WEBVTT 00:00:00.000 --> 00:00:02.839 okay we're going to cover the basal ganglia because 00:00:02.839 --> 00:00:05.160 last winter we covered it in quite detail in 00:00:05.160 --> 00:00:07.580 several different episodes and this is where 00:00:07.580 --> 00:00:13.099 movements happen so there's a lot of humans are 00:00:13.099 --> 00:00:15.660 constantly doing movements and actions this is 00:00:15.660 --> 00:00:18.980 action so the episodes we covered with the basal 00:00:18.980 --> 00:00:23.980 ganglia is episode 48 autism and the basal ganglia 00:00:23.980 --> 00:00:31.859 motivations movements from learning and habits 00:00:31.859 --> 00:00:35.679 episode 49 autism in Parkinson's Parkinson's 00:00:35.679 --> 00:00:39.659 is a hot spot right here especially here here 00:00:39.659 --> 00:00:44.320 and here we probably won't cover much on Parkinson's 00:00:44.320 --> 00:00:47.280 in this whiteboard but we will later I promise 00:00:47.280 --> 00:00:52.520 you episode 50 autism in the basal ganglia repetition 00:00:52.520 --> 00:01:01.200 sameness and habits and Also, episode 47. We 00:01:01.200 --> 00:01:04.359 could include episode 47 here. The autistic phenotype 00:01:04.359 --> 00:01:08.359 and how internal calculators shape our preference. 00:01:08.780 --> 00:01:12.280 We talk about internal calculators a lot. And 00:01:12.280 --> 00:01:14.319 they should. They should be talked about. So 00:01:14.319 --> 00:01:19.780 these two specifically, basal ganglia, we're 00:01:19.780 --> 00:01:22.099 going to talk about the basal ganglia. This is 00:01:22.099 --> 00:01:24.920 one side of the basal ganglia. They're just spots 00:01:24.920 --> 00:01:26.900 right now. But we're going to get through it. 00:01:27.280 --> 00:01:33.200 Okay? The base of ganglia is essentially five 00:01:33.200 --> 00:01:40.459 subcortical areas. Okay? There's input areas 00:01:40.459 --> 00:01:44.040 and this is called the dorsal striatum. Input 00:01:44.040 --> 00:01:47.560 areas. Markers going out already. The dorsal 00:01:47.560 --> 00:01:53.599 striatum is two areas. The cadet nucleus and 00:01:53.599 --> 00:01:57.239 the pertainment. Putamen sometimes. So these 00:01:57.239 --> 00:02:00.700 two areas receive the inputs. And then there 00:02:00.700 --> 00:02:06.519 are also relays. Relays are Globus pallidus external 00:02:06.519 --> 00:02:12.199 and subthalamic nucleus. Globus pallidus are 00:02:12.199 --> 00:02:16.860 these two. They almost make a triangle. But the 00:02:16.860 --> 00:02:20.340 external, because this is going to be center, 00:02:20.939 --> 00:02:23.060 and then we'll draw out the contralateral here 00:02:23.060 --> 00:02:27.419 in a minute. So this is Globus Pallidus external 00:02:27.419 --> 00:02:32.159 and this is the subthalamic nucleus. This is 00:02:32.159 --> 00:02:36.020 the thalamus. The subthalamic nucleus is just 00:02:36.020 --> 00:02:38.539 basically another assistant for the thalamus. 00:02:38.639 --> 00:02:41.280 The thalamus is a workhorse and it needs help. 00:02:41.379 --> 00:02:45.659 And then the output areas in blue. Globus Pallidus 00:02:45.659 --> 00:02:52.460 internal and Substantia nigra pars fritikulata. 00:02:54.050 --> 00:03:00.270 These two nuclei are very identical. Globus pallidus 00:03:00.270 --> 00:03:05.610 internal here because it's internal medial and 00:03:05.610 --> 00:03:08.509 the substantia nigra pars reticulata. This is 00:03:08.509 --> 00:03:11.270 the substantia nigra. This is in the midbrain 00:03:11.270 --> 00:03:16.330 the mesencephalon. So if we were to look at it 00:03:16.330 --> 00:03:20.150 it would look more like this flat looking at 00:03:20.150 --> 00:03:23.069 it from this posterior end but I had to rotate 00:03:23.069 --> 00:03:28.300 it up so we can see the reticulata which is here 00:03:28.300 --> 00:03:33.219 and then the pars compacta which is so reticulata 00:03:33.219 --> 00:03:36.840 pars compacta they have different roles we're 00:03:36.840 --> 00:03:39.340 going to get through it these five subcortical 00:03:39.340 --> 00:03:43.620 areas orchestrate our movements every movement 00:03:43.620 --> 00:03:47.259 besides those funky reflexes that we have if 00:03:47.259 --> 00:03:51.300 we hit an elbow or a knee when the doctor hits 00:03:51.300 --> 00:03:54.780 taps our knee with a little spike hammer like 00:03:54.780 --> 00:03:59.000 thing and it goes every movement is orchestrated 00:03:59.000 --> 00:04:01.919 here. So this is why it's important. So we have 00:04:01.919 --> 00:04:04.979 the input areas and I'll just go ahead and draw 00:04:04.979 --> 00:04:08.699 out contralateral because we're gonna do the 00:04:08.699 --> 00:04:14.520 go side. That's a good point here. This is go 00:04:14.520 --> 00:04:21.139 no go. This is go no go. This is orchestrating 00:04:21.139 --> 00:04:24.240 movements and suppressing movements. So I'll 00:04:24.240 --> 00:04:27.480 just draw this out contralateral. Remember, ipsilateral 00:04:27.480 --> 00:04:31.759 is one side. Contralateral is both sides. So 00:04:31.759 --> 00:04:34.920 we have the cadet nucleus here, and the butamen, 00:04:35.439 --> 00:04:38.500 putamen. These are the inputs. We're gonna get, 00:04:38.720 --> 00:04:40.839 we're gonna make sense of what the inputs mean. 00:04:41.000 --> 00:04:43.220 And then we have the globus pallidus external 00:04:43.220 --> 00:04:48.699 on one side. A little relay station. It has hidden 00:04:48.699 --> 00:04:51.079 rules. We're going to dissect these hidden rules 00:04:51.079 --> 00:04:55.620 for sure because it's missed. It's new. Textbooks 00:04:55.620 --> 00:04:58.519 don't teach it. And then the subthalamic nucleus, 00:04:58.819 --> 00:05:01.620 just a little flat spot right below the thalamus. 