WEBVTT 00:00:08.490 --> 00:00:11.169 So we have an episode about spindle neurons, 00:00:11.710 --> 00:00:16.649 sometimes called von -economo neurons. And these 00:00:16.649 --> 00:00:21.149 are very relevant to the autistic phenotype. 00:00:22.550 --> 00:00:33.270 So these are spindle, sometimes called von -economo 00:00:33.270 --> 00:00:41.679 or V -E -N. Von Economo neurons. Von Economo 00:00:41.679 --> 00:00:45.920 kind of discovered these in the 1920s. Before 00:00:45.920 --> 00:00:48.399 that, though, in medical literature and medical 00:00:48.399 --> 00:00:51.679 textbooks, there were some mentions of it around 00:00:51.679 --> 00:00:55.659 the late 19th century, 1880s and so forth. I 00:00:55.659 --> 00:00:57.780 think there were some mentions of it, how these 00:00:57.780 --> 00:01:01.280 certain type of neuron shaped a little bit different. 00:01:01.500 --> 00:01:04.159 We'll draw them out shortly. But these are called 00:01:04.159 --> 00:01:07.379 spindle neurons because of the shape. More recently, 00:01:07.659 --> 00:01:10.760 over the last 20 years, a researcher named John 00:01:10.760 --> 00:01:15.799 Allman has studied these quite extensively. He 00:01:15.799 --> 00:01:18.400 has a lot of good research on dispental neurons. 00:01:18.920 --> 00:01:21.719 These are very fascinating because they are only 00:01:21.719 --> 00:01:26.200 found in a few type of creatures, very socially 00:01:26.200 --> 00:01:29.060 active type of creatures. So humans have them, 00:01:29.359 --> 00:01:35.040 larger primates like orangutans, gorillas, bonobos. 00:01:35.340 --> 00:01:40.379 A few seditions like whales and dolphins have 00:01:40.379 --> 00:01:45.900 them. Elephants. So there's only like 10 or 12 00:01:45.900 --> 00:01:48.439 different species that these are discovered in. 00:01:49.620 --> 00:01:55.599 And humans have them in primarily two different 00:01:55.599 --> 00:01:59.379 regions. Two regions that we've discussed quite 00:01:59.379 --> 00:02:03.500 in detail. the anterior cingulate cortex or the 00:02:03.500 --> 00:02:07.379 ACC and the insula, specifically the frontal 00:02:07.379 --> 00:02:12.080 or the anterior insula. So these spinal neurons 00:02:12.080 --> 00:02:17.780 are, they're provided to have rapid transmission 00:02:17.780 --> 00:02:22.120 for social context is what they're doing. They're 00:02:22.120 --> 00:02:26.900 very larger than normal neurons and they only 00:02:26.900 --> 00:02:29.650 act mainly on the different types of monoamines, 00:02:29.870 --> 00:02:34.330 especially dopamine and serotonin, and a specific 00:02:34.330 --> 00:02:38.530 cell, a peptide, that we've never discussed, 00:02:38.550 --> 00:02:42.789 I don't believe, and that's neuropeptide Y. So 00:02:42.789 --> 00:02:50.330 very, it's not really discussed quite frankly. 00:02:51.150 --> 00:02:53.490 And some of these things are, well this is a 00:02:53.490 --> 00:02:58.199 peptide, so if you remember, oxytocin and vasopressin 00:02:58.199 --> 00:03:02.620 episode. Peptides are just a collection of proteins, 00:03:02.960 --> 00:03:06.979 amino acids. So oxytocin and vasopressin are 00:03:06.979 --> 00:03:09.460 pretty easy because there's only nine and they 00:03:09.460 --> 00:03:13.039 share the seven of the nine peptides. But neuropeptide 00:03:13.039 --> 00:03:18.199 Y has 36 protein bonds or chains of proteins. 