779 The mesencephalon, a big region of interest for 00:11:41.779 --> 00:11:45.899 us. This is a very curious region. We will get 00:11:45.899 --> 00:11:48.340 into more detail on it towards the end of the 00:11:48.340 --> 00:11:51.820 episode. But this also emerges at the same time 00:11:51.820 --> 00:11:56.379 as the proencephalon around day 22 or 23. And 00:11:56.379 --> 00:11:59.600 it's in the middle portion of the neural tube. 00:12:00.500 --> 00:12:02.899 It makes sense that it's in the middle portion 00:12:02.899 --> 00:12:07.320 because this will eventually be called the midbrain. 00:12:08.590 --> 00:12:12.129 However, unlike the other two areas, the proencephalon 00:12:12.129 --> 00:12:16.409 and rompencephalon, you know, the mesencephalon 00:12:16.409 --> 00:12:21.230 does not subdivide into further vesicles. It 00:12:21.230 --> 00:12:25.450 remains the mesencephalon. And this is very, 00:12:25.590 --> 00:12:34.230 very curious to me. The rompencephalon, the hindbrain, 00:12:34.669 --> 00:12:38.559 to no surprise, forms around day 22. and 23 as 00:12:38.559 --> 00:12:41.500 well. This is the posterior end of the neural 00:12:41.500 --> 00:12:46.299 tube. By the end of the fourth week, it divides 00:12:46.299 --> 00:12:52.779 into two further areas of the brain. The first 00:12:52.779 --> 00:12:56.480 one is the metencephalon, and this develops the 00:12:56.480 --> 00:13:00.860 pons and cerebellum. The cerebellum is a very 00:13:00.860 --> 00:13:05.460 underrated region of interest for essentially 00:13:05.460 --> 00:13:09.659 all humans. but especially autism. This is a 00:13:09.659 --> 00:13:13.379 big part of motor coordination, motor control. 00:13:15.120 --> 00:13:19.820 And if you look at the brain stem or any part 00:13:19.820 --> 00:13:23.299 of the brain, you can just see this just looking 00:13:23.299 --> 00:13:26.720 at the full brain from the lateral position. 00:13:27.379 --> 00:13:30.820 The pons is a little football -shaped region 00:13:30.820 --> 00:13:35.649 on the anterior part of the brain stem. And lastly, 00:13:35.950 --> 00:13:40.509 the myencephalon. The myencephalon is responsible 00:13:40.509 --> 00:13:47.850 for the medulla. This part of the inferior brainstem 00:13:47.850 --> 00:13:52.210 is responsible for several automatic responses. 00:13:52.570 --> 00:13:56.330 Physiology and just reflexes, all of these things 00:13:56.330 --> 00:13:58.269 that we don't have to necessarily think about 00:13:58.269 --> 00:14:03.149 doing. We just do them, like breathing. So, all 00:14:03.149 --> 00:14:06.509 three areas. The proncephalon, mesencephalon, 00:14:07.269 --> 00:14:11.830 and rhombencephalon occur around day 22 and 23 00:14:11.830 --> 00:14:16.490 when the neural tube forms and begins to differentiate 00:14:16.490 --> 00:14:20.429 into a larger, more complex organ called the 00:14:20.429 --> 00:14:25.570 brain. Then around day 28, these other primary 00:14:25.570 --> 00:14:30.830 vesicles start subdividing except for that mesencephalon. 00:14:32.009 --> 00:14:34.879 And what we're doing here is just developing 00:14:34.879 --> 00:14:41.139 the brain, the large complex brain. And a big 00:14:41.139 --> 00:14:44.779 region of interest here, from the previous episode, 00:14:45.620 --> 00:14:48.419 the subdivision and signaling, the molecules 00:14:48.419 --> 00:14:53.679 used the sonic hedgehog to undergo this task. 00:14:54.159 --> 00:14:57.200 The sonic hedgehog is a big region of interest 00:14:57.200 --> 00:15:01.639 for this process to happen. Okay, before we get 00:15:01.639 --> 00:15:04.980 into the different nuclei in specialized roles 00:15:04.980 --> 00:15:08.200 of the mesencephalon. Let's just kind of zoom 00:15:08.200 --> 00:15:12.519 out here and understand the mesencephalon from 00:15:12.519 --> 00:15:19.019 an evolutionarily perspective here. So the mesencephalon 00:15:19.019 --> 00:15:21.840 is a very ancient part of the brain. If you think 00:15:21.840 --> 00:15:25.379 about it, it's at the bottom. So it's conserved 00:15:25.379 --> 00:15:29.399 across many different species and across evolution. 