scholarly journals Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes

2021 ◽  
Author(s):  
V. Zerbi ◽  
M. Pagani ◽  
M. Markicevic ◽  
M. Matteoli ◽  
D. Pozzi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Brain Mapping ◽  
Brain Connectivity ◽  
Autism Spectrum ◽  
Functional Brain ◽  
Mouse Mutants ◽  
Diagnostic Label ◽  
Syndromic Asd ◽  
Etiological Heterogeneity

AbstractAutism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modeled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.

scholarly journals Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes

2020 ◽  
Author(s):  
V. Zerbi ◽  
M. Pagani ◽  
M. Markicevic ◽  
M. Matteoli ◽  
D. Pozzi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Brain Mapping ◽  
Brain Connectivity ◽  
Autism Spectrum ◽  
Functional Brain ◽  
Mouse Mutants ◽  
Diagnostic Label ◽  
Syndromic Asd ◽  
Etiological Heterogeneity

AbstractAutism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modelled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.

scholarly journals An Autism Spectrum Disorder Adaptive Identification Based on the Elimination of Brain Connections: A Proof of Long-Range Underconnectivity

2021 ◽  
Author(s):  
Fatima zahra Benabdallah ◽  
Ahmed Drissi El Maliani ◽  
Dounia Lotfi ◽  
Rachid Jennane ◽  
Mohammed El hassouni
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Long Range ◽  
Data Exchange ◽  
Brain Connectivity ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Imaging Data ◽  
Brain Imaging Data

Abstract Autism spectrum disorder (ASD) is theoretically characterized by alterations in functional connectivity between brain regions. Many works presented approaches to determine informative patterns that help to predict autism from typical development. However, most of the proposed pipelines are not specifically designed for the autism problem, i.e they do not corroborate with autism theories about functional connectivity. In this paper, we propose a framework that takes into account the properties of local connectivity and long range under-connectivity in the autistic brain. The originality of the proposed approach is to adopt elimination as a technique in order to well emerge the autistic brain connectivity alterations, and show how they contribute to differentiate ASD from controls. Experimental results conducted on the large multi-site Autism Brain Imaging Data Exchange (ABIDE) show that our approach provides accurate prediction up to 70% and succeeds to prove the existence of deficits in the long-range connectivity in the ASD subjects brains.

Classification of Autism Spectrum Disorder from EEG-based Functional Brain Connectivity Analysis

2021 ◽  
pp. 1-27
Author(s):  
Noura Alotaibi ◽  
Koushik Maharatna
Keyword(s):  
Machine Learning ◽  
Autism Spectrum Disorder ◽  
Brain Connectivity ◽  
Phase Locking ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Functional Brain ◽  
Graph Theoretic ◽  
Phase Locking Value

Abstract Autism is a psychiatric condition that is typically diagnosed with behavioral assessment methods. Recent years have seen a rise in the number of children with autism. Since this could have serious health and socioeconomic consequences, it is imperative to investigate how to develop strategies for an early diagnosis that might pave the way to an adequate intervention. In this study, the phase-based functional brain connectivity derived from electroencephalogram (EEG) in a machine learning framework was used to classify the children with autism and typical children in an experimentally obtained data set of 12 autism spectrum disorder (ASD) and 12 typical children. Specifically, the functional brain connectivity networks have quantitatively been characterized by graph-theoretic parameters computed from three proposed approaches based on a standard phase-locking value, which were used as the features in a machine learning environment. Our study was successfully classified between two groups with approximately 95.8% accuracy, 100% sensitivity, and 92% specificity through the trial-averaged phase-locking value (PLV) approach and cubic support vector machine (SVM). This work has also shown that significant changes in functional brain connectivity in ASD children have been revealed at theta band using the aggregated graph-theoretic features. Therefore, the findings from this study offer insight into the potential use of functional brain connectivity as a tool for classifying ASD children.

Atypicalities in the developmental trajectory of cortico-striatal functional connectivity in autism spectrum disorder

Autism ◽  
2021 ◽  
pp. 136236132110419
Author(s):  
Zeng-Hui Ma ◽  
Bin Lu ◽  
Xue Li ◽  
Ting Mei ◽  
Yan-Qing Guo ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Brain Connectivity ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Typically Developing ◽  
Sensorimotor Network ◽  
Intrinsic Functional Connectivity ◽  
Age Related ◽  
Atypical Development

The last decades of neuroimaging research has revealed atypical development of intrinsic functional connectivity within and between large-scale cortical networks in autism spectrum disorder, but much remains unknown about cortico-subcortical developmental connectivity atypicalities. This study examined cortico-striatal developmental intrinsic functional connectivity changes in autism spectrum disorder and explored how those changes may be correlated with autistic traits. We studied 49 individuals with autism spectrum disorder and 52 age-, sex-, and head motion–matched typically developing individuals (5–30 years old (14.0 ± 5.6)) using resting-state functional magnetic resonance imaging. Age-related differences in striatal intrinsic functional connectivity were compared between the two groups by adopting functional network–based parcellations of the striatum as seeds. Relative to typically developing individuals, autism spectrum disorder individuals showed atypical developmental changes in intrinsic functional connectivities between almost all striatal networks and sensorimotor network/default network, with connectivity increasing with age in the autism spectrum disorder group and decreasing or constant in typically developing individuals. Age-related degree centrality and voxel-mirrored homotopic connectivity atypicalities in sensorimotor network/default network and voxel-mirrored homotopic connectivity disruptions in striatal regions were also observed in autism spectrum disorder. Significant correlations were found between cortico-striatal intrinsic functional connectivities and Autism Diagnostic Observation Schedule communication/repetitive and restricted-behavior subscores in autism spectrum disorder. Our results indicated that developmental atypicalities of cortico-striatal intrinsic functional connectivities might contribute to the neuropathology of autism spectrum disorder. Lay abstract Autism spectrum disorder has long been conceptualized as a disorder of “atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions).” However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6–30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

scholarly journals The functional brain organization of an individual predicts measures of social abilities in autism spectrum disorder: Predicting symptoms in autism with brain imaging

