Browsing by Author "Mostofsky, Stewart H."

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    ADHD-related sex differences in emotional symptoms across development
    (Springer, 2024) De Ronda, Alyssa C.; Rice, Laura; Zhao, Yi; Rosch, Keri S.; Mostofsky, Stewart H.; Seymour, Karen E.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    To investigate developmental changes in emotion dysregulation (ED) and associated symptoms of emotional lability, irritability, anxiety, and depression, among girls and boys with and without ADHD from childhood through adolescence. Data were collected from a sample of 8-18-year-old children with (n = 264; 76 girls) and without (n = 153; 56 girls) ADHD, with multiple time-points from a subsample of participants (n = 121). Parents and youth completed rating scales assessing child ED, emotional lability, irritability, anxiety, and depression. Mixed effects models were employed to examine effects and interactions of diagnosis, sex [biological sex assigned at birth], age among boys and girls with and without ADHD. Mixed effects analyses showed sexually dimorphic developmental patterns between boys and girls, such that boys with ADHD showed a greater reduction in ED, irritability, and anxiety with age compared to girls with ADHD, whose symptom levels remained elevated relative to TD girls. Depressive symptoms were persistently elevated among girls with ADHD compared to boys with ADHD, whose symptoms decreased with age, relative to same-sex TD peers. While both boys and girls with ADHD showed higher levels of ED during childhood (compared to their sex-matched TD peers), mixed effects analyses revealed substantial sexually dimorphic patterns of emotional symptom change during adolescence: Boys with ADHD showed robust improvements in emotional symptoms from childhood to adolescence while girls with ADHD continued to show high and/or increased levels of ED, emotional lability, irritability, anxiety and depression.
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    Beyond Massive Univariate Tests: Covariance Regression Reveals Complex Patterns of Functional Connectivity Related to Attention-Deficit/Hyperactivity Disorder, Age, Sex, and Response Control
    (Elsevier, 2022) Zhao, Yi; Nebel, Mary Beth; Caffo, Brian S.; Mostofsky, Stewart H.; Rosch, Keri S.; Biostatistics and Health Data Science, School of Medicine
    Background: Studies of brain functional connectivity (FC) typically involve massive univariate tests, performing statistical analysis on each individual connection. In this study we apply a novel whole-matrix regression approach referred to as Covariate Assisted Principal (CAP) regression to identify resting-state FC brain networks associated with attention-deficit/hyperactivity disorder (ADHD) and response control. Methods: Participants included 8-12 year-old children with ADHD (n=115, 29 girls) and typically developing controls (n=102, 35 girls) who completed a resting-state fMRI scan and a go/no-go task (GNG). We modeled three sets of covariates to identify resting-state networks associated with an ADHD diagnosis, sex, and response inhibition (commission errors) and variability (ex-Gaussian parameter tau). Results: The first network includes FC between striatal-cognitive control (CC) network subregions and thalamic-default mode network (DMN) subregions and is positively related to age. The second consists of FC between CC-visual-somatomotor regions and between CC-DMN subregions and is positively associated with response variability in boys with ADHD. The third consists of FC within the DMN and between DMN-CC-visual regions and differs between boys with and without ADHD. The fourth consists of FC between visual-somatomotor regions and between visual-DMN regions and differs between girls and boys with ADHD and is associated with response inhibition and variability in boys with ADHD. Unique networks were also identified in each of the three models suggesting some specificity to the covariates of interest. Conclusions: These findings demonstrate the utility of our novel covariance regression approach to studying functional brain networks relevant for development, behavior, and psychopathology.
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    Covariate Assisted Principal Regression for Covariance Matrix Outcomes
    (Oxford, 2019) Zhao, Yi; Wang, Bingkai; Mostofsky, Stewart H.; Ca, Brian S.; Luo, Xi; Biostatistics, School of Public Health
    In this study, we consider the problem of regressing covariance matrices on associated covariates. Our goal is to use covariates to explain variation in covariance matrices across units. As such, we introduce Covariate Assisted Principal (CAP) regression, an optimization-based method for identifying components associated with the covariates using a generalized linear model approach. We develop computationally efficient algorithms to jointly search for common linear projections of the covariance matrices, as well as the regression coefficients. Under the assumption that all the covariance matrices share identical eigencomponents, we establish the asymptotic properties. In simulation studies, our CAP method shows higher accuracy and robustness in coefficient estimation over competing methods. In an example resting-state functional magnetic resonance imaging study of healthy adults, CAP identifies human brain network changes associated with subject demographics.
