scholarly journals Differential neural circuitry behind autism subtypes with imbalanced social-communicative and restricted repetitive behavior symptoms

2020 ◽  
Author(s):  
Natasha Bertelsen ◽  
Isotta Landi ◽  
Richard A. I. Bethlehem ◽  
Jakob Seidlitz ◽  
Elena Maria Busuoli ◽  
...  
Keyword(s):  
Social Communication ◽  
Repetitive Behavior ◽  
Resting State Fmri ◽  
Neural Circuitry ◽  
Repetitive Behaviors ◽  
Typically Developing ◽  
Out Of Sample ◽  
Genetic Mechanisms ◽  
Social Communicative ◽  
The Eu

AbstractSocial-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC=RRB, SC>RRB, and RRB>SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n=509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show subtype-specific qualitative differences compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC>RRB and visual association circuitry in SC=RRB. The SC=RRB subtype also showed hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these subtype-specific networks show a differential enrichment pattern with known ASD associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share some commonalities but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.

scholarly journals Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Natasha Bertelsen ◽  
◽  
Isotta Landi ◽  
Richard A. I. Bethlehem ◽  
Jakob Seidlitz ◽  
...  
Keyword(s):  
Repetitive Behavior ◽  
Resting State Fmri ◽  
Neural Circuitry ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Typically Developing ◽  
Out Of Sample ◽  
Genetic Mechanisms ◽  
Social Communicative ◽  
The Eu

AbstractSocial-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97–99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.

Rigidity coincides with reduced cognitive control to affective cues in children with autism

2018 ◽  
Author(s):  
Dienke J. Bos ◽  
Melanie R. Silverman ◽  
Eliana L. Ajodan ◽  
Cynthia Martin ◽  
Benjamin Silver ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
False Alarms ◽  
Typically Developing ◽  
Insistence On Sameness ◽  
Typically Developing Children ◽  
Children With Asd ◽  
Affective Cues

The present study tested whether salient affective cues would negatively influence cognitive control in children with and without autism spectrum disorder (ASD). 100 children aged 6-12 years who were either typically developing or had ASD performed a novel go/nogo task to cues of their interest versus cues of non-interest. Using Linear Mixed-Effects models group differences in hit rate, false alarms and d-prime were tested. Caregivers completed the Repetitive Behavior Scale - Revised (RBS-R) to test associations between repetitive behaviors and task performance. Children with ASD had reduced cognitive control towards their interests compared to typically developing children. Further, children with ASD showed reduced cognitive control to interests as compared to their own non-interests, a pattern not observed in typically developing children. Decreased cognitive control towards interests was associated with higher insistence on sameness behavior in ASD, but there was no association between sameness behavior and cognitive control for non-interests. Together, children with ASD demonstrated decreased cognitive flexibility in the context of increased affective salience related to interests. These results provide a mechanism for how salient affective cues, such as interests, interfere with daily functioning and social communication in ASD. Further, the findings have broader clinical implications for understanding how affective cues can drive interactions between restricted patterns of behavior and cognitive control.

scholarly journals Individuals with autism have no detectable deficit in neural markers of prediction error when presented with auditory rhythms of varied temporal complexity

2020 ◽  
Author(s):  
Emily J. Knight ◽  
Leona A. Oakes ◽  
Susan L. Hyman ◽  
Edward G. Freedman ◽  
John J. Foxe
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Prediction Error ◽  
Repetitive Behavior ◽  
Predictive Coding ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Brain Wave ◽  
Temporal Complexity

ABSTRACTThe brain’s ability to encode temporal patterns and predict upcoming events is critical for speech perception and other aspects of social communication. Deficits in predictive coding may contribute to difficulties with social communication and overreliance on repetitive predictable environments in individuals with autism spectrum disorder (ASD). Using a mismatch negativity (MMN) task involving rhythmic tone sequences of varying complexity, we tested the hypotheses that 1) individuals with ASD have reduced MMN response to auditory stimuli that deviate in presentation timing from expected patterns, particularly as pattern complexity increases and 2) amplitude of MMN signal is inversely correlated with level of impairment in social communication and repetitive behaviors. Electroencephalography was acquired as individuals (age 6-21years) listened to repeated five-rhythm tones that varied in the Shannon entropy of the rhythm across three conditions (zero, medium-1 bit) and high-2 bit entropy). The majority of the tones conformed to the established rhythm (standard tones); occasionally the 4th tone was temporally shifted relative to its expected time of occurrence (deviant tones). Social communication and repetitive behaviors were measured using the Social Responsiveness Scale and Repetitive Behavior Scale-Revised. Both neurotypical controls (n=19) and individuals with ASD (n=21) show stepwise decreases in MMN as a function of increasing entropy. Contrary to the result forecasted by a predictive coding hypothesis, individuals with ASD do not differ from controls in these neural mechanisms of prediction error to auditory rhythms of varied temporal complexity, and there is no relationship between these signals and social communication or repetitive behavior measures.Lay SummaryWe tested the idea that the brain’s ability to use previous experience to influence processing of sounds is weaker in individuals with autism spectrum disorder (ASD) than in neurotypical individuals. We found no difference between individuals with ASD and neurotypical controls in brain wave responses to sounds that occurred earlier than expected in either simple or complex rhythms. There was also no relationship between these brain waves and social communication or repetitive behavior scores.

