WEBVTT 00:00:00.680 --> 00:00:04.459 For today's episode, we will cover a special 00:00:04.459 --> 00:00:10.580 inhibitory neuron called the Parf Albium Interneuron. 00:00:11.279 --> 00:00:16.019 We will cover a recent article by Fujima Etta 00:00:16.019 --> 00:00:22.399 just released in late August 2025 in Cell Press, 00:00:22.839 --> 00:00:27.239 a top journal for medicine and neuroscience titled 00:00:27.239 --> 00:00:32.049 Parf Albium Interneurons in the insular cortex 00:00:32.049 --> 00:00:38.729 control social familiarity and emotion recognition 00:00:38.729 --> 00:00:43.009 Now if you know about cell press They have many 00:00:43.009 --> 00:00:45.390 different types of journals. This one's called 00:00:45.390 --> 00:00:49.990 cell reports However with all of these journals 00:00:49.990 --> 00:00:54.609 Cell press really has a huge benefit in my opinion 00:00:54.920 --> 00:00:57.420 because they release a graphical abstraction, 00:00:57.799 --> 00:01:00.759 which is easy to follow, kind of a graphical 00:01:00.759 --> 00:01:04.920 summary of the article, and some highlights. 00:01:05.280 --> 00:01:08.340 Three to four, typically four bullet points. 00:01:09.159 --> 00:01:12.159 It is almost like a cover letter for the article. 00:01:12.280 --> 00:01:15.879 I love this page because it also provides room 00:01:15.879 --> 00:01:19.040 for notes. I'll just read the highlights, the 00:01:19.040 --> 00:01:22.859 four bullet points from this article now. A subset 00:01:22.859 --> 00:01:28.340 of Insular parvalbian interneurons exhibits increased 00:01:28.340 --> 00:01:34.579 activity during social interaction. Second one, 00:01:34.819 --> 00:01:38.260 inhibiting parvalbian interneurons prevents the 00:01:38.260 --> 00:01:43.900 loss of preference for familiar peers. Third, 00:01:44.579 --> 00:01:48.359 inhibiting parvalbian interneurons impairs the 00:01:48.359 --> 00:01:53.060 preference for stressed peers. And finally, the 00:01:53.060 --> 00:01:58.150 fourth. Parvalbian interneurons modulate pyramidal 00:01:58.150 --> 00:02:02.129 neuron activity related to social target preference. 00:02:03.090 --> 00:02:05.870 And just a side note on the pyramidal neurons, 00:02:05.989 --> 00:02:09.449 these are excitatory. So we have a dance here 00:02:09.449 --> 00:02:14.310 between inhibitory, the parvalbian, and the pyramidal, 00:02:14.590 --> 00:02:20.009 the excitations. We will recap several critical 00:02:20.009 --> 00:02:23.870 areas here. The medial prefrontal cortex, the 00:02:23.870 --> 00:02:29.969 insular cortex, the default mode network, and 00:02:29.969 --> 00:02:34.490 remember the inhibition problem with the autistic 00:02:34.490 --> 00:02:39.990 phenotype, the excitation, and inhibition balance. 00:02:40.389 --> 00:02:44.409 In large part, the parvalbium interneuron is 00:02:44.409 --> 00:02:48.750 helping this. It has a role in this. With autism, 00:02:49.229 --> 00:02:54.360 there's high excitation and or low inhibition. 00:02:54.979 --> 00:02:58.639 And for those really dedicated here, this cell 00:02:58.639 --> 00:03:02.620 type has roles in the basal ganglia. We've covered 00:03:02.620 --> 00:03:06.139 the basal ganglia in several, maybe four, five 00:03:06.139 --> 00:03:10.539 episodes. Huge problem with the autistic phenotype. 00:03:11.159 --> 00:03:14.860 And we will once again get into the saying at 00:03:14.860 --> 00:03:19.659 all article released last year from UCLA on six 00:03:19.659 --> 00:03:23.509 weeks old. These are human infants. six weeks 00:03:23.509 --> 00:03:27.770 old study. We will parse this out and add layers 00:03:27.770 --> 00:03:31.490 to this even more. Because something autism research, 00:03:31.490 --> 00:03:35.990 in my opinion, fails to do is expand on these 00:03:35.990 --> 00:03:39.189 good articles that are released and are meaningful. 00:03:39.969 --> 00:03:42.770 What are we going to do with these articles now? 00:03:43.669 --> 00:03:47.009 And finally, we will have a brief recap on a 00:03:47.009 --> 00:03:53.340 protein, CNT, NAP2. which is heavily involved 00:03:53.340 --> 00:03:57.460 in autism research and plays a big function here 00:03:57.460 --> 00:04:00.419 with developing the autistic phenotype. We've 00:04:00.419 --> 00:04:05.060 covered this in episodes four or five and with 00:04:05.060 --> 00:04:10.680 Dr. Hannah Stevens. But first a word about Daylight 00:04:10.680 --> 00:04:14.960 Computer Company and Chroma Light Devices. I 00:04:14.960 --> 00:04:17.259 have something exciting. I want to introduce 00:04:17.259 --> 00:04:20.139 a product unlike any other product available. 