WEBVTT 00:00:01.710 --> 00:00:06.230 Today's episode is all about the thalamic reticular 00:00:06.230 --> 00:00:12.650 nucleus or TRN. In the previous episode about 00:00:12.650 --> 00:00:17.690 sonic hedgehog and inhibitory neurons, we mentioned 00:00:17.690 --> 00:00:22.589 this nuclei that surrounds the thalamus for inhibiting 00:00:22.589 --> 00:00:28.989 signals or noise. The TRN is a shell designed 00:00:28.989 --> 00:00:34.210 to quiet unnecessary noise coming in to the thalamus. 00:00:34.549 --> 00:00:39.009 Remember the thalamus receives all sensory inputs 00:00:39.009 --> 00:00:42.270 and it's on a constant feed -forward feedback 00:00:42.270 --> 00:00:48.030 loop with other areas of the brain. We'll review 00:00:48.030 --> 00:00:51.990 this nuclei in good detail and use a security 00:00:51.990 --> 00:00:56.090 guard analogy for each type of sensory processing 00:00:56.090 --> 00:01:00.719 and nuclei. that makes up this shell known as 00:01:00.719 --> 00:01:06.799 the thalamic reticular nucleus. This is all GABAERGIC 00:01:06.799 --> 00:01:10.900 or inhibition. The more I think about it, the 00:01:10.900 --> 00:01:17.579 more the TRN is like a shield or armor. The TRN 00:01:17.579 --> 00:01:21.439 is a critical brain structure composed of GABAERGIC 00:01:21.439 --> 00:01:25.519 neurons that envelopes the thalamus, acting as 00:01:25.519 --> 00:01:29.450 a gatekeeper. I know, another analogy here, but 00:01:29.450 --> 00:01:34.150 it all fits, they all make sense. For this thalamocortical 00:01:34.150 --> 00:01:38.609 communication, the TRN modulates sensory processing, 00:01:39.549 --> 00:01:44.230 attention, memory consolidation, sleep -wake 00:01:44.230 --> 00:01:47.989 transitions even, and brain wave generation, 00:01:48.890 --> 00:01:52.230 with a significant implication to the autistic 00:01:52.230 --> 00:01:56.150 phenotype, where its altered function contributes 00:01:56.150 --> 00:01:59.579 to cognitive strengths such as strong learning 00:01:59.579 --> 00:02:03.219 ability. Remember the biology that gives us autism 00:02:03.219 --> 00:02:07.200 allows us to be comfortable inside of ourself. 00:02:08.500 --> 00:02:12.639 This shell, this t -r -n with the autistic phenotype 00:02:12.639 --> 00:02:16.080 prevents all of that outside noise, all of that 00:02:16.080 --> 00:02:20.819 outside external insults and care. It's also 00:02:20.819 --> 00:02:23.560 responsible for some of the visual thinking. 00:02:24.659 --> 00:02:28.340 However, It also implicates some challenges such 00:02:28.340 --> 00:02:31.960 as sensory hypersensitivity as discussed in the 00:02:31.960 --> 00:02:36.900 previous episode and impaired integration. The 00:02:36.900 --> 00:02:41.419 TRN is a very thin sheet -like layer of GABAergic 00:02:41.419 --> 00:02:45.240 neurons that surrounds the lateral and anterior 00:02:45.240 --> 00:02:49.560 thalamus and it forms a reticular shell between 00:02:49.560 --> 00:02:53.300 the thalamus and the cortex. Remember from last 00:02:53.300 --> 00:02:56.349 week's episode in a previous episode all about 00:02:56.349 --> 00:03:00.789 the parv albium interneuron. This is the major 00:03:00.789 --> 00:03:05.530 neuron here within this TRN shell. Remember the 00:03:05.530 --> 00:03:09.030 parv albium interneuron is very fast acting, 00:03:09.729 --> 00:03:13.370 fast spikes for precise inhibition. Remember 00:03:13.370 --> 00:03:18.270 the GABA -A receptor in comparison to GABA -B. 00:03:19.530 --> 00:03:23.949 And a small subset of the somatostatin, SOM, 00:03:24.169 --> 00:03:30.169 neurons for a more broad modulation. The receptors 00:03:30.169 --> 00:03:33.349 here are the GABA -A for the fast inhibition 00:03:33.349 --> 00:03:38.590 and GABA -B more with the somatostatin for the 00:03:38.590 --> 00:03:42.569 slower inhibition. Let's review some functional 00:03:42.569 --> 00:03:47.990 goals of the TRN. One of course is sensor gating. 00:03:48.530 --> 00:03:51.949 This is the major one. So enhancing signal to 00:03:51.949 --> 00:03:56.800 noise ratios. inhibiting irrelevant activity, 00:03:57.639 --> 00:04:01.500 and even prioritizing salient stimuli. For example, 00:04:02.080 --> 00:04:04.900 visual patterns over the background noise. So 00:04:04.900 --> 00:04:08.780 different sensory organs there. Attentional modulation, 00:04:10.860 --> 00:04:15.939 brainwave generation, sleep -wake regulation, 00:04:17.850 --> 00:04:22.149 Cross Modal Integration. So coordinating activity 00:04:22.149 --> 00:04:26.449 across sensory and limbic circuits for integration 00:04:26.449 --> 00:04:31.050 of perception and behavior. It's kind of helping 00:04:31.050 --> 00:04:34.329 coordinate or bridge the limbic areas in the 00:04:34.329 --> 00:04:38.350 cortex. We'll talk more about that later. Neuro 00:04:38.350 --> 00:04:42.610 overload prevention. This is huge. We'll use 00:04:42.610 --> 00:04:45.670 a little security guard example at the end of 00:04:45.670 --> 00:04:49.430 the show. And it's also a support for the thalamus. 00:04:49.589 --> 00:04:52.910 The TRN helps the thalamus by sharpening signals, 00:04:53.430 --> 00:04:56.670 coordinating timing, preventing overexcitation. 00:04:57.029 --> 00:05:00.910 And this is enabling flexible processing. So 00:05:00.910 --> 00:05:04.589 it enhances the thalamic efficiency. And that's 00:05:04.589 --> 00:05:10.189 a big part. So what signals come in to the TRN? 00:05:10.509 --> 00:05:14.850 The afferents, or inputs. Well, it receives inputs 00:05:14.850 --> 00:05:19.680 from the thalamus itself. excitatory glutamatergic 00:05:19.680 --> 00:05:23.600 inputs from relay nuclei such as the lateral 00:05:23.600 --> 00:05:28.000 geniculate nuclei remember for vision and the 00:05:28.000 --> 00:05:34.100 medial geniculate nuclei which is for auditory 00:05:34.100 --> 00:05:38.959 and the ventral basal and the medial dorsal via 00:05:38.959 --> 00:05:45.300 AMPA and NMDA receptors. which is organizing 00:05:45.300 --> 00:05:48.720 for modality -specific processing. We'll have 00:05:48.720 --> 00:05:52.500 a whole episode on those excitation neurons, 00:05:52.720 --> 00:05:55.660 just like we're doing for the inhibitory neurons. 00:05:56.879 --> 00:06:00.899 It receives cortical inputs, again more excitatory 00:06:00.899 --> 00:06:06.079 inputs from cortical layers, especially six for 00:06:06.079 --> 00:06:10.300 the sensory and prefrontal cortex, enabling top 00:06:10.300 --> 00:06:13.300 -down control of attention and sensory gating. 