WEBVTT 00:00:01.320 --> 00:00:05.740 For today's episode, we will cover autism and 00:00:05.740 --> 00:00:10.880 communication disorders. These are a few, four, 00:00:10.880 --> 00:00:15.119 five, or six disorders right before the autism 00:00:15.119 --> 00:00:19.940 section of the DSM -5 -TR. These are heavily 00:00:19.940 --> 00:00:23.000 involved with speech and language abilities. 00:00:24.480 --> 00:00:27.940 We will cover the brain regions, connectivity, 00:00:29.079 --> 00:00:34.240 brainwave patterns, how they are measured, longitudinal 00:00:34.240 --> 00:00:36.820 studies, and a rare region of interest for the 00:00:36.820 --> 00:00:41.859 podcast, interventions. I don't love it, but 00:00:41.859 --> 00:00:45.619 some genetics as well. We will mostly cover this 00:00:45.619 --> 00:00:49.659 as part of expanding on the autism and speech 00:00:49.659 --> 00:00:53.780 and language episode from the spring and last 00:00:53.780 --> 00:00:56.659 week's Decoding the Brain, how reading works 00:00:56.659 --> 00:01:00.020 in autism and dyslexia. We are kind of piecing 00:01:00.020 --> 00:01:02.820 this together because this is all in play here 00:01:02.820 --> 00:01:08.040 as well. Mostly we are talking about criteria 00:01:08.040 --> 00:01:12.159 A, the abnormalities in social communication 00:01:12.159 --> 00:01:16.000 and interaction of the autistic phenotype criteria 00:01:16.000 --> 00:01:21.819 A. These are things like language abilities, 00:01:22.719 --> 00:01:26.500 nonverbal communication, starting and stopping 00:01:26.500 --> 00:01:30.780 conversation. understanding sarcasm, and even 00:01:30.780 --> 00:01:34.540 maintaining conversational flow. All pretty much 00:01:34.540 --> 00:01:39.079 challenges for the autistic phenotype. For social 00:01:39.079 --> 00:01:43.420 or pragmatic communication disorder, this is 00:01:43.420 --> 00:01:48.959 SCD. This is kind of pragmatic problems. 50 to 00:01:48.959 --> 00:01:54.200 70 percent of individuals with autism show pragmatic 00:01:54.200 --> 00:01:58.859 deficits that resembles social pragmatic communication 00:01:58.859 --> 00:02:03.819 disorder. However, these cannot coexist. You 00:02:03.819 --> 00:02:09.000 should never have a co -diagnosis of autism and 00:02:09.000 --> 00:02:11.919 social communication disorder, sometimes called 00:02:11.919 --> 00:02:17.159 pragmatic disorder. Here's a wide range. 4 to 00:02:17.159 --> 00:02:22.280 22 percent experience childhood onset fluency 00:02:22.280 --> 00:02:25.639 disorder. Now previously, this was just called 00:02:25.639 --> 00:02:29.860 stuttering. In the DSM -5, they think they're 00:02:29.860 --> 00:02:33.580 being kind now, I guess. I don't know. Child 00:02:33.580 --> 00:02:38.400 onset fluency disorder with stuttering highlighted. 00:02:39.919 --> 00:02:44.759 20 % to 30 % have speech sound disorder, and 00:02:44.759 --> 00:02:48.620 up to 50 % meet criteria for developmental language 00:02:48.620 --> 00:02:52.840 disorder. So those are the four. Social communication 00:02:52.840 --> 00:02:57.789 disorder, or pragmatic. child onset fluency disorder 00:02:57.789 --> 00:03:04.069 or stuttering, speech sound disorder, and developmental 00:03:04.069 --> 00:03:09.909 language disorder. These overlaps stem from disruptions 00:03:09.909 --> 00:03:14.090 in shared neural circuits, particularly those 00:03:14.090 --> 00:03:17.469 involved in language processing and motor control 00:03:17.469 --> 00:03:22.090 and social cognition modulated by some genetic 00:03:22.090 --> 00:03:24.280 factors. And here are the two that we're going 00:03:24.280 --> 00:03:28.860 to kind of spend most of the time on. FOXP2. 00:03:29.659 --> 00:03:31.520 And one you might recognize if you listen to 00:03:31.520 --> 00:03:34.900 the podcast, as it's been mentioned several different 00:03:34.900 --> 00:03:41.259 times and even with Dr. Hannah Stevens. CNT -NAP2. 00:03:42.479 --> 00:03:47.500 These specific comorbidities are crucial for 00:03:47.500 --> 00:03:50.500 developing targeted interventions that address 00:03:50.500 --> 00:03:54.330 both the autistic phenotype and these other communication 00:03:54.330 --> 00:03:59.509 style disorders. So here are some shared neural 00:03:59.509 --> 00:04:02.770 features, some brain regions involved, and pretty 00:04:02.770 --> 00:04:05.550 much all of these. And they're very popular. 00:04:05.650 --> 00:04:07.550 If you listen to the podcast, these are very 00:04:07.550 --> 00:04:11.389 popular. The medial prefrontal cortex, which 00:04:11.389 --> 00:04:15.569 is one of my favorites. Temporal parietal junction. 00:04:16.629 --> 00:04:18.670 We've talked about that in several episodes, 00:04:18.810 --> 00:04:22.060 both of those regions actually. The superior 00:04:22.060 --> 00:04:25.459 temporal sulcus. Remember that from the decoding 00:04:25.459 --> 00:04:29.360 the brain episode on reading. These three are 00:04:29.360 --> 00:04:33.139 critical for social cognition and a so -called 00:04:33.139 --> 00:04:36.279 theory of mind, which is kind of incomplete. 00:04:37.819 --> 00:04:40.399 The ability to understand others' perspectives 00:04:40.399 --> 00:04:43.560 and intentions are what we basically are talking 00:04:43.560 --> 00:04:47.360 about. In the autistic phenotype, these regions 00:04:47.360 --> 00:04:52.269 consistently show hypo activation. during tasks 00:04:52.269 --> 00:04:57.110 requiring social understanding, such as interpreting 00:04:57.110 --> 00:05:01.329 facial expressions or conversational context 00:05:01.329 --> 00:05:05.310 leading to difficulties in social communication. 