scholarly journals Disrupted intrinsic connectivity links to language and social deficits in toddlers with autism

2021 ◽  
Author(s):  
Yaqiong Xiao ◽  
Teresa H. Wen ◽  
Lauren Kupis ◽  
Lisa T. Eyler ◽  
Disha Goel ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Functional Connectivity ◽  
Social Engagement ◽  
Autism Spectrum ◽  
Language Abilities ◽  
Social Functions ◽  
Language Communication ◽  
Communication Ability ◽  
Cortical Regions ◽  
Temporal Language

Social and language abilities are closely intertwined during early development. Yet, it is still unknown how neural features underlying early social and language deficits are linked in toddlers with autism spectrum disorders (ASD). We examined functional connectivity of left and right temporal language regions and its correlations with language and social abilities in a cohort of 1-4 years old toddlers (52 ASD/34 non-ASD). Further, ASD toddlers were stratified into those who strongly prefer social visual stimuli (ASDSoc) vs. those who do not (ASDnonSoc) based on performance on an eye-tracking paradigm. In non-ASD toddlers, connectivity between temporal regions and other language- and social-related cortical regions was significantly correlated with language, communication, and social scores. Conversely, ASD toddlers showed atypical correlations between temporal-visual cortex (cuneus) connectivity and communication ability. This temporal-visual connectivity was also correlated with social visual attention in ASDnonSoc but not in ASDSoc toddlers. These findings suggest language- and social-related functional connectivity was not correlated with language and social functions in ASD toddlers. Abnormal engagement of temporal-visual cortex connectivity may be an early-age signature of ASD and may help explain why interventions targeting social skills and language are so challenging, particularly in those with poor social engagement.

scholarly journals Early alterations of social brain networks in young children with autism

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Holger Franz Sperdin ◽  
Ana Coito ◽  
Nada Kojovic ◽  
Tonia Anahi Rihs ◽  
Reem Kais Jan ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Brain Activity ◽  
Brain Networks ◽  
Autism Spectrum ◽  
Brain Network ◽  
Social Brain ◽  
Compensatory Mechanisms ◽  
Source Imaging ◽  
Gaze Patterns ◽  
Cortical Regions

Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. We recorded the gaze patterns and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic social scenes. Directed functional connectivity analyses based on electrical source imaging revealed frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as alterations in both the driving and the connections from key nodes of the social brain associated with autism. Analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with less atypical gaze patterns and lower clinical impairment. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD.

scholarly journals Homozygous loss of autism-risk geneCNTNAP2results in reduced local and long-range prefrontal functional connectivity

2016 ◽  
Author(s):  
Adam Liska ◽  
Alice Bertero ◽  
Ryszard Gomolka ◽  
Mara Sabbioni ◽  
Alberto Galbusera ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Long Range ◽  
Brain Connectivity ◽  
Resting State Fmri ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Functional Impairments ◽  
Social Investigation ◽  
Reduced Frequency ◽  
Cortical Regions

AbstractFunctional connectivity aberrancies, as measured with resting-state fMRI (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, the genetic and neurobiological underpinnings of these findings remain unclear. Homozygous mutations in Contactin Associated Protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to autism and epilepsy. Here we used rsfMRI to show that homozygous mice lackingCntnap2exhibit reduced long-range and local functional connectivity in prefrontal and midline brain “connectivity hubs”. Long-range rsfMRI connectivity impairments affected heteromodal cortical regions and were prominent between fronto-posterior components of the mouse default-mode network (DMN), an effect that was associated with reduced social investigation, a core “autism trait” in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex ofCntnap2−/−mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white matter organization appeared to be otherwise preserved in these animals. These findings reveal a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.

scholarly journals Early alterations of social brain networks in young children with autism

2017 ◽  
Author(s):  
Holger Franz Sperdin ◽  
Ana Coito ◽  
Nada Kojovic ◽  
Tonia Rihs ◽  
Reem Kais Jan ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Brain Activity ◽  
Brain Networks ◽  
Autism Spectrum ◽  
Brain Network ◽  
Social Brain ◽  
Compensatory Mechanisms ◽  
Gaze Patterns ◽  
Clinical Impairment ◽  
Cortical Regions

ABSTRACTSocial impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. Here, we recorded the gaze patterns and brain activity of toddlers and preschoolers with ASD and their typically developing (TD) peers while they explored dynamic social scenes. Source-space directed functional connectivity analyses revealed the presence of network alterations in the theta frequency band, manifesting as increased driving (hyper-activity) and stronger connections (hyper-connectivity) from key nodes of the social brain associated with autism. Further analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with lower clinical impairment and less atypical gaze patterns. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD.