00:06:13.769 --> 00:06:16.829 We'll talk a lot about the sensory gating. It's 00:06:16.829 --> 00:06:20.370 a good overarching theme and description of this 00:06:20.370 --> 00:06:25.750 shell. And also, a favorite of mine, the basal 00:06:25.750 --> 00:06:31.110 ganglia inputs. Inhibitory GABAergic inputs from 00:06:31.110 --> 00:06:37.009 the Globus pallidus external GPE and the substantia 00:06:37.009 --> 00:06:40.230 nigra pars reticulata. Remember in the basal 00:06:40.230 --> 00:06:43.670 ganglia episodes, these two little nuclei the 00:06:43.670 --> 00:06:49.389 GPE and the SNR are pretty similar in function. 00:06:50.410 --> 00:06:53.430 And this modulates motor and cognitive processing. 00:06:55.089 --> 00:06:58.009 Now the basal ganglia is a major region of interest 00:06:58.009 --> 00:07:01.449 for us here. Remember when we discussed the basal 00:07:01.449 --> 00:07:04.509 ganglia nuclei? There's five different nuclei 00:07:04.509 --> 00:07:09.069 there. And there's an additional assistant for 00:07:09.069 --> 00:07:11.870 the thalamus, which is sort of like the TRN. 00:07:12.009 --> 00:07:16.370 the subthalamic nucleus. This is another assistant 00:07:16.370 --> 00:07:20.769 to this thalamus. The basal ganglia role here 00:07:20.769 --> 00:07:25.009 with the TRN is some of the functions or action 00:07:25.009 --> 00:07:29.129 selection and suppression. So a normal role, 00:07:29.370 --> 00:07:33.930 a normal brain, let's say the basal ganglia disinhibits 00:07:33.930 --> 00:07:38.970 the thalamus and the TRN will send tonic releases 00:07:38.970 --> 00:07:43.240 of the neurons for sustaining adaptive behavior. 00:07:44.220 --> 00:07:46.839 However, in the autistic phenotype, there's an 00:07:46.839 --> 00:07:50.819 excessive TRN burst. So a difference between 00:07:50.819 --> 00:07:55.839 tonic firing and burst firing. And this oversuppression 00:07:55.839 --> 00:08:00.079 will lead to repetitive stereotypies. You know 00:08:00.079 --> 00:08:04.379 that with the autistic phenotype. Sensory motor 00:08:04.379 --> 00:08:08.639 gating. The TRN here in a normal brain filters 00:08:08.639 --> 00:08:12.660 the limbic input. Let's say from the ventral 00:08:12.660 --> 00:08:17.480 anterior or the ventral lateral. But for the 00:08:17.480 --> 00:08:21.279 autistic phenotype, the TRN is hyper excitability 00:08:21.279 --> 00:08:26.160 and sensory overload. And under filtering causes 00:08:26.160 --> 00:08:31.560 this so -called hyper and hypo sensitivity, well 00:08:31.560 --> 00:08:34.539 known and understood in the autistic phenotype. 00:08:36.019 --> 00:08:39.620 The basal ganglia to the thalamic reticular nucleus. 00:08:40.080 --> 00:08:43.639 is also involved with cognitive flexibility. 00:08:44.600 --> 00:08:47.019 You know about this with the adaptive responses. 00:08:47.139 --> 00:08:51.379 We talked a lot good detail about this. Major 00:08:51.379 --> 00:08:53.860 regions of interest here are the medial prefrontal 00:08:53.860 --> 00:08:58.139 cortex sending signals to the input areas of 00:08:58.139 --> 00:09:01.919 the basal ganglia called the dorsal striatum 00:09:01.919 --> 00:09:06.059 and this will orchestrate the basal ganglia for 00:09:06.059 --> 00:09:10.960 the no no -go areas and it's kind of conducting 00:09:10.960 --> 00:09:14.840 what we do next. This is huge in the autistic 00:09:14.840 --> 00:09:19.299 phenotype, a so -called lack of adaptive responses. 00:09:19.860 --> 00:09:23.500 Remember the medial prefrontal cortex is essentially 00:09:23.500 --> 00:09:28.539 conducting these movements and our healthy responses 00:09:28.539 --> 00:09:32.519 to this very unpredictable and chaotic social 00:09:32.519 --> 00:09:35.960 world. So depending on the projections coming 00:09:35.960 --> 00:09:39.860 in, from the prefrontal cortex especially the 00:09:39.860 --> 00:09:43.799 medial part and even the dorsal lateral part. 00:09:43.879 --> 00:09:46.759 We talked about these two regions in great detail 00:09:46.759 --> 00:09:52.740 last episode. These connections here will determine 00:09:52.740 --> 00:09:57.500 where the cells and signals will connect to the 00:09:57.500 --> 00:10:00.899 dorsal striata and this provides meaning. Okay 00:10:00.899 --> 00:10:04.480 this is happening because these cells are active 00:10:04.639 --> 00:10:09.519 So this is what I do in response to that. These 00:10:09.519 --> 00:10:12.299 specific signals and connections from the prefrontal 00:10:12.299 --> 00:10:17.460 cortex to the dorsal striatum will house our 00:10:17.460 --> 00:10:21.759 movements. What we do, remember the prefrontal 00:10:21.759 --> 00:10:26.740 cortex is a rule setting machine. And we want, 00:10:27.100 --> 00:10:30.960 we need a flexible rule setting type of machine. 00:10:31.179 --> 00:10:35.500 having different skills available to us for different 00:10:35.500 --> 00:10:38.899 situations. Now you know about this with the 00:10:38.899 --> 00:10:43.080 autistic phenotype, very rigid. So these signals 00:10:43.080 --> 00:10:46.340 coming into the dorsal striatum is also very 00:10:46.340 --> 00:10:50.919 rigid. We only have these limited amounts of 00:10:50.919 --> 00:10:54.919 kind of response types. And this is very big 00:10:54.919 --> 00:10:58.440 here. These are the neural correlates and the 00:10:58.440 --> 00:11:02.549 cellular functions of the lack of adaptive responses, 00:11:03.190 --> 00:11:05.730 the rigidness, the black and white thinking, 00:11:06.570 --> 00:11:11.549 and so forth. This is all happening here. So 00:11:11.549 --> 00:11:15.210 with this cognitive flexibility, for the normal 00:11:15.210 --> 00:11:19.129 brain, let's say, the TRN switches thalamic output 00:11:19.129 --> 00:11:23.009 so it can just... Remember, we talked about action 00:11:23.009 --> 00:11:26.629 selection. This is all coming together here. 00:11:26.889 --> 00:11:29.940 For the autistic phenotype, we have those rigid 00:11:29.940 --> 00:11:34.899 routines and the poor task switching. This is 00:11:34.899 --> 00:11:38.360 why this basal ganglia to dilemmic reticular 00:11:38.360 --> 00:11:42.720 nucleus connection is just downstream from those 00:11:42.720 --> 00:11:45.779 prefrontal cortex to the basal ganglia inputs. 