00:05:06.529 --> 00:05:09.769 Some examples for you. When individuals with 00:05:09.769 --> 00:05:15.209 autism process social cues, MRI studies reveal 00:05:15.209 --> 00:05:19.170 reduced activity in the right temporal parietal 00:05:19.170 --> 00:05:23.449 junction. which is essential for perspective 00:05:23.449 --> 00:05:28.610 taking. The so -called mirror neuron system. 00:05:29.370 --> 00:05:34.290 Now mirror neurons are kind of hit or miss, but 00:05:34.290 --> 00:05:37.430 I think for this topic it's kind of important 00:05:37.430 --> 00:05:40.990 to mention. These are located in the inferior 00:05:40.990 --> 00:05:44.209 frontal gyrus. Remember last week's episode on 00:05:44.209 --> 00:05:47.730 decoding the brain. This includes Broca. So it's 00:05:47.730 --> 00:05:52.470 huge for language processing. and also the inferior 00:05:52.470 --> 00:05:57.889 parietal lobe. This is responsible for imitating 00:05:57.889 --> 00:06:01.129 actions and understanding others' intentions. 00:06:01.709 --> 00:06:05.569 So hard stop. I just really want to mention this. 00:06:06.910 --> 00:06:09.769 The benefit of the autistic phenotype is to be 00:06:09.769 --> 00:06:13.730 our own person, not be influenced or caught up 00:06:13.730 --> 00:06:17.110 or care even about what other people are doing. 00:06:17.339 --> 00:06:22.800 That is not that bad of a thing. Our so -called 00:06:22.800 --> 00:06:26.100 internal state, remember the definition or translation 00:06:26.100 --> 00:06:31.519 of autism itself. It's very entertaining and 00:06:31.519 --> 00:06:36.139 intense with these imaginations and visual thinking. 00:06:36.740 --> 00:06:40.480 Whereas the outside world is one very chaotic. 00:06:41.040 --> 00:06:44.040 Remember the sensory processing episodes in those 00:06:44.040 --> 00:06:49.079 so -called heightened states. hyper, brain waves, 00:06:49.439 --> 00:06:52.639 staying in gamma. The outside world is complicated. 00:06:53.360 --> 00:06:55.660 And most of the time, it's not as interesting, 00:06:56.079 --> 00:06:59.879 just quite frank. In the autistic phenotype, 00:07:00.139 --> 00:07:04.319 these so -called mirror neurons exhibits reduced 00:07:04.319 --> 00:07:08.839 activation during tasks like observing gestures, 00:07:10.540 --> 00:07:13.660 contributing to deficits in social interaction 00:07:13.660 --> 00:07:19.629 and communication. The cerebellum is also involved. 00:07:19.629 --> 00:07:24.689 Remember Dr. Reza Shadmir, particularly in the 00:07:24.689 --> 00:07:28.610 cerebellum, the vermis. This plays a role in 00:07:28.610 --> 00:07:32.949 motor coordination and speech porosity, porosity 00:07:32.949 --> 00:07:37.550 maybe, which is melodic lines of speech, such 00:07:37.550 --> 00:07:40.910 as the frequency, the intensity and duration 00:07:40.910 --> 00:07:46.250 of the spoken word. Pitch, volume, pace, and 00:07:46.250 --> 00:07:51.990 rhythm. Think monotone is not that. The autistic 00:07:51.990 --> 00:07:54.610 phenotype, there's plenty of impressive data 00:07:54.610 --> 00:07:58.490 here. And remember our guest, Dr. Shadmere, sharing 00:07:58.490 --> 00:08:01.810 information here. Such a great episode. He's 00:08:01.810 --> 00:08:05.730 such a great human being. Shows reduced Purgenji 00:08:05.730 --> 00:08:09.610 cell density. This is very, very common and leads 00:08:09.610 --> 00:08:13.329 to atypical speech patterns such as monotone 00:08:13.329 --> 00:08:17.379 or irregular porosity. These tongue movements, 00:08:17.860 --> 00:08:22.519 too. These are reduced. Some shared functional 00:08:22.519 --> 00:08:26.899 and structural connectivity. The autism phenotype 00:08:26.899 --> 00:08:30.600 is characterized by disrupted connectivity patterns 00:08:30.600 --> 00:08:33.320 that affect communication and social processing. 00:08:35.440 --> 00:08:38.080 Functional connectivity assessed through resting 00:08:38.080 --> 00:08:42.620 state. FMRI reveals under -connectivity in long 00:08:42.620 --> 00:08:46.330 -range networks. such as those linking frontal 00:08:46.330 --> 00:08:50.629 to temporal regions. Remember these are extremely 00:08:50.629 --> 00:08:54.409 distal. We could probably spend every episode 00:08:54.409 --> 00:08:57.629 talking about distal connections. Even remember 00:08:57.629 --> 00:09:02.970 Dr. Richard Fry talking about Leukovorin. Leukovorin 00:09:02.970 --> 00:09:06.850 rescues these distal connections. It's one of 00:09:06.850 --> 00:09:09.009 the things that is helping with the autistic 00:09:09.009 --> 00:09:12.450 phenotype especially the non -verbals. This is 00:09:12.450 --> 00:09:15.649 a very interesting product and I'm glad it's 00:09:15.649 --> 00:09:18.909 taking place and getting some highlights here 00:09:18.909 --> 00:09:22.330 now with the administration saying this should 00:09:22.330 --> 00:09:26.110 be a treatment option. Luke O 'Voren see the 00:09:26.110 --> 00:09:29.370 episode with Dr. Richard Fry from the spring. 00:09:30.570 --> 00:09:33.009 Those poor distal connections that are under 00:09:33.009 --> 00:09:36.490 connected. They have a hard time keeping up with 00:09:36.490 --> 00:09:39.750 sensory processing and kind of orchestrating 00:09:39.750 --> 00:09:42.029 different movements and understanding of the 00:09:42.029 --> 00:09:46.669 social world. Local circuits such as those within 00:09:46.669 --> 00:09:50.789 the occipital or temporal regions often show 00:09:50.789 --> 00:09:53.389 over -connectivity. Remember, we've talked about 00:09:53.389 --> 00:09:56.330 this quite in detail with the sensory processing 00:09:56.330 --> 00:10:00.509 episode and the decoding the brain episode. We 00:10:00.509 --> 00:10:03.509 won't have to go into this, but that diffusion 00:10:03.509 --> 00:10:07.610 tensor imaging is wild. The data here are so 00:10:07.610 --> 00:10:12.899 wild. Remember the arcuate fasciculus. Here's 00:10:12.899 --> 00:10:17.179 a new one, the superior longitudinal fasciculus, 00:10:17.419 --> 00:10:21.720 SLF, and this supports social and executive functions. 