00:04:20.649 --> 00:04:25.670 A highlight is the product from Daylight Computer 00:04:25.670 --> 00:04:29.149 Company created their product based on these 00:04:29.149 --> 00:04:34.129 factors. The Daylight Computer is completely 00:04:34.129 --> 00:04:39.629 blue light free. It has no flicker. Short wavelength 00:04:39.629 --> 00:04:44.230 flicker is extremely harmful for our eyes and 00:04:44.230 --> 00:04:48.149 downstream biology. Light flicker is constantly 00:04:48.149 --> 00:04:51.819 turning our central nervous system on and off. 00:04:52.420 --> 00:04:56.040 Essentially, it is like going to a light switch 00:04:56.040 --> 00:05:00.439 and repeatedly turning it on and off. The problem 00:05:00.439 --> 00:05:06.439 is blue light and LED light does this and it 00:05:06.439 --> 00:05:09.720 is so rapid you cannot even perceive this in 00:05:09.720 --> 00:05:15.199 real time. The daylight computer is the lowest 00:05:15.199 --> 00:05:19.180 stimulation and foremost for sensory sensitive 00:05:19.180 --> 00:05:24.439 users. It is no question that the alternative 00:05:24.439 --> 00:05:29.699 product, especially when used at night, do not 00:05:29.699 --> 00:05:34.139 address or consider this in their product. It 00:05:34.139 --> 00:05:39.060 is so toxic to human biology. Big tech corporations 00:05:39.060 --> 00:05:43.819 have patents on how their short wavelength implicate 00:05:43.819 --> 00:05:49.399 the human nervous system. And a bonus. Despite 00:05:49.399 --> 00:05:53.560 daylight computer not having backlight, it is 00:05:53.560 --> 00:05:57.740 very functional for outdoor use. And of course, 00:05:58.759 --> 00:06:03.759 increased sunlight is always preferred. I am 00:06:03.759 --> 00:06:07.139 happy to offer a discount for the daylight computer. 00:06:08.139 --> 00:06:13.259 You can use the code autism for a $50 off discount. 00:06:13.839 --> 00:06:18.220 Again, use the code autism and the discount code 00:06:18.509 --> 00:06:23.470 for $50 off. See the link in the show notes to 00:06:23.470 --> 00:06:26.569 Daylight Computer Company or just give it a quick 00:06:26.569 --> 00:06:30.670 search in your internet browser. Use the code 00:06:30.670 --> 00:06:37.329 AUTISM for $50 off. 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From sleep aids and 00:09:10.820 --> 00:09:15.500 wound healing to mitochondrial energy. full body 00:09:15.500 --> 00:09:18.960 lights and blue light blocking glasses. They 00:09:18.960 --> 00:09:24.039 are US made and chroma ships globally and accepts 00:09:24.039 --> 00:09:31.759 FSA and HSA payments. Use autism at checkout 00:09:31.759 --> 00:09:38.539 for a 10 % off discount. That's autism at checkout 00:09:38.539 --> 00:09:46.340 for a 10 % off discount. Okay, the medial prefrontal 00:09:46.340 --> 00:09:50.840 cortex. Remember, it's medial, meaning middle. 00:09:51.679 --> 00:09:55.980 So evolutionarily, it came on board before the 00:09:55.980 --> 00:10:01.000 lateral or basically before the outer surfaces, 00:10:02.159 --> 00:10:05.460 the sides and the top of the prefrontal cortex. 00:10:05.840 --> 00:10:09.200 Remember the human head, our brain above the 00:10:09.200 --> 00:10:12.850 eyes. If you draw a line back from the eyes to 00:10:12.850 --> 00:10:16.169 the back of the head, the occipital lobe, our 00:10:16.169 --> 00:10:20.250 heads extend up and full like no other species. 00:10:21.629 --> 00:10:25.169 So the medial prefrontal cortex, it is a huge 00:10:25.169 --> 00:10:28.690 area for the internal calculators that we discuss. 00:10:30.029 --> 00:10:34.269 It includes decision making, it considers risk 00:10:34.269 --> 00:10:39.009 versus reward and future planning, conflict monitoring, 00:10:39.500 --> 00:10:43.519 and error detection. A huge way the living organism 00:10:43.519 --> 00:10:47.980 learns, grows, and evolves is updating from errors, 00:10:48.159 --> 00:10:52.139 making errors, and then correcting them. This 00:10:52.139 --> 00:10:54.659 is huge here in the medial prefrontal cortex, 00:10:55.539 --> 00:10:57.779 which is basically adaptive responses. We have 00:10:57.779 --> 00:11:00.940 a whole episode on this allowing the living organism 00:11:00.940 --> 00:11:05.980 to adapt, shift, utilize healthy skills in real 00:11:05.980 --> 00:11:11.929 