Thalamocortical connectivity is associated with autism symptoms in high-functioning adults with autism and typically developing adults

Ayub, Rafi; Sun, Kai; Flores, Ryan; Lam, Vicky T.; Jo, Booil; Saggar, Manish; Fung, Lawrence K.

doi:10.1038/s41398-021-01221-0

“…The PRC is the primary motor cortex (M1) and PC is the primary somatosensory cortex (S1). The implications of PRC and PC in ASD had been reported previously (32,33). Interestingly, we also found the functional connectivity including right S1 (S1R) and M1 (M1R) regions were specifically decreased in MECP2 transgenic monkeys, the non-human primate model for autism, comparing to wild-type monkeys (34)(35)(36).…”

Section: Expression Of Asd Risk Genes Enriched At Pc Prc and Bst Regions In The Developing Human Brainsupporting

confidence: 82%

Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism

Yuan

¹

,

Wang

²

,

Wu

³

et al. 2021

Preprint

1

0

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Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts is still under-represented in the genome-wide genetic studies. Here we performed whole-exome sequencing on 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combining with single-cell sequencing data from the developing human brain, we found that expression of genes with de novo mutations were specifically enriched in pre-, post-central gyrus (PRC, PC) and banks of superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and health controls, we found that the gray volume of the right BST in ASD patients significantly decreased comparing to health controls, suggesting the potential structural deficits associated with ASD. Finally, we found that there was decrease in the seed-based functional connectivity (FC) between BST/PC/PRC and sensory areas, insula, as well as frontal lobes in ASD patients. This work indicated that the combinatorial analysis with genome-wide screening, single-cell sequencing and brain imaging data would reveal brain regions contributing to etiology of ASD.

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“…Prior research demonstrated the sensitivity of thalamus to language (Münte & Kutas, 2008), and various lines of evidence have observed the activation of thalamus in language-related tasks, such as phonological word retrieval processes (Perani et al, 2003) and verbal and semantic uency tasks (Rodrigo et al, 2008a). The abnormalities appeared in thalamus among ASD have also been discovered (Ayub, 2021;Tomasi & Volkow, 2019). Our results also revealed the increased FC between left thalamus and Broca area in ASD, indicating that atypical connectivity between Broca and thalamus might connect with the language dysfunction in ASD.…”

Section: Altered Fc Between Broca Area and The Whole Brain In The Con...supporting

confidence: 72%

The Atypical Functional Connectivity of Broca Area at Multiple Frequency Bands in Autism Spectrum Disorder

Zhan

¹

,

Gao

²

,

Huang

³

et al. 2022

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0

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As a developmental disorder, autism spectrum disorder has drawn much attention due to its severe impacts on language capacity. Broca area, an important brain region of language network, has largely involved in language-related functions. Using Autism Brain Image Data Exchange (ABIDE) dataset, a total of 1454 participants (618 ASD and 836 HCs) were included in our research. In order to detect the pathophysiological mechanism of autism spectrum disorder from the perspective of language, we conducted a functional connectivity analysis with Broca as the seed in multiple frequency bands (conventional: 0.01–0.08 Hz; slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz). We found that compared with healthy controls, patients with autism spectrum disorder have demonstrated increased functional connectivity in left thalamus, left precuneus, left anterior cingulate and paracingulate gyri, and left medial orbital of the superior frontal gyrus in conventional frequency band (0.01-0.08Hz). The results of slow-5 frequency band (0.01-0.027Hz) presented increased functional connectivity values of left precuneus, left medial orbital of the superior frontal gyrus, right medial orbital of the superior frontal gyrus and right thalamus. No significant cluster was detected in the slow-4 frequency band (0.027-0.073Hz). In conclusion, the abnormal functional connectivity in patients with autism spectrum disorder has frequency-specific properties. Furthermore, the findings of conventional frequency bands (0.01-0.08Hz) were mainly contributed by slow-5 (0.01-0.027Hz). The current study might shed new light on the pathophysiological mechanism of language impairments in autism spectrum disorder.

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“…The PRC is the primary motor cortex (M1) and PC is the primary somatosensory cortex (S1). The implications of PRC and PC in ASD had been reported previously 32,33 . Interestingly, we also found the functional connectivity including right S1 (S1R) and M1 (M1R) regions were speci cally decreased in MECP2 transgenic monkeys, the non-human primate model for autism, comparing to wild-type monkeys 34,35,36 .…”

Section: Expression Of Asd Risk Genes Enriched At Pc Prc and Bst Regions In The Developing Human Brainmentioning

confidence: 79%

Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism

Yuan

¹

,

Wang

²

,

Wu

³

et al. 2021

Preprint

1

0

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts is still under-represented in the genome-wide genetic studies. Here we performed whole-exome sequencing on 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combining with single-cell sequencing data from the developing human brain, we found that expression of genes with de novo mutations were specifically enriched in pre-, post-central gyrus (PRC, PC) and banks of superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and health controls, we found that the gray volume of the right BST in ASD patients significantly decreased comparing to health controls, suggesting the potential structural deficits associated with ASD. Finally, we found that there was decrease in the seed-based functional connectivity (FC) between BST/PC/PRC and sensory areas, insula, as well as frontal lobes in ASD patients. This work indicated that the combinatorial analysis with genome-wide screening, single-cell sequencing and brain imaging data would reveal brain regions contributing to etiology of ASD.

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Thalamocortical connectivity is associated with autism symptoms in high-functioning adults with autism and typically developing adults

Cited by 39 publications

References 75 publications

Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism

Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism

The Atypical Functional Connectivity of Broca Area at Multiple Frequency Bands in Autism Spectrum Disorder

Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism

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