00:10:22.500 --> 00:10:27.440 So this is huge here. And also lower fractional 00:10:27.440 --> 00:10:31.159 encetropy, again, remember it's measuring water, 00:10:32.059 --> 00:10:35.600 indicates compromised fiber integrity that correlates 00:10:35.600 --> 00:10:38.399 with language and social deficits. So there's 00:10:38.399 --> 00:10:42.059 a new fasciculi. We have many different fasciculi. 00:10:43.360 --> 00:10:48.039 The arcuate fasciculi or arcuate fasciculus is 00:10:48.039 --> 00:10:51.100 for those speech and language connections. This 00:10:51.100 --> 00:10:54.799 new superior longitudinal fasciculus this is 00:10:54.799 --> 00:10:57.159 so -called connecting executive functioning to 00:10:57.159 --> 00:11:01.279 language so it's also including language mainly 00:11:01.279 --> 00:11:06.820 in the frontal parietal and temporal lobes. Now 00:11:06.820 --> 00:11:10.929 if you're a lumper You will combine the arcuate 00:11:10.929 --> 00:11:15.269 fasciculi into this superior longitudinal fasciculus. 00:11:15.350 --> 00:11:17.990 Now some people say the arcuate is just a part 00:11:17.990 --> 00:11:22.769 of this SLF. That's a lumper. They lump regions 00:11:22.769 --> 00:11:27.389 together. If you are a splitter, you will split 00:11:27.389 --> 00:11:31.950 the arcuate fasciculus and the superior longitudinal 00:11:31.950 --> 00:11:36.730 fasciculus apart into two distinct fasciculi. 00:11:38.090 --> 00:11:42.629 So brainwave patterns. Brainwaves measured through 00:11:42.629 --> 00:11:47.210 EEG and MEG provides insight into the temporal 00:11:47.210 --> 00:11:51.029 dynamics of neural activity in the autistic phenotype. 00:11:51.330 --> 00:11:54.970 Temporal, not meaning the temporal lobe, but 00:11:54.970 --> 00:12:01.269 time, the time component here. Reduce gamma band 00:12:01.269 --> 00:12:08.279 30 Hertz to 80 Hertz and synchrony as a hallmark 00:12:08.279 --> 00:12:11.980 of autistic phenotype so a reduced gamma band 00:12:11.980 --> 00:12:15.220 and this reflects impaired local processing and 00:12:15.220 --> 00:12:19.759 sensory integration particularly in frontal and 00:12:19.759 --> 00:12:25.000 temporal regions. This reduction is evident during 00:12:25.000 --> 00:12:29.340 tasks requiring attention to social stimuli such 00:12:29.340 --> 00:12:35.899 as processing faces or voices. Once again the 00:12:35.899 --> 00:12:40.700 study on six weeks old humans from UCLA, showing 00:12:40.700 --> 00:12:45.440 that different connection from the salient network, 00:12:46.759 --> 00:12:50.460 the salient network with these younger autistic 00:12:50.460 --> 00:12:54.120 subjects in this study. Now they later track 00:12:54.120 --> 00:12:58.200 them to indicate, yes, autism, no, not autism. 00:12:59.220 --> 00:13:02.899 The autistic ones had different connections of 00:13:02.899 --> 00:13:07.399 the salient network. Insula to the sensory motor 00:13:07.399 --> 00:13:11.340 compared to the typicals. Insula to the frontal 00:13:11.340 --> 00:13:15.720 cortex. This is all in play here. This is all 00:13:15.720 --> 00:13:20.480 connected. In addition, a typical alpha band, 00:13:20.759 --> 00:13:24.360 so remember the 812 Hertz, suppression, alpha 00:13:24.360 --> 00:13:27.820 band suppression, which typically occurs during 00:13:27.820 --> 00:13:32.279 attentional tasks, suggests deficits in modulating 00:13:32.279 --> 00:13:37.389 attention. to relevant stimuli. This contributes 00:13:37.389 --> 00:13:41.970 to social and communication challenges. However, 00:13:42.289 --> 00:13:48.350 increased theta band 4 to 8 Hz, increased theta 00:13:48.350 --> 00:13:53.950 band power in frontal regions indicates compensatory 00:13:53.950 --> 00:13:57.950 effort as the brain attempts to overcome processing 00:13:57.950 --> 00:14:02.899 deficits during complex tasks like language comprehension. 00:14:03.840 --> 00:14:06.600 So it's trying to rescue itself in these frontal 00:14:06.600 --> 00:14:09.960 areas, but it's having a hard time keeping up. 00:14:10.779 --> 00:14:14.340 A measurement technique. A range of neural imaging 00:14:14.340 --> 00:14:18.340 and electrophysiological tools are used to study 00:14:18.340 --> 00:14:24.580 autism's neural profile. Task -based fMRI indicates 00:14:24.580 --> 00:14:28.919 regional hypoactivation. For instance here in 00:14:28.919 --> 00:14:31.279 the medial prefrontal cortex or that temporal 00:14:31.279 --> 00:14:34.600 parietal junction during social and language 00:14:34.600 --> 00:14:41.539 task. While resting state fMRI quantifies connectivity 00:14:41.539 --> 00:14:44.480 disruptions in networks like the default mode 00:14:44.480 --> 00:14:49.240 network. The resting state fMRI is what the UCLA 00:14:49.240 --> 00:14:55.799 study used on six -week code. EEG measures event 00:14:55.799 --> 00:14:59.039 -related potentials. You might recognize that 00:14:59.039 --> 00:15:03.980 from the Sensory Processing Part 2 episode. This 00:15:03.980 --> 00:15:08.419 is such as N400, which is reduced in the autistic 00:15:08.419 --> 00:15:12.100 phenotype during semantic or pragmatic processing, 00:15:12.759 --> 00:15:17.480 indicating difficulties with context integration. 