00:03:18.860 --> 00:03:22.120 And these are, the neuropeptide Y is heavily 00:03:22.120 --> 00:03:27.650 involved with fear buffering. So It kind of makes 00:03:27.650 --> 00:03:31.210 sense if you're navigating a social world. And 00:03:31.210 --> 00:03:33.330 whenever I'm talking about social world, it's 00:03:33.330 --> 00:03:36.530 not just necessarily communication or hanging 00:03:36.530 --> 00:03:39.169 out with others and so forth. It's not really 00:03:39.169 --> 00:03:42.409 what this is about. This is more of a specific 00:03:42.409 --> 00:03:46.050 type of social environment. This is just interacting 00:03:46.050 --> 00:03:49.509 with anything from the environment. Humans are 00:03:49.509 --> 00:03:53.310 very social creatures, so we're constantly being 00:03:53.310 --> 00:03:55.590 entangled with many different types of things 00:03:55.590 --> 00:03:59.629 in the environment. Other things with the neuropeptide 00:03:59.629 --> 00:04:03.810 Y is regulating things like food intake and metabolism 00:04:03.810 --> 00:04:06.789 and autonomic functions, things like breathing 00:04:06.789 --> 00:04:11.389 and heart rate. So, you know, it's a peptide, 00:04:11.729 --> 00:04:15.469 so they have a pretty diverse type of functioning 00:04:15.469 --> 00:04:18.509 the peptides do, similar to the oxytocin and 00:04:18.509 --> 00:04:25.750 vasopressin. So, These two brain regions right 00:04:25.750 --> 00:04:28.050 here are very critical, and that's why I just 00:04:28.050 --> 00:04:30.410 listed them out before we got started so we can 00:04:30.410 --> 00:04:34.829 go over the roles of them. So the ACC, the anterior 00:04:34.829 --> 00:04:39.009 cingulate cortex, which is here, it's part of 00:04:39.009 --> 00:04:43.670 the medial prefrontal cortex. It's commonly just 00:04:43.670 --> 00:04:46.829 highlighted as a medial prefrontal cortex nuclei 00:04:46.829 --> 00:04:50.290 or subdivision. It has massive roles, and we've 00:04:50.290 --> 00:04:52.910 covered these roles in several different episodes. 00:04:53.129 --> 00:04:55.470 But conflict monitoring and error detection, 00:04:56.689 --> 00:05:00.990 evaluating risk and reward. So potential choices 00:05:00.990 --> 00:05:04.350 and outcomes is what this is kind of doing. We 00:05:04.350 --> 00:05:08.029 talk a lot about internal calculators. ACC is 00:05:08.029 --> 00:05:10.550 a huge internal calculator for these types of 00:05:10.550 --> 00:05:14.050 things. Go -directed type of behaviors. So it's 00:05:14.050 --> 00:05:19.759 in the medial part. Typically with things like 00:05:19.759 --> 00:05:22.339 the prefrontal cortex and the dorsal striatum, 00:05:22.600 --> 00:05:26.699 the more medial you are, the more in the middle 00:05:26.699 --> 00:05:31.019 or inside, deep inside the brain, is more reflective 00:05:31.019 --> 00:05:36.100 of goal type behaviors. And then the habits kind 00:05:36.100 --> 00:05:40.439 of branch off laterally, okay, as we evolve as 00:05:40.439 --> 00:05:43.540 species, different types of species. It's goal 00:05:43.540 --> 00:05:47.199 directed on the inside. and then habit forming 00:05:47.199 --> 00:05:50.379 will come later because that that requires a 00:05:50.379 --> 00:05:53.639 lot of repetition so it grows outward is a good 00:05:53.639 --> 00:05:58.240 way of thinking about that. In mice and rat studies 00:05:58.240 --> 00:06:02.680 there are good go directive versus habit formation 00:06:02.680 --> 00:06:05.980 and you can do things like outcome devaluation 00:06:05.980 --> 00:06:09.379 to kind of disassociate the behavior because 00:06:09.379 --> 00:06:12.259 you can't ask the rat or mouse they they can't 00:06:12.259 --> 00:06:15.620 tell you. controlling autonomic functions as 00:06:15.620 --> 00:06:18.759 well, and physiology. And we often say right 00:06:18.759 --> 00:06:22.040 here, adaptive responses. When we're responding 00:06:22.040 --> 00:06:25.300 well in the environment, that's called adaptive 00:06:25.300 --> 00:06:28.079 responses. And with autism, you can think about 00:06:28.079 --> 00:06:30.819 just an overarching way of describing it as a 00:06:30.819 --> 00:06:33.720 lack of adaptive responses, because there's not 00:06:33.720 --> 00:06:37.060 a lot of skill set. There's not a lot of social 00:06:37.060 --> 00:06:40.420 databases and skills to pull from as we navigate 00:06:40.420 --> 00:06:47.060 the world. Second is the insula. The insula is 00:06:47.060 --> 00:06:51.040 a very fascinating region because it has privilege. 