00:11:47.840 --> 00:11:50.279 So salience, remember we've discussed the salience 00:11:50.279 --> 00:11:53.179 network as well. I know a lot of different kind 00:11:53.179 --> 00:11:57.210 of nomenclature and terminology here but... It's 00:11:57.210 --> 00:12:00.649 really not that difficult. So what is salient 00:12:00.649 --> 00:12:05.230 to us? Where do we want to spend and send our 00:12:05.230 --> 00:12:09.629 attention for the so -called normal brain? The 00:12:09.629 --> 00:12:15.289 TRN is helping mark social and reward cues. This 00:12:15.289 --> 00:12:20.090 is very big in how mammals, complex living organisms 00:12:20.090 --> 00:12:24.870 kind of navigate the society based off of cues. 00:12:26.570 --> 00:12:30.350 In the autistic phenotype, there's this so -called 00:12:30.350 --> 00:12:35.730 blunted social motivation here and very abnormal 00:12:35.730 --> 00:12:39.789 kind of reward processing for the outside world. 00:12:41.129 --> 00:12:45.889 In addition, this TRN here, as we just described 00:12:45.889 --> 00:12:48.929 it over the last couple of minutes, it can cause 00:12:48.929 --> 00:12:53.190 us that so -called stuck feeling or repetitive 00:12:53.190 --> 00:12:57.509 actions. So maybe a lot there about the basal 00:12:57.509 --> 00:13:01.809 ganglia and the thalamic reticular nucleus connection 00:13:01.809 --> 00:13:06.669 and interaction. So let's get back to the afferents. 00:13:07.990 --> 00:13:13.169 There's interactions with the major neuromodulation 00:13:13.169 --> 00:13:16.549 inputs, the neuromodulators that we talk about 00:13:16.549 --> 00:13:20.830 and you probably know about, such as cholinergic 00:13:20.830 --> 00:13:24.789 acetylcholine from the basal forebrain. Remember 00:13:24.789 --> 00:13:29.200 the Nucleus basalis of Minert is a hotspot for 00:13:29.200 --> 00:13:34.840 acetylcholine. And serotonin from the raphe nuclei. 00:13:35.899 --> 00:13:38.960 And norepinephrine from the locus coeruleus. 00:13:39.639 --> 00:13:42.299 And dopamine from the ventral tegmental area, 00:13:42.480 --> 00:13:46.919 VTA. And the substantia nigra pars compacta. 00:13:47.200 --> 00:13:49.860 Remember, this is different than pars reticulata. 00:13:50.559 --> 00:13:54.850 Reticulata is all GABAergic. that's helped modulating 00:13:54.850 --> 00:13:58.789 the basal ganglia no -go area. The substantia 00:13:58.789 --> 00:14:04.070 nigra pars compacta is a seat of dopamine. Remember, 00:14:04.309 --> 00:14:08.210 it's in the midbrain, the mesencephalon. This 00:14:08.210 --> 00:14:14.169 house releases excitatory and inhibitory dopamine. 00:14:16.250 --> 00:14:20.250 And these inputs from these neuromodulators regulate 00:14:20.250 --> 00:14:24.879 firing modes, such as tonic, or burst firing. 00:14:25.259 --> 00:14:29.100 This is very huge. This is at the at the heart 00:14:29.100 --> 00:14:34.059 of how we operate or these firing modes and brain 00:14:34.059 --> 00:14:37.419 waves. It's really underrated here in my opinion. 00:14:38.720 --> 00:14:42.159 So some of the efferents, the outputs, what does 00:14:42.159 --> 00:14:47.460 the TRN do? Where does it send information to? 00:14:48.600 --> 00:14:51.600 One, there's a feedback inhibition. This is a 00:14:51.600 --> 00:14:56.039 so -called closed loop control of the cortico 00:14:56.039 --> 00:15:01.120 -thalamic axons. Excitatory neurons, pyramidal 00:15:01.120 --> 00:15:04.480 neurons to be exact, project to both the relay 00:15:04.480 --> 00:15:08.639 nuclei of the thalamus such as the lateral geniculate 00:15:08.639 --> 00:15:13.480 and the TRN. So the excitatory neurons coming 00:15:13.480 --> 00:15:18.340 in from the cortex is received by various areas, 00:15:18.700 --> 00:15:21.940 various nuclei within the thalamus. such as the 00:15:21.940 --> 00:15:25.220 lateral geniculate and other subdivisions here, 00:15:25.259 --> 00:15:30.519 and the TRN. And these nuclei within the thalamus 00:15:30.519 --> 00:15:33.559 itself are interacting. They're sending information 00:15:33.559 --> 00:15:36.919 back and forth to each other. And the TRN will 00:15:36.919 --> 00:15:40.440 receive that information and then decide to shut 00:15:40.440 --> 00:15:44.559 it off. It just turns it off. It's disinhibiting. 00:15:46.320 --> 00:15:49.799 And this is purposeful for sharpening sensory 00:15:49.799 --> 00:15:54.690 tuning. regulating attention, suppressing noise, 00:15:55.409 --> 00:15:59.549 and promotes oscillatory rhythms. This is huge 00:15:59.549 --> 00:16:04.590 for sleep spindles and gamma waves. In addition, 00:16:04.889 --> 00:16:09.330 another efferent interaction here is a phi -forward 00:16:09.330 --> 00:16:13.669 inhibition or a so -called open -loop modulation. 00:16:14.330 --> 00:16:17.309 There are some ascending sensory pathways here 00:16:17.309 --> 00:16:20.480 from the brain stem or the retina. that sends 00:16:20.480 --> 00:16:23.960 collaterals to the TRN before reaching relayed 00:16:23.960 --> 00:16:27.340 nuclei. So it's kind of privileged here. The 00:16:27.340 --> 00:16:30.940 retina, of course, massive amounts of visual 00:16:30.940 --> 00:16:34.120 input and sensory coming in from the retina. 00:16:34.399 --> 00:16:38.659 And also the brainstem, the so -called major 00:16:38.659 --> 00:16:41.460 highway. The brainstem is very underrated as 00:16:41.460 --> 00:16:44.259 well. It's major highway here of information 00:16:44.259 --> 00:16:49.179 from the brain, from the body, and just interacting 00:16:49.179 --> 00:16:53.700 here. It's just making sense of so much. We'll 00:16:53.700 --> 00:16:57.399 talk more eventually about the reticular formation. 00:16:57.720 --> 00:16:59.620 Remember, this is different than the thalamic 00:16:59.620 --> 00:17:02.940 reticular nuclei, but the reticular formation 00:17:02.940 --> 00:17:06.799 within the brainstem has two major pathways, 00:17:07.799 --> 00:17:11.980 ascending sensory pathway and descending sensory 00:17:11.980 --> 00:17:17.440 pathway. But for this example, The region of 00:17:17.440 --> 00:17:20.500 interest for us is the ascending sensory pathway 00:17:20.500 --> 00:17:24.940 and the trn will then inhibit relay neurons and 00:17:24.940 --> 00:17:28.640 it delays or sculpts the sensory interaction. 