00:15:19.179 --> 00:15:22.950 ItMeG's provides high temporal resolution to 00:15:22.950 --> 00:15:27.730 detect abnormal gamma and beta coherence reflecting 00:15:27.730 --> 00:15:34.070 abnormal neural synchrony. DTIs quantifies white 00:15:34.070 --> 00:15:38.750 matter integrity through the FA diffusion tensor 00:15:38.750 --> 00:15:42.370 image. Remember diffusion is nerd speak for movement. 00:15:42.970 --> 00:15:45.769 It's measuring water and the arcuate fasciculus 00:15:45.769 --> 00:15:48.889 is abnormal here. It's very under connected. 00:15:50.460 --> 00:15:56.100 Okay, some genetic contributions. The FOXP2 and 00:15:56.100 --> 00:16:00.820 CNT -NAP2. I don't love it. It's not my role 00:16:00.820 --> 00:16:04.100 to love it. Just convey it. I don't love the 00:16:04.100 --> 00:16:06.419 genetic stuff though. It seems like a dead end 00:16:06.419 --> 00:16:10.600 with the autism research. It's very suspicious. 00:16:11.100 --> 00:16:18.840 It's very even perhaps nefarious. FOXP2 and CNT 00:16:18.840 --> 00:16:22.190 - NAP2 genes are pivotal though in shaping the 00:16:22.190 --> 00:16:24.649 neural circuits underlying the autistic phenotype 00:16:24.649 --> 00:16:27.450 and its comorbid speech and language disorders. 00:16:27.970 --> 00:16:30.470 So this is why these are kind of a region of 00:16:30.470 --> 00:16:33.470 interest for us. This influences language, motor, 00:16:33.610 --> 00:16:38.350 and social processing. FOXP2 is a transcription 00:16:38.350 --> 00:16:42.549 factor that regulates genes critical for neural 00:16:42.549 --> 00:16:46.210 development particularly. in regions like the 00:16:46.210 --> 00:16:49.690 inferior frontal gyrus and a favorite of mine 00:16:49.690 --> 00:16:54.129 the basal ganglia and the cerebellum which are 00:16:54.129 --> 00:16:58.450 essential for language production and motor coordination. 00:17:00.009 --> 00:17:04.089 By modulating synaptic plasticity and dendritic 00:17:04.089 --> 00:17:09.049 growth FoxP2 ensures the formation of robust 00:17:09.049 --> 00:17:13.609 neural connections make it necessary for articulating 00:17:13.609 --> 00:17:19.150 speech and complex language processing. So pretty 00:17:19.150 --> 00:17:22.150 important there. Sounds like a region of interest 00:17:22.150 --> 00:17:28.490 for us. Mutations in the FoxP2 disrupt articulation 00:17:28.490 --> 00:17:33.289 in the speech sound disorder and synaptic processing 00:17:33.289 --> 00:17:37.970 and the delayed language disorder and speech 00:17:37.970 --> 00:17:43.650 planning and stuttering. In the autistic phenotype, 00:17:44.009 --> 00:17:48.089 FOXP2 variants contribute to language delays 00:17:48.089 --> 00:17:53.509 and pragmatic deficits by impairing the inferior 00:17:53.509 --> 00:17:57.710 frontal gyrus function, which is of course a 00:17:57.710 --> 00:18:01.630 crucial area for both the language production 00:18:01.630 --> 00:18:07.029 and social communication. Some longitudinal studies 00:18:07.029 --> 00:18:11.049 have shown that FOXP2 expression levels correlate 00:18:11.049 --> 00:18:15.069 with language development trajectories in the 00:18:15.069 --> 00:18:18.990 autistic phenotype, with lower expression associated 00:18:18.990 --> 00:18:22.450 with persistent delays in verbal communication. 00:18:24.069 --> 00:18:28.529 That's shown in a 2013 study from molecular autism. 00:18:30.509 --> 00:18:33.910 So here's fascinating. This is a very fascinating 00:18:33.910 --> 00:18:39.000 part here. The FOXP2 regulates downstream genes 00:18:39.000 --> 00:18:44.619 like the CNT -NAP2. So it's kind of a sequela 00:18:44.619 --> 00:18:48.619 here. If upstream is abnormal, downstream is 00:18:48.619 --> 00:18:51.619 going to be abnormal. This is a very big message 00:18:51.619 --> 00:18:55.079 constantly repeated across the podcast in many 00:18:55.079 --> 00:18:58.839 different episodes. Upstream is always the place 00:18:58.839 --> 00:19:04.900 to go. The CNT -NAP2 encodes a Norexin family 00:19:04.900 --> 00:19:08.920 protein. This is involved in cell adhesion and 00:19:08.920 --> 00:19:13.420 synaptic transmission. With high expression in 00:19:13.420 --> 00:19:17.240 frontal and temporal cortices, the basal ganglia 00:19:17.240 --> 00:19:21.960 and the cerebellum. All regions of critical interest 00:19:21.960 --> 00:19:26.660 for language and social processing. This gene 00:19:26.660 --> 00:19:30.200 regulates potassium channel clustering and myelination. 00:19:31.019 --> 00:19:35.480 No surprise. Processes that ensure efficiency. 00:19:35.720 --> 00:19:41.079 neural communication and connectivity. So the 00:19:41.079 --> 00:19:44.440 autistic phenotype and social communication disorder, 00:19:44.720 --> 00:19:48.180 the pragmatic disorder. Remember these don't 00:19:48.180 --> 00:19:52.500 coexist. So some overview here though between 00:19:52.500 --> 00:19:56.160 the two. Social communication disorders characterized 00:19:56.160 --> 00:19:59.680 by difficulties in the social use of language, 00:20:00.299 --> 00:20:03.339 such as maintaining conversational relevance, 00:20:04.099 --> 00:20:07.400 interpreting, non -verbal cues like eye contact 00:20:07.400 --> 00:20:12.539 or gestures or understanding non -literal language 00:20:12.539 --> 00:20:16.920 such as metaphors and things. Now you can see 00:20:16.920 --> 00:20:21.240 why these aren't really comorbid problems. If 00:20:21.240 --> 00:20:24.259 you have the things that it has said and you 00:20:24.259 --> 00:20:26.960 have the repetitive restricted behaviors, the 00:20:26.960 --> 00:20:31.420 criteria B, well you have autism. So there's 00:20:31.420 --> 00:20:34.579 a chance that you can differentiate between these 00:20:34.579 --> 00:20:38.160 two and just have the social communication disorder 00:20:38.160 --> 00:20:42.380 and not have autism but if