time. Remember, The autism and medial prefrontal 00:11:11.929 --> 00:11:14.830 cortex, whenever we are making healthy choices, 00:11:14.929 --> 00:11:17.669 when we are utilizing our skills as a living 00:11:17.669 --> 00:11:21.649 organism, the medial prefrontal cortex and specifically 00:11:21.649 --> 00:11:27.029 the ACC anterior cingulate cortex lead the way. 00:11:27.129 --> 00:11:30.429 They orchestrate all of these downstream movements 00:11:30.429 --> 00:11:33.950 and behaviors that control even thoughts and 00:11:33.950 --> 00:11:38.710 feelings. When we do not adaptively respond, 00:11:39.159 --> 00:11:43.639 Our lower brain area overtakes the medial prefrontal 00:11:43.639 --> 00:11:47.000 cortex. It kind of shuts it out, pushes it away. 00:11:48.919 --> 00:11:54.500 So with adaptive responses, this is huge in autism. 00:11:55.399 --> 00:11:59.159 Also, social cognition, which will be covered 00:11:59.159 --> 00:12:03.139 in the main article for today, and self -referential 00:12:03.139 --> 00:12:07.769 thinking, self -referential thoughts. That intense 00:12:07.769 --> 00:12:11.509 dreamlike state autistics have, a specific region 00:12:11.509 --> 00:12:16.610 of the ACC, which is in the medial prefrontal 00:12:16.610 --> 00:12:19.870 cortex. The ACC is just a little subdivision 00:12:19.870 --> 00:12:24.769 here. More on that in a future episode, how this 00:12:24.769 --> 00:12:27.970 area is huge for those dreamlike states and visual 00:12:27.970 --> 00:12:31.289 thinking. So you ought to be able to see some 00:12:31.289 --> 00:12:34.889 emotional regulation. also happening here in 00:12:34.889 --> 00:12:38.490 this medial prefrontal cortex area. So let's 00:12:38.490 --> 00:12:42.429 discuss the insula, the insular cortex. It has 00:12:42.429 --> 00:12:46.450 several subdivisions as well, subregions. Specifically 00:12:46.450 --> 00:12:49.289 for today, we'll talk more about the anterior 00:12:49.289 --> 00:12:53.529 insula. Now remember, the insula is a central 00:12:53.529 --> 00:12:59.029 hub for analyzing emotional brain states, thoughts 00:12:59.029 --> 00:13:03.320 and feelings even, bodily signals. those physiological 00:13:03.320 --> 00:13:06.340 responses like heart rate and how you're breathing 00:13:06.340 --> 00:13:09.440 if you're sweating how your gut feels it's receiving 00:13:09.440 --> 00:13:12.659 all of that data as well and it's also incorporating 00:13:12.659 --> 00:13:16.259 the environment what is going on on the outside 00:13:16.259 --> 00:13:20.940 the interior insula integrates entire receptive 00:13:20.940 --> 00:13:25.279 signals with those emotional and cognitive information 00:13:25.279 --> 00:13:29.460 that contributes to these subjective experiences 00:13:29.460 --> 00:13:33.480 it's involved with things like disgust or empathy, 00:13:33.919 --> 00:13:38.080 and even some anxiety. Whenever those sub -regions 00:13:38.080 --> 00:13:41.559 overtake the medial prefrontal cortex, the insula 00:13:41.559 --> 00:13:46.139 will register that. Those physiological responses 00:13:46.139 --> 00:13:50.620 happening in real time will be salient. And if 00:13:50.620 --> 00:13:54.399 you remember the salience network, the insula, 00:13:54.919 --> 00:13:58.340 especially this anterior part, is heavily involved 00:13:58.340 --> 00:14:01.480 in the so -called salience network. which is 00:14:01.480 --> 00:14:05.840 huge in that UCLA study and is huge in everybody's 00:14:05.840 --> 00:14:09.860 life. An interesting consideration is the interior 00:14:09.860 --> 00:14:13.820 insula also registers social cues specifically 00:14:13.820 --> 00:14:18.539 with trust and fairness. Remember Katie Asher 00:14:18.539 --> 00:14:22.179 coming on when Houston, she says that Houston 00:14:22.179 --> 00:14:26.240 can detect evil at high rates and with high accuracy. 00:14:27.539 --> 00:14:30.970 This is part of intuition. Autistics have an 00:14:30.970 --> 00:14:35.070 outstanding intuition because of these brain 00:14:35.070 --> 00:14:39.629 regions that we're discussing today and the anteroceptive 00:14:39.629 --> 00:14:43.409 functions. The anteroceptive functions is a good 00:14:43.409 --> 00:14:46.629 way of thinking about this. What is happening 00:14:46.629 --> 00:14:51.049 on our insides? Okay, we should talk about the 00:14:51.049 --> 00:14:55.230 parvalbumin interneurons. Remember, basically, 00:14:55.309 --> 00:14:57.590 in the central nervous system, there are three... 