00:17:30.500 --> 00:17:35.119 The function here is controls gain timing and 00:17:35.119 --> 00:17:40.420 salience of the incoming sensory input. It's 00:17:40.420 --> 00:17:43.420 kind of like it's privileged here it's getting 00:17:43.420 --> 00:17:48.410 first privilege information of what is happening 00:17:48.410 --> 00:17:54.690 so we can stay ahead of any unwanted stimuli, 00:17:55.630 --> 00:17:58.509 unwanted things from the environment or signals 00:17:58.509 --> 00:18:02.769 from within ourself even. Another major efferent 00:18:02.769 --> 00:18:07.789 and role of the TRN for the outputs is regulating 00:18:07.789 --> 00:18:11.609 burst versus tonic firing. And this is huge as 00:18:11.609 --> 00:18:15.109 we just discussed earlier. The TRN neurons switch 00:18:15.109 --> 00:18:19.849 between burst mode which is for strong inhibition 00:18:19.849 --> 00:18:23.849 promoting sleep seizures or sensory suppression 00:18:23.849 --> 00:18:29.769 or tonic mode sustained inhibition which helps 00:18:29.769 --> 00:18:34.130 fine -tune attention and sensory discrimination. 00:18:35.009 --> 00:18:37.230 What do you want to pay attention to? Remember 00:18:37.230 --> 00:18:42.049 just imagine if the thalamus had to discriminate 00:18:42.049 --> 00:18:45.049 all of the sensory inputs coming in from the 00:18:45.049 --> 00:18:50.210 environment, vision, hearing, taste, touch, etc. 00:18:50.869 --> 00:18:54.910 There is no way that you'd want that. In short, 00:18:55.230 --> 00:18:59.690 and in summary, the TRN is a major dynamic gate 00:18:59.690 --> 00:19:03.150 that is central to state -dependent processing, 00:19:04.190 --> 00:19:08.089 meaning between sleep and wake, or something 00:19:08.089 --> 00:19:13.000 like attention. versus distraction. Signal to 00:19:13.000 --> 00:19:18.339 noise. So you might ask, and you ought to ask 00:19:18.339 --> 00:19:22.539 maybe, what is the thalamic reticular nucleus 00:19:22.539 --> 00:19:26.940 made of? I know I'm not saying GABA -ergic, but 00:19:26.940 --> 00:19:30.640 let's zoom in to the thalamic reticular nucleus. 00:19:31.019 --> 00:19:34.960 What is it made out of? What is each area trying 00:19:34.960 --> 00:19:39.099 to accomplish? That's a good way of asking yourself 00:19:39.400 --> 00:19:43.160 a question about our biology. Why is it there 00:19:43.160 --> 00:19:46.720 and what is it trying to accomplish? Well, the 00:19:46.720 --> 00:19:50.680 TRN has different sectors. We are going to say 00:19:50.680 --> 00:19:55.000 it has four major sectors here, four major kind 00:19:55.000 --> 00:19:59.400 of hubs or responsibilities. One is the visual 00:19:59.400 --> 00:20:04.140 sector. The second is the somatosensory sector. 00:20:05.720 --> 00:20:09.880 The third is the auditory sector. Remember last 00:20:09.880 --> 00:20:14.799 week we talked about V1, S1, and A1. This is 00:20:14.799 --> 00:20:17.019 what's happening here. This is where we're going 00:20:17.019 --> 00:20:21.420 into. And the last and the fourth sector is the 00:20:21.420 --> 00:20:28.480 limbic sector. So the visual sector is located 00:20:28.480 --> 00:20:31.920 in the rostral, the limbic reticular nucleus, 00:20:32.359 --> 00:20:35.460 and it's adjacent to the lateral geniculate nucleus. 00:20:36.269 --> 00:20:39.930 which is the major relay station here, one of 00:20:39.930 --> 00:20:43.549 the first stops for vision. And this is using, 00:20:43.730 --> 00:20:47.910 no surprise, the parvalbium interneurons, and 00:20:47.910 --> 00:20:52.390 it's also using the VIP interneurons. Remember 00:20:52.390 --> 00:20:57.529 the vasoactive intestinal peptide. And it's using 00:20:57.529 --> 00:21:00.990 all three of the GABA receptors, A, B, and C. 00:21:01.289 --> 00:21:04.930 A for the fast inhibition of the lateral geniculate 00:21:04.930 --> 00:21:09.539 nucleus. So it's just kind of quieting visual 00:21:09.539 --> 00:21:13.480 distractions. Gaba B for the slow inhibition, 00:21:13.700 --> 00:21:16.859 for the sustained modulation, trying to help 00:21:16.859 --> 00:21:21.859 you maintain attention. And Gaba C for sustained 00:21:21.859 --> 00:21:26.420 tonic, like inhibition, for fine tuning that 00:21:26.420 --> 00:21:30.140 visual gating. How long can you sustain your 00:21:30.140 --> 00:21:36.819 attention on a visual input? Think about children 00:21:36.819 --> 00:21:41.180 doing the staring contest. This is a good example 00:21:41.180 --> 00:21:44.880 here. Children doing the staring contest will 00:21:44.880 --> 00:21:49.640 utilize probably gaba B and definitely gaba C 00:21:49.640 --> 00:21:53.339 in order to just quiet themselves while they're 00:21:53.339 --> 00:21:56.160 staring at you. How long can you sustain that 00:21:56.160 --> 00:22:00.759 without being uncomfortable? Functions of the 00:22:00.759 --> 00:22:04.890 typical brain is the sensory gating. No surprise, 00:22:04.890 --> 00:22:08.650 we just talked about the staring contest. The 00:22:08.650 --> 00:22:12.369 gamma oscillations. This visual sector helps 00:22:12.369 --> 00:22:16.710 drive gamma power in the lateral geniculate loop. 00:22:17.490 --> 00:22:20.230 Lateral geniculate to visual cortex one loop. 00:22:20.970 --> 00:22:24.109 And this supports visual feature integration. 00:22:25.650 --> 00:22:28.829 And synchrony. Facilitates gamma synchrony between 00:22:28.829 --> 00:22:33.349 V1 and downstream dorsal lateral prefrontal cortex. 00:22:33.579 --> 00:22:39.460 for visual cognitive integration. What's happening 00:22:39.460 --> 00:22:42.900 in the autistic phenotype is a reduced inhibition 00:22:42.900 --> 00:22:47.039 here. So the decreased parvalbium interneuron 00:22:47.039 --> 00:22:51.819 with especially GABA A and GABA C receptors impairs 00:22:51.819 --> 00:22:55.900 lateral geniculate gating. And this increases 00:22:55.900 --> 00:23:00.359 excitatory input to visual cortex one and elevates 00:23:00.359 --> 00:23:04.420 gamma power. We talked about this a lot and I 00:23:04.420 --> 00:23:08.279 hope people have a good takeaway here. The sensory 00:23:08.279 --> 00:23:12.599 processing is mostly gamma, even higher gamma, 00:23:12.900 --> 00:23:15.440 and this is one of the mechanisms by which that 00:23:15.440 --> 00:23:19.559 happens. Remember visual thinking and attention 00:23:19.559 --> 00:23:26.039 to detail. This is huge here. You know about 00:23:26.039 --> 00:23:31.039 how eye contact is a pretty much a no -go for 00:23:31.039 --> 00:23:34.640 the autistic phenotype. especially for me and 00:23:34.640 --> 00:23:37.880 as I've learned about others and talked to others 00:23:37.880 --> 00:23:41.960 during speaking. Eye contact during speaking 00:23:41.960 --> 00:23:45.519 is a huge problem. There's so much happening. 