00:05:01.699 --> 00:05:04.620 And we have the thalamus. The thalamus is the 00:05:04.620 --> 00:05:08.000 target. Remember, it's a workhorse. And the pars 00:05:08.000 --> 00:05:11.899 reticulata, the globus pallidus internal. So 00:05:11.899 --> 00:05:15.899 why is the thalamus blue? The same as the outputs. 00:05:16.300 --> 00:05:20.300 This is the target. This orchestrates everything. 00:05:21.399 --> 00:05:24.220 It's a sensory relay station. It receives all 00:05:24.220 --> 00:05:27.660 sensations and then it's also on that feed forward 00:05:27.660 --> 00:05:31.860 feedback loop. Remember the mini columns. Everything 00:05:31.860 --> 00:05:34.399 is orchestrated through the thalamus and then 00:05:34.399 --> 00:05:38.620 the substantia nigra pars compacta is also involved. 00:05:40.220 --> 00:05:43.240 We're gonna, we're gonna, we're gonna understand 00:05:43.240 --> 00:05:47.759 why. This is a modulator. So we can add modulator. 00:05:47.800 --> 00:05:53.839 Biggest one, Substantia nigra, pars compact. 00:05:57.459 --> 00:06:03.480 SNC, you can see that abbreviated as SNC, and 00:06:03.480 --> 00:06:09.399 reticulata is SNR. Lowercase, the C and R are 00:06:09.399 --> 00:06:14.019 lowercase. This is the basal ganglia. So what 00:06:14.019 --> 00:06:18.839 does it mean? Just real general We'll map out 00:06:18.839 --> 00:06:22.079 the ghost side here and the no ghost side here 00:06:22.079 --> 00:06:26.139 because these have distinct names direct pathway 00:06:26.139 --> 00:06:34.040 equals go Okay, so inputs excitatories projections 00:06:34.040 --> 00:06:38.879 come in to the chidot nucleus and The containment 00:06:38.879 --> 00:06:42.220 and these orchestrate our movements. These are 00:06:42.220 --> 00:06:47.420 conductors They're recruiting, activating, and 00:06:47.420 --> 00:06:51.959 turning off and activating downstream regions. 00:06:52.240 --> 00:06:55.620 For the goal side, simple. Projections come in 00:06:55.620 --> 00:06:57.839 excitatory from the cortex. We're going to map 00:06:57.839 --> 00:07:00.779 these out because this is going to sound too 00:07:00.779 --> 00:07:03.779 simple. The dorsal striatum of the cardiac amputation 00:07:03.779 --> 00:07:10.319 will send inhibition. Everything coming out of 00:07:10.319 --> 00:07:13.589 the dorsal striatum is inhibitory. you know about 00:07:13.589 --> 00:07:16.810 autism and the lack of inhibitory or a problem 00:07:16.810 --> 00:07:20.269 with the inhibitory so it will inhibit the globus 00:07:20.269 --> 00:07:27.050 pallidus internal and the porous reticulata that 00:07:27.050 --> 00:07:31.670 will in turn while shutting these off allow them 00:07:31.670 --> 00:07:34.870 to it will feed up to the thalamus and and that 00:07:34.870 --> 00:07:38.490 frees up the thalamus to send projections back 00:07:38.490 --> 00:07:41.209 up remember layer four of the many columns if 00:07:41.209 --> 00:07:43.810 we have these many columns right remember we 00:07:43.810 --> 00:07:47.430 can just map these out like this we have the 00:07:47.430 --> 00:07:51.050 the cells the collection of different cells here 00:07:51.050 --> 00:07:54.509 and then we have the stellette cells in layer 00:07:54.509 --> 00:07:58.589 four and then we have more cells down through 00:07:58.589 --> 00:08:03.129 layers five and six remember five is about firing 00:08:03.129 --> 00:08:08.360 five a is tonic five b is burst firing then layer 00:08:08.360 --> 00:08:13.199 6 has A and B as well. It's a cortical thalamus 00:08:13.199 --> 00:08:18.899 so it speaks back to the thalamus and 6B is cortical 00:08:18.899 --> 00:08:23.019 to cortical speaking throughout the cortex. So 00:08:23.019 --> 00:08:26.720 there's a 5A and 5B based off of the firing and 00:08:26.720 --> 00:08:31.839 6. Where is it going? Remember down below 6 is 00:08:31.839 --> 00:08:35.440 a lot of white matter tracks. Okay so remember 00:08:35.440 --> 00:08:38.870 you have these cells here And also this is where 00:08:38.870 --> 00:08:42.029 the spindle neurons are in some of the areas. 00:08:42.330 --> 00:08:44.929 Spindle neurons are a little flat and funky looking, 00:08:45.149 --> 00:08:47.190 but these are loaded with cells through here. 00:08:47.409 --> 00:08:50.590 Whenever the thalamus is freed up, so let's just 00:08:50.590 --> 00:08:55.409 go back. Excitatory inputs hit the caudate amputamen. 