00:15:30.720 --> 00:15:34.919 In simpler organisms, the midbrain Especially 00:15:34.919 --> 00:15:38.279 that optic tectum area that we covered in the 00:15:38.279 --> 00:15:41.500 Autism in Eye Movements episode when we first 00:15:41.500 --> 00:15:44.259 kind of introduced the mesencephalon. This is 00:15:44.259 --> 00:15:48.419 a machine -like, first responding type of structure 00:15:48.419 --> 00:15:52.179 and it's dominant for sensory input and integrating 00:15:52.179 --> 00:15:57.519 sensory, especially the vision. And with humans, 00:15:58.440 --> 00:16:01.279 the forebrain takes over many of those higher 00:16:01.279 --> 00:16:04.320 functioning. included in vision remember the 00:16:04.320 --> 00:16:09.500 brain is roughly 40 to 45 percent dedicated to 00:16:09.500 --> 00:16:14.580 vision but the midbrain retains this critical 00:16:14.580 --> 00:16:19.419 unified roles for processing this sensory input 00:16:19.419 --> 00:16:26.000 this is kind of the first stop even so functionally 00:16:26.000 --> 00:16:29.059 the mesencephalon develops into the midbrain 00:16:29.059 --> 00:16:31.799 which we will cover And that includes structures 00:16:31.799 --> 00:16:36.340 like the tectum. So the superior and inferior 00:16:36.340 --> 00:16:41.840 coeliculi. The inferior is auditory reflexes. 00:16:42.139 --> 00:16:46.000 And the tegmentum area. So a region of interest 00:16:46.000 --> 00:16:50.080 here covered in many, many episodes. The substantia 00:16:50.080 --> 00:16:54.039 nigra. And also, we'll introduce the red nucleus. 00:16:54.480 --> 00:16:57.100 And this is involved in movement and reward. 00:16:59.049 --> 00:17:03.529 These functions also integrate sensory reflexes 00:17:03.529 --> 00:17:07.930 and motor coordination. The subdivision might 00:17:07.930 --> 00:17:11.329 disrupt the midbrain's role as a relay and integration 00:17:11.329 --> 00:17:15.910 hub between the forebrain and the hindbrain. 00:17:16.049 --> 00:17:18.869 So it kind of connects the different areas of 00:17:18.869 --> 00:17:23.589 the brain. Now one thing to consider, because 00:17:23.589 --> 00:17:27.170 as brains evolve, they grow in size, they grow 00:17:27.170 --> 00:17:32.220 laterally, and posteriorly, okay? They just move 00:17:32.220 --> 00:17:39.799 out and up. The midbrain here is kind of squished. 00:17:40.759 --> 00:17:45.980 It's kind of a tight fit between the ROM encephalon, 00:17:46.380 --> 00:17:51.519 the lower areas, and then this huge pro -encephalon 00:17:51.519 --> 00:17:57.359 area, the human cortex and so forth. Evolutionarily, 00:17:58.410 --> 00:18:02.809 Functionally, this mesencephalon is very limited 00:18:02.809 --> 00:18:10.269 on its capacity to expand. However, it seems 00:18:10.269 --> 00:18:14.230 like the living organism and the roles here that 00:18:14.230 --> 00:18:18.970 we will get into with the mesencephalon, it cannot 00:18:18.970 --> 00:18:24.190 allow for more description, more roles and functions. 00:18:25.029 --> 00:18:28.190 Relatively speaking, the mesencephalon is very 00:18:28.190 --> 00:18:33.710 small. So just to recap and a kind of a summary, 00:18:34.250 --> 00:18:38.029 for the mature brain, once developed, the proencephalon, 00:18:38.549 --> 00:18:41.230 including the telencephalon and diencephalon, 00:18:41.950 --> 00:18:44.609 this is the biggest expansion. This has the biggest 00:18:44.609 --> 00:18:49.990 role as far as brain size, real estate. And this 00:18:49.990 --> 00:18:54.450 is for complex cognition and the sensory processing. 