you have the autism 00:20:42.380 --> 00:20:45.740 and you have these conditions well you have autism 00:20:45.740 --> 00:20:49.059 and it might very well be who is diagnosing you 00:20:49.059 --> 00:20:52.279 who is assessing you through the autism is it 00:20:52.279 --> 00:20:54.559 somebody with clinical relevance and training 00:20:54.559 --> 00:20:59.019 or not and it's very much a problem here in 2025 00:20:59.019 --> 00:21:03.660 so some longitudinal studies here The longitudinal 00:21:03.660 --> 00:21:06.960 research provides critical insights into the 00:21:06.960 --> 00:21:10.299 developmental trajectory of these two situations 00:21:10.299 --> 00:21:13.259 here, the autistic phenotype and social communication 00:21:13.259 --> 00:21:18.400 disorder. A five -year fMRI study by Lombardo 00:21:18.400 --> 00:21:22.339 et al. in 2015 from Nature Communications, very 00:21:22.339 --> 00:21:27.200 good journal. They followed children with autism 00:21:27.200 --> 00:21:31.329 and found persistent hypoactivation. in the medial 00:21:31.329 --> 00:21:34.450 prefrontal cortex and the temporal parietal junction 00:21:34.450 --> 00:21:38.650 during tasks requiring pragmatic understanding 00:21:38.650 --> 00:21:43.369 such as interpreting irony. Yeah, good luck with 00:21:43.369 --> 00:21:49.170 that. This hypo activation correlated with social 00:21:49.170 --> 00:21:53.210 communication disorder like deficits and CNT 00:21:53.210 --> 00:21:57.549 NAP to risk Ls predicting worse social communication 00:21:57.549 --> 00:22:02.329 outcomes over the time. The study also showed 00:22:02.329 --> 00:22:05.630 slower maturation of the default mode network. 00:22:06.130 --> 00:22:09.009 Now, if you remember the temporal parietal junction, 00:22:09.809 --> 00:22:12.150 and if you remember the autism in default mode 00:22:12.150 --> 00:22:15.410 network episode, that's probably your connection 00:22:15.410 --> 00:22:19.710 there. And the study also showed reduced fractional 00:22:19.710 --> 00:22:23.769 anzeotrophy and the superior longitudinal fasciculi. 00:22:24.450 --> 00:22:30.369 And this persisted into adolescence. But... Early 00:22:30.369 --> 00:22:34.029 social skills interventions such as structured 00:22:34.029 --> 00:22:37.230 social training improve default mode connectivity 00:22:37.230 --> 00:22:41.470 in some children suggesting neuroplasticity and 00:22:41.470 --> 00:22:45.369 the potential for targeted interventions to mitigate 00:22:45.369 --> 00:22:49.349 deficits. So some personalized interventions 00:22:49.349 --> 00:22:54.309 more specifically will help improve this connectivity 00:22:54.309 --> 00:22:57.170 between the medial prefrontal cortex and the 00:22:57.170 --> 00:23:00.799 temporal parietal junction. for social skills 00:23:00.799 --> 00:23:06.240 development. These programs teach explicit social 00:23:06.240 --> 00:23:10.799 rules such as how to initiate and maintain conversations, 00:23:11.680 --> 00:23:14.559 which if you want improvement in this area, there 00:23:14.559 --> 00:23:16.920 are options here. If you want improvement in 00:23:16.920 --> 00:23:22.579 this area, repetitive transcranial magnetic stimulation 00:23:22.579 --> 00:23:26.200 targeting the medial prefrontal cortex shows 00:23:26.200 --> 00:23:30.180 promise in improving social communication by 00:23:30.180 --> 00:23:34.200 modulating neural activity in social brain regions. 00:23:35.299 --> 00:23:38.400 With studies reporting, improved default mode 00:23:38.400 --> 00:23:42.680 network coherence in both autistic phenotype 00:23:42.680 --> 00:23:49.019 and social communication disorders. Experimental 00:23:49.019 --> 00:23:54.299 CNT -NAP2 -based therapies such as, here you 00:23:54.299 --> 00:23:59.779 go, CRISPR gene editing in animal models, aimed 00:23:59.779 --> 00:24:02.619 to restore synaptic function in social circuits, 00:24:03.200 --> 00:24:06.440 offering a potential future treatment. This is 00:24:06.440 --> 00:24:11.559 done by Daniel Gershwin. Daniel Gershwin just 00:24:11.559 --> 00:24:15.259 received one of the 13 autism new initiative 00:24:15.259 --> 00:24:21.440 funding by the new NIH. Okay. This was done in 00:24:21.440 --> 00:24:26.960 2011 in Cell Press, a top journal. cell press. 00:24:27.740 --> 00:24:30.599 These CRISPR gene studies in animal models and 00:24:30.599 --> 00:24:35.420 even humans now, I think, is a you pick, you 00:24:35.420 --> 00:24:40.079 choose. So autism and the childhood onset fluency 00:24:40.079 --> 00:24:44.140 disorder. In other words, autism and stuttering. 00:24:45.119 --> 00:24:49.759 This is my childhood. Childhood onset fluency 00:24:49.759 --> 00:24:53.700 disorder. These are disruptions in speech fluency, 00:24:54.000 --> 00:24:58.380 such as repetitions, prolongations, or blocks. 00:24:59.140 --> 00:25:03.900 Often I kind of refer to my speech as blockage. 00:25:03.980 --> 00:25:07.559 I have blockage sometimes. In the podcast, I 00:25:07.559 --> 00:25:10.980 can just redo it. In real life, I have to just 00:25:10.980 --> 00:25:13.599 kind of stick with it and hopefully it lands. 00:25:15.500 --> 00:25:18.640 Stuttering here affects 4 to 22 percent of the 00:25:18.640 --> 00:25:22.140 children with autistic phenotype. And this prevalence 00:25:22.140 --> 00:25:25.619 is significantly higher than the 1 % observed 00:25:25.619 --> 00:25:30.099 in general population. So what I just said, if 00:25:30.099 --> 00:25:33.839 you have autism, it increases your chances and 00:25:33.839 --> 00:25:37.539 it will kind of hit 4 to 22 % of the children 00:25:37.539 --> 00:25:42.220 instead of 1 % of the children. It's a big thing. 