scholarly journals Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

2020 ◽  
Author(s):  
Brittany D. Needham ◽  
Mark D. Adame ◽  
Gloria Serena ◽  
Destanie R. Rose ◽  
Gregory M. Preston ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Molecular Signatures ◽  
Typically Developing ◽  
Peripheral Tissues ◽  
Behavioral Traits ◽  
Metabolite Profiles

ABSTRACTAutism Spectrum Disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal (GI) dysfunction, and altered gut microbiome compositions. We sought to better understand non-behavioral features of ASD by determining molecular signatures in peripheral tissues. Herein, we present the untargeted metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing (TD) controls. Differences in lipid, amino acid, and xenobiotic metabolism discriminate ASD and TD samples. We reveal correlations between specific metabolite profiles and clinical behavior scores, and identify metabolites particularly associated with GI dysfunction in ASD. These findings support a connection between GI physiology, metabolism, and complex behavioral traits, and may advance discovery and development of molecular biomarkers for ASD.

Emotion Dysregulation in Autism Spectrum Disorder

2018 ◽  
pp. 282-298
Author(s):  
Emily Neuhaus
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Educational Outcomes ◽  
Emotion Dysregulation ◽  
Research Priorities ◽  
Theoretical Models ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder

Autism spectrum disorder (ASD) is defined by deficits in social communication and interaction, and restricted and repetitive behaviors and interests. Although current diagnostic conceptualizations of ASD do not include emotional difficulties as core deficits, the disorder is associated with emotion dysregulation across the lifespan, with considerable implications for long-term psychological, social, and educational outcomes. The overarching goal of this chapter is to integrate existing knowledge of emotion dysregulation in ASD and identify areas for further investigation. The chapter reviews the prevalence and expressions of emotion dysregulation in ASD, discusses emerging theoretical models that frame emotion dysregulation as an inherent (rather than associated) feature of ASD, presents neurobiological findings and mechanisms related to emotion dysregulation in ASD, and identifies continuing controversies and resulting research priorities.

scholarly journals Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder

2021 ◽  
Author(s):  
Viktor Román ◽  
Nika Adham ◽  
Andrew G. Foley ◽  
Lynsey Hanratty ◽  
Bence Farkas ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Partial Agonist ◽  
Social Play ◽  
Autism Spectrum ◽  
Social Recognition ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Exposure Model ◽  
Behavioral Deficits

Abstract Rationale Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist, is already approved for the treatment of schizophrenia and bipolar I disorder in adults; investigation in patients with ASD is warranted. Objectives The aim of this study was to investigate the effects of cariprazine, compared with risperidone and aripiprazole, in the rat prenatal valporic acid (VPA) exposure model on behavioral endpoints representing the core and associated symptoms of ASD. Methods To induce the ASD model, time-mated Wistar rat dams were treated with VPA during pregnancy. Male offspring were assigned to groups and studied in a behavioral test battery at different ages, employing social play, open field, social approach-avoidance, and social recognition memory tests. Animals were dosed orally, once a day for 8 days, with test compounds (cariprazine, risperidone, aripiprazole) or vehicle before behavioral assessment. Results Cariprazine showed dose-dependent efficacy on all behavioral endpoints. In the social play paradigm, only cariprazine was effective. On the remaining behavioral endpoints, including the reversal of hyperactivity, risperidone and aripiprazole displayed similar efficacy to cariprazine. Conclusions In the present study, cariprazine effectively reversed core behavioral deficits and hyperactivity present in juvenile and young adult autistic-like rats. These findings indicate that cariprazine may be useful in the treatment of ASD symptoms.

scholarly journals Sex-dependent role for EPHB2 in brain development and autism-associated behavior

2021 ◽  
Author(s):  
Ahlem Assali ◽  
Jennifer Y. Cho ◽  
Evgeny Tsvetkov ◽  
Abha R. Gupta ◽  
Christopher W. Cowan
Keyword(s):  
Pyramidal Neurons ◽  
De Novo ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Male Mice ◽  
Sensory Sensitivity ◽  
Hyperactivity Disorder ◽  
Specific Effects ◽  
Layer V