00:08:56.070 --> 00:09:00.070 We'll just discriminate those in a minute. And 00:09:00.070 --> 00:09:03.929 that will inhibit the globus pallidus internal. 00:09:04.250 --> 00:09:07.090 and the pars reticulata substantial nigra pars 00:09:07.090 --> 00:09:10.889 reticulata and that frees up the thalamus inhibit 00:09:10.889 --> 00:09:14.870 the thalamus anymore so the thalamus will speak 00:09:14.870 --> 00:09:21.690 back up to you know where layer four this is 00:09:21.690 --> 00:09:24.230 where the inputs come in on the many columns 00:09:24.230 --> 00:09:28.799 then it goes to layer two and three Because this 00:09:28.799 --> 00:09:31.220 is where we live. This is where our intelligence 00:09:31.220 --> 00:09:35.519 lives, our memory, our experiences, our ability, 00:09:35.720 --> 00:09:38.620 and so forth. And then two to three will speak 00:09:38.620 --> 00:09:42.220 back down to five and six. How much intensity 00:09:42.220 --> 00:09:45.620 does it want to send? And then where is it going? 00:09:46.620 --> 00:09:48.980 That's the mini column. This is pretty much the 00:09:48.980 --> 00:09:51.519 function here. Every movement, every movement 00:09:51.519 --> 00:09:54.860 that we're making is orchestrated through that. 00:09:54.940 --> 00:09:58.539 Sounds simple. This is the indirect. pathway 00:09:58.539 --> 00:10:06.620 no go stop stop so excitatory inputs come in 00:10:06.620 --> 00:10:10.539 to the cadet and to the putamen okay and here 00:10:10.539 --> 00:10:14.519 there's a little bit more going on the cadet 00:10:14.519 --> 00:10:18.720 and putamen will send signals to the globus pallidus 00:10:18.720 --> 00:10:23.299 external and then this will kind of do a lot 00:10:23.299 --> 00:10:25.620 of different things but we'll parse out what 00:10:25.620 --> 00:10:29.799 this is doing in detail And this will also speak 00:10:29.799 --> 00:10:33.960 over to the subthalamic nucleus. The subthalamic 00:10:33.960 --> 00:10:40.879 nucleus will shut off. Nope, excite. Will excite 00:10:40.879 --> 00:10:46.019 these. And then that allows these output areas, 00:10:46.340 --> 00:10:48.980 the globus pallidus internal and the substantia 00:10:48.980 --> 00:10:52.799 nigra pars reticulata, to go back to the thalamus. 00:10:52.960 --> 00:10:55.820 It will instruct the thalamus to stop. So you 00:10:55.820 --> 00:10:57.960 can see there's a little bit more coordination. 00:10:58.190 --> 00:11:03.009 for the for the stop for the suppression and 00:11:03.009 --> 00:11:04.870 there's timing involved here that we're going 00:11:04.870 --> 00:11:07.710 to get into and essentially that's the direct 00:11:07.710 --> 00:11:11.750 pathway and the indirect pathway it seems simple 00:11:11.750 --> 00:11:14.870 that's a simplistic way of looking at it so let's 00:11:14.870 --> 00:11:18.009 talk about the input areas because this is going 00:11:18.009 --> 00:11:25.409 to be huge what are these what are those so the 00:11:25.409 --> 00:11:29.080 input areas yeah That's a good way of thinking 00:11:29.080 --> 00:11:32.840 about it. Because these are input areas of what's 00:11:32.840 --> 00:11:37.120 coming in. So the biggest thing here is the cortex. 00:11:37.399 --> 00:11:40.059 This is the biggest thing that sends signals 00:11:40.059 --> 00:11:45.019 excitatory, they're always excitatory, to these 00:11:45.019 --> 00:11:48.620 areas. The second one is the thalamus. The thalamus 00:11:48.620 --> 00:11:53.340 will send inputs, projections back to the dorsal 00:11:53.340 --> 00:11:58.240 striatum. And a lot of this is This is all excitatory 00:11:58.240 --> 00:12:00.460 as well, but this is the thalamus is telling 00:12:00.460 --> 00:12:04.340 it to pay attention Something important is or 00:12:04.340 --> 00:12:08.940 unexpected is about to happen. So Help be on 00:12:08.940 --> 00:12:11.639 alert here because remember the thalamus is always 00:12:11.639 --> 00:12:15.879 asking and needing help okay, this will also 00:12:15.879 --> 00:12:19.500 help provide a little bit of arousal and context 00:12:19.500 --> 00:12:23.480 to what is happening because It's a workhorse 00:12:23.480 --> 00:12:27.480 the thalamus is a workhorse The second thing 00:12:27.480 --> 00:12:31.940 or the third thing is Substantia Nigra Pars Compacta. 00:12:32.559 --> 00:12:36.440 Here, this is a big input area because we're 00:12:36.440 --> 00:12:38.500 going to talk about the specific cell types, 00:12:38.860 --> 00:12:42.840 medium spiny neurons here and make sense of like 00:12:42.840 --> 00:12:47.899 so -called typicals versus autistics. So, Substantia 00:12:47.899 --> 00:12:54.059 Nigra Pars Compacta is dopamine. D1 and D2 dopamine. 00:12:55.049 --> 00:12:59.269 This is excitatory and D2 are inhibitory. So 00:12:59.269 --> 00:13:02.149 it's modulating. It's modulating the attention, 00:13:02.570 --> 00:13:07.629 the intensity and so forth. These use DR1 and 00:13:07.629 --> 00:13:12.629 DR5 receptors. Dopamine receptor 1, dopamine 00:13:12.629 --> 00:13:15.309 receptor 5. Dopamine only has five receptors. 