scholarly journals Four Social Brain Regions, Their Dysfunctions, and Sequelae, Extensively Explain Autism Spectrum Disorder Symptomatology

2019 ◽  
Vol 9 (6) ◽  
pp. 130 ◽  
Author(s):  
Charles S. E. Weston
Keyword(s):  
Autism Spectrum Disorder ◽  
Brain Research ◽  
Inferior Frontal Gyrus ◽  
Research Question ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Brain

Autism spectrum disorder (ASD) is a challenging neurodevelopmental disorder with symptoms in social, language, sensory, motor, cognitive, emotional, repetitive behavior, and self-sufficient living domains. The important research question examined is the elucidation of the pathogenic neurocircuitry that underlies ASD symptomatology in all its richness and heterogeneity. The presented model builds on earlier social brain research, and hypothesizes that four social brain regions largely drive ASD symptomatology: amygdala, orbitofrontal cortex (OFC), temporoparietal cortex (TPC), and insula. The amygdala’s contributions to ASD largely derive from its major involvement in fine-grained intangible knowledge representations and high-level guidance of gaze. In addition, disrupted brain regions can drive disturbance of strongly interconnected brain regions to produce further symptoms. These and related effects are proposed to underlie abnormalities of the visual cortex, inferior frontal gyrus (IFG), caudate nucleus, and hippocampus as well as associated symptoms. The model is supported by neuroimaging, neuropsychological, neuroanatomical, cellular, physiological, and behavioral evidence. Collectively, the model proposes a novel, parsimonious, and empirically testable account of the pathogenic neurocircuitry of ASD, an extensive account of its symptomatology, a novel physiological biomarker with potential for earlier diagnosis, and novel experiments to further elucidate the mechanisms of brain abnormalities and symptomatology in ASD.

scholarly journals Brain Responses Underlying Anthropomorphism, Agency, and Social Attribution in Autism Spectrum Disorder

2018 ◽  
Vol 12 (1) ◽  
pp. 16-29 ◽  
Author(s):  
Carla J. Ammons ◽  
Constance F. Doss ◽  
David Bala ◽  
Rajesh K. Kana
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Movement ◽  
Mental States ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Brain ◽  
Social Attribution ◽  
Brain Responses ◽  
Fmri Study

Background:Theory of Mind (ToM), the ability to attribute mental states to oneself and others, is frequently impaired in Autism Spectrum Disorder (ASD) and may result from altered activation of social brain regions. Conversely, Typically Developing (TD) individuals overextend ToM and show a strong tendency to anthropomorphize and interpret biological motion in the environment. Less is known about how the degree of anthropomorphism influences intentional attribution and engagement of the social brain in ASD.Objective:This fMRI study examines the extent of anthropomorphism, its role in social attribution, and the underlying neural responses in ASD and TD using a series of human stick figures and geometrical shapes.Methods:14 ASD and 14 TD adults watched videos of stick figures and triangles interacting in random or socially meaningful ways while in an fMRI scanner. In addition, they completed out-of-scanner measures of ToM skill and real-world social deficits. Whole brain statistical analysis was performed for regression and within and between group comparisons of all conditions using SPM12’s implementation of the general linear model.Results:ToM network regions were activated in response to social movement and human-like characters in ASD and TD. In addition, greater ToM ability was associated with increased TPJ and MPFC activity while watching stick figures; whereas more severe social symptoms were associated with reduced right TPJ activation in response to social movement.Conclusion:These results suggest that degree of anthropomorphism does not differentially affect social attribution in ASD and highlights the importance of TPJ in ToM and social attribution.

scholarly journals Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder

2019 ◽  
Vol 20 (8) ◽  
pp. 1878 ◽  
Author(s):  
Rita Barone ◽  
Renata Rizzo ◽  
Giovanni Tabbì ◽  
Michele Malaguarnera ◽  
Richard E. Frye ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Peroxisome Proliferator Activated Receptors

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by defective social communication and interaction and restricted, repetitive behavior with a complex, multifactorial etiology. Despite an increasing worldwide prevalence of ASD, there is currently no pharmacological cure to treat core symptoms of ASD. Clinical evidence and molecular data support the role of impaired mitochondrial fatty acid oxidation (FAO) in ASD. The recognition of defects in energy metabolism in ASD may be important for better understanding ASD and developing therapeutic intervention. The nuclear peroxisome proliferator-activated receptors (PPAR) α, δ, and γ are ligand-activated receptors with distinct physiological functions in regulating lipid and glucose metabolism, as well as inflammatory response. PPAR activation allows a coordinated up-regulation of numerous FAO enzymes, resulting in significant PPAR-driven increases in mitochondrial FAO flux. Resveratrol (RSV) is a polyphenolic compound which exhibits metabolic, antioxidant, and anti-inflammatory properties, pointing to possible applications in ASD therapeutics. In this study, we review the evidence for the existing links between ASD and impaired mitochondrial FAO and review the potential implications for regulation of mitochondrial FAO in ASD by PPAR activators, including RSV.