2018 ◽  
Author(s):  
Evelyn MR Lake ◽  
Emily S Finn ◽  
Stephanie M Noble ◽  
Tamara Vanderwal ◽  
Xilin Shen ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Brain Imaging ◽  
Data Exchange ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Imaging Data ◽  
Brain Organization ◽  
Functional Brain ◽  
Functional Brain Organization

ABSTRACTAutism Spectrum Disorder (ASD) is associated with multiple complex abnormalities in functional brain connectivity measured with functional magnetic resonance imaging (fMRI). Despite much research in this area, to date, neuroimaging-based models are not able to characterize individuals with ASD with sufficient sensitivity and specificity; this is likely due to the heterogeneity and complexity of this disorder. Here we apply a data-driven subject-level approach, connectome-based predictive modeling, to resting-state fMRI data from a set of individuals from the Autism Brain Imaging Data Exchange. Using leave-one-subject-out and split-half analyses, we define two functional connectivity networks that predict continuous scores on the Social Responsiveness Scale (SRS) and Autism Diagnostic Observation Schedule (ADOS) and confirm that these networks generalize to novel subjects. Notably, these networks were found to share minimal anatomical overlap. Further, our results generalize to individuals for whom SRS/ADOS scores are unavailable, predicting worse scores for ASD than typically developing individuals. In addition, predicted SRS scores for individuals with attention-deficit/hyperactivity disorder (ADHD) from the ADHD-200 Consortium are linked to ADHD symptoms, supporting the hypothesis that the functional brain organization changes relevant to ASD severity share a component associated with attention. Finally, we explore the membership of predictive connections within conventional (atlas-based) functional networks. In summary, our results suggest that an individual’s functional connectivity profile contains information that supports dimensional, non-binary classification in ASD, aligning with the goals of precision medicine and individual-level diagnosis.

scholarly journals Evaluating Functional Connectivity Alterations in Autism Spectrum Disorder Using Network-Based Statistics

Diagnostics ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 51 ◽  
Author(s):  
Aitana Pascual-Belda ◽  
Antonio Díaz-Parra ◽  
David Moratal
Keyword(s):  
Autism Spectrum Disorder ◽  
Brain Connectivity ◽  
Brain Networks ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Typical Development ◽  
Functional Brain ◽  
Functional Brain Networks ◽  
Management Functions ◽  
The Brain

The study of resting-state functional brain networks is a powerful tool to understand the neurological bases of a variety of disorders such as Autism Spectrum Disorder (ASD). In this work, we have studied the differences in functional brain connectivity between a group of 74 ASD subjects and a group of 82 typical-development (TD) subjects using functional magnetic resonance imaging (fMRI). We have used a network approach whereby the brain is divided into discrete regions or nodes that interact with each other through connections or edges. Functional brain networks were estimated using the Pearson’s correlation coefficient and compared by means of the Network-Based Statistic (NBS) method. The obtained results reveal a combination of both overconnectivity and underconnectivity, with the presence of networks in which the connectivity levels differ significantly between ASD and TD groups. The alterations mainly affect the temporal and frontal lobe, as well as the limbic system, especially those regions related with social interaction and emotion management functions. These results are concordant with the clinical profile of the disorder and can contribute to the elucidation of its neurological basis, encouraging the development of new clinical approaches.

scholarly journals Constructing high-order functional connectivity network based on central moment features for diagnosis of autism spectrum disorder

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11692
Author(s):  
Qingsong Xie ◽  
Xiangfei Zhang ◽  
Islem Rekik ◽  
Xiaobo Chen ◽  
Ning Mao ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Neurological Diseases ◽  
Brain Connectivity ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Central Moment ◽  
High Order ◽  
Spectrum Disorder ◽  
Moment Feature

The sliding-window-based dynamic functional connectivity network (D-FCN) has been becoming an increasingly useful tool for understanding the changes of brain connectivity patterns and the association of neurological diseases with these dynamic variations. However, conventional D-FCN is essentially low-order network, which only reflects the pairwise interaction pattern between brain regions and thus overlooking the high-order interactions among multiple brain regions. In addition, D-FCN is innate with temporal sensitivity issue, i.e., D-FCN is sensitive to the chronological order of its subnetworks. To deal with the above issues, we propose a novel high-order functional connectivity network framework based on the central moment feature of D-FCN. Specifically, we firstly adopt a central moment approach to extract multiple central moment feature matrices from D-FCN. Furthermore, we regard the matrices as the profiles to build multiple high-order functional connectivity networks which further capture the higher level and more complex interaction relationships among multiple brain regions. Finally, we use the voting strategy to combine the high-order networks with D-FCN for autism spectrum disorder diagnosis. Experimental results show that the combination of multiple functional connectivity networks achieves accuracy of 88.06%, and the best single network achieves accuracy of 79.5%.

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.

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