00:13:16.889 --> 00:13:22.110 R2, 3, and 4. Substantia nigra pars compacta. 00:13:22.490 --> 00:13:25.779 It's major projection, major target. is the dorsal 00:13:25.779 --> 00:13:30.139 striatum. This is dopamine. We also have the 00:13:30.139 --> 00:13:33.620 ventral tegmental area for dopamine. So dopamine 00:13:33.620 --> 00:13:36.899 is very important. This is telling the dorsal 00:13:36.899 --> 00:13:41.740 striatum that this is good or this is bad. It's 00:13:41.740 --> 00:13:45.139 providing some value and intensity. It will amplify 00:13:45.139 --> 00:13:50.419 it if needed. Okay, it's teaching it what is 00:13:50.419 --> 00:13:54.519 worth doing. Do I want to do this? And so forth. 00:13:54.659 --> 00:13:59.179 Also, as modulators to Alessero, these are the 00:13:59.179 --> 00:14:03.100 three biggest input areas to the caudate and 00:14:03.100 --> 00:14:06.039 the putamen. But also, there are modulators like 00:14:06.039 --> 00:14:09.580 serotonin. So the dorsal graph A for serotonin. 00:14:09.679 --> 00:14:15.360 This is providing some information here to say, 00:14:15.740 --> 00:14:19.259 have patience. Just give it a moment type of 00:14:19.259 --> 00:14:23.110 thing. Okay? That's serotonin. That's what it's 00:14:23.110 --> 00:14:25.710 doing. So, you also know about like the mood 00:14:25.710 --> 00:14:28.610 thing. So, I'm okay right now. In this situation, 00:14:28.990 --> 00:14:34.309 you're okay. Or, no. And then, choline. Not... 00:14:34.309 --> 00:14:37.009 So, it's acetylcholine, essentially, but it's 00:14:37.009 --> 00:14:41.450 not from the forebrain. The nucleus basalis of 00:14:41.450 --> 00:14:45.690 Minert does not really project to these areas 00:14:45.690 --> 00:14:49.690 for the choline. We've talked about in the mesencephalon 00:14:49.690 --> 00:14:53.460 episode that There's also little regions down 00:14:53.460 --> 00:14:56.019 in the brain stem, the mesencephalon, that releases 00:14:56.019 --> 00:15:00.220 choline. Remember the Edinger -Westphal nuclei 00:15:00.220 --> 00:15:04.500 that's heavily involved with cranial nerve 3 00:15:04.500 --> 00:15:07.940 as well. There's little subdivisions down here 00:15:07.940 --> 00:15:11.360 that also release choline. And this is one of 00:15:11.360 --> 00:15:15.200 them. It's the very long and complicated nomenclature. 00:15:15.700 --> 00:15:22.710 But PPG... L, T, D, and so forth. This is helping 00:15:22.710 --> 00:15:26.350 shift between focus and attention. It's helping 00:15:26.350 --> 00:15:29.230 provide a little bit of flexibility. Pay attention 00:15:29.230 --> 00:15:31.710 to this type of thing. You know, that's what 00:15:31.710 --> 00:15:35.490 a stable choline does. And then even less than 00:15:35.490 --> 00:15:38.789 these two are things like from the limbic areas, 00:15:39.370 --> 00:15:44.049 like the amygdala and hippocampi. So most of 00:15:44.049 --> 00:15:47.559 these are excitatory but there's an unknown role 00:15:47.559 --> 00:15:51.700 with the globus pallidus external that's speaking 00:15:51.700 --> 00:15:55.200 back up to the dorsal striatum we're going to 00:15:55.200 --> 00:15:57.899 get there in a minute but for now we need to 00:15:57.899 --> 00:16:00.240 understand the the signals coming in from the 00:16:00.240 --> 00:16:04.799 cortex because that's that determines everything 00:16:04.799 --> 00:16:08.200 so let's just map this out from a side view and 00:16:08.200 --> 00:16:11.379 I will use just one color for all the subcortical 00:16:11.379 --> 00:16:13.539 areas if we're looking at this from the side 00:16:13.539 --> 00:16:15.980 let's say the thalamus is here now there's a 00:16:15.980 --> 00:16:18.019 reason I'm not going to color all of this in 00:16:18.019 --> 00:16:22.340 because the thalamus is very midline it's very 00:16:22.340 --> 00:16:25.399 medial so we're going to have to work out this 00:16:25.399 --> 00:16:27.899 way we're going to have to work out this way 00:16:27.899 --> 00:16:31.000 and you can see there's a lot of overlap so it's 00:16:31.000 --> 00:16:33.740 going to be hard to map this out laterally if 00:16:33.740 --> 00:16:37.759 we're looking at it like this this way These 00:16:37.759 --> 00:16:41.700 are lateral. So yeah, it's gonna be hard now 00:16:41.700 --> 00:16:45.639 for me to draw this out But the cadet is long. 00:16:45.639 --> 00:16:50.000 It has a tail it even wraps around and connects 00:16:50.000 --> 00:16:55.480 kind of to the to the amygdala So this is it's 00:16:55.480 --> 00:16:58.940 like a shrimp. It reminds me of a shrimp So this 00:16:58.940 --> 00:17:01.899 is here now. It just depends on how deep you 00:17:01.899 --> 00:17:04.200 want to go if you're looking at it from behind 00:17:04.640 --> 00:17:07.559 is how much this is going to show up and which 00:17:07.559 --> 00:17:09.799 part because if you're looking at it from this 00:17:09.799 --> 00:17:12.779 way you'll be