00:23:45.640 --> 00:23:49.880 Remember the B -movie example. The sensory processing 00:23:49.880 --> 00:23:53.880 in the outside world is chaotic. Carl Dyseroth 00:23:53.880 --> 00:23:57.240 calls it a fire hose of information, a torrent 00:23:57.240 --> 00:24:00.720 of information. It's like a machine gun, a torrent. 00:24:01.480 --> 00:24:05.720 This is very accurate. If that's not you, you 00:24:05.720 --> 00:24:08.700 will have no idea what it is or what it feels 00:24:08.700 --> 00:24:14.259 like. In addition, there's a disrupted synchrony. 00:24:14.519 --> 00:24:17.680 So that reduced gamma synchrony between V1 and 00:24:17.680 --> 00:24:21.220 the dorsolateral prefrontal cortex impairs the 00:24:21.220 --> 00:24:23.579 visual cognitive processing. We just kind of 00:24:23.579 --> 00:24:28.380 discussed that. But V1 to the dorsolateral prefrontal 00:24:28.380 --> 00:24:34.089 cortex is very long distance. The dorsal lateral 00:24:34.089 --> 00:24:36.789 prefrontal cortex is essentially at the very 00:24:36.789 --> 00:24:42.289 top, as far out as you can go. And V1 is at the 00:24:42.289 --> 00:24:47.049 very bottom back of the occipital lobe, right 00:24:47.049 --> 00:24:50.710 above the midbrain. It's a very long distance 00:24:50.710 --> 00:24:55.890 there. And also there's a disruption in the autistic 00:24:55.890 --> 00:24:59.230 phenotype with brain -derived neutropre factor 00:24:59.230 --> 00:25:02.329 influence. This is mostly excitatory. We'll talk 00:25:02.329 --> 00:25:06.569 a lot about this in the excitation episode. But 00:25:06.569 --> 00:25:10.170 this really amplifies that hyperactivity and 00:25:10.170 --> 00:25:13.990 sensory processing. And you should also remember 00:25:13.990 --> 00:25:17.470 the social cues now that you think you know about 00:25:17.470 --> 00:25:21.670 autistic phenotype and the social cues. This 00:25:21.670 --> 00:25:25.809 is all happening here as well. So the somatosensory 00:25:25.809 --> 00:25:30.549 sector, S1. This is in the central. to lamic 00:25:30.549 --> 00:25:35.890 reticular nucleus. And it has connections to 00:25:35.890 --> 00:25:39.089 other areas of the thalamus, excitatory inputs 00:25:39.089 --> 00:25:44.809 from a so -called ventral basal complex and gabaergic 00:25:44.809 --> 00:25:49.369 projections back to the ventral basal complex. 00:25:50.269 --> 00:25:53.769 In the cortex, there's a bidirectional with S1 00:25:53.769 --> 00:25:59.180 and the secondary somatosensory areas. It also 00:25:59.180 --> 00:26:02.319 uses inhibitory neurons, of course, parvalbium 00:26:02.319 --> 00:26:08.480 interneuron and somatostatin and the VIP. So 00:26:08.480 --> 00:26:11.500 it's using three of the inhibitory neurons we 00:26:11.500 --> 00:26:15.140 discussed before, parvalbium, somatostatin and 00:26:15.140 --> 00:26:19.279 the VIP. And the major region of interest here 00:26:19.279 --> 00:26:25.140 is kind of modulating and gating tactile, filtering 00:26:25.140 --> 00:26:29.779 out irrelevant touch stimuli. And it's also helped 00:26:29.779 --> 00:26:34.299 driving gamma oscillations to the VB, the ventral 00:26:34.299 --> 00:26:40.119 basal, and the S1 somatosensory sector loop. 00:26:40.380 --> 00:26:44.099 These are communicating back and forth for tactile 00:26:44.099 --> 00:26:48.440 discrimination. And it supports gamma synchrony 00:26:48.440 --> 00:26:52.619 with anterior insula for sensory emotional integration. 00:26:53.480 --> 00:26:57.500 The big part is that insula, especially the anterior 00:26:57.500 --> 00:27:01.119 insula. major region of interest with the parvalbum 00:27:01.119 --> 00:27:06.400 episode. It's the anterior insula. So what about 00:27:06.400 --> 00:27:10.339 the autistic phenotype? There's an impaired parvalbum 00:27:10.339 --> 00:27:14.259 inhibition so that increases the ventral basal 00:27:14.259 --> 00:27:18.259 activity and elevates gamma power and the S1. 00:27:18.799 --> 00:27:25.109 So you're thinking about touch responses. Reduced 00:27:25.109 --> 00:27:28.289 synchrony with the anterior insula impairs sensory 00:27:28.289 --> 00:27:32.490 -emotional processing. And because of the lack 00:27:32.490 --> 00:27:37.109 of inhibition, this will amplify excitatory inputs 00:27:37.109 --> 00:27:42.849 from the S1. So tactile hypersensitivity is huge 00:27:42.849 --> 00:27:46.109 here, with downstream deficits, which impair 00:27:46.109 --> 00:27:49.509 synchrony with the anterior insula, affecting 00:27:49.509 --> 00:27:52.869 emotional processing of touch, impacting social 00:27:52.869 --> 00:27:57.390 interactions. discomfort with physical contact, 00:27:57.589 --> 00:28:02.289 if you will. The third sector, auditory sector. 00:28:02.970 --> 00:28:07.970 This is in the caudal trn and it's adjacent to 00:28:07.970 --> 00:28:11.210 the medial geniculate nucleus. You should probably 00:28:11.210 --> 00:28:15.490 have guessed that because of its auditory roles 00:28:15.490 --> 00:28:19.349 here. So the connections to the thalamus, excitatory 00:28:19.349 --> 00:28:23.130 inputs from the medial geniculate nucleus and 00:28:23.130 --> 00:28:27.420 then The TRN will send back GABA -ergic projections 00:28:27.420 --> 00:28:32.720 to help balance the auditory stimuli coming in 00:28:32.720 --> 00:28:37.259 and also to the cortex as a bidirectional with 00:28:37.259 --> 00:28:42.480 the auditory cortex 1 and the superior temporal 00:28:42.480 --> 00:28:48.900 gyrus. We will talk about autism and the auditory 00:28:48.900 --> 00:28:52.319 cortex. We'll do a whole episode on that soon. 00:28:54.799 --> 00:28:58.500 This sector uses the parvalium interneurons. 00:28:58.579 --> 00:29:01.359 Remember, these are the most dense. These are 00:29:01.359 --> 00:29:04.519 the most common type of inhibitory neurons. So 00:29:04.519 --> 00:29:07.960 no surprise there. And this also is modulated 00:29:07.960 --> 00:29:14.720 by the somatostatin interneuron and the VIP interneuron. 