00:18:57.120 --> 00:19:00.500 The mesencephalon, or just the midbrain, we've 00:19:00.500 --> 00:19:04.359 covered that. The ROM encephalon evolves into 00:19:04.359 --> 00:19:07.579 the MET encephalon and my encephalon. And this 00:19:07.579 --> 00:19:10.200 is kind of specialized for control of movement 00:19:10.200 --> 00:19:14.539 and automatic functions. Those reflexes, like 00:19:14.539 --> 00:19:17.059 breathing and heart rate and so forth. We don't 00:19:17.059 --> 00:19:20.880 have to think about that stuff. We often don't 00:19:20.880 --> 00:19:23.299 have to think about movements either. Have you 00:19:23.299 --> 00:19:25.519 ever just paid attention to how much a human 00:19:25.519 --> 00:19:29.569 moves? even whenever it's not really goal -directed, 00:19:29.569 --> 00:19:33.769 there's not a task at hand. It's very fascinating. 00:19:35.809 --> 00:19:39.150 So some factors of the subdivisions here. The 00:19:39.150 --> 00:19:43.390 subdivisions process, this is orchestrated by 00:19:43.390 --> 00:19:46.730 kind of intricate patterns along the anterior 00:19:46.730 --> 00:19:50.490 to posterior and the dorsal to ventral axis of 00:19:50.490 --> 00:19:55.130 the neural tube. And some key drivers here include 00:19:55.130 --> 00:20:00.460 morphogen gradients. Things like fibroblast growth 00:20:00.460 --> 00:20:05.119 factors and WNT proteins and sonic hedgehog. 00:20:05.640 --> 00:20:09.920 Now with autism research the WNT proteins is 00:20:09.920 --> 00:20:12.480 highly researched. It's a region of interest 00:20:12.480 --> 00:20:16.779 as well. There are transcription factors and 00:20:16.779 --> 00:20:20.740 gene expressions. So a couple of different examples 00:20:20.740 --> 00:20:23.700 here if you want to kind of go into the rabbit 00:20:23.700 --> 00:20:31.980 hole if you will. These include OTX2 and GBX2, 00:20:33.200 --> 00:20:42.700 Pax6, PAX6, and EMX2, and HOX genes, H -O -X. 00:20:43.519 --> 00:20:46.160 You can look up those if you wish. And there 00:20:46.160 --> 00:20:48.859 are signaling centers, like the anterior neural 00:20:48.859 --> 00:20:53.779 ridge, A -N -R. This is kind of helps regulate 00:20:53.779 --> 00:20:58.400 the WNT. And from earlier, with that midbrain, 00:20:58.480 --> 00:21:01.720 the mesencephalon, being kind of compact, it's 00:21:01.720 --> 00:21:05.859 kind of tightly squeezed into this region, there's 00:21:05.859 --> 00:21:09.180 a midbrain -hindbrain boundary, it's called. 00:21:09.680 --> 00:21:12.440 And this kind of stabilizes the midbrain as a 00:21:12.440 --> 00:21:16.200 single unit while allowing the cerebellum to 00:21:16.200 --> 00:21:21.140 kind of evolve. Cellular proliferation and migration. 00:21:21.279 --> 00:21:25.920 We will have future episodes diving deep. deep 00:21:25.920 --> 00:21:30.640 into this kind of dense and hot topic for the 00:21:30.640 --> 00:21:34.559 autistic brain. So proliferation and migration. 00:21:35.359 --> 00:21:38.500 This is a very hot topic for the autistic brain. 00:21:41.019 --> 00:21:44.799 I would like to mention Chroma. Lights designed 00:21:44.799 --> 00:21:50.200 for humans. 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They 00:24:24.609 --> 00:24:29.710 are US made and chroma ships globally and accepts 00:24:29.710 --> 00:24:37.430 FSA and HSA payments. Use autism at checkout 00:24:37.430 --> 00:24:44.170 for a 10 % off discount. That's autism at checkout 00:24:44.170 --> 00:24:49.440 for a 10 % off discount. So let's get into the 00:24:49.440 --> 00:24:53.220 mesencephalon here, the midbrain. Let's understand 00:24:53.220 --> 00:24:57.299 its roles, some of the nuclei involved, and what 00:24:57.299 --> 00:25:04.059 it's trying to accomplish. Overall, it's very 00:25:04.059 --> 00:25:08.220 important for various functions as motor control 00:25:08.220 --> 00:25:12.680 and sensory processing and the autonomic regulation. 