able to see different parts of 00:17:12.779 --> 00:17:15.039 it different it's going to look bigger but the 00:17:15.039 --> 00:17:21.480 putamen is right here and these are connected 00:17:21.480 --> 00:17:27.819 just briefly so cadet nucleus putamen thalamus 00:17:27.819 --> 00:17:31.480 right here so if you notice the putamen is going 00:17:31.480 --> 00:17:34.910 to block the globus pallidus so the globus pallidus 00:17:34.910 --> 00:17:37.809 would sit just right here okay this isn't as 00:17:37.809 --> 00:17:40.950 important so this is the thalamus septalemic 00:17:40.950 --> 00:17:45.390 would sit about right here and then the reticulata 00:17:45.390 --> 00:17:49.690 and compacta would be down here remember we drew 00:17:49.690 --> 00:17:53.470 out we drew out the brainstem if you're looking 00:17:53.470 --> 00:17:55.170 at the brainstem like this if you just want to 00:17:55.170 --> 00:18:00.289 slice it open that way you can see the pars reticulata 00:18:00.289 --> 00:18:04.440 and compacta are in the kind of anterior part 00:18:04.440 --> 00:18:09.619 of the mesencephalon so if it's like this if 00:18:09.619 --> 00:18:13.000 the brain stem remember if we have the pons a 00:18:13.000 --> 00:18:15.319 little football shape and then the brain stem 00:18:15.319 --> 00:18:20.319 goes down so mesencephalon it would be like here 00:18:20.319 --> 00:18:24.799 superior colliculus inferior colliculus so substantia 00:18:24.799 --> 00:18:28.140 nigra compacta and reticulata here and then we 00:18:28.140 --> 00:18:33.529 would have the cerebellum like this cerebellum 00:18:33.529 --> 00:18:36.950 is going to have a role you know motor movements 00:18:36.950 --> 00:18:40.450 fine tuning it's going to have a role we might 00:18:40.450 --> 00:18:44.609 get into it so the cortex here would be all of 00:18:44.609 --> 00:18:48.630 this area all right so the occipital lobe parietal 00:18:48.630 --> 00:18:52.250 the sensory motor which is here parietal is back 00:18:52.250 --> 00:18:55.170 through here and then the frontal cortex the 00:18:55.170 --> 00:19:00.220 prefrontal cortex okay so the major part coming 00:19:00.220 --> 00:19:05.140 into here is the sensory motor area which is 00:19:05.140 --> 00:19:08.460 essentially here. Remember we have things like 00:19:08.460 --> 00:19:13.200 the somatosensory cortex here and then the sensory 00:19:13.200 --> 00:19:16.359 motor here we have the frontal eye fields are 00:19:16.359 --> 00:19:22.440 up here frontal eye fields um sensory motor there's 00:19:22.440 --> 00:19:26.039 a lot of habits living up through here okay and 00:19:26.039 --> 00:19:30.740 then we have the somatosensory This is a large 00:19:30.740 --> 00:19:33.359 part. This is probably the second most inputs 00:19:33.359 --> 00:19:36.220 coming in. This is probably the most inputs. 00:19:36.299 --> 00:19:39.759 Remember, we love to build habits and store them 00:19:39.759 --> 00:19:43.660 up through here. We love repetition and habits. 00:19:43.779 --> 00:19:46.359 This is who we are. This is why we're covering 00:19:46.359 --> 00:19:48.900 this. And then some prefrontal areas. Remember 00:19:48.900 --> 00:19:52.680 the dorsal striatum? No, the dorsal lateral prefrontal 00:19:52.680 --> 00:19:57.000 cortex up through here. This area of the prefrontal 00:19:57.000 --> 00:19:59.660 cortex right through here. Okay. and then the 00:19:59.660 --> 00:20:02.740 orbital frontal cortex right through here right 00:20:02.740 --> 00:20:05.980 here this is providing this is good with working 00:20:05.980 --> 00:20:09.019 memory and providing a plan so it will project 00:20:09.019 --> 00:20:11.859 down through here to kind of give it some instructions 00:20:11.859 --> 00:20:16.000 on what to do based off of this what we're encountering 00:20:16.000 --> 00:20:20.119 the orbital prefrontal cortex here remember it's 00:20:20.119 --> 00:20:25.200 mostly sensory it has a a lot of specificity 00:20:25.200 --> 00:20:28.950 of what the living organism wants and kind of 00:20:28.950 --> 00:20:32.789 desires in real time is providing value and reward. 00:20:33.410 --> 00:20:38.430 Is this worth it or not? With the specificity, 00:20:39.109 --> 00:20:42.549 if you want, let's say, if you're thinking that 00:20:42.549 --> 00:20:45.150 you need caffeine, the orbital frontal cortex 00:20:45.150 --> 00:20:47.269 is going to tell you exactly the source of the 00:20:47.269 --> 00:20:49.349 caffeine that you want. Maybe I want coffee. 00:20:49.450 --> 00:20:52.430 Maybe I don't want coffee. Maybe I want tea or 00:20:52.430 --> 00:20:56.490 whatever. That's going to help this out. And 00:20:56.490 --> 00:20:58.549 then the medial prefrontal cortex is in through 00:20:58.549 --> 00:21:03.250 here. Remember, the ACC is here. And then the 00:21:03.250 --> 00:21:06.230 insula would live right through here, the anterior 00:21:06.230 --> 00:21:09.410 insula. Not involved though. This is involved. 00:21:10.009 --> 00:21:13.190 This is involved because this is a big calculator. 