00:29:15.400 --> 00:29:18.660 In typical brains, this inhibition of the medial 00:29:18.660 --> 00:29:22.259 geniculate nucleus is for the auditory sensory 00:29:22.259 --> 00:29:29.319 gating. filtering out irrelevant sounds and drives 00:29:29.319 --> 00:29:33.099 gamma oscillations in this medial geniculate 00:29:33.099 --> 00:29:38.859 nucleus to A1 cortex loop for auditory featuring 00:29:38.859 --> 00:29:43.339 and integration. And it supports synchrony with 00:29:43.339 --> 00:29:46.720 the dorsolateral prefrontal cortex and the superior 00:29:46.720 --> 00:29:52.099 temporal gyrus for auditory social processing. 00:29:53.609 --> 00:29:57.769 In the autistic phenotype, that reduced parvalbum 00:29:57.769 --> 00:30:02.650 inhibition increases the medial geniculate nucleus, 00:30:03.049 --> 00:30:08.049 so it cannot have that push -pull tactic. And 00:30:08.049 --> 00:30:12.309 this will elevate gamma power in our auditory, 00:30:12.390 --> 00:30:16.529 auditory cortex one. This disrupted synchrony 00:30:16.529 --> 00:30:19.329 with the downstream or distal connection, I should 00:30:19.329 --> 00:30:23.839 say, and downstream. Actually, that works. Which 00:30:23.839 --> 00:30:26.440 are distal connections and remember these are 00:30:26.440 --> 00:30:30.180 all distant and this is that impairing that auditory 00:30:30.180 --> 00:30:33.220 social integration So you should be thinking 00:30:33.220 --> 00:30:36.720 about the elevated gamma power and auditory cortex 00:30:36.720 --> 00:30:41.819 one Enhances auditory detail processing and sensitivity 00:30:41.819 --> 00:30:47.480 to loud sounds very good hearing Because of this 00:30:47.480 --> 00:30:51.680 though downstream deficits that reduce synchrony 00:30:51.680 --> 00:30:55.039 with those distal connections and processing 00:30:55.039 --> 00:30:58.920 speech in noisy environments. This is me. Remember 00:30:58.920 --> 00:31:02.299 I used the example of the later Beatles songs. 00:31:02.619 --> 00:31:05.400 At the end of the songs they're experimenting 00:31:05.400 --> 00:31:08.700 with different types of musical instruments and 00:31:08.700 --> 00:31:10.940 things that aren't musical instruments. They're 00:31:10.940 --> 00:31:13.460 just making noises out of like whatever they 00:31:13.460 --> 00:31:17.660 can find around the recording studio. This is 00:31:17.660 --> 00:31:21.039 me. This is clusters of noise and conversation 00:31:21.039 --> 00:31:25.220 and social settings are really amplified. I can 00:31:25.220 --> 00:31:28.200 pay attention to different clusters of conversations 00:31:28.200 --> 00:31:31.980 happening around me and it's very difficult. 00:31:32.420 --> 00:31:36.839 It's very heightened and tough to sustain. So 00:31:36.839 --> 00:31:41.480 the last sector, the limbic sector. This is in 00:31:41.480 --> 00:31:44.559 the anterior, so the front of the the limbic 00:31:44.559 --> 00:31:48.569 reticular nucleus and it's adjacent to the mediodorsal 00:31:48.569 --> 00:31:52.150 nucleus and the anterior nucleus. I know a lot 00:31:52.150 --> 00:31:55.069 of language there about the different subdivisions 00:31:55.069 --> 00:31:58.990 of the thalamus, but very relevant. Connections 00:31:58.990 --> 00:32:02.690 here with the thalamus. The thalamus will send 00:32:02.690 --> 00:32:06.869 excitatory inputs from these regions, the mediodorsal 00:32:06.869 --> 00:32:10.150 and the anterior nuclei, and the TRN will send 00:32:10.150 --> 00:32:13.829 back GABA -ergic projections into the cortex 00:32:13.829 --> 00:32:17.670 as well. Bidirectional with the dorsolateral 00:32:17.670 --> 00:32:21.890 prefrontal cortex and the anterior insula and 00:32:21.890 --> 00:32:29.150 the orbital frontal cortex and the ACC, the anterior 00:32:29.150 --> 00:32:33.549 cingulate cortex. So the limbic sector here is 00:32:33.549 --> 00:32:38.329 responsible for a few additional major hubs, 00:32:38.730 --> 00:32:42.950 major nuclei here with the anterior insula, the 00:32:42.950 --> 00:32:48.880 orbital frontal, and the ACC. The inhibitory 00:32:48.880 --> 00:32:52.000 neurons here are similar, but we're going to 00:32:52.000 --> 00:32:55.960 add that two -for -one from the previous episode, 00:32:56.319 --> 00:33:00.259 parvalbium, no surprise, and then it's modulated 00:33:00.259 --> 00:33:05.380 by the somatostatin and the VIP, and we finally 00:33:05.380 --> 00:33:09.740 introduce again the calbindin and the calretinin 00:33:09.740 --> 00:33:13.819 in the dorsolateral prefrontal cortex and insula 00:33:13.819 --> 00:33:17.400 connections. Remember those last two that two 00:33:17.400 --> 00:33:22.819 for one are very, very rare. In functional brains, 00:33:22.980 --> 00:33:26.440 the limbic sector is responsible for inhibiting 00:33:26.440 --> 00:33:30.440 the medial dorsal nucleus for attention and emotional 00:33:30.440 --> 00:33:34.660 regulation. And this drives gamma oscillations 00:33:34.660 --> 00:33:38.539 in the medial dorsal to the dorsal lateral prefrontal 00:33:38.539 --> 00:33:43.559 cortex loop for cognitive processing. And it 00:33:43.559 --> 00:33:46.329 supports synchrony. with the interior insula 00:33:46.329 --> 00:33:50.769 and the ACC for emotional integration. Now remember, 00:33:51.009 --> 00:33:54.869 an early episode of the podcast, Autism and Adaptive 00:33:54.869 --> 00:33:58.470 Responses and how the medial prefrontal cortex, 00:33:58.529 --> 00:34:04.609 ACC, and insula are in play here. When we are 00:34:04.609 --> 00:34:08.110 adaptive responding, when we are applying adaptive 00:34:08.110 --> 00:34:12.510 behaviors in society as we navigate life, the 00:34:12.510 --> 00:34:16.210 medial prefrontal cortex and the ACC lead the 00:34:16.210 --> 00:34:19.909 way. About minute 15 of that episode that I just 00:34:19.909 --> 00:34:23.230 mentioned really highlights this. It's there's 00:34:23.230 --> 00:34:30.550 a time stamp. MPFC, ACC lead the way. This means 00:34:30.550 --> 00:34:34.909 it's regulating those downstream behaviors. Remember 00:34:34.909 --> 00:34:38.349 the basal ganglia conversation that we just had. 00:34:39.030 --> 00:34:43.800 These inputs lead our responses, the skills that 00:34:43.800 --> 00:34:48.599 we have available to us. Whenever we are kind 00:34:48.599 --> 00:34:52.019 of heightened or hijacked, people will call it 00:34:52.019 --> 00:34:56.039 hijacked. The insula, because it's receiving 00:34:56.039 --> 00:34:59.480 so much, it receives inputs from the brain, brain 00:34:59.480 --> 00:35:02.599 states, what's happening in the brain with thought, 00:35:03.539 --> 00:35:06.400 and it's receiving inputs from the body, and 00:35:06.400 --> 00:35:09.150 it's receiving inputs from the environment. It 00:35:09.150 --> 00:35:12.070 has three sources, the three main sources there. 