00:06:51.379 --> 00:06:54.860 It's very privileged to having information coming 00:06:54.860 --> 00:06:57.560 in about the brain, what's going on inside the 00:06:57.560 --> 00:07:00.000 brain, the thoughts and the feelings and so forth, 00:07:00.279 --> 00:07:03.519 the different brain waves, and the body. So it's 00:07:03.519 --> 00:07:06.839 getting information from the physiology. My heart 00:07:06.839 --> 00:07:10.439 rate's okay. I'm okay right now. My breathing, 00:07:10.759 --> 00:07:13.540 the depth and rate, I'm okay right now. But what 00:07:13.540 --> 00:07:15.639 if you're not what if you're I'm just sitting 00:07:15.639 --> 00:07:18.939 here or you're just sitting around not doing 00:07:18.939 --> 00:07:22.319 much physical activity and your heart rates jumping 00:07:22.319 --> 00:07:25.899 and your breathing's kind of The rate in depth 00:07:25.899 --> 00:07:28.680 is kind of off. You might register. Oh, something's 00:07:28.680 --> 00:07:31.139 not right here Well, that's feeding up to the 00:07:31.139 --> 00:07:34.339 insula to inform the rest of the brain. Something's 00:07:34.339 --> 00:07:37.680 not right here and The insula is also getting 00:07:37.680 --> 00:07:40.819 information from the environment. So three main 00:07:41.259 --> 00:07:44.360 Data sources to pull from, the brain state, the 00:07:44.360 --> 00:07:46.959 body state, and the environment. How is the living 00:07:46.959 --> 00:07:49.779 organism incorporating all three of those? So 00:07:49.779 --> 00:07:52.439 the insula is a very fascinating little region 00:07:52.439 --> 00:07:55.779 here, and it's right here. This is the frontal 00:07:55.779 --> 00:07:59.720 part, and then the posterior part kind of expands 00:07:59.720 --> 00:08:04.180 this way. Now the insula is very lateral, okay, 00:08:04.360 --> 00:08:08.259 especially in comparison to the ACC and all of 00:08:08.259 --> 00:08:11.500 these other subcortical areas. that will go over. 00:08:11.899 --> 00:08:15.259 It's very lateral. It's more likely that it came 00:08:15.259 --> 00:08:21.100 on board later in the evolution. This is also 00:08:21.100 --> 00:08:23.959 known as a gatekeeper in task switching. So one 00:08:23.959 --> 00:08:26.360 thing that's fascinating about the cingulate 00:08:26.360 --> 00:08:30.879 cortex is, and it doesn't matter if it's the 00:08:30.879 --> 00:08:35.059 anterior, the posterior, the subgenual, whatever, 00:08:35.580 --> 00:08:38.590 the cingulate Let's imagine these are white fiber 00:08:38.590 --> 00:08:42.070 tracks, nerve tracks, nerve fibers, or so forth. 00:08:42.769 --> 00:08:47.970 Okay. Remember, we've talked about things like 00:08:47.970 --> 00:08:51.649 the fasciculi and things, um, these nerve fibers, 00:08:51.950 --> 00:08:56.590 myelination and so forth. They, um, they connect 00:08:56.590 --> 00:08:58.809 brain regions. This will bring brain regions. 00:08:58.950 --> 00:09:01.190 We'll go over the many columns as well, because 00:09:01.190 --> 00:09:04.529 spindle neurons are heavy and layer five B, but 00:09:04.529 --> 00:09:07.779 the cingulate And I learned this from Nolan Williams, 00:09:08.419 --> 00:09:13.700 MD, PhD, just passed away. Very, very brilliant 00:09:13.700 --> 00:09:18.940 researcher. Huge with investigating depression 00:09:18.940 --> 00:09:21.500 and things like that. So hopefully his soul is 00:09:21.500 --> 00:09:28.240 resting in peace. But the cingulate wraps. Wraps 00:09:28.240 --> 00:09:40.100 around. white matter tracks like like like this 00:09:40.100 --> 00:09:55.740 Okay So it's just wrapping around white matter 00:09:55.740 --> 00:09:59.700 tracks and that gives the cingulate a lot of 00:09:59.700 --> 00:10:04.110 access a lot of fast -acting access as well So 00:10:04.110 --> 00:10:09.850 the insula and cingulate cortex, it makes sense 00:10:09.850 --> 00:10:14.049 why it's really involved in these kind of fast 00:10:14.049 --> 00:10:17.690 -acting rapid transmission type of social bonding 00:10:17.690 --> 00:10:26.509 type of neuron. Okay, so if you remember, we've 00:10:26.509 --> 00:10:30.789 covered a network, the so -called salience network. 