Developmental trajectory of subtle motor signs in attention-deficit/hyperactivity disorder: a longitudinal study from childhood to adolescence

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

ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is associated with atypical fronto-subcortical neural circuitry and heightened delay discounting, or a stronger preference for smaller, immediate rewards over larger, delayed rewards. Recent evidence of ADHD-related sex differences in brain structure and function suggests anomalies in fronto-subcortical circuitry may differ among girls and boys with ADHD. The current study examined whether the functional connectivity (FC) within fronto-subcortical neural circuitry differs among girls and boys with ADHD compared to same-sex typically developing (TD) controls and relates to delay discounting. Methods Participants include 8–12-year-old children with ADHD (n = 72, 20 girls) and TD controls (n = 75, 21 girls). Fronto-subcortical regions of interest were functionally defined by applying independent component analysis to resting-state fMRI data. Intrinsic FC between subcortical components, including the striatum and amygdala, and prefrontal components, including ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and anterior dorsolateral prefrontal cortex (dlPFC), was compared across diagnostic groups overall and within sex. Correlations between intrinsic FC of the six fronto-subcortical pairs and delay discounting