00:35:12.489 --> 00:35:15.170 The anterior insula is kind of privileged for 00:35:15.170 --> 00:35:20.829 that. This will lead the way and allow the subcortical 00:35:20.829 --> 00:35:26.269 areas, areas like the amygdala and all of these 00:35:26.269 --> 00:35:30.429 things that are kind of making us be physiologically 00:35:30.429 --> 00:35:33.690 out of control, will start paying attention to 00:35:33.690 --> 00:35:36.610 the heartbeat, the heart rate, the rate of speech, 00:35:36.789 --> 00:35:40.260 our phase locking. and we will just kind of panic. 00:35:41.260 --> 00:35:45.699 Remember the para -aqueductal gray in the mesencephalon, 00:35:45.739 --> 00:35:49.460 the midbrain. There's different areas there with 00:35:49.460 --> 00:35:54.280 that happening here as well. It's what is regulating, 00:35:54.360 --> 00:35:57.420 what is controlling these circuitries, these 00:35:57.420 --> 00:36:01.639 neural correlates. This is a good example of 00:36:01.639 --> 00:36:04.480 this because you've probably even heard of the 00:36:04.480 --> 00:36:09.070 limbic system. which is mostly subcortical or 00:36:09.070 --> 00:36:12.989 all subcortical. And we can get hijacked with 00:36:12.989 --> 00:36:18.889 this. So some inputs or some functions of the 00:36:18.889 --> 00:36:23.309 autistic phenotype is impaired and or a lack 00:36:23.309 --> 00:36:26.969 of parv albium inhibition reduces the gamma power 00:36:26.969 --> 00:36:30.090 and synchrony in the dorsolateral prefrontal 00:36:30.090 --> 00:36:34.349 cortex and the anterior insula. And this will 00:36:34.349 --> 00:36:38.699 cause over excitation inputs from the dorsal 00:36:38.699 --> 00:36:41.880 lateral prefrontal cortex and amplify dysfunction. 00:36:44.159 --> 00:36:47.559 So with the autistic phenotype implication, there's 00:36:47.559 --> 00:36:50.300 a lot of cognitive and social deficits happening 00:36:50.300 --> 00:36:56.619 here. In addition, there are some OCD -like behaviors 00:36:56.619 --> 00:36:59.559 here because of the dysfunction of the medial 00:36:59.559 --> 00:37:03.760 dorsal and the orbital frontal cortex circuits. 00:37:03.949 --> 00:37:09.030 that contributes to repetitive behaviors. So 00:37:09.030 --> 00:37:13.150 how strict is this TRN? What can get in and what 00:37:13.150 --> 00:37:17.329 has a more challenging time of getting in? The 00:37:17.329 --> 00:37:21.670 security guard examples. So with normal senses 00:37:21.670 --> 00:37:25.650 like sight, sound and touch, the TRN exhibits 00:37:25.650 --> 00:37:30.010 strong control over these. It's like a guard 00:37:30.010 --> 00:37:34.099 checking every bag at an airport. Very detailed 00:37:34.099 --> 00:37:38.159 and deliberate checks. Can things bypass? Not 00:37:38.159 --> 00:37:43.519 easily. No. It's fully filtered. Thoughts and 00:37:43.519 --> 00:37:47.579 plans. The TRN has a kind of a weaker control 00:37:47.579 --> 00:37:51.960 over this. The TRN barely touches it. The guard 00:37:51.960 --> 00:37:56.639 waves, the VIP enter neurons through. And there's 00:37:56.639 --> 00:38:00.860 just a little delay. Can things bypass this? 00:38:01.079 --> 00:38:04.119 Can thoughts and plans bypass this? And the answer 00:38:04.119 --> 00:38:08.019 is yes, quite easily. If you think about evolution, 00:38:09.260 --> 00:38:11.659 the thoughts and plans aren't really an external 00:38:11.659 --> 00:38:15.800 insult. So evolution doesn't equip us with protecting 00:38:15.800 --> 00:38:19.039 it, protecting ourselves from thoughts and plans. 00:38:20.099 --> 00:38:24.639 Evolutionarily, these are very critical and productive 00:38:24.639 --> 00:38:30.010 and necessary things. However, now, But the human's 00:38:30.010 --> 00:38:34.070 infinite capacity to just think will spend all 00:38:34.070 --> 00:38:37.230 of our time occupying our time thinking about 00:38:37.230 --> 00:38:43.050 maybe good things, maybe bad things. Loud and 00:38:43.050 --> 00:38:46.710 painful shocks. Well, this is dependent. The 00:38:46.710 --> 00:38:51.829 TRN is a little limited here. It tries to, but 00:38:51.829 --> 00:38:56.150 it can fail. The guard can only stop so much. 00:38:56.480 --> 00:39:00.840 Too much input overwhelms it. Can things bypass 00:39:00.840 --> 00:39:05.420 it? Yes, it can break through. Wake -up chemicals 00:39:05.420 --> 00:39:08.440 from the brain stem. Remember the sleep -wake 00:39:08.440 --> 00:39:12.280 cycles? Well, the wake -up signals modulates 00:39:12.280 --> 00:39:18.239 the TRN. It's kind of dependent. It can be strict 00:39:18.239 --> 00:39:23.400 or it can just be laid back. There's a lot going 00:39:23.400 --> 00:39:25.340 on here. There's a lot of variables with the 00:39:25.340 --> 00:39:29.489 sleep -wake. So there's a rule changes. It's 00:39:29.489 --> 00:39:35.429 just too dependent pain and danger alerts Well, 00:39:35.429 --> 00:39:39.309 this is kind of minimal the TRN is minimal here 00:39:39.309 --> 00:39:45.250 because there's we have to kind of bias towards 00:39:45.250 --> 00:39:49.329 safety and Another way of looking at this is 00:39:49.329 --> 00:39:53.190 high -intensity stimuli Well, this can bypass 00:39:53.190 --> 00:39:56.780 the inhibition if there's life threatening if 00:39:56.780 --> 00:40:00.980 there's one trial learning type of things going 00:40:00.980 --> 00:40:07.500 on. The TRN is very limited at this point because 00:40:07.500 --> 00:40:13.260 remember the evolution example, security and 00:40:13.260 --> 00:40:20.059 safety typically wins. Visual attention can be. 00:40:20.539 --> 00:40:22.980 There's a lot happening with the visual inputs. 00:40:23.239 --> 00:40:28.630 So that's it's kind of dependent but it's mostly 00:40:28.630 --> 00:40:32.710 yes especially in the typical brain. Now the 00:40:32.710 --> 00:40:36.050 autistic phenotype will pick out kind of subtle 00:40:36.050 --> 00:40:38.849 things in the environment without people even 00:40:38.849 --> 00:40:42.130 knowing that it's happening. That's a huge benefit 00:40:42.130 --> 00:40:45.269 and that has a lot to do with the the high gamma 00:40:45.269 --> 00:40:50.610 and the lack of gating here. So the the security 00:40:50.610 --> 00:40:54.750 guard can just kind of depends on Maybe they 00:40:54.750 --> 00:40:56.869 have a buddy and they let them in. Nobody knows 00:40:56.869 --> 00:41:00.989 it. They just got this secret message or whatever. 