00:10:31.070 --> 00:10:34.500 These two regions are essentially the main regions, 00:10:34.679 --> 00:10:37.700 the hubs of the salience network. So this is 00:10:37.700 --> 00:10:45.139 a big thing. The salience network allows us to 00:10:45.139 --> 00:10:47.000 divide our attention. What are we going to pay 00:10:47.000 --> 00:10:49.159 attention to? What is most important to the living 00:10:49.159 --> 00:10:55.259 organism? Okay, so you have the ACC and interior 00:10:55.259 --> 00:10:57.519 insula and then you have all of these subcortical 00:10:57.519 --> 00:11:01.639 areas. Things like the ventral striatum, which 00:11:01.639 --> 00:11:07.600 is a Mostly the nucleus accumbens. The nucleus 00:11:07.600 --> 00:11:10.399 accumbens is a very large region, to be frank. 00:11:10.820 --> 00:11:14.580 The thalamus, of course, the hippocampus, the 00:11:14.580 --> 00:11:17.700 substantia nigra compacta. Remember the episode 00:11:17.700 --> 00:11:21.480 with Parkinson's and the basal ganglia? The substantia 00:11:21.480 --> 00:11:25.559 nigra compacta is dopamine. The reticulata, which 00:11:25.559 --> 00:11:29.279 is kind of, it's like a Nike check almost. And 00:11:29.279 --> 00:11:32.110 the check part, the part that comes up. is the 00:11:32.110 --> 00:11:34.549 reticulata. And then also the VTA, the ventral 00:11:34.549 --> 00:11:37.250 tegmental area. This is dopamine. So these two 00:11:37.250 --> 00:11:40.889 are dopamine areas. And then the amygdala and 00:11:40.889 --> 00:11:44.950 the hypothalamus here. So the salience network, 00:11:45.149 --> 00:11:48.070 these are mostly the hubs and these subcortical 00:11:48.070 --> 00:11:52.789 areas are kind of nodes, what's called nodes. 00:11:54.029 --> 00:11:56.730 So collectively these are kind of all working 00:11:56.730 --> 00:12:00.840 together to help the living organism send our 00:12:00.840 --> 00:12:04.659 spotlight of attention to whatever we find most 00:12:04.659 --> 00:12:08.299 salient, salience network. And then also the 00:12:08.299 --> 00:12:14.320 spindle neuron, there's, in 2008, there's small 00:12:14.320 --> 00:12:17.840 clusters of the spindle neurons found in the 00:12:17.840 --> 00:12:20.360 dorsolateral prefrontal cortex, just like clusters 00:12:20.360 --> 00:12:27.480 of two. So they're very, very sparse, rare. with 00:12:27.480 --> 00:12:30.200 the anterior cingulate cortex and the insula. 00:12:30.500 --> 00:12:41.659 So we have approximately 100 ,000 to 200 ,000 00:12:41.659 --> 00:12:44.500 spindle neurons in the central nervous system. 00:12:45.200 --> 00:12:52.139 These are just neurons, okay? Now, overall the 00:12:52.139 --> 00:12:58.879 human body has roughly 85, 88 billion neurons 00:12:58.879 --> 00:13:01.600 in the central nervous system. So there's not 00:13:01.600 --> 00:13:05.139 a whole lot of these spindle neurons in comparison 00:13:05.139 --> 00:13:14.340 to overall neuron. What I want to really say 00:13:14.340 --> 00:13:18.620 about, here let's just go ahead and erase this. 00:13:21.419 --> 00:13:24.899 because I've talked a little bit about several 00:13:24.899 --> 00:13:30.960 different times the paper from 2024 about the 00:13:30.960 --> 00:13:37.000 salience network with six week old human beings 00:13:37.000 --> 00:13:40.620 human infants and the salience network this was 00:13:40.620 --> 00:13:54.200 done at UCLA UCLA sang at all and Lucinda Uden 