AbstractAutism spectrum disorder (ASD) is characterized by impairments in social communication and interaction and restricted, repetitive behaviors. It is frequently associated with comorbidities, such as attention-deficit hyperactivity disorder, altered sensory sensitivity, and intellectual disability. A de novo nonsense mutation in EPHB2 (Q857X) was discovered in a female patient with ASD [13], revealing EPHB2 as a candidate ASD risk gene. EPHB2 is a receptor tyrosine kinase implicated in axon guidance, synaptogenesis, and synaptic plasticity, positioning it as a plausible contributor to the pathophysiology of ASD and related disorders. In this study, we show that the Q857X mutation produced a truncated protein lacking forward signaling and that global disruption of one EphB2 allele (EphB2+/−) in mice produced several behavioral phenotypes reminiscent of ASD and common associated symptoms. EphB2+/− female, but not male, mice displayed increased repetitive behavior, motor hyperactivity, and learning and memory deficits, revealing sex-specific effects of EPHB2 hypofunction. Moreover, we observed a significant increase in the intrinsic excitability, but not excitatory/inhibitory ratio, of motor cortex layer V pyramidal neurons in EphB2+/− female, but not male, mice, suggesting a possible mechanism by which EPHB2 hypofunction may contribute to sex-specific motor-related phenotypes. Together, our findings suggest that EPHB2 hypofunction, particularly in females, is sufficient to produce ASD-associated behaviors and altered cortical functions in mice.

RELATIONSHIP AMONG SENSORY ISSUES AND REPETITIVE BEHAVIORS IN CHILDREN WITH AUTISM SPECTRUM DISORDER

2020 ◽  
pp. 59-64
Author(s):  
OJS Admin
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Sensory Stimuli ◽  
Key Features ◽  
Communication Impairments ◽  
Autism Disorder

Sensory issues and Repetitive Behaviors are the key features of Autism Disorder Syndrome (ASD). This is a neurodevelopmental condition marked by social communication impairments and the occurrence ofrestricted and repeated behavioral habits and desires, including irregular responses to sensory stimuli.

Early cognitive and brain development in infants and children with ASD

2021 ◽  
Author(s):  
Anna Kolesnik-Taylor ◽  
Emily Jones
Keyword(s):  
Brain Development ◽  
Social Communication ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Infants And Children ◽  
Behavioral Symptoms ◽  
Late Emergence ◽  
Exact Etiology ◽  
Diagnostic Window ◽  
In Infants And Children

Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, restrictive, and repetitive behaviors. The exact etiology of the condition is unknown, and the heterogeneity and the late emergence of characteristic symptoms of ASD limits our ability to identify infants and children who may require early intervention. One way to address the complexity of this condition is to examine early cognitive and brain development prior to the consolidation of behavioral symptoms at around 2–3 years. This chapter overviews early brain and cognitive development in ASD-relevant domains, and putative underlying brain mechanisms. Isolating critical features of early development may be used to reduce the diagnostic window and establish effective intervention options.

scholarly journals Development of the Stanford Social Dimensions Scale: initial validation in autism spectrum disorder and in neurotypicals

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jennifer M. Phillips ◽  
Mirko Uljarević ◽  
Rachel K. Schuck ◽  
Salena Schapp ◽  
Elizabeth M. Solomon ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Individual Differences ◽  
Root Mean Square ◽  
Social Communication ◽  
Social Motivation ◽  
Autism Spectrum ◽  
Mean Square ◽  
Typically Developing ◽  
Social Dimensions ◽  
Initial Validation

Abstract Background The aim of this paper was to provide an initial validation of a newly developed parent questionnaire—the Stanford Social Dimensions Scale (SSDS), designed to capture individual differences across several key social dimensions including social motivation in children and adolescents with and without psychiatric disorders. Methods The initial validation sample was comprised of parents of 175 individuals with autism spectrum disorder (ASD) (35 females, 140 males; Mage = 7.19 years, SDage = 3.96) and the replication sample consisted of 624 parents of children who were either typically developing or presented with a range of neurodevelopmental and neuropsychiatric disorders (302 females, 322 males; Mage = 11.49 years, SDage = 4.48). Parents from both samples completed the SSDS and the Social Responsiveness Scale (SRS-2). Results Exploratory Structural Equation Modeling indicated that a 5-factor model provided adequate to excellent fit to the data in the initial ASD sample (comparative fit index [CFI] = .940, Tucker-Lewis Index [TLI] = .919, root mean square error of approximation [RMSEA] = .048, standardized root mean square residual [SRMR] = .038). The identified factors were interpreted as Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach. This factor structure was further confirmed in Sample 2 (CFI = 946, TLI = .930, RMSEA = .044, SRMR = .026). Internal consistency for all subscales was in the good to excellent range across both samples as indicated by Composite Reliability scores of ≥ .72. Convergent and divergent validity was strong as indexed by the pattern of correlations with relevant SRS-2 and Child Behavior Checklist domains and with verbal and non-verbal intellectual functioning scores in Sample 1 and with the Need to Belong Scale and Child Social Preference Scale scores in Sample 2. Across both samples, females had higher social motivation and expressive social communication scores. Discriminant validity was strong given that across all SSDS subscales, the ASD sample had significantly higher impairment than both the typically developing group and the group with other clinical conditions, which in turn, had significantly higher impairment than the typically developing group. Conclusions Our findings provide initial validation of a new scale designed to comprehensively capture individual differences in social motivation and other key social dimensions in ASD.

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