00:14:57.950 --> 00:15:01.929 main types of neurons, sensory neuron, motor 00:15:01.929 --> 00:15:06.610 neuron, and interneuron. So the par of albium 00:15:06.610 --> 00:15:11.429 interneurons can be seen as abbreviated as PVIN 00:15:11.429 --> 00:15:15.769 in a lot of research. They are found in various 00:15:15.769 --> 00:15:19.830 brain regions, including the cortex, these areas 00:15:19.830 --> 00:15:22.669 that we're discussing today, the hippocampus, 00:15:22.730 --> 00:15:25.909 which is a large part from memory, and the basal 00:15:25.909 --> 00:15:29.840 ganglia. So with the inhibition, of course, they 00:15:29.840 --> 00:15:36.019 are GABAergic, G -A -B -A GABA. What's interesting 00:15:36.019 --> 00:15:40.159 about these P -V -I -Ns is the morphology and 00:15:40.159 --> 00:15:43.340 they're often so called basket or chandelier 00:15:43.340 --> 00:15:47.799 type cells, which means they have extensive axonal 00:15:47.799 --> 00:15:52.820 arborization, which aids in the synapsis. These 00:15:52.820 --> 00:15:56.899 parvalbium cells provide a strong inhibition 00:15:56.889 --> 00:16:00.850 If you think about the level of strength or if 00:16:00.850 --> 00:16:05.009 you want to layer these or rank these with excitation 00:16:05.009 --> 00:16:09.830 cells or GABAergic cells, these parvalbiums are 00:16:09.830 --> 00:16:14.490 strong and they are fast spiking with rapid action 00:16:14.490 --> 00:16:18.370 potential in the gamma oscillation or the gamma 00:16:18.370 --> 00:16:22.509 waves. This is as fast spiking as you can get. 00:16:23.289 --> 00:16:27.360 This is because It provides precise timing and 00:16:27.360 --> 00:16:31.379 neural responses. It synchronizes the excitation 00:16:31.379 --> 00:16:35.259 inhibition. It helps modulate and control behaviors. 00:16:36.039 --> 00:16:38.720 So of course there are some space and time domains 00:16:38.720 --> 00:16:42.980 here because the living organism needs to adapt, 00:16:43.320 --> 00:16:46.580 respond, and move throughout its environment 00:16:46.580 --> 00:16:50.840 with great efficiency for those survival instincts, 00:16:51.460 --> 00:16:55.159 for those goal -directed instincts. And these 00:16:55.159 --> 00:16:59.899 PVINs are really, really, really zooming in and 00:16:59.899 --> 00:17:04.220 showing how this is being conducted in our biology. 00:17:05.160 --> 00:17:08.200 It's very, very fascinating. Okay, let's go into 00:17:08.200 --> 00:17:12.000 that study. So the methodology here is very important 00:17:12.000 --> 00:17:14.000 to look at when you're parsing out scientific 00:17:14.000 --> 00:17:18.779 literature. So the researchers use microendoscopic 00:17:18.779 --> 00:17:22.859 calcium imaging and chemogenetic manipulation 00:17:22.859 --> 00:17:25.940 in mice. Yes, this study is going to be done 00:17:25.940 --> 00:17:30.700 on mice. In neuroscience, there are kind of manipulations 00:17:30.700 --> 00:17:35.240 that a model that people can follow. So their 00:17:35.240 --> 00:17:38.759 animals, their subjects are very similar from 00:17:38.759 --> 00:17:43.220 study to study, supposedly. The calcium imaging 00:17:43.220 --> 00:17:46.900 enabled real -time observations of the neuronal 00:17:46.900 --> 00:17:50.640 activity during social interactions, while the 00:17:50.640 --> 00:17:55.490 chemo genetic tools allowed for selective inhibition 00:17:55.490 --> 00:17:59.730 of the PVINs and that allowed them to assess 00:17:59.730 --> 00:18:05.109 their functional role. Very fascinating. So the 00:18:05.109 --> 00:18:09.029 study found that the PVINs with the social and 00:18:09.029 --> 00:18:13.029 emotional processing are essential for encoding 00:18:13.029 --> 00:18:18.849 social familiarity. So distinguishing family 00:18:18.849 --> 00:18:23.009 versus Novel conspecifics. Remember these are 00:18:23.009 --> 00:18:27.470 mice. I'm reminded of our oxytocin episode with 00:18:27.470 --> 00:18:30.349 the two different types of oxytocin. Magnocellular 00:18:30.349 --> 00:18:32.910 and parbocellular. And how each one of these 00:18:32.910 --> 00:18:37.829 types of oxytocin kind of helps with the parental 00:18:37.829 --> 00:18:41.069 bonding versus the peer -to -peer bonding. This 00:18:41.069 --> 00:18:46.769 is exactly that. The study also shows emotional 00:18:46.769 --> 00:18:51.089 recognition. So, responding to a stressed peer's 00:18:51.089 --> 00:18:54.289 emotional state and a specific subset of these 00:18:54.289 --> 00:18:59.549 PVINs show increased activity during peer interactions. 