Influence of Primary Auditory Cortex in the Characterization of Autism Spectrum in Young Adults using Brain Connectivity Parameters and Deep Belief Networks: An fMRI Study

2020 ◽  
Vol 16 (9) ◽  
pp. 1059-1073
Author(s):  
Vidhusha Srinivasan ◽  
N. Udayakumar ◽  
Kavitha Anandan
Keyword(s):  
Functional Connectivity ◽  
Auditory Cortex ◽  
Language Processing ◽  
Brain Connectivity ◽  
Primary Auditory Cortex ◽  
Autism Spectrum ◽  
Belief Networks ◽  
Deep Belief Networks ◽  
High Functioning ◽  
Low Functioning

Background: The spectrum of autism encompasses High Functioning Autism (HFA) and Low Functioning Autism (LFA). Brain mapping studies have revealed that autism individuals have overlaps in brain behavioural characteristics. Generally, high functioning individuals are known to exhibit higher intelligence and better language processing abilities. However, specific mechanisms associated with their functional capabilities are still under research. Objective: This work addresses the overlapping phenomenon present in autism spectrum through functional connectivity patterns along with brain connectivity parameters and distinguishes the classes using deep belief networks. Methods: The task-based functional Magnetic Resonance Images (fMRI) of both high and low functioning autistic groups were acquired from ABIDE database, for 58 low functioning against 43 high functioning individuals while they were involved in a defined language processing task. The language processing regions of the brain, along with Default Mode Network (DMN) have been considered for the analysis. The functional connectivity maps have been plotted through graph theory procedures. Brain connectivity parameters such as Granger Causality (GC) and Phase Slope Index (PSI) have been calculated for the individual groups. These parameters have been fed to Deep Belief Networks (DBN) to classify the subjects under consideration as either LFA or HFA. Results: Results showed increased functional connectivity in high functioning subjects. It was found that the additional interaction of the Primary Auditory Cortex lying in the temporal lobe, with other regions of interest complimented their enhanced connectivity. Results were validated using DBN measuring the classification accuracy of 85.85% for high functioning and 81.71% for the low functioning group. Conclusion: Since it is known that autism involves enhanced, but imbalanced components of intelligence, the reason behind the supremacy of high functioning group in language processing and region responsible for enhanced connectivity has been recognized. Therefore, this work that suggests the effect of Primary Auditory Cortex in characterizing the dominance of language processing in high functioning young adults seems to be highly significant in discriminating different groups in autism spectrum.

scholarly journals Structural and functional brain-wide alterations in A350V Iqsec2 mutant mice displaying autistic-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Lichtman ◽  
Eyal Bergmann ◽  
Alexandra Kavushansky ◽  
Nadav Cohen ◽  
Nina S. Levy ◽  
...  
Keyword(s):  
Social Behavior ◽  
Functional Connectivity ◽  
Mouse Model ◽  
Ampa Receptor ◽  
Social Preference ◽  
Autism Spectrum ◽  
Receptor Trafficking ◽  
Anterior Cingulate ◽  
The Impact ◽  
Ampa Receptor Trafficking

AbstractIQSEC2 is an X-linked gene that is associated with autism spectrum disorder (ASD), intellectual disability, and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cerebral cortex and hippocampus. Moreover, using a data-driven approach we identify putative alterations in structure–function relations of the frontal, auditory, and visual networks in A350V mice. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three-chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations.

A Preliminary Study of Abnormal Centrality of Cortical Regions and Subsystems in Whole Brain Functional Connectivity of Autism Spectrum Disorder Boys

2021 ◽  
pp. 155005942110262
Author(s):  
Bo Chen
Keyword(s):  
Autism Spectrum Disorder ◽  
Activity Patterns ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Eigenvector Centrality ◽  
Information Process ◽  
Whole Brain ◽  
Functional Connections ◽  
Cortical Regions ◽  
Prefrontal Lobe

The abnormal cortices of autism spectrum disorder (ASD) brains are uncertain. However, the pathological alterations of ASD brains are distributed throughout interconnected cortical systems. Functional connections (FCs) methodology identifies cooperation and separation characteristics of information process in macroscopic cortical activity patterns under the context of network neuroscience. Embracing the graph theory concepts, this paper introduces eigenvector centrality index (EC score) ground on the FCs, and further develops a new framework for researching the dysfunctional cortex of ASD in holism significance. The important process is to uncover noticeable regions and subsystems endowed with antagonistic stance in EC-scores of 26 ASD boys and 28 matched healthy controls (HCs). For whole brain regional EC scores of ASD boys, orbitofrontal superior medial cortex, insula R, posterior cingulate gyrus L, and cerebellum 9 L are endowed with different EC scores significantly. In the brain subsystems level, EC scores of DMN, prefrontal lobe, and cerebellum are aberrant in the ASD boys. Generally, the EC scores display widespread distribution of diseased regions in ASD brains. Meanwhile, the discovered regions and subsystems, such as MPFC, AMYG, INS, prefrontal lobe, and DMN, are engaged in social processing. Meanwhile, the CBCL externalizing problem scores are associated with EC scores.

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