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    Developmental trajectory of subtle motor signs in attention-deficit/hyperactivity disorder: a longitudinal study from childhood to adolescence
    (Taylor & Francis, 2021-04) Crasta, Jewel E.; Zhao, Yi; Seymour, Karen E.; Suskauer, Stacy J.; Mostofsky, Stewart H.; Rosch, Keri S.; Biostatistics, School of Public Health
    This study examined the developmental trajectory of neurodevelopmental motor signs among boys and girls with attention-deficit/hyperactivity disorder (ADHD) and typically-developing (TD) children. Seventy children with ADHD and 48 TD children, aged 8–17 years, were evaluated on at least two time-points using the Physical and Neurological Assessment of Subtle Signs (PANESS). Age-related changes in subtle motor signs (overflow, dysrhythmia, speed) were modeled using linear mixed-effects models to compare the developmental trajectories among four subgroups (ADHD girls and boys and TD girls and boys). Across visits, both boys and girls with ADHD showed greater overflow, dysrhythmia, and slower speed on repetitive motor tasks compared to TD peers; whereas, only girls with ADHD were slower on sequential motor tasks than TD girls. Developmental trajectory analyses revealed a greater reduction in overflow with age among boys with ADHD than TD boys; whereas, trajectories did not differ among girls with and without ADHD, or among boys and girls with ADHD. For dysrhythmia and speed, there were no trajectory differences between the subgroups, with all groups showing similar reductions with age. Children with ADHD show developmental trajectories of subtle motor signs that are consistent with those of TD children, with one clear exception: Boys with ADHD show more significant reductions in overflow from childhood to adolescence than do their TD peers. Our findings affirm the presence of subtle motor signs in children with ADHD and suggest that some of these signs, particularly motor overflow in boys, resolve through adolescence while dysrhythmia and slow speed, may persist.
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    Distinct Patterns of Impaired Cognitive Control Among Boys and Girls with ADHD Across Development
    (Springer, 2021) DeRonda, Alyssa; Zhao, Yi; Seymour, Karen E.; Mostofsky, Stewart H.; Rosch, Keri S.; Biostatistics, School of Public Health
    This study examined whether girls and boys with ADHD show similar impairments in cognitive control from childhood into adolescence and the developmental relationship between cognitive control and ADHD symptoms. Participants include 8-17-year-old children with ADHD (n = 353, 104 girls) and typically developing (TD) controls (n = 241, 86 girls) with longitudinal data obtained from n = 137. Participants completed two go/no-go (GNG) tasks that varied in working memory demand. Linear mixed-effects models were applied to compare age-related changes in cognitive control for each GNG task among girls and boys with ADHD and TD controls and in relation to ADHD symptoms. Boys with ADHD showed impaired response inhibition and increased response variability across tasks. In contrast, girls with ADHD showed impaired response inhibition only with greater working memory demands whereas they displayed increased response variability regardless of working memory demands. Analysis of age-related change revealed that deficits in cognitive control under minimal working memory demands increase with age among girls with ADHD and decrease with age among boys with ADHD. In contrast, deficits in cognitive control with greater working memory demands decrease with age among both boys and girls with ADHD compared to TD peers. Among children with ADHD poor response inhibition during childhood predicted inattentive symptoms in adolescence and was associated with less age-related improvement in inattentive symptoms. These findings suggest that girls and boys with ADHD show differential impairment in cognitive control across development and response inhibition in childhood may be an important predictor of ADHD symptoms in adolescence.
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    Learning of Skilled Movements via Imitation in ASD
    (Wiley, 2020-05) McAuliffe, Danielle; Zhao, Yi; Pillai, Ajay S.; Ament, Katarina; Adamek, Jack; Caffo, Brian S.; Mostofsky, Stewart H.; Ewen, Joshua B.; Biostatistics, School of Public Health
    Autism spectrum disorder (ASD) consists of altered performance of a range of skills, including social/communicative and motor skills. It is unclear whether this altered performance results from atypical acquisition or learning of the skills or from atypical “online” performance of the skills. Atypicalities of skilled actions that require both motor and cognitive resources, such as abnormal gesturing, are highly prevalent in ASD and are easier to study in a laboratory context than are social/communicative skills. Imitation has long been known to be impaired in ASD; because learning via imitation is a prime method by which humans acquire skills, we tested the hypothesis that children with ASD show alterations in learning novel gestures via imitation. Eighteen participants with ASD and IQ > 80, ages 8–12.9 years, and 19 typically developing peers performed a task in which they watched a video of a model performing a novel, meaningless arm/hand gesture and copied the gesture. Each gesture video/copy sequence was repeated 4–6 times. Eight gestures were analyzed. Examination of learning trajectories revealed that while children with ASD made nearly as much progress in learning from repetition 1 to repetition 4, the shape of the learning curves differed. Causal modeling demonstrated the shape of the learning curve influenced both the performance of overlearned gestures and autism severity, suggesting that it is in the index of learning mechanisms relevant both to motor skills and to autism core features.