00:19:00.109 --> 00:19:02.250 And this is highlighting their role in processing 00:19:02.250 --> 00:19:06.029 social and emotional cues. Everything that we 00:19:06.029 --> 00:19:10.089 just kind of outlined before we get into the 00:19:10.089 --> 00:19:13.569 study is kind of showing that with the medial 00:19:13.569 --> 00:19:18.059 prefrontal cortex, the ACC, the insula, and I've 00:19:18.059 --> 00:19:21.900 added in the oxytocin now. Very, very fascinating. 00:19:21.980 --> 00:19:24.880 Very, very much aligned with the autistic phenotype. 00:19:25.859 --> 00:19:29.640 So some of the behavioral effects of these PVIN 00:19:29.640 --> 00:19:35.240 whenever with these inhibition cells. So they 00:19:35.240 --> 00:19:38.579 disrupted the mice's ability to reduce preference 00:19:38.579 --> 00:19:42.960 for familiar peers and increase interactions 00:19:42.960 --> 00:19:47.960 with stressed conspecifics. And this indicates 00:19:47.960 --> 00:19:52.740 that the PVINs regulate context -dependent social 00:19:52.740 --> 00:19:56.839 behaviors. Context -dependent here is so good. 00:19:57.579 --> 00:20:01.579 And this modulates pyramidal neurons. We've discussed 00:20:01.579 --> 00:20:06.680 pyramidal neurons during the spindle neuron episode. 00:20:07.460 --> 00:20:11.859 So this interaction with PVINs in the pyramidal 00:20:11.859 --> 00:20:15.680 neurons is specifically in the anterior insula. 00:20:15.849 --> 00:20:20.630 allows the living organism to maintain a proper 00:20:20.630 --> 00:20:26.589 excitation inhibition balance for adaptive social 00:20:26.589 --> 00:20:30.410 exploration. I love this stuff. Stuff like this 00:20:30.410 --> 00:20:35.490 is why I do the podcast. PVINs also dynamically 00:20:35.490 --> 00:20:39.329 adjust for the pyramidal responses to ensure 00:20:39.329 --> 00:20:43.230 appropriate neural circuit activity. These PVINs 00:20:43.230 --> 00:20:48.049 are in large part disorchestrating. And it's 00:20:48.049 --> 00:20:50.849 allowing the living organism to detect social 00:20:50.849 --> 00:20:54.349 salience, more of that salience, and processing 00:20:54.349 --> 00:20:58.529 emotional states. So good. Dysfunction in this 00:20:58.529 --> 00:21:02.769 balance impairs the ability to prioritize novel 00:21:02.769 --> 00:21:07.750 stimuli or respond to emotional cues that social 00:21:07.750 --> 00:21:11.490 cues, such as the stress in others, and providing 00:21:11.490 --> 00:21:15.309 a cellular mechanism for the social cognition. 00:21:15.609 --> 00:21:21.890 deficits. Okay, the Sang et al article once again. 00:21:22.289 --> 00:21:26.309 Salience Network connectivity is altered in six 00:21:26.309 --> 00:21:30.470 weeks old infants at heightened likelihood for 00:21:30.470 --> 00:21:34.509 developing autism. Now sometimes in autism research 00:21:34.509 --> 00:21:37.750 there are high likelihood groups and atypical 00:21:37.750 --> 00:21:40.470 likelihood groups. That's what this is saying. 00:21:41.150 --> 00:21:44.730 This was released in April 2024. This was done 00:21:44.730 --> 00:21:49.029 on 53 infants, 24 of which are high likelihood 00:21:49.029 --> 00:21:53.130 for autism due to having an older sibling with 00:21:53.130 --> 00:21:58.130 an already autism diagnosis, which is very questionable 00:21:58.130 --> 00:22:05.170 even. It's hard to parse that out. And 29 at 00:22:05.170 --> 00:22:09.009 typical likelihood with no family history. And 00:22:09.009 --> 00:22:12.609 they used resting state functional magnetic resonance 00:22:12.609 --> 00:22:17.829 imaging. RS fMRI at six weeks of age during natural 00:22:17.829 --> 00:22:22.150 sleep. The focus here was on the salience network 00:22:22.150 --> 00:22:26.390 connectivity, particularly the interactions with 00:22:26.390 --> 00:22:29.789 sensorimotor regions. Now the sensorimotor regions 00:22:29.789 --> 00:22:34.109 is at the top middle of your head. So if you 00:22:34.109 --> 00:22:36.990 think about those distal connections sometimes 00:22:36.990 --> 00:22:40.230 even with the midbrain, the mesencephalon or 00:22:40.230 --> 00:22:44.440 these subcortical areas. That's a large distance. 