00:25:13.680 --> 00:25:16.460 These things are vast for the central nervous 00:25:16.460 --> 00:25:20.190 system, which is what we are creating here the 00:25:20.190 --> 00:25:23.130 goal of the central nervous system is to move 00:25:23.130 --> 00:25:27.690 the living organism and in large part the brain 00:25:27.690 --> 00:25:32.109 is conserving and allocating and recruiting different 00:25:32.109 --> 00:25:36.230 regions how is the living organism going to move 00:25:36.230 --> 00:25:40.529 while sustaining its species by remaining safe 00:25:40.529 --> 00:25:46.950 by staying alive so a big part here and key nuclei 00:25:47.210 --> 00:25:50.809 is the Substantia Nigra. We've covered this in 00:25:50.809 --> 00:25:54.430 the Autism in Parkinson's episode and in all 00:25:54.430 --> 00:25:58.650 of the Autism in Basal Ganglia episodes. There's 00:25:58.650 --> 00:26:02.690 probably four to six episodes on that features 00:26:02.690 --> 00:26:07.230 the Substantia Nigra. This is a very interesting 00:26:07.230 --> 00:26:13.410 little nuclei. Remember, just a quick recap here. 00:26:13.529 --> 00:26:17.329 It's divided into two parts. the substantia nigra 00:26:17.329 --> 00:26:23.789 pars compacta which produces the dopamine d1 00:26:23.789 --> 00:26:28.410 dopamine so excitatory dopamine which are receptors 00:26:28.410 --> 00:26:34.589 dr1 and 5 and d2 dopamine which is inhibitory 00:26:34.589 --> 00:26:42.309 so receptors dr2 3 and 4 this is involved in 00:26:42.309 --> 00:26:45.920 the motor control motor coordination the basal 00:26:45.920 --> 00:26:51.940 ganglia our go no -go area right next to that 00:26:51.940 --> 00:26:54.460 is the red nucleus now this is an introduction 00:26:54.460 --> 00:26:58.940 to the red nucleus it plays a role in motor coordination 00:26:58.940 --> 00:27:04.240 as well more specifically voluntary movements 00:27:04.240 --> 00:27:10.039 and it is part of a so -called extra pyramidal 00:27:10.039 --> 00:27:16.500 motor system So the extrapyramidal motor system 00:27:16.500 --> 00:27:20.279 is essentially a network of some neural pathways 00:27:20.279 --> 00:27:23.880 in the central nervous system that regulates 00:27:23.880 --> 00:27:28.180 involuntary and automatic movements. And it's 00:27:28.180 --> 00:27:31.059 responsible for some posture and muscle tone 00:27:31.059 --> 00:27:34.819 as well. You might have heard of the pyramidal 00:27:34.819 --> 00:27:38.160 system, but the extrapyramidal is a little bit 00:27:38.160 --> 00:27:41.759 different. Some key components of the extrapyramidal 00:27:41.849 --> 00:27:45.049 system include the basal ganglia. I don't have 00:27:45.049 --> 00:27:47.670 to go into more detail about that. We've covered 00:27:47.670 --> 00:27:52.730 that. The cerebellum. So it helps control fine 00:27:52.730 --> 00:27:58.890 motor control and balance and timing. The brainstem 00:27:58.890 --> 00:28:02.170 nuclei. The red nucleus and substantia nigra. 00:28:03.049 --> 00:28:05.650 The reticular formation. We briefly mentioned 00:28:05.650 --> 00:28:09.049 the reticular formation before. This is scattered 00:28:09.049 --> 00:28:12.519 throughout the brainstem and regulates posture, 00:28:12.799 --> 00:28:16.539 gait, and reflexive movements. Also involved 00:28:16.539 --> 00:28:19.920 in the extra -paramental system is the thalamus. 00:28:20.640 --> 00:28:24.420 We've covered the thalamus. However, if you think 00:28:24.420 --> 00:28:28.779 about this extra -paramental roles and autism, 00:28:29.680 --> 00:28:32.880 let's specifically mention its roles with autism. 