00:21:13.730 --> 00:21:17.470 This is conflict monitoring and evaluating risk 00:21:17.470 --> 00:21:22.019 reward. So it's providing constant updates. This 00:21:22.019 --> 00:21:24.680 isn't just a one -time thing and you're done. 00:21:24.980 --> 00:21:28.000 This is constant. These two networks are dancing 00:21:28.000 --> 00:21:32.000 around constant. There are so many. This is a 00:21:32.000 --> 00:21:34.200 lot of electrical activity and projections right 00:21:34.200 --> 00:21:39.000 here. And it will also allow it to update because 00:21:39.000 --> 00:21:44.039 you're evaluating reward and the environment. 00:21:44.579 --> 00:21:47.500 Okay, that action didn't give me what I wanted. 00:21:47.769 --> 00:21:50.349 I have to do something else. The ACC will help 00:21:50.349 --> 00:21:53.890 conduct that, adjust your behavior. It's also 00:21:53.890 --> 00:21:57.349 doing the conflict monitoring and so forth. And 00:21:57.349 --> 00:22:00.970 then the parietal lobe is back here, remember? 00:22:01.589 --> 00:22:06.430 So if this is the occipital, and then the parietal, 00:22:06.569 --> 00:22:08.390 see we're just building the brain here. And the 00:22:08.390 --> 00:22:10.690 temporal lobe will run through here, so we're 00:22:10.690 --> 00:22:14.210 just mapping out the brain here. The parietal 00:22:14.210 --> 00:22:16.490 lobe will also send some inputs through here. 00:22:16.809 --> 00:22:21.930 And it's going to be, because the parietal is 00:22:21.930 --> 00:22:26.569 sensory integration a lot, it's providing some 00:22:26.569 --> 00:22:30.269 context dependent cues. Okay, look here or don't 00:22:30.269 --> 00:22:33.089 look here. What was that noise type of thing? 00:22:33.150 --> 00:22:36.950 That noise got loud and so forth. So it will 00:22:36.950 --> 00:22:39.390 help orchestrate movements here. So these are 00:22:39.390 --> 00:22:46.039 the biggest cortex inputs coming in. So. What 00:22:46.039 --> 00:22:51.160 does that mean? We are all different. This conversation 00:22:51.160 --> 00:22:54.480 today is based off of who we are, what we are, 00:22:54.640 --> 00:22:57.940 what we do, what we like and so forth. This is 00:22:57.940 --> 00:23:01.500 why we're so different. So let's just really 00:23:01.500 --> 00:23:04.059 zoom in here because this is getting way too 00:23:04.059 --> 00:23:09.099 long. Let's just zoom in here, okay? Let's just 00:23:09.099 --> 00:23:12.880 extract a single cell from one of these two areas, 00:23:12.940 --> 00:23:16.509 okay? First thing I want to say though is, the 00:23:16.509 --> 00:23:20.349 more medial you are in these subcortical areas, 00:23:20.990 --> 00:23:24.849 and even in the cortex, more likely it is something 00:23:24.849 --> 00:23:29.210 new, novel, or goal -directed. And then habits 00:23:29.210 --> 00:23:33.750 will live outward, lateral. So the putamen is 00:23:33.750 --> 00:23:37.170 more about habits. So it receives a lot more 00:23:37.170 --> 00:23:40.329 inputs from that sensory motor area because we 00:23:40.329 --> 00:23:43.450 love to send our information and our abilities 00:23:43.450 --> 00:23:47.970 to this area. So more goal directed through here, 00:23:48.109 --> 00:23:51.549 habits go lateral. If you think about the evolution 00:23:51.549 --> 00:23:54.809 of the living organism and humanity, it makes 00:23:54.809 --> 00:23:57.549 sense because we had to have motivation to do 00:23:57.549 --> 00:24:01.309 and get what we want first. And then we can shift 00:24:01.309 --> 00:24:05.829 those over. We can shift those over. And I think 00:24:05.829 --> 00:24:09.710 that frees up space for the goal -directed behavior. 00:24:10.089 --> 00:24:13.329 We can all understand that change is hard. Because 00:24:13.329 --> 00:24:15.470 we're going to talk about morphology and these 00:24:15.470 --> 00:24:18.450 synaptic connections. So let's just extract a 00:24:18.450 --> 00:24:20.849 single cell. I'm just picking one. It's just 00:24:20.849 --> 00:24:25.869 a general example. Because these are medium spiny 00:24:25.869 --> 00:24:29.569 neurons. So we have the cell body, the nucleus, 00:24:29.789 --> 00:24:33.130 okay? So let's just say this is a cell. Be it 00:24:33.130 --> 00:24:35.329 good or bad drawing, I don't know. The cells 00:24:35.329 --> 00:24:39.029 in the dorsal striatum are very special. They're 00:24:39.029 --> 00:24:45.029 called medium spiny neurons MSN and that's why 00:24:45.029 --> 00:24:48.990 the dopamine is a big part of this with the D1 00:24:48.990 --> 00:24:53.670 D2. So if you think about this, these are like 00:24:53.670 --> 00:24:58.509 branches or limbs off of a tree and then these 00:24:58.509 --> 00:25:01.349 are dendrites, okay, and then they have little 00:25:01.349 --> 00:25:04.599 spines on them. Okay, all of these spines are 00:25:04.599 --> 00:25:06.960 little parking spots. The projections coming 00:25:06.960 --> 00:25:09.420 in from those other areas that we drew out in 00:25:09.420 --> 00:25:13.200 the cortex, or wherever it