00:41:03.309 --> 00:41:06.190 I have something exciting. I want to introduce 00:41:06.190 --> 00:41:09.090 a product unlike any other product available. 00:41:10.030 --> 00:41:14.590 A highlight is the product from Daylight Computer 00:41:14.590 --> 00:41:18.070 Company created their product based on these 00:41:18.070 --> 00:41:22.829 factors. The Daylight Computer is completely 00:41:23.000 --> 00:41:28.559 blue light free. It has no flicker. Short wavelength 00:41:28.559 --> 00:41:33.119 flicker is extremely harmful for our eyes and 00:41:33.119 --> 00:41:37.059 downstream biology. Light flicker is constantly 00:41:37.059 --> 00:41:40.639 turning our central nervous system on and off. 00:41:41.360 --> 00:41:44.960 Essentially it is like going to a light switch 00:41:44.960 --> 00:41:49.360 and repeatedly turning it on and off. The problem 00:41:49.360 --> 00:41:55.380 is blue light and LED light does this and it 00:41:55.380 --> 00:41:58.659 is so rapid you cannot even perceive this in 00:41:58.659 --> 00:42:04.139 real time. The daylight computer is the lowest 00:42:04.139 --> 00:42:08.079 stimulation and foremost for sensory sensitive 00:42:08.079 --> 00:42:13.340 users. It is no question that the alternative 00:42:13.340 --> 00:42:18.639 product especially when used at night do not 00:42:18.639 --> 00:42:23.059 address or consider this in their product. It 00:42:23.059 --> 00:42:28.019 is so toxic to human biology. Big tech corporations 00:42:28.019 --> 00:42:32.739 have patents on how their short wavelength implicate 00:42:32.739 --> 00:42:38.360 the human nervous system. And a bonus, despite 00:42:38.360 --> 00:42:42.500 daylight computer not having backlight, it is 00:42:42.500 --> 00:42:46.880 very functional for outdoor use. And of course, 00:42:47.639 --> 00:42:52.670 increased sunlight is always preferred. I am 00:42:52.670 --> 00:42:56.050 happy to offer a discount for the Daylight Computer. 00:42:57.130 --> 00:43:02.250 You can use the code Autism for a $50 off discount. 00:43:02.789 --> 00:43:07.289 Again, use the code Autism and the discount code 00:43:07.289 --> 00:43:12.289 for $50 off. See the link in the show notes to 00:43:12.289 --> 00:43:15.489 Daylight Computer Company or just give it a quick 00:43:15.489 --> 00:43:19.610 search in your internet browser. Use the code 00:43:19.610 --> 00:43:25.199 Autism. for $50 off. I would like to mention 00:43:25.199 --> 00:43:31.500 Chroma, lights designed for humans. Chroma, a 00:43:31.500 --> 00:43:35.920 Seattle -based innovator founded by ex -NASA 00:43:35.920 --> 00:43:40.380 and Air Force engineer Michael Shapiro, is on 00:43:40.380 --> 00:43:43.900 a mission to enhance physical and mental health 00:43:43.900 --> 00:43:49.019 with purpose -built devices, unlocking peak human 00:43:49.019 --> 00:43:52.789 health. cognitive function, and performance. 00:43:54.010 --> 00:43:56.849 Shapiro launched Chroma to restore the natural 00:43:56.849 --> 00:44:02.269 light lost to screens in indoor living, and delivers 00:44:02.269 --> 00:44:06.110 faster recovery, sharper minds, and better sleep. 00:44:07.190 --> 00:44:11.130 Their products hit hard. The Iron Forge speeds 00:44:11.130 --> 00:44:15.210 muscle repair with red and near -infrared light, 00:44:15.789 --> 00:44:19.039 while the Skylight mimics sunlight. to boost 00:44:19.039 --> 00:44:24.719 sleep and energy. A standout, the Forge Lamp, 00:44:25.059 --> 00:44:30.119 is a portable gym that fires 660 nanometer and 00:44:30.119 --> 00:44:35.840 850 nanometer light to energize mitochondria 00:44:35.840 --> 00:44:40.480 and heal tissues on the go. Remember the four 00:44:40.480 --> 00:44:43.579 red light chromophores on cytochrome c -oxidase 00:44:43.579 --> 00:44:47.460 frequently talked about in the podcast. This 00:44:47.460 --> 00:44:51.699 is why. Their products are built with military 00:44:51.699 --> 00:44:57.619 -grade durability that have lasting impact. Chromis 00:44:57.619 --> 00:45:03.539 Tech fuses precision and power. Gallium titride 00:45:03.539 --> 00:45:07.679 power supplies. Smaller, cooler, and stronger 00:45:07.679 --> 00:45:11.900 than silicon. Provide flicker -free light that's 00:45:11.900 --> 00:45:16.599 easy on the eyes. High powered LEDs target key 00:45:16.599 --> 00:45:21.179 wavelengths for skin, tissue, and cellular health 00:45:21.179 --> 00:45:25.099 with smart heat management for the lasting impact. 00:45:26.079 --> 00:45:29.440 Every design decision Chroma makes serves a purpose 00:45:29.440 --> 00:45:33.920 to create devices that are precise, durable, 00:45:34.440 --> 00:45:39.760 and effective for improving human life. Remember, 00:45:40.239 --> 00:45:42.780 humans use different wavelengths of light for 00:45:42.780 --> 00:45:47.679 different functions of life. Remember when I 00:45:47.679 --> 00:45:54.800 ask, what do you think light is? Chroma designs 00:45:54.800 --> 00:45:59.719 with our biology in mind. From sleep aids and 00:45:59.719 --> 00:46:04.380 wound healing to mitochondrial energy, full body 00:46:04.380 --> 00:46:07.840 lights and blue light blocking glasses. They 00:46:07.840 --> 00:46:12.739 are US made and chroma ships globally and accepts 00:46:14.060 --> 00:46:20.719 FSA and HSA payments. Use autism at checkout 00:46:20.719 --> 00:46:27.420 for a 10 % off discount. That's autism at checkout 00:46:27.420 --> 00:46:31.800 for a 10 % off discount. If you're listening 00:46:31.800 --> 00:46:34.760 to the podcast, listening to the episode, please 00:46:34.760 --> 00:46:38.239 feel free to leave a review or rating. In podcasting, 00:46:38.420 --> 00:46:41.019 reviews, ratings and downloads are huge and I 00:46:41.019 --> 00:46:43.659 very much appreciate your feedback. You can contact 00:46:43.659 --> 00:46:50.039 me on X at RPS 47586. We can discuss anything 00:46:50.039 --> 00:46:52.780 and everything about autism. I very much appreciate 00:46:52.780 --> 00:46:56.559 your comments and your interactions on X. You 00:46:56.559 --> 00:46:59.579 can check out the YouTube page for all the videos, 00:47:00.099 --> 00:47:03.960 full -length videos, shorts, and clips. You can 00:47:03.960 --> 00:47:11.179 email me info .fromthespectrum .gmail .com. Thank 00:47:11.179 --> 00:47:14.650 you for listening. to From the Spectrum Podcast.