00:28:34.460 --> 00:28:36.799 So with the substantia nigra and the dopamine 00:28:36.799 --> 00:28:41.200 dysregulation, you know that In the autistic 00:28:41.200 --> 00:28:43.900 phenotype, there are some implications here, 00:28:44.160 --> 00:28:48.160 some signaling processes that are abnormal, and 00:28:48.160 --> 00:28:51.279 it's linked to repetitive behaviors and motor 00:28:51.279 --> 00:28:55.859 stereotypies. This is where that is occurring 00:28:55.859 --> 00:29:00.119 here. It's a very easy thing in autism to evaluate 00:29:00.119 --> 00:29:04.720 and observe. The red nucleus and motor coordination. 00:29:05.259 --> 00:29:10.369 So in autism, it contributes to that motor clumsiness, 00:29:10.589 --> 00:29:15.269 which is very common, and motor delays. Those 00:29:15.269 --> 00:29:19.009 delays in certain milestones like crawling, walking, 00:29:20.049 --> 00:29:23.049 grip strength, and being able to just function 00:29:23.049 --> 00:29:28.069 and coordinate movements. The basal ganglia circuits, 00:29:28.130 --> 00:29:31.309 of course, because of the substantia nigra. There 00:29:31.309 --> 00:29:34.569 are structural and functional MRI studies that 00:29:34.569 --> 00:29:37.809 show the basal ganglia It's abnormal in the autistic 00:29:37.809 --> 00:29:42.569 phenotype and both brain volume and connectivity. 00:29:42.829 --> 00:29:45.990 Remember Dr. Hannah Stevens. She has wonderful 00:29:45.990 --> 00:29:50.109 work on the dorsal striatum and it's kind of 00:29:50.109 --> 00:29:53.890 enlargement. It's very dense here with dendrites 00:29:53.890 --> 00:29:58.329 and axons. Remember the dorsal striatum is the 00:29:58.329 --> 00:30:01.990 input area of the basal ganglia. It coordinates, 00:30:02.490 --> 00:30:06.619 recruits different areas. for the related outcome 00:30:06.619 --> 00:30:13.039 of the movement. So back to the nuclei within 00:30:13.039 --> 00:30:16.680 the mesencephalon, there's an ocular motor nucleus, 00:30:17.079 --> 00:30:21.740 which is the third cranial nerve. And this is 00:30:21.740 --> 00:30:24.039 controlling eye movements. So if you think about 00:30:24.039 --> 00:30:27.819 autism, we ought to go here. We ought to go to 00:30:27.819 --> 00:30:30.559 the eye movements. It's not difficult to see 00:30:30.559 --> 00:30:35.539 this is involved. An additional oculomotor nucleus 00:30:35.539 --> 00:30:41.039 role is mediating pupillary constriction. So, 00:30:41.599 --> 00:30:44.619 with the sympathetic versus parasympathetic fibers 00:30:44.619 --> 00:30:48.039 here. It has a problem and its main goal here 00:30:48.039 --> 00:30:51.599 is mediating the pupillary constriction for the 00:30:51.599 --> 00:30:55.019 parasympathetic arm of the autonomic nervous 00:30:55.019 --> 00:31:00.480 system. There's an accessory to the oculomotor 00:31:00.480 --> 00:31:05.640 nucleus. It's proper nouns. Edinger Westfall 00:31:05.640 --> 00:31:09.339 Neculus. This is also related to the parasympathetic 00:31:09.339 --> 00:31:15.460 nucleus for the pupillary constriction. Then 00:31:15.460 --> 00:31:21.180 the trochlear nucleus. Cranial nerve IV. And 00:31:21.180 --> 00:31:25.279 this kind of intervates the muscles of the eye. 00:31:25.359 --> 00:31:28.079 It's responsible for downward and inward eye 00:31:28.079 --> 00:31:32.880 movements. There's a mesencephalic... nucleus 00:31:32.880 --> 00:31:38.400 of the trigeminal nerve cranial nerve 5 this 00:31:38.400 --> 00:31:42.299 is part of the para -aqueductal gray we will 00:31:42.299 --> 00:31:46.299 introduce momentarily this has involvements with 00:31:46.299 --> 00:31:51.319 pro -proceptive input from the muscles in addition 00:31:51.319 --> 00:31:54.000 the superior colliculus which we've covered and 00:31:54.000 --> 00:31:56.859 the inferior colliculus which we've covered so 00:31:56.859 --> 00:32:02.420 I will skip those but We are to the para -aqueductal 00:32:02.420 --> 00:32:07.220 gray, the PAG. This is a very good region of 00:32:07.220 --> 00:32:10.380 interest here because it contains nuclei involved 00:32:10.380 --> 00:32:13.400 in pain modulation. Think about autistics and 00:32:13.400 --> 00:32:17.779 that pain regulation. Sometimes our pain perception 00:32:17.779 --> 00:32:23.259 is off and oftentimes with temperature as well. 00:32:23.779 --> 00:32:27.759 In the late 80s and 90s that pain regulation 00:32:27.759 --> 00:32:31.859 or that kind of perception, it was common for 00:32:31.859 --> 00:32:37.180 it to be nicknamed retard strength. And today, 00:32:37.539 --> 00:32:40.160 today's society probably wouldn't allow that. 00:32:40.259 --> 00:32:44.119 They wouldn't like that, I should say. But retard 00:32:44.119 --> 00:32:47.440 strength was very much a thing back in my childhood. 00:32:48.519 --> 00:32:53.039 The PHE also is involved in autonomic regulation. 00:32:53.240 --> 00:32:56.660 So with the heart rate and breathing, and it's 00:32:56.670 --> 00:33:00.410 also involved in defensive behaviors. This is 00:33:00.410 --> 00:33:05.470 a very cool area of the PAG. And just today on 00:33:05.470 --> 00:33:10.970 311, a study showing that the ACC to the PAG 00:33:10.970 --> 00:33:14.829 transforms signals tied to empathy to certain 00:33:14.829 --> 00:33:18.769 behavioral responses. Remember the ACC? We've 00:33:18.769 --> 00:33:21.509 talked about the ACC in quite detail. It's a 00:33:21.509 --> 00:33:24.420 part of the medial prefrontal cortex. The ACC 00:33:24.420 --> 00:33:27.579 is the anterior cingulate cortex. It's involved 00:33:27.579 --> 00:33:31.819 in that internal calculation. It's a big region 00:33:31.819 --> 00:33:36.640 of interest here. But when freezing, if you've 00:33:36.640 --> 00:33:40.380 heard of the freeze, fight, flight, when freezing, 00:33:40.500 --> 00:33:43.660 the PAG is involved here. And it shuts down the 00:33:43.660 --> 00:33:47.519 body by sending signals down the spinal cord. 00:33:48.140 --> 00:33:53.319 This is a very cool feature of the PAG. So the 00:33:53.319 --> 00:33:56.880 next time you find yourself frozen, you're freezing, 00:33:57.380 --> 00:34:01.440 as they say. Just think about how the PAG in 00:34:01.440 --> 00:34:03.799 the mesencephalon, the top of the brain stem 00:34:03.799 --> 00:34:07.099 there, is just shutting it off, shutting down 00:34:07.099 --> 00:34:12.300 the downstream signals to the spinal cord. And 00:34:12.300 --> 00:34:17.260 your extremities are not moving. It's very fascinating. 00:34:18.380 --> 00:34:21.340 So let's look at the broader mesencephalon impact. 00:34:21.449 --> 00:34:26.110 with autism. The superior colliculus we've covered, 00:34:26.369 --> 00:34:30.269 it's a very fascinating little region here. And 00:34:30.269 --> 00:34:32.969 the whole reason I got into the mesencephalon, 00:34:33.329 --> 00:34:36.329 because the superior colliculus and the inferior 00:34:36.329 --> 00:34:42.530 colliculus, its primary role is biasing the attention 00:34:42.530 --> 00:34:47.329 of the living organism. Just imagine what this 00:34:47.329 --> 00:34:51.860 has functionally with learning. learning the 00:34:51.860 --> 00:34:54.860 environment. This is so easy to connect here 00:34:54.860 --> 00:34:58.599 with the autistic phenotype. This is ought to 00:34:58.599 --> 00:35:01.579 be one of the most significant regions of interest 00:35:01.579 --> 00:35:05.099 here for understanding the brain development 00:35:05.099 --> 00:35:09.179 during neural relation even and creating this 00:35:09.179 --> 00:35:13.179 autistic phenotype. What makes autistics autistic? 00:35:14.039 --> 00:35:19.039 This is so fascinating and underrated and overlooked. 