might be, will land 00:25:13.200 --> 00:25:18.140 on a specific spine. Okay, now with the medium 00:25:18.140 --> 00:25:22.839 spiny neurons, spines are bigger. They're just 00:25:22.839 --> 00:25:26.720 a little bit larger than normal cells. So they 00:25:26.720 --> 00:25:30.740 will look more, if you look at a tree. okay this 00:25:30.740 --> 00:25:34.240 is an easy example some trees are loaded with 00:25:34.240 --> 00:25:39.180 leaves and some are not okay these medium spiny 00:25:39.180 --> 00:25:43.259 ones are like a nice oak tree nice oak tree in 00:25:43.259 --> 00:25:46.700 the summer okay now let's really zoom in again 00:25:46.700 --> 00:25:50.079 so let's look at let's look at this one let's 00:25:50.079 --> 00:25:53.259 look at this branch this dendrite and then this 00:25:53.259 --> 00:25:56.420 spine right here let's just say this is the spine 00:25:56.420 --> 00:26:02.200 okay This specific spine will receive a specific 00:26:02.200 --> 00:26:05.140 projection coming in, and it will mean the same 00:26:05.140 --> 00:26:10.099 thing every time. The thing that connects to 00:26:10.099 --> 00:26:12.740 this, that sends a projection to this spine, 00:26:12.980 --> 00:26:19.059 will be the same. Okay, so we have the pre -synaptic, 00:26:19.319 --> 00:26:22.859 the clef, and the post -synaptic. Okay, this 00:26:23.759 --> 00:26:26.720 Connection here will mean the exact same thing 00:26:26.720 --> 00:26:31.180 every time. So it's providing a little bit of 00:26:31.180 --> 00:26:33.779 update information. So that's what we're talking 00:26:33.779 --> 00:26:37.359 about. These neural correlates. So let's just 00:26:37.359 --> 00:26:39.539 say this came in from the sensory motor area 00:26:39.539 --> 00:26:44.140 and it projected down to the putamen because 00:26:44.140 --> 00:26:47.259 we're building a habit and it's hitting this 00:26:47.259 --> 00:26:52.589 cell with that specific spine. So this information 00:26:52.589 --> 00:26:57.329 will come in, signal to this spine and this cell 00:26:57.329 --> 00:27:01.369 will know what to do with it and how to help 00:27:01.369 --> 00:27:05.150 conduct these downstream actions or inactions 00:27:05.150 --> 00:27:08.210 which is still inaction because you're suppressing 00:27:08.210 --> 00:27:11.890 the target. You're suppressing movement. It's 00:27:11.890 --> 00:27:15.609 what the living organism is doing. This is why 00:27:15.609 --> 00:27:18.569 things like motivation or do you define motivation 00:27:18.569 --> 00:27:21.920 or your central nervous system does because as 00:27:21.920 --> 00:27:27.420 these are firing with repetition these grow so 00:27:27.420 --> 00:27:32.839 post -synaptic or pre -synaptic and post -synaptic 00:27:32.839 --> 00:27:35.420 okay and there's like little parking spots here 00:27:35.420 --> 00:27:39.500 remember like an mda and amp a amp a is going 00:27:39.500 --> 00:27:43.440 to be huge here it's huge with learning because 00:27:43.440 --> 00:27:47.529 this is what we're talking about as You build 00:27:47.529 --> 00:27:50.750 repetition and habits, these things get bigger. 00:27:50.829 --> 00:27:55.690 This is called morphology. It's synaptic plasticity. 00:27:57.130 --> 00:28:01.890 So let's compare this size. Remember, let's just 00:28:01.890 --> 00:28:05.269 say the inside diameter here versus something 00:28:05.269 --> 00:28:07.789 that you don't do very much. You're not very 00:28:07.789 --> 00:28:10.589 good at so forth. Maybe you want to be good at 00:28:10.589 --> 00:28:13.859 it. Maybe you want to. but you just don't have 00:28:13.859 --> 00:28:16.660 the skill set yet. This in the central nervous 00:28:16.660 --> 00:28:19.900 system is going to be preferred. The brain does 00:28:19.900 --> 00:28:22.460 not like to work. The central nervous system 00:28:22.460 --> 00:28:25.059 does not like to work. It just likes to respond. 00:28:25.440 --> 00:28:30.259 So when things are larger, like this, that is 00:28:30.259 --> 00:28:34.720 going to get the privilege. So this cell that 00:28:34.720 --> 00:28:38.400 is in this nuclei, that means this information 00:28:38.400 --> 00:28:42.250 will connect and carry out the movement with 00:28:42.250 --> 00:28:45.950 the autistic phenotype these cells are different 00:28:45.950 --> 00:28:50.069 these medium spiny neurons are different okay 00:28:50.069 --> 00:28:55.250 so dendrites are a little bit larger and the 00:28:55.250 --> 00:29:00.910 spines have a unique specificity and special 00:29:00.910 --> 00:29:05.529 privilege so this information coming in from 00:29:05.529 --> 00:29:10.349 the cortex will sure fire over anything else 00:29:10.680 --> 00:29:13.839 Because all of these different flexibilities, 00:29:14.200 --> 00:29:16.940 you can call these different spines flexibility, 00:29:17.339 --> 00:29:21.460 that the living organism might have, is not there 00:29:21.460 --> 00:29:26.000 with the autistic phenotype cell. So this certain 00:29:26.000 --> 00:29:31.059 spine, let's say, is larger like