Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder

Kim, Hyopil; Lim, Chae‐Seok; Kaang, Bong‐Kiun

doi:10.1186/s12993-016-0087-y

Cited by 113 publications

(124 citation statements)

References 103 publications

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“…Additionally, we observed that DAN connectivity with subcortical regions, primarily the putamen/lentiform nucleus and cerebellum, was uniquely associated with stereotyped behavior. These findings provide further empirical support for significant involvement of cortico-striatal-thalamo-cortical circuitry in stereotypies (70–72). Further, atypical recruitment and regulation of visual cortical regions and atypical visual attention have been linked with RRB symptomology (73–75) and abnormalities in the control of visual attention have been shown to persist throughout infancy in children who are later diagnosed with ASD (23, 76–78).…”

Section: Discussionsupporting

confidence: 63%

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

Eggebrecht

Todorov

et al. 2019

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Background Restricted and repetitive behaviors (RRBs), detectable by 12 months (mo) in many infants later diagnosed with autism spectrum disorder (ASD), may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. Methods Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24mo (n=38 at both time points). Twenty infants met criteria for ASD at 24 mo. We divided RRBs intofour subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. Results Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 mo. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 mo. At 24 mo, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 mo, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, while restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. Conclusion These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.

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Section: Discussionsupporting

confidence: 63%

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

Eggebrecht

Todorov

et al. 2019

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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“…3b). In turn, NMDA receptors have been implicated in the regulation of grooming and other repetitive behaviors (Jaramillo et al 2016;Kim et al 2016).…”

Section: Discussionmentioning

confidence: 99%

QTLand systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field

Delprato

Algéo

Bonheur

et al. 2017

Genes Brain and Behavior

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The open field is a classic test used to assess exploratory behavior, anxiety, and locomotor activity in rodents. Here we mapped quantitative trait loci (QTLs) underlying behaviors displayed in an open field, using a panel of 53 BXD recombinant inbred mouse strains with deep replication (10 per strain and sex). The use of these strains permits the integration and comparison of data obtained in different laboratories, and also offers the possibility to study trait covariance by exploiting powerful bioinformatics tools and resources. We quantified behavioral traits during 20 min test sessions including (1) percent time spent and distance travelled near the wall (thigmotaxis), (2) leaning against the wall, (3) rearing, (4) jumping, (5) grooming duration, (6) grooming frequency, (7) locomotion, and (8) defecation. All traits exhibit moderate heritability making them amenable to genetic analysis. We identified a significant QTL on chromosome M.m. 4 at ~104 Mb that modulates grooming duration in both males and females (LRS values of ~18, explaining 25% and 14% of the variance, respectively) and a suggestive QTL modulating locomotion that maps to the same locus. Bioinformatic analysis indicates Disabled 1 (Dab1, a key protein in the reelin signaling pathway) as a particularly strong candidate gene modulating these behaviors. We also found two highly suggestive QTLs for a sex by strain interaction for grooming duration on chromosomes 13 and 17. In addition, we identified a pairwise epistatic interaction between loci on chromosomes 12 at 36-37 Mb and 14 at 34-36 Mb that influences rearing frequency in males.

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“…Focusing entirely on behaviorally-defined diagnostic criteria and response to treatment risks a two-dimensional phenomenological approach to ASDs. The multi-dimensional aspects of presentation are increasingly recognized as aberrations in the biological pathways at the molecular and cellular levels, with alterations in circuitry linked to behavior [121, 122]. Furthermore, the limitations of the clinician paradigm as a standard for the diagnosis of ASD [24] support a move beyond this historical model to one increasingly guided by biological measurement [123].…”

Section: Treatment Options In Asdmentioning

confidence: 99%

An Overview of Autism Spectrum Disorder, Heterogeneity and Treatment Options

et al. 2017

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Since the documented observations of Kanner in 1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is now known as autism spectrum disorder (ASD). Reflecting this complicated history, there has been continual refinement from DSM-III with ‘Infantile Autism’ to the current DSM-V diagnosis. The disorder is now widely accepted as a complex, pervasive, heterogeneous condition with multiple etiologies, sub-types, and developmental trajectories. Diagnosis remains based on observation of atypical behaviors, with criteria of persistent deficits in social communication and restricted and repetitive patterns of behavior. This review provides a broad overview of the history, prevalence, etiology, clinical presentation, and heterogeneity of ASD. Factors contributing to heterogeneity, including genetic variability, comorbidity, and gender are reviewed. We then explore current evidence-based pharmacological and behavioral treatments for ASD and highlight the complexities of conducting clinical trials that evaluate therapeutic efficacy in ASD populations. Finally, we discuss the potential of a new wave of research examining objective biomarkers to facilitate the evaluation of sub-typing, diagnosis, and treatment response in ASD.

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Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder

Cited by 113 publications

References 103 publications

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

QTLand systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field

An Overview of Autism Spectrum Disorder, Heterogeneity and Treatment Options

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