00:22:45.640 --> 00:22:48.480 A large part of the sensory motor region involves 00:22:48.480 --> 00:22:51.759 sensory processing and movement. And then the 00:22:51.759 --> 00:22:54.599 prefrontal regions, which includes the medial 00:22:54.599 --> 00:22:59.420 prefrontal cortex. So the behavioral assessments 00:22:59.420 --> 00:23:02.839 here, because they're just six weeks old at 12 00:23:02.839 --> 00:23:05.980 months, included the autism observation scale 00:23:05.980 --> 00:23:11.180 for infants, AOSI, and the early social communication 00:23:11.180 --> 00:23:16.119 scale. infant toddler sensory profile. This is 00:23:16.119 --> 00:23:20.700 helping evaluate the likelihood of and the connection 00:23:20.700 --> 00:23:25.200 of the autistic phenotype to these subgroups 00:23:25.200 --> 00:23:29.039 the likelihood versus the typical. So just right 00:23:29.039 --> 00:23:31.339 away the key finding here is infants at high 00:23:31.339 --> 00:23:34.880 likelihood for autism show stronger salience 00:23:34.880 --> 00:23:38.079 network connectivity with those sensory motor 00:23:38.079 --> 00:23:42.609 regions compared to the typical developing group 00:23:42.609 --> 00:23:45.990 that showed stronger salience network connectivity 00:23:45.990 --> 00:23:49.630 with the prefrontal regions including, you guessed 00:23:49.630 --> 00:23:54.589 it, the medial prefrontal cortex. So there's 00:23:54.589 --> 00:23:57.190 a trade -off here they're suggesting that there 00:23:57.190 --> 00:23:59.690 was an inverse relationship between the salience 00:23:59.690 --> 00:24:03.509 network connectivity to sensory motor and prefrontal 00:24:03.509 --> 00:24:06.430 regions and the high likelihood influence with 00:24:06.430 --> 00:24:12.319 the stronger sensory motor connection had weaker 00:24:12.319 --> 00:24:15.400 salience network to prefrontal connectivity. 00:24:16.559 --> 00:24:19.400 In addition, they found that the salience network 00:24:19.400 --> 00:24:22.460 connectivity patterns for these at six weeks 00:24:22.460 --> 00:24:26.039 old predicted behavioral outcomes at one year 00:24:26.039 --> 00:24:29.740 old. And the stronger salience network sensory 00:24:29.740 --> 00:24:32.859 motor connectivity is associated with increased 00:24:32.859 --> 00:24:37.500 sensory over responsiveness, which is very common. 00:24:37.680 --> 00:24:40.779 You can see this with the Autistic Phenotype. 00:24:41.059 --> 00:24:44.339 See Autism and Sensory Processing, the two episodes 00:24:44.339 --> 00:24:50.200 on that from Spring of 2025. In contrast, the 00:24:50.200 --> 00:24:54.900 stronger salience network to the prefrontal connectivity 00:24:54.900 --> 00:24:59.539 with specifics to the medial prefrontal cortex 00:24:59.539 --> 00:25:03.079 predicted better social attention skills, such 00:25:03.079 --> 00:25:07.579 as just initiating joint attention. And this 00:25:07.579 --> 00:25:10.660 is all relevant for a future episode where we 00:25:10.660 --> 00:25:13.759 parse out the precuneus and dive a little bit 00:25:13.759 --> 00:25:16.819 deeper into visual thinking and the default mode 00:25:16.819 --> 00:25:20.839 network. This is providing a bit of a foundation. 00:25:22.400 --> 00:25:25.779 So tying in previous research on this salience 00:25:25.779 --> 00:25:29.700 network kind of dysfunction with the autistic 00:25:29.700 --> 00:25:38.099 phenotype. This is consistent and A 2013 study 00:25:38.099 --> 00:25:40.640 reported hyper -connectivity with the salience 00:25:40.640 --> 00:25:44.700 network in children with autism and achieved 00:25:44.700 --> 00:25:49.380 78 % accuracy in classifying autism versus typical 00:25:49.380 --> 00:25:55.180 based off of this salience network pattern. In 00:25:55.180 --> 00:25:59.220 addition, a 2016 study linked increased salience 00:25:59.220 --> 00:26:02.640 network connectivity with the sensory processing 00:26:02.640 --> 00:26:07.769 areas And a different study in 2024 also found 00:26:07.769 --> 00:26:11.329 the reduced salience network connectivity between 00:26:11.329 --> 00:26:16.250 a rostral prefrontal cortex and the left cerebellum 00:26:16.250 --> 00:26:19.990 and autism, alongside increased connectivity 00:26:19.990 --> 00:26:24.009 between the right supramarginal gyrus and the 00:26:24.009 --> 00:26:27.250 temporal regions, which linked these changes 00:26:27.250 --> 00:26:30.490 to deficits in self -awareness and emotional 00:26:30.490 --> 00:26:35.099 processing. Some other worthy mentions here with 00:26:35.099 --> 00:26:38.980 the anterior insula. A 2010 study found that 00:26:38.980 --> 00:26:42.960 reduced anterior insula activation correlates 00:26:42.960 --> 00:26:47.160 with alexithymia. Alexithymia is the inability 00:26:47.160 --> 00:26:52.940 to define, recognize your fillings. And this 00:26:52.940 --> 00:26:56.900 is kind of common with the autistic phenotype. 