this and just 00:29:31.059 --> 00:29:36.140 limits flexibility and causes sameness or habits 00:29:36.140 --> 00:29:40.420 will always win. This is a big part of the autistic 00:29:40.420 --> 00:29:46.440 phenotype. This is why, autistic or not, you 00:29:46.440 --> 00:29:50.480 don't necessarily define motivation. These neural 00:29:50.480 --> 00:29:54.380 correlates and connections do. This is why change 00:29:54.380 --> 00:29:58.519 is hard. The central nervous system is going 00:29:58.519 --> 00:30:02.299 to determine what you do. Now I'm not saying 00:30:02.299 --> 00:30:04.960 that you can't reverse this I can't say that 00:30:04.960 --> 00:30:08.200 I'm not saying you can't change and build better 00:30:08.200 --> 00:30:11.259 connections through here maybe more connections 00:30:11.259 --> 00:30:13.920 maybe strengthen this one up because it's more 00:30:13.920 --> 00:30:17.980 preferred and these receptors will hit I'm not 00:30:17.980 --> 00:30:21.039 saying that at all but with the autistic phenotype 00:30:21.039 --> 00:30:24.200 the dorsal striatum and these sensory input areas 00:30:24.200 --> 00:30:27.339 and the lack of the prefrontal areas coming in 00:30:27.339 --> 00:30:30.529 to the dorsal striatum are limited Remember the 00:30:30.529 --> 00:30:34.470 ACC. We talk a lot about the ACC. It's action 00:30:34.470 --> 00:30:36.930 selection. Next episode is about the basal ganglia. 00:30:37.029 --> 00:30:40.849 We'll parse out this area right here. The globus 00:30:40.849 --> 00:30:45.069 palate is external because this is sending updated 00:30:45.069 --> 00:30:50.369 feedback to the dorsal striatum and is not well 00:30:50.369 --> 00:30:53.970 known. And also the subthalamic neculus. This 00:30:53.970 --> 00:30:56.769 little thalamus helper. It's receiving direct 00:30:56.769 --> 00:30:59.730 inputs from the cortex as well. to help providing 00:30:59.730 --> 00:31:03.650 it some help, helping the thalamus respond and 00:31:03.650 --> 00:31:08.509 so forth. But the big takeaway here is the kind 00:31:08.509 --> 00:31:13.650 of so -called abnormal medium spiny neurons and 00:31:13.650 --> 00:31:16.730 the limited flexibility with connections coming 00:31:16.730 --> 00:31:19.549 into the dorsal striata. Remember, this is just 00:31:19.549 --> 00:31:22.930 extracted out in one of these nihilas and then 00:31:22.930 --> 00:31:25.990 the connections happen. The big takeaway as well 00:31:25.990 --> 00:31:31.460 is this one spine receives information from one 00:31:31.460 --> 00:31:37.380 presynaptic area and is providing information 00:31:37.380 --> 00:31:41.259 and as which each synapses with each connection 00:31:41.259 --> 00:31:44.059 coming down into from the cortex down to the 00:31:44.059 --> 00:31:47.720 dorsal striatum it's building a summary each 00:31:47.720 --> 00:31:51.660 synaptic connection builds summary summary summary 00:31:51.660 --> 00:31:54.779 and it's building a bigger story overall and 00:31:54.779 --> 00:31:57.480 then it gets to the time where it's orchestrating 00:31:57.740 --> 00:32:01.640 the go or no go movement which is speaking back 00:32:01.640 --> 00:32:04.359 up to the cortex and it's just a constant feed 00:32:04.359 --> 00:32:08.960 forward feedback loop this is constantly going 00:32:08.960 --> 00:32:10.740 i don't know if i covered everything i wanted 00:32:10.740 --> 00:32:13.740 to cover though i do want to say this with the 00:32:13.740 --> 00:32:16.920 autistic phenotype because this is a big thing 00:32:16.920 --> 00:32:19.819 this is a big thing because you can now know 00:32:19.819 --> 00:32:24.859 about b2 it's just on samus and flexible adherence 00:32:24.859 --> 00:32:28.359 to routines or ritualized patterns of verbal 00:32:28.359 --> 00:32:32.539 or nonverbal behavior speech is heavily involved 00:32:32.539 --> 00:32:36.119 in here speech will run through here and b3 highly 00:32:36.119 --> 00:32:38.319 restricted fixated interests that are abnormal 00:32:38.319 --> 00:32:41.819 in intensity or focus strong attachment to or 00:32:41.819 --> 00:32:45.220 preoccupation with unusual objects excessively 00:32:45.220 --> 00:32:50.240 circumscribed or perseverative interest this 00:32:50.240 --> 00:32:53.380 is autism b3 is the core of autism restricted 00:32:53.380 --> 00:32:56.039 fixated interests that are abnormal in intensity 00:32:56.039 --> 00:33:01.720 or focus right here. We build habits. We have 00:33:01.720 --> 00:33:04.220 these so -called splinter skills. Asperger's 00:33:04.220 --> 00:33:07.460 little professors. Because these connections 00:33:07.460 --> 00:33:11.980 are constantly firing and it's easy for us to 00:33:11.980 --> 00:33:14.920 sit here. Remember the sensory processing with 00:33:14.920 --> 00:33:17.920 the the amount of being able to absorb information. 00:33:19.220 --> 00:33:21.789 That information goes here. We're kind of mapping 00:33:21.789 --> 00:33:24.789 this out. Basil Ganglia, do you define your motivation 00:33:24.789 --> 00:33:25.309 or not?