00:13:54.200 --> 00:14:01.039 is on this paper. U -D -D -I -N. Lucinda Uden 00:14:01.039 --> 00:14:05.480 kind of really captured the role of the insula 00:14:05.480 --> 00:14:11.019 in about 2008, 2010, and so forth was a really 00:14:11.019 --> 00:14:14.259 high year for the insula or years. Still is, 00:14:14.279 --> 00:14:17.779 it still is. But on six weeks, this study on 00:14:17.779 --> 00:14:23.889 six weeks though, they used fMRI during Not non 00:14:23.889 --> 00:14:26.649 -activity, so it's almost like a sleep state 00:14:26.649 --> 00:14:32.129 on humans though they found that children that 00:14:32.129 --> 00:14:35.669 would Had a high likelihood of having autism 00:14:35.669 --> 00:14:38.330 so they had autism as their siblings already 00:14:38.330 --> 00:14:42.750 had autism so they would hook fMRI up to these 00:14:42.750 --> 00:14:48.669 human babies and just check their check their 00:14:48.669 --> 00:14:52.240 connections essentially and The high likelihood 00:14:52.240 --> 00:14:56.379 found that the salience network had a strong 00:14:56.379 --> 00:15:02.159 connection to this area right here. The sensory 00:15:02.159 --> 00:15:06.320 motor area, which is right here. A lot of our 00:15:06.320 --> 00:15:08.740 adaptive, not adaptive responses, but a lot of 00:15:08.740 --> 00:15:14.220 our automatic responses will live here versus 00:15:14.220 --> 00:15:18.500 here. We'd like to send a lot more reflexive 00:15:18.500 --> 00:15:22.100 things. Habitual things up to here and then it 00:15:22.100 --> 00:15:25.100 can just feed down into the dorsal striatum and 00:15:25.100 --> 00:15:28.539 then Kind of start the basal ganglia for movements 00:15:28.539 --> 00:15:33.860 and actions so they found six weeks old a stronger 00:15:33.860 --> 00:15:37.379 connection to the sensory motor area and if you 00:15:37.379 --> 00:15:39.659 think about autism and kind of the rigid thinking 00:15:39.659 --> 00:15:45.200 this and lack of cognitive flexibility right 00:15:45.200 --> 00:15:50.129 here versus the the typical likelihood the other 00:15:50.129 --> 00:15:53.289 children six weeks old they had a stronger connection 00:15:53.289 --> 00:15:59.929 with areas here it's a big finding but nobody 00:15:59.929 --> 00:16:02.730 does anything with it it's just kind of lost 00:16:02.730 --> 00:16:06.830 in the academic literature nobody does anything 00:16:06.830 --> 00:16:14.830 with this stuff and what's fascinating here is 00:16:14.860 --> 00:16:17.779 you know it's UCLA it's like an ivory tower they 00:16:17.779 --> 00:16:21.879 followed these kids up that um because they were 00:16:21.879 --> 00:16:24.320 only six weeks old they followed them up to like 00:16:24.320 --> 00:16:28.159 years two and three and they could confirm like 00:16:28.159 --> 00:16:30.460 the ones that had a stronger connection to here 00:16:30.460 --> 00:16:34.480 definitely indeed autistic phenotype nobody does 00:16:34.480 --> 00:16:37.399 anything with this stuff though so let's draw 00:16:37.399 --> 00:16:42.039 out the spindle neurons versus um things like 00:16:42.039 --> 00:16:49.200 the pyramidal neurons okay so you know pyramidal 00:16:49.200 --> 00:16:53.080 neurons they have this pyramid okay and then 00:16:53.080 --> 00:16:59.320 you have the things like um these dendrites and 00:16:59.320 --> 00:17:15.140 axons falling off of it and like so you get the 00:17:15.140 --> 00:17:19.859 good idea here it's more like a like a typical 00:17:19.859 --> 00:17:24.099 neuron especially the spindle or the the pyramidal 00:17:24.099 --> 00:17:31.259 the spindle neuron the cell body is like that 00:17:31.259 --> 00:17:33.220 it's more of like this that's why it's a spindle 00:17:33.220 --> 00:17:45.279 neuron and it's bipolar So it looks a lot like 00:17:45.279 --> 00:17:48.980 this. So here's a big thing too. It's it's