scholarly journals Role of Oligodendrocytes and Myelin in the Pathophysiology of Autism Spectrum Disorder

2020 ◽  
Vol 10 (12) ◽  
pp. 951
Author(s):  
Alma Y. Galvez-Contreras ◽  
David Zarate-Lopez ◽  
Ana L. Torres-Chavez ◽  
Oscar Gonzalez-Perez
Keyword(s):  
Autism Spectrum Disorder ◽  
Interpersonal Communication ◽  
Neurodevelopmental Disorder ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Abnormal Development ◽  
Matter Production

Autism Spectrum Disorder (ASD) is an early neurodevelopmental disorder that involves deficits in interpersonal communication, social interaction, and repetitive behaviors. Although ASD pathophysiology is still uncertain, alterations in the abnormal development of the frontal lobe, limbic areas, and putamen generate an imbalance between inhibition and excitation of neuronal activity. Interestingly, recent findings suggest that a disruption in neuronal connectivity is associated with neural alterations in white matter production and myelination in diverse brain regions of patients with ASD. This review is aimed to summarize the most recent evidence that supports the notion that abnormalities in the oligodendrocyte generation and axonal myelination in specific brain regions are involved in the pathophysiology of ASD. Fundamental molecular mediators of these pathological processes are also examined. Determining the role of alterations in oligodendrogenesis and myelination is a fundamental step to understand the pathophysiology of ASD and identify possible therapeutic targets.

scholarly journals Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qian Wang ◽  
Ying Kong ◽  
Ding-Yu Wu ◽  
Ji-Hong Liu ◽  
Wei Jie ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Conditional Knockout ◽  
Spectrum Disorder ◽  
Null Mutant ◽  
Intracellular Ca ◽  
Null Mutant Mice

AbstractAutism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.

scholarly journals Response Patterns in the Developing Social Brain are Organized by Social and Emotion Features and Disrupted in Children Diagnosed with Autism Spectrum Disorder

2019 ◽  
Author(s):  
Hilary Richardson ◽  
Hyowon Gweon ◽  
David Dodell-Feder ◽  
Caitlin Malloy ◽  
hannah pelton ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Multivariate Analyses ◽  
Developmental Change ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Response Patterns ◽  
Social Brain ◽  
Condition Model ◽  
Control Models

Adults and children recruit a specific network of brain regions when engaged in “Theory of Mind” (ToM) reasoning. Recently, fMRI studies of adults have used multivariate analyses to provide a deeper characterization of responses in these regions. These analyses characterize representational distinctions within the social domain, rather than comparing responses across preferred (social) and non-preferred stimuli. Here, we conducted opportunistic multivariate analyses in two previously collected datasets (Experiment 1: n=20 5-11 year old children and n=37 adults; Experiment 2: n=76 neurotypical and n=29 5-12 year old children diagnosed with Autism Spectrum Disorder (ASD)) in order to characterize the structure of representations in the developing social brain, and in order to discover if this structure is disrupted in ASD. Children listened to stories that described characters’ mental states (Mental), non-mentalistic social information (Social), and causal events in the environment (Physical), while undergoing fMRI. We measured the extent to which neural responses in ToM brain regions were organized according to two ToM-relevant models: 1) a condition model, which reflected the experimenter-generated condition labels, and 2) a data-driven emotion model, which organized stimuli according to their emotion content. We additionally constructed two control models based on linguistic and narrative features of the stories. In both experiments, the two ToM-relevant models outperformed the control models. The fit of the condition model increased with age in neurotypical children. Moreover, the fit of the condition model to neural response patterns was reduced in the RTPJ in children diagnosed with ASD. These results provide a first glimpse into the conceptual structure of information in ToM brain regions in childhood, and suggest that there are real, stable features that predict responses in these regions in children. Multivariate analyses are a promising approach for sensitively measuring conceptual and neural developmental change and individual differences in ToM. This is a post-peer-review, pre-copyedit version of an article published in Cortex. The final authenticated version is available online at: https://doi.org/10.1016/j.cortex.2019.11.021 .