00:26:58.730 --> 00:27:02.230 Hyper -responsiveness to adverse stimuli was 00:27:02.230 --> 00:27:07.230 also found in the insula cortex, suggesting altered 00:27:07.230 --> 00:27:11.289 sensory -emotional integration, which is potentially 00:27:11.289 --> 00:27:14.970 driven by these PVIN cells that we've discussed 00:27:14.970 --> 00:27:20.549 today. The PVINs in the insula cortex, so reduced 00:27:20.549 --> 00:27:25.690 PVINs in the insula cortex is observed in autism 00:27:25.690 --> 00:27:31.539 mouse models. for instance with the CNT -NAP2 00:27:31.539 --> 00:27:35.140 knockout studies. And this leads to impaired 00:27:35.140 --> 00:27:39.619 inhibition control, which disrupts social processing, 00:27:40.259 --> 00:27:43.359 which is very much in line with the Fujima study. 00:27:44.240 --> 00:27:49.259 So since we mentioned it, this CNT -NAP2 is very 00:27:49.259 --> 00:27:52.539 worthy of mentioning here. This organizes neural 00:27:52.539 --> 00:27:56.019 circuits, most specifically at the synaptic level. 00:27:56.400 --> 00:27:59.579 And also remember in previous episodes, episode 00:27:59.579 --> 00:28:03.779 four or five, Neurorexin and Neuroligin, those 00:28:03.779 --> 00:28:09.839 pre and post synaptic proteins and genes. CNT 00:28:09.839 --> 00:28:14.220 -NAP also is involved with cell adhesion with 00:28:14.220 --> 00:28:19.400 neurons and glia. And it regulates migration, 00:28:19.960 --> 00:28:24.240 dendritic arborization. Remember some density 00:28:24.240 --> 00:28:27.609 issues for the autistic phenotype. Specifically, 00:28:27.690 --> 00:28:32.230 two areas of the dorsal striatum. The input area 00:28:32.230 --> 00:28:37.309 of the basal ganglia, our no -go area. In autism, 00:28:37.670 --> 00:28:43.049 the dorsal striatum has a lot of dendrites. More 00:28:43.049 --> 00:28:48.690 ability to activate and be overwhelmed. Dr. Hannah 00:28:48.690 --> 00:28:54.529 Stevens studies this. And also, the dendritic 00:28:54.529 --> 00:28:58.970 issues with the thalamus. Remember autism, sensory 00:28:58.970 --> 00:29:04.289 map, and serotonin. The thalamus in the autistic 00:29:04.289 --> 00:29:10.609 phenotype typically isn't pruned correctly. CNT 00:29:10.609 --> 00:29:16.869 -NAP2 also, and this is huge, balances excitation 00:29:16.869 --> 00:29:22.650 and inhibition. This is huge in autism. Remember 00:29:22.650 --> 00:29:29.940 the Rubenstein and Merzenich. paper in 2003 this 00:29:29.940 --> 00:29:33.680 paper was released it's it's highly cited like 00:29:33.680 --> 00:29:38.279 3200 citations and mike merzenek is a it's kind 00:29:38.279 --> 00:29:42.700 of a leader for neuroplasticity how living organisms 00:29:42.700 --> 00:29:47.960 are constructed what makes us who we are now 00:29:47.960 --> 00:29:49.720 something relevant here because we mentioned 00:29:49.720 --> 00:29:52.640 the oxytocin connection or the similarity let's 00:29:52.640 --> 00:29:56.480 just say i don't know if it's related and this 00:29:56.480 --> 00:30:01.079 ability to understand social cues and have social 00:30:01.079 --> 00:30:06.599 familiarity with family versus peers. The medial 00:30:06.599 --> 00:30:10.660 prefrontal cortex roll with social cognition. 00:30:11.200 --> 00:30:13.900 Remember I mentioned this. There are consistent 00:30:13.900 --> 00:30:19.299 findings with a reduction of PVINs in a hypofunction. 00:30:19.920 --> 00:30:23.500 PVINs in the medial prefrontal cortex with autism. 00:30:24.589 --> 00:30:28.170 A 2017 post -mortem study, these are excellent 00:30:28.170 --> 00:30:33.549 types of studies, report 38 to 70 percent reduction 00:30:33.549 --> 00:30:38.009 of PVINs in the prefrontal regions in autism, 00:30:38.490 --> 00:30:43.450 which correlate with the social deficits. Now, 00:30:43.470 --> 00:30:47.529 38 to 70 percent reduction is a wide range, but 00:30:47.529 --> 00:30:51.750 significant in these mouse models. Remember, 00:30:51.750 --> 00:30:55.170 we can standardize kind of these behavior models. 