00:35:21.039 --> 00:35:25.800 So the PAG with autism, so for that autonomic 00:35:25.800 --> 00:35:29.960 and emotional regulation. Autistic individuals, 00:35:31.219 --> 00:35:35.039 through the work of these, this biology and neuroplasticity 00:35:35.039 --> 00:35:38.119 with the experience and being forced into social 00:35:38.119 --> 00:35:42.119 norms, we have a heightened rates of anxiety 00:35:42.119 --> 00:35:46.679 and that atypical pain perception. This is a 00:35:46.679 --> 00:35:50.940 very fascinating how the, this is the pain perception 00:35:50.940 --> 00:35:55.940 in autism is very abnormal. The eye movements 00:35:55.940 --> 00:36:00.780 as mentioned earlier with oculomotor, nuclei 00:36:00.780 --> 00:36:07.280 that eye saccades. Remember the episode on eye 00:36:07.280 --> 00:36:10.360 tracking as a biomarker. This is a very useful 00:36:10.360 --> 00:36:14.400 tool to diagnosing autism at an earlier rate. 00:36:14.960 --> 00:36:19.360 earlier stages in life. This is huge for kind 00:36:19.360 --> 00:36:25.679 of interventions, kind of suppressing the harms 00:36:25.679 --> 00:36:29.059 via the neuroplasticity, the changes in the brain 00:36:29.059 --> 00:36:37.059 from experience. This is a big region here. And 00:36:37.059 --> 00:36:42.070 proprioception. This is huge in autism. with 00:36:42.070 --> 00:36:46.369 that motor planning the deficits in motor control 00:36:46.369 --> 00:36:51.530 and oral motor difficulties so the speech articulation 00:36:51.530 --> 00:36:53.889 that we've covered and autism and speech and 00:36:53.889 --> 00:36:57.690 language which it should be language and speech 00:36:57.690 --> 00:37:00.190 because language comes first and then the speech 00:37:00.190 --> 00:37:07.849 but with the acuit fasciculus connecting verneki 00:37:07.849 --> 00:37:12.900 and broca and then the midbrain down here. It's 00:37:12.900 --> 00:37:18.880 huge, huge for autism. So I can't undervalue 00:37:18.880 --> 00:37:23.139 here the mesencephalon and autism because of 00:37:23.139 --> 00:37:27.780 its critical relay. It's the hub for integrating 00:37:27.780 --> 00:37:30.460 all of these sensories and biasing the attention 00:37:30.460 --> 00:37:34.760 of the living organism and all of the autonomic 00:37:34.760 --> 00:37:40.219 responses. Sensory motor integration It's vast 00:37:40.219 --> 00:37:45.760 here. Probably the top reason that the mesencephalon 00:37:45.760 --> 00:37:50.500 is overlooked. And then the connectivity. We've 00:37:50.500 --> 00:37:54.460 covered some connectivity with the Autism in 00:37:54.460 --> 00:37:57.840 Eye Movements episode with the diffusion tensor 00:37:57.840 --> 00:38:03.300 imaging DTI and the white matter tracks and the 00:38:03.300 --> 00:38:06.199 timing of the neurodevelopmental. This is what 00:38:06.199 --> 00:38:09.239 the whole episode and the last week's episode 00:38:09.239 --> 00:38:12.159 is about, forming the central nervous system, 00:38:12.380 --> 00:38:16.340 the brain and spine. Think about what we've covered 00:38:16.340 --> 00:38:20.440 here today with the mesencephalon's role and 00:38:20.440 --> 00:38:22.940 access to the spinal cord for motor movements 00:38:22.940 --> 00:38:30.440 even. This is huge here. If you're listening 00:38:30.440 --> 00:38:33.340 to the podcast or listening to the episode, please 00:38:33.340 --> 00:38:37.579 feel free to leave a review or rating. In podcasting, 00:38:37.820 --> 00:38:40.320 reviews, ratings, and downloads are huge and 00:38:40.320 --> 00:38:44.119 I very much appreciate your feedback. You can 00:38:44.119 --> 00:38:51.219 contact me on X at RPS 47586. You can check out 00:38:51.219 --> 00:38:55.039 the hop link for links to all of the podcasts 00:38:55.039 --> 00:38:58.059 across many different platforms. You can check 00:38:58.059 --> 00:39:01.300 out the YouTube channel for full length videos 00:39:01.480 --> 00:39:11.480 and shorts and clips. You can email me info .fromthespectrumatgmail 00:39:11.480 --> 00:39:17.340 .com. Thank you for listening to From the Spectrum 00:39:17.340 --> 00:39:18.079 Podcast.