much 00:17:48.980 --> 00:17:53.500 larger and This allows for that rapid transmission 00:17:53.500 --> 00:18:01.380 so The ones in the ACC are actually found to 00:18:01.380 --> 00:18:06.019 be a little bit larger even the ones in the ACC 00:18:06.019 --> 00:18:12.799 They can extend down quite a bit so it looks 00:18:12.799 --> 00:18:16.859 more like that now if you remember the layers 00:18:16.859 --> 00:18:41.599 of the many columns we had all of these type 00:18:41.599 --> 00:19:08.140 of cells here and then layer four has the select 00:19:08.140 --> 00:19:16.150 cells So forth and then down here we have more 00:19:16.150 --> 00:19:37.049 of these And here's where you can find some of 00:19:37.049 --> 00:19:41.650 these spindle neurons so they they can be like 00:19:47.900 --> 00:20:00.160 much larger and so forth but they're very they're 00:20:00.160 --> 00:20:04.339 very rare but they're predominantly in layer 00:20:04.339 --> 00:20:07.960 five right here now not covered in the mini columns 00:20:07.960 --> 00:20:11.940 little video is this layer down here directly 00:20:11.940 --> 00:20:15.420 below these mini columns remember this is would 00:20:15.420 --> 00:20:18.630 be considered a mini mini column and then we 00:20:18.630 --> 00:20:22.349 would have very many different many columns and 00:20:22.349 --> 00:20:24.809 it would eventually become a micro column and 00:20:24.809 --> 00:20:29.750 so forth. This layer right below layer 6a and 00:20:29.750 --> 00:20:33.789 6b is white matter. This is where a lot of distal 00:20:33.789 --> 00:20:38.250 connections will happen. So these spindle neurons 00:20:38.250 --> 00:20:41.049 remember inputs come here to layer four from 00:20:41.049 --> 00:20:43.769 the thalamus and then it goes to two and three 00:20:43.769 --> 00:20:47.549 because this is where the subjective experiences 00:20:47.549 --> 00:20:50.130 of the living organisms essentially live is layer 00:20:50.130 --> 00:20:53.990 three. It's a glare, all right? And then it will 00:20:53.990 --> 00:20:58.109 shoot down to five. This larger spindle neuron 00:20:58.109 --> 00:21:02.910 will allow this information to be received and 00:21:02.910 --> 00:21:05.150 transmitted down to these white matter tracks 00:21:05.150 --> 00:21:08.509 faster. And that way we can respond faster to 00:21:08.509 --> 00:21:12.680 the environment. This is... Not so much a social 00:21:12.680 --> 00:21:14.660 thing like I'm gonna go hang out with friends. 00:21:14.680 --> 00:21:17.779 This is a survival thing. This is an ability 00:21:17.779 --> 00:21:21.859 to Get information from the environment fast 00:21:21.859 --> 00:21:27.440 so you can make decisions this is Space -time 00:21:27.440 --> 00:21:30.900 again we're always talking about space -time 00:21:30.900 --> 00:21:34.140 and these different spiral neurons are very rare 00:21:34.140 --> 00:21:39.559 and they're regarding socialness and autistics 00:21:41.990 --> 00:21:46.950 have kind of a complicated number with the spindle 00:21:46.950 --> 00:21:50.609 neurons. At first, in the first four years of 00:21:50.609 --> 00:21:54.769 life, it's kind of off and then later on in life 00:21:54.769 --> 00:22:01.690 as well. It's just post -mortem studies. We'll 00:22:01.690 --> 00:22:08.470 hit this. So there's a lack of kind of these 00:22:08.470 --> 00:22:13.490 types of cells. And, you know, if you think about 00:22:13.490 --> 00:22:18.269 the comment about the adaptive responses from 00:22:18.269 --> 00:22:22.109 earlier, it's just, it makes socialness, the 00:22:22.109 --> 00:22:25.990 outside world, I should say, complicated. And 00:22:25.990 --> 00:22:30.829 because of this region right here, the insula, 00:22:32.230 --> 00:22:34.670 the outside world, and the salience network, 00:22:35.569 --> 00:22:41.859 our attention is going to be inward. to the self.