00:30:55.450 --> 00:31:00.970 We can manipulate animals to have similar deficits, 00:31:01.750 --> 00:31:09.210 be it autism or mania, depression, etc. In autism 00:31:09.210 --> 00:31:14.930 mouse models, there's a PVIN hypofunction in 00:31:14.930 --> 00:31:18.009 the medial prefrontal cortex that contributes 00:31:18.009 --> 00:31:21.789 to rigid thinking. Okay, that's huge in autism 00:31:21.789 --> 00:31:25.359 and often kind of hard to observe from the outside. 00:31:25.960 --> 00:31:29.160 These autism diagnosis, these assessments, have 00:31:29.160 --> 00:31:33.079 a hard time picking that up. And also impaired 00:31:33.079 --> 00:31:37.559 social behavior. However, optogenetic, remember 00:31:37.559 --> 00:31:42.460 Carl Dysaroff, optogenetic stimulation of these 00:31:42.460 --> 00:31:48.079 medial prefrontal cortex, these PVIN cells, enhances 00:31:48.079 --> 00:31:52.660 sociability. In other words, they can kind of 00:31:52.660 --> 00:31:57.240 rescue these social deficits. And lastly on the 00:31:57.240 --> 00:32:00.200 theory of mind think. Remember Sir Simon Barron 00:32:00.200 --> 00:32:03.700 Cohen released this in 1985 and it kind of provided 00:32:03.700 --> 00:32:07.599 a foundation, a direction forward about how we 00:32:07.599 --> 00:32:10.559 should perceive the autistic phenotype. However, 00:32:11.440 --> 00:32:13.519 there's a lot of errors with that. There are 00:32:13.519 --> 00:32:16.859 a lot of errors. If you read the Canter paper, 00:32:17.299 --> 00:32:20.250 those case studies They knew exactly what was 00:32:20.250 --> 00:32:23.509 happening in the environment. And they were mostly 00:32:23.509 --> 00:32:26.990 young. Boys. 3, 4, 5 years old. Remember the 00:32:26.990 --> 00:32:30.250 girls were a little bit older. 7, 8, 9 or so 00:32:30.250 --> 00:32:32.450 forth. But they knew exactly what was happening. 00:32:33.829 --> 00:32:38.269 I don't want us to underestimate, overlook, the 00:32:38.269 --> 00:32:41.029 interoception here of the autistic phenotype. 00:32:41.430 --> 00:32:46.210 And this intuition. This ability to process sensory. 00:32:46.640 --> 00:32:51.259 including within the self, including being able 00:32:51.259 --> 00:32:54.960 to recognize what is happening. This is a trade 00:32:54.960 --> 00:32:58.220 -off here. The sensory trade -off versus the 00:32:58.220 --> 00:33:02.539 social trade -off. The autistic phenotype is 00:33:02.539 --> 00:33:05.799 very comfortable within themselves. This is a 00:33:05.799 --> 00:33:09.779 large part what is happening. The biology that 00:33:09.779 --> 00:33:13.500 gives us autism allows us to be comfortable within 00:33:13.500 --> 00:33:17.910 ourselves. This has massive benefits for learning 00:33:17.910 --> 00:33:22.789 and understanding Do people understand that? 00:33:23.849 --> 00:33:26.730 We are going to dive into this in great detail 00:33:26.730 --> 00:33:29.470 in a future episode with the visual thinking 00:33:29.470 --> 00:33:33.069 Because these regions are involved and how autistic 00:33:33.069 --> 00:33:36.789 brain is similar to AI how there's massive amounts 00:33:36.789 --> 00:33:43.650 of catalogs for different categories Massive 00:33:43.650 --> 00:33:49.210 amounts of information being absorbed. This is 00:33:49.210 --> 00:33:53.009 the autistic phenotype. This is what autism is. 00:33:55.029 --> 00:33:57.150 If you're listening to the podcast, listening 00:33:57.150 --> 00:34:00.069 to the episode, please feel free to leave a review 00:34:00.069 --> 00:34:03.930 or rating. In podcasting, reviews, ratings, and 00:34:03.930 --> 00:34:06.569 downloads are huge, and I very much appreciate 00:34:06.569 --> 00:34:11.630 your feedback. You can contact me on X at RPS. 00:34:12.939 --> 00:34:16.800 47586 you can identify it as from the spectrum 00:34:16.800 --> 00:34:21.980 finding superpowers with autism name we can have 00:34:21.980 --> 00:34:25.039 any discussion about autism that you wish i very 00:34:25.039 --> 00:34:28.199 much appreciate your conversation you can contact 00:34:28.199 --> 00:34:33.940 me by email info dot from the spectrum at gmail 00:34:33.940 --> 00:34:38.480 .com you can check out the youtube page for all 00:34:38.480 --> 00:34:43.889 the videos Shorts and clips as well. Don't forget 00:34:43.889 --> 00:34:46.210 to check out Daylight Computer Company and Chroma 00:34:46.210 --> 00:34:49.210 Light Devices. These are products made for humans. 00:34:49.510 --> 00:34:53.929 They put humans over anything. And I very much 00:34:53.929 --> 00:34:58.429 appreciate that mission. Thank you for listening 00:34:58.429 --> 00:35:01.849 to From the Spectrum Podcast.