00:25:44.460 --> 00:25:48.160 This high comorbid rate reflects shared deficits 00:25:48.160 --> 00:25:52.079 in motor and language networks, particularly 00:25:52.079 --> 00:25:54.839 those involved in speech planning and timing, 00:25:55.259 --> 00:25:58.160 making it very critical to understand the neural 00:25:58.160 --> 00:26:03.140 overlap for effective intervention. So the basal 00:26:03.140 --> 00:26:06.789 ganglia here is heavily involved. and this includes 00:26:06.789 --> 00:26:10.569 the putamen and the caudate. Remember the four, 00:26:10.569 --> 00:26:14.029 five, maybe even six episodes from last winter 00:26:14.029 --> 00:26:19.250 of basal ganglia? The putamen and caudate are 00:26:19.250 --> 00:26:23.910 the input areas and there's a high kind of connection 00:26:23.910 --> 00:26:27.150 with the medial prefrontal cortex and the sensory 00:26:27.150 --> 00:26:31.410 motor cortex that's kind of above and in the 00:26:31.410 --> 00:26:34.450 middle of your head at the top middle. That's 00:26:34.450 --> 00:26:38.700 the sensory motor area. So the basal ganglia 00:26:38.700 --> 00:26:42.759 is involved with the motor timing and coordination. 00:26:43.259 --> 00:26:47.000 And this is in large part the substantia nigra 00:26:47.000 --> 00:26:51.380 pars compacta in the midbrain. This is dopamine 00:26:51.380 --> 00:26:56.519 one or excitation and dopamine two or inhibition. 00:26:58.000 --> 00:27:03.690 The one dopamine is receptors one and five. And 00:27:03.690 --> 00:27:09.089 those are excitation, D2 dopamine, or receptors 00:27:09.089 --> 00:27:13.769 two, three, and four. And these are inhibition. 00:27:14.329 --> 00:27:18.430 This is all related to orchestrating timing of 00:27:18.430 --> 00:27:21.190 motor movements. Remember the basal ganglia is 00:27:21.190 --> 00:27:26.950 a go, no -go area. In other words, go and stop. 00:27:27.390 --> 00:27:29.569 And if you think about stuttering, stuttering 00:27:29.569 --> 00:27:34.940 is go, stop, go, stop. Go stop. Just trying to 00:27:34.940 --> 00:27:39.359 find a smooth connection here. And it's not happening. 00:27:40.980 --> 00:27:46.920 FMRI studies show heightened motor planning efforts. 00:27:47.460 --> 00:27:51.119 Really want to highlight the efforts part. It's 00:27:51.119 --> 00:27:55.000 trying. It's building up. It's ratcheting. But 00:27:55.000 --> 00:27:59.720 the go no go area say, okay, no, okay, no, okay, 00:27:59.960 --> 00:28:04.150 no. It's kind of disrupted there. Longitudinal 00:28:04.150 --> 00:28:09.089 studies here, a 10 -year longitudinal DTI, diffusion 00:28:09.089 --> 00:28:13.089 tensor imaging study by Chang et al. in 2019, 00:28:13.210 --> 00:28:18.329 human brain mapping, followed children with autism 00:28:18.329 --> 00:28:23.289 and stuttering. They found persistent FA reductions 00:28:23.289 --> 00:28:27.269 in the arcuate fasciculus, no surprise, and the 00:28:27.269 --> 00:28:31.700 cortical spinal tract. That's new. also though 00:28:31.700 --> 00:28:35.539 loaded with water, that's water, which correlated 00:28:35.539 --> 00:28:40.000 with stuttering severity. Some personalized interventions 00:28:40.000 --> 00:28:44.039 here are targeting the basal ganglia in the motor 00:28:44.039 --> 00:28:49.420 circuits to improve fluency. Repetition or repetitive 00:28:49.420 --> 00:28:55.059 transcranial magnetic stimulation, or RTMS, target 00:28:55.059 --> 00:28:58.579 the pertainment. This modulates dopamine signaling. 00:28:59.500 --> 00:29:02.640 reduced stuttering severity with preliminary 00:29:02.640 --> 00:29:07.039 success in autism and stuttering. Now remember 00:29:07.039 --> 00:29:11.119 the Dr. Hannah Stevens episode and she talked 00:29:11.119 --> 00:29:14.680 about, she has a paper which led me to her about 00:29:14.680 --> 00:29:20.059 the high density of dendrites in the dorsal striatum 00:29:20.059 --> 00:29:22.700 in the autistic phenotype. There's no pruning. 00:29:23.079 --> 00:29:28.609 It's just very dense here. Autism really... highlights 00:29:28.609 --> 00:29:32.170 and increases the risk of stuttering problems. 00:29:32.569 --> 00:29:37.170 I think over time practice and so forth just 00:29:37.170 --> 00:29:40.509 having the chance for our connections and brains 00:29:40.509 --> 00:29:44.109 to kind of clean up and clear out these deficits 00:29:44.109 --> 00:29:49.650 help. So over time hopefully you have some improvements 00:29:49.650 --> 00:29:53.210 in stuttering. That intense blockage you can 00:29:53.210 --> 00:29:57.190 feel it you can feel it in your neck even in 00:29:57.190 --> 00:29:59.799 the back of the head. You can just feel that 00:29:59.799 --> 00:30:04.799 blockage. Okay, autism and speech sound disorder. 00:30:05.880 --> 00:30:09.619 This is a thing, speech sound disorder. This 00:30:09.619 --> 00:30:13.180 involves difficulties with producing speech sounds 00:30:13.180 --> 00:30:19.279 accurately, leading to an articulation or phonological 00:30:19.279 --> 00:30:23.700 error. This involves Broca's area or the left 00:30:23.700 --> 00:30:27.180 inferior frontal gyrus. in the superior temporal 00:30:27.180 --> 00:30:31.140 gyrus remember last time with the decoding the 00:30:31.140 --> 00:30:34.400 brain and reading a lot of these brain regions 00:30:34.400 --> 00:30:39.140 are shared from that episode longitudinal studies 00:30:39.140 --> 00:30:44.319 a seven -year longitudinal fmri study by red 00:30:44.319 --> 00:30:49.099 clay et al 2018 developmental cognitive neuroscience 00:30:49.099 --> 00:30:54.319 followed children with autism and speech sound 00:30:54.319 --> 00:30:59.180 disorder Finding persistent hypoactivation in 00:30:59.180 --> 00:31:04.279 the inferior frontal gyrus and the superior temporal 00:31:04.279 --> 00:31:09.460 gyrus during articulation task. This is correlating 00:31:09.460 --> 00:31:14.259 with speech sound errors. Once again, reduced 00:31:14.259 --> 00:31:20.259 FA in the articulate fasciculus was also observed. 