Shared atypical brain anatomy and intrinsic functional architecture in male youth with autism spectrum disorder and their unaffected brothers

2016 ◽  
Vol 47 (4) ◽  
pp. 639-654 ◽  
Author(s):  
H.-Y. Lin ◽  
W.-Y. I. Tseng ◽  
M.-C. Lai ◽  
Y.-T. Chang ◽  
S. S.-F. Gau
Keyword(s):  
Autism Spectrum Disorder ◽  
Statistical Power ◽  
Inferior Frontal Gyrus ◽  
Neurodevelopmental Disorder ◽  
Gray Matter Volume ◽  
Cingulate Cortex ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Brain Anatomy ◽  
Male Youth

BackgroundAutism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males.MethodThe 94 participants (aged 9–19 years) – 20 male youth with ASD, 20 unaffected brothers and 54 TD males – received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference.ResultsWe found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers.ConclusionsAtypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.

scholarly journals Gut microbiota on gender bias in autism spectrum disorder

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Xia Hao ◽  
Jiao Pan ◽  
Xiumei Gao ◽  
Shiyu Zhang ◽  
Yue Li
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Specific Treatment ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Communication Disorder ◽  
Gender Dimorphism ◽  
Men And Women

AbstractAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Its three core symptoms are social communication disorder, communication disorder, narrow interest and stereotyped repetitive behavior. The proportion of male and female autistic patients is 4:1. Many researchers have studied this phenomenon, but the mechanism is still unclear. This review mainly discusses the related mechanism from the perspective of gut microbiota and introduces the influence of gut microbiota on the difference of ASD between men and women, as well as how gut microbiota may affect the gender dimorphism of ASD through metabolite of microbiota, immunity, and genetics, which provide some useful information for those who are interested in this research and find more gender-specific treatment for autistic men and women.

scholarly journals Examining the boundary sharpness coefficient as an index of cortical microstructure and its relationship to age and sex in autism spectrum disorder

2020 ◽  
Author(s):  
Emily Olafson ◽  
Saashi Bedford ◽  
Gabriel A. Devenyi ◽  
Raihaan Patel ◽  
Stephanie Tullo ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
White Matter ◽  
Cortical Thickness ◽  
Meta Analysis ◽  
Inferior Frontal Gyrus ◽  
Superior Temporal Gyrus ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sharpness Coefficient

AbstractAutism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration. Here, we propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient). Using a vertex-based meta-analysis and a large multi-center magnetic resonance structural imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male) and 721 controls (283 female; 438 male), we observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities. Increases were observed in different brain regions in males and females, with larger effect sizes in females. Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus. BSC correlated with ADOS-2 CSS in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared to cortical thickness. These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.

scholarly journals The Parvalbumin Hypothesis of Autism Spectrum Disorder

2020 ◽  
Vol 14 ◽  
Author(s):  
Federica Filice ◽  
Lucia Janickova ◽  
Thomas Henzi ◽  
Alessandro Bilella ◽  
Beat Schwaller
Keyword(s):  
Autism Spectrum Disorder ◽  
Messenger Rna ◽  
Energy Requirement ◽  
Neurodevelopmental Disorder ◽  
High Energy ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Supporting Evidence

The prevalence of autism spectrum disorder (ASD)—a type of neurodevelopmental disorder—is increasing and is around 2% in North America, Asia, and Europe. Besides the known genetic link, environmental, epigenetic, and metabolic factors have been implicated in ASD etiology. Although highly heterogeneous at the behavioral level, ASD comprises a set of core symptoms including impaired communication and social interaction skills as well as stereotyped and repetitive behaviors. This has led to the suggestion that a large part of the ASD phenotype is caused by changes in a few and common set of signaling pathways, the identification of which is a fundamental aim of autism research. Using advanced bioinformatics tools and the abundantly available genetic data, it is possible to classify the large number of ASD-associated genes according to cellular function and pathways. Cellular processes known to be impaired in ASD include gene regulation, synaptic transmission affecting the excitation/inhibition balance, neuronal Ca2+ signaling, development of short-/long-range connectivity (circuits and networks), and mitochondrial function. Such alterations often occur during early postnatal neurodevelopment. Among the neurons most affected in ASD as well as in schizophrenia are those expressing the Ca2+-binding protein parvalbumin (PV). These mainly inhibitory interneurons present in many different brain regions in humans and rodents are characterized by rapid, non-adaptive firing and have a high energy requirement. PV expression is often reduced at both messenger RNA (mRNA) and protein levels in human ASD brain samples and mouse ASD (and schizophrenia) models. Although the human PVALB gene is not a high-ranking susceptibility/risk gene for either disorder and is currently only listed in the SFARI Gene Archive, we propose and present supporting evidence for the Parvalbumin Hypothesis, which posits that decreased PV level is causally related to the etiology of ASD (and possibly schizophrenia).

scholarly journals Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology

2015 ◽  
Vol 112 (40) ◽  
pp. 12498-12503 ◽  
Author(s):  
Bharathi S. Gadad ◽  
Wenhao Li ◽  
Umar Yazdani ◽  
Stephen Grady ◽  
Trevor Johnson ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Rhesus Macaques ◽  
Neurodevelopmental Disorder ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Mmr Vaccine ◽  
Negative Behaviors ◽  
Infant Rhesus

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

Sign in / Sign up

Export Citation Format

Share Document