Functional homotopy, the high degree of synchrony in spontaneous activity between geometrically corresponding interhemispheric (i.e., homotopic) regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, despite its prominence, the lifespan development of the homotopic resting-state functional connectivity (RSFC) of the human brain is rarely directly examined in functional magnetic resonance imaging studies. Here, we systematically investigated age-related changes in homotopic RSFC in 214 healthy individuals ranging in age from 7 to 85 years. We observed marked age-related changes in homotopic RSFC with regionally specific developmental trajectories of varying levels of complexity. Sensorimotor regions tended to show increasing homotopic RSFC, whereas higher-order processing regions showed decreasing connectivity (i.e., increasing segregation) with age. More complex maturational curves were also detected, with regions such as the insula and lingual gyrus exhibiting quadratic trajectories and the superior frontal gyrus and putamen exhibiting cubic trajectories. Sex-related differences in the developmental trajectory of functional homotopy were detected within dorsolateral prefrontal cortex (Brodmann areas 9 and 46) and amygdala. Evidence of robust developmental effects in homotopic RSFC across the lifespan should serve to motivate studies of the physiological mechanisms underlying functional homotopy in neurodegenerative and psychiatric disorders.
Background Models of Autism Spectrum Disorders (ASD) as neural dysconnection syndromes have been predominantly supported by examinations of abnormalities in cortico-cortical networks in adults with autism. A broader body of research implicates subcortical structures, particularly the striatum, in the physiopathology of autism. Resting state fMRI has revealed detailed maps of striatal circuitry in healthy and psychiatric populations, and vividly captured maturational changes in striatal circuitry during typical development. Methods Using resting state fMRI, we examined striatal functional connectivity in 20 children with ASD and 20 typically developing children (TDC) between the age of 7.6 and 13.5 years. Whole-brain voxel-wise statistical maps quantified within-group striatal FC and between-group differences for three caudate and three putamen seeds, for each hemisphere. Results Children with ASD mostly exhibited prominent patterns of ectopic striatal functional connectivity (i.e., functional connectivity present in ASD but not in TDC), with increased functional connectivity between nearly all striatal subregions and heteromodal associative and limbic cortex previously implicated in the physiopathology of ASD (e.g., insular and right superior temporal gyrus). Additionally, we found striatal functional hyperconnectivity with the pons, thus expanding the scope of functional alterations implicated in ASD. Secondary analyses revealed ASD-related hyperconnectivity between the pons and insular cortex. Conclusions Examination of functional connectivity of striatal networks in children with ASD revealed abnormalities in circuits involving early developing areas such as the brainstem and insula, with a pattern of increased functional connectivity in ectopic circuits that likely reflects developmental derangement rather than immaturity of functional circuits.
Background Individuals with autism spectrum disorders (ASD) often exhibit symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Across both disorders, observations of distributed functional abnormalities suggest aberrant large-scale brain network connectivity. Yet, common and distinct network correlates of ASD and ADHD remain unidentified. Here, we aimed to examine patterns of dysconnection in school-age children with ASD, ADHD and typically developing children (TDC) who completed a resting state fMRI (R-fMRI) scan. Methods We measured voxel-wise network centrality, functional connectivity metrics indexing local (degree centrality; DC) and global (eigenvector centrality; EC) functional relationships across the entire brain connectome, in R-fMRI data from 56 children with ASD, 45 children with ADHD and 50 TDC. A one-way ANCOVA, with group as fixed factor (whole-brain corrected), was followed by post-hoc pair-wise comparisons. Results Cortical and subcortical areas exhibited centrality abnormalities; some common to both ADHD and ASD, such as in precuneus. Others were disorder-specific and included ADHD-related increases in DC in right striatum/pallidum, in contrast with ASD-related increases in bilateral temporolimbic areas. Secondary analyses differentiating children with ASD into those with or without ADHD-like comorbidity (ASD+ and ASD−, respectively) revealed that the ASD+ group shared ADHD-specific abnormalities in basal ganglia. By contrast, centrality increases in temporolimbic areas characterized children with ASD regardless of ADHD-like comorbidity. At the cluster level eignevector centrality group patterns were similar to DC. Conclusions ADHD and ASD are neurodevelopmental disorders with distinct and overlapping clinical presentations. This work provides evidence for both shared and distinct underlying mechanisms at the large-scale network level.
Psychometric properties and initial validity of the Brief Observation of Social Communication Change (BOSCC), a measure of treatment-response for social-communication behaviors, are described. The BOSCC coding scheme is applied to 177 video observations of 56 young children with ASD and minimal language abilities. The BOSCC has high to excellent inter-rater and test-retest reliability and shows convergent validity with measures of language and communication skills. The BOSCC Core total demonstrates statistically significant amounts of change over time compared to a no change alternative while the ADOS CSS over the same period of time did not. This work is a first step in the development of a novel outcome measure for social-communication behaviors with applications to clinical trials and longitudinal studies.
The heterogeneous clinical presentations of individuals with autism spectrum disorders (ASDs) poses a significant challenge for sample characterization and limits the interpretability and replicability of research studies. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria for ASD, with its dimensional approach, may be a useful framework to increase the homogeneity of research samples. In this review, we summarize the revisions to the diagnostic criteria for ASD, briefly highlight the literature supporting these changes, and illustrate how DSM-5 can improve sample characterization and provide opportunities for researchers to identify possible subtypes within ASD.
We examined to what extent increased parent reports of autistic traits in some children with Attention Deficit Hyperactivity Disorder (ADHD) are the result of ADHD-related symptoms or qualitatively similar to the core characteristics of autism spectrum disorders (ASD). Results confirm the presence of a subgroup of children with ADHD and elevated ratings of core ASD traits (ADHD+) not accounted for by ADHD or behavioral symptoms. Further, analyses revealed greater oppositional behaviors, but not ADHD severity or anxiety, in the ADHD+ subgroup compared to those with ADHD only. These results highlight the importance of specifically examining autistic traits in children with ADHD for better characterization in studies of the underlying physiopathology and treatment.
BackgroundChildren with attention deficit/hyperactivity disorder (ADHD) often present with social difficulties, though the extent to which these clearly overlap with symptoms of autism spectrum disorder (ASD) is not well understood.MethodsWe explored parent-reported and directly-observed ASD symptoms on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in children referred to ASD-specialty clinics who received diagnoses of either ADHD (n = 48) or ASD (n = 164).ResultsOf the ADHD sample, 21 % met ASD cut-offs on the ADOS and 30 % met ASD cut-offs on all domains of the ADI-R. Four social communication ADOS items (Quality of Social Overtures, Unusual Eye Contact, Facial Expressions Directed to Examiner, and Amount of Reciprocal Social Communication) adequately differentiated the groups while none of the items on the ADI-R met the criteria for adequate discrimination.ConclusionsResults of this work highlight the challenges that clinicians and researchers face when distinguishing ASD from other disorders in verbally fluent, school-age children.
This study aims to determine the validity and reliability of applying the coding strategy from the Brief Observation of Social Communication Change (BOSCC), a newly validated treatment outcome measure, to videotaped segments of the Autism Diagnostic Observation Schedule (ADOS). Results indicate strong reliability and validity of the BOSCC ratings using the ADOS segments in detecting changes in social communication over the course of treatment in young, minimally verbal children with ASD. Results also suggest that the BOSCC, when applied to ADOS segments, may be more sensitive in detecting subtle changes in social communication compared to the ADOS Calibrated Severity Scores (CSS). These results may support the application of the BOSCC to pre-existing datasets of ADOS videos to examine treatment responses.
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