00:31:21.579 --> 00:31:27.420 And these variants in the FOXP2 and CNT -NAP 00:31:27.420 --> 00:31:31.039 variants predicted poorer outcomes with speech 00:31:31.039 --> 00:31:36.680 therapy. However, early speech therapy initiated 00:31:36.680 --> 00:31:41.660 before the age of 6 improved FA in the arcuate 00:31:41.660 --> 00:31:46.019 fasciculus and articulation accuracy in some 00:31:46.019 --> 00:31:49.339 children, highlighting the potential for early 00:31:49.339 --> 00:31:52.500 intervention to enhance neural connectivity. 00:31:52.829 --> 00:31:58.529 speech outcomes. Most autistics are hopefully 00:31:58.529 --> 00:32:02.970 getting some sort of speech therapy. I remember 00:32:02.970 --> 00:32:06.789 in the 1980s getting some and this is even rare 00:32:06.789 --> 00:32:11.970 in the 1980s. The small group reading interventions. 00:32:12.470 --> 00:32:15.750 Remember a previous episode I was putting small 00:32:15.750 --> 00:32:19.390 groups in the 1980s elementary school and the 00:32:19.390 --> 00:32:23.480 groups are like maybe four or five with Ms. Blazey 00:32:23.480 --> 00:32:26.640 was the teacher's aide. I was the slowest of 00:32:26.640 --> 00:32:32.259 the slow. A so -called task base fMRI reveals 00:32:32.259 --> 00:32:37.019 reduced inferior frontal gyrus and superior temporal 00:32:37.019 --> 00:32:42.259 gyrus activation during articulating task. While 00:32:42.259 --> 00:32:48.259 resting state fMRI confirms auditory motor under 00:32:48.259 --> 00:32:55.690 connectivity. EEG measures the P1N1P2 complex, 00:32:56.450 --> 00:32:59.730 which is reduced in response to speech sounds. 00:33:00.329 --> 00:33:03.190 This indicates impaired auditory processing. 00:33:04.910 --> 00:33:08.470 We'll have a future episode on autism and auditory 00:33:08.470 --> 00:33:13.990 processing. MEGs detect decreased gamma band 00:33:13.990 --> 00:33:19.109 power in the superior temporal gyrus during speech 00:33:19.109 --> 00:33:25.950 perception. task, and DTI quantifies lower FA 00:33:25.950 --> 00:33:30.150 in the arcuate fasciculus. This was showed way 00:33:30.150 --> 00:33:35.250 back in 2003 in annuals of New York Academy of 00:33:35.250 --> 00:33:41.750 Sciences by Ledlow and Laux. There's a specific 00:33:41.750 --> 00:33:46.130 articulation focus therapy called prompts for 00:33:46.130 --> 00:33:52.740 restructuring oral, muscular, Photonic Targets 00:33:52.740 --> 00:33:57.339 or PROMPT for short. This is tailored to autistic 00:33:57.339 --> 00:34:00.599 phenotype sensory sensitivities and improves 00:34:00.599 --> 00:34:04.900 the inferior frontal gyrus superior temporal 00:34:04.900 --> 00:34:08.420 gyrus connectivity. And this is shown through 00:34:08.420 --> 00:34:12.460 post -intervention fMRIs. This is highlighted 00:34:12.460 --> 00:34:17.619 in Morgan et al. in 2018 of Journal of Speech 00:34:17.619 --> 00:34:22.550 Language and Hearing Research. so prompt. These 00:34:22.550 --> 00:34:27.050 therapies use tactile cues to guide articulation 00:34:27.050 --> 00:34:32.630 movements and enhancing speech accuracy. RTMS 00:34:32.630 --> 00:34:37.130 targeting the left inferior frontal gyrus enhances 00:34:37.130 --> 00:34:40.449 phonological processing by stimulating neural 00:34:40.449 --> 00:34:44.449 activity in language areas. With preliminary 00:34:44.449 --> 00:34:48.110 successes, in the autistic phenotype and speech 00:34:48.110 --> 00:34:54.489 sound disorders. EEG -based neurofeedback targets 00:34:54.489 --> 00:34:59.030 gamma band power and the superior temporal gyrus 00:34:59.030 --> 00:35:02.750 improves speech sound perception by training 00:35:02.750 --> 00:35:07.130 the brain to enhance auditory processing. That 00:35:07.130 --> 00:35:11.590 kind of sounds complicated, but it is an option. 00:35:12.170 --> 00:35:15.349 So... the autistic phenotype and speech sound 00:35:15.349 --> 00:35:20.449 disorders kind of highlight articulation errors 00:35:20.449 --> 00:35:25.309 okay and lastly autism and developmental language 00:35:25.309 --> 00:35:33.489 disorder dld dld is characterized by persistent 00:35:33.489 --> 00:35:37.670 difficulties in language comprehension or production 00:35:37.670 --> 00:35:43.909 affecting vocabulary grammar or discourse, and 00:35:43.909 --> 00:35:48.150 this affects up to 50 % of children with autism. 00:35:49.929 --> 00:35:53.309 This high comorbidity rate reflects significant 00:35:53.309 --> 00:35:56.909 overlap in language networks, making it a critical 00:35:56.909 --> 00:35:59.829 area for understanding communication challenges 00:35:59.829 --> 00:36:04.769 in the autistic phenotype. Some neural networks 00:36:04.769 --> 00:36:10.829 include dysfunction in the Broca's area and Wernicke's 00:36:10.829 --> 00:36:15.309 area. This is critical for syntax and language 00:36:15.309 --> 00:36:19.909 comprehension. The dorsolateral prefrontal cortex 00:36:19.909 --> 00:36:23.610 is also affected here, impairing executive aspects 00:36:23.610 --> 00:36:27.989 of language, such as planning complex sentences. 00:36:29.030 --> 00:36:32.530 Cerebellar abnormalities in both disorders disrupt 00:36:32.530 --> 00:36:37.389 porosity and language timing. Contributing to 00:36:37.389 --> 00:36:41.210 atypical speech patterns, the autistic phenotypes 00:36:41.440 --> 00:36:45.440 broader sensory and social deficits involving 00:36:45.440 --> 00:36:48.119 regions like the medial prefrontal cortex and 00:36:48.119 --> 00:36:53.539 occipital cortex accelerate developmental language 00:36:53.539 --> 00:36:58.179 disorders, language specific impairments. This 00:36:58.179 --> 00:37:01.199 creates a more complex communication profile 00:37:01.199 --> 00:37:05.699 whenever they coexist. Longitudinal studies show 00:37:05.699 --> 00:37:10.780 a 12 -year longitudinal DTI study. in the Journal 00:37:10.780 --> 00:37:15.340 of Neurodevelopmental Disorders. This followed 00:37:15.340 --> 00:37:18.539 children with both autism and developmental language 00:37:18.539 --> 00:37:22.800 disorder, finding persistent F .A. reductions 00:37:22.800 --> 00:37:26.920 in the archicoid fasciculus, correlating with 00:37:26.920 --> 00:37:32.739 severe language delays. CNT -NAP2 variants predicted 00:37:32.739 --> 00:37:36.780 poorer outcomes, with effects persisting into 00:37:36.780 --> 00:37:41.170 adolescence. Early language therapy initiated 00:37:41.170 --> 00:37:45.349 before the age of five improved FA in the arcuate 00:37:45.349 --> 00:37:49.690 vesiculus and language outcomes in some children. 00:37:50.489 --> 00:37:52.630 It's easy for me to say and you don't have to 00:37:52.630 --> 00:37:55.389 hear that early intervention especially with 00:37:55.389 --> 00:37:59.710 speech language is very beneficial. Earlier the 00:37:59.710 --> 00:38:04.550 better. Task -based fMRI reveals reduced inferior 00:38:04.550 --> 00:38:09.280 frontal gyrus and superior temporal gyrus activation 00:38:09.280 --> 00:38:12.519 during sentence processing task while resting 00:38:12.519 --> 00:38:18.099 state fMRI confirms language network under connectivity 00:38:18.099 --> 00:38:24.860 EEG measures delayed in 400 so remember roughly 00:38:24.860 --> 00:38:29.099 400 milliseconds responses during semantic task 00:38:29.099 --> 00:38:32.920 indicating comprehension deficits this is well 00:38:32.920 --> 00:38:37.099 aligning with the data and coverage of Decoding 00:38:37.099 --> 00:38:42.039 the Brain, Reading an Autism and Dyslexia episode. 00:38:42.579 --> 00:38:48.400 This fits the timing. MEG deficits detect reduced 00:38:48.400 --> 00:38:52.039 gamma band power in the inferior frontal gyrus 00:38:52.039 --> 00:38:54.960 and the superior temporal gyrus during language 00:38:54.960 --> 00:39:00.679 task. DTI quantifies lower FA in the arcuate 00:39:00.679 --> 00:39:04.539 fasciculus with even more severe reductions in 00:39:04.590 --> 00:39:09.030 the autistic phenotype plus developmental delayed 00:39:09.030 --> 00:39:13.389 disorder. So some personalized interventions 00:39:13.389 --> 00:39:18.349 for these two. Syntax -focused therapies such 00:39:18.349 --> 00:39:21.449 as narrative -based interventions are tailored 00:39:21.449 --> 00:39:24.750 to the autistic phenotype's sensory and social 00:39:24.750 --> 00:39:30.190 deficits, improving the IFG inferior frontal 00:39:30.190 --> 00:39:33.550 gyrus and the superior temporal gyrus connectivity. 00:39:33.929 --> 00:39:40.250 as shown by post -intervention fMRI and 2016 00:39:40.250 --> 00:39:46.250 autism. These therapies focused on building grammatical 00:39:46.250 --> 00:39:49.849 skills through storytelling, which engages both 00:39:49.849 --> 00:39:55.090 language and social circuits. RTMS targeting 00:39:55.090 --> 00:40:00.269 the left Broca area enhances syntactic processing 00:40:00.269 --> 00:40:03.710 by stimulating neural activity in language areas 00:40:03.710 --> 00:40:08.190 with preliminary success in the autistic phenotype 00:40:08.190 --> 00:40:11.590 and developmental learning disorder comorbid 00:40:11.590 --> 00:40:17.030 condition. EEG's based neural feedback targeting 00:40:17.030 --> 00:40:21.809 gamma band power in language areas improves comprehension 00:40:21.809 --> 00:40:25.510 by training the brain to enhance processing efficiency. 00:40:27.150 --> 00:40:31.800 This goes in line with that delayed processing 00:40:31.800 --> 00:40:36.559 in the downstream connections. Earlier, it's 00:40:36.559 --> 00:40:41.320 heightened. But downstream, that arrival point 00:40:41.320 --> 00:40:44.639 from point A to point B, there are five steps. 00:40:45.219 --> 00:40:48.019 Those last steps are going to be under connected 00:40:48.019 --> 00:40:52.940 and delayed. However, some things are really 00:40:52.940 --> 00:40:55.980 significant here. Earlier, the intervention, 00:40:56.239 --> 00:41:00.590 the better. And kind of pinpointing Which problems 00:41:00.590 --> 00:41:04.349 are consistent with that Autistic Phenotype, 00:41:04.409 --> 00:41:07.909 with that individual? What kind of additional 00:41:07.909 --> 00:41:11.210 speech language communication problems is the 00:41:11.210 --> 00:41:16.690 Autistic Phenotype having? Remember, earlier 00:41:16.690 --> 00:41:21.369 intervention the better. If you are listening 00:41:21.369 --> 00:41:24.250 to the podcast, listening to the episode, please 00:41:24.250 --> 00:41:27.610 feel free to leave a review or rating. In podcasting, 00:41:27.610 --> 00:41:30.710 Reviews ratings and downloads are huge and I 00:41:30.710 --> 00:41:33.449 very much appreciate your feedback. You can contact 00:41:33.449 --> 00:41:40.409 me on X at RPS 47586 We can have discussions 00:41:40.409 --> 00:41:43.409 about autism. I always appreciate your discussions 00:41:43.409 --> 00:41:47.329 about autism You can check out the YouTube channel 00:41:47.329 --> 00:41:52.590 for all full -length shorts and clip videos You 00:41:52.590 --> 00:42:02.000 can email me info dot from the spectrum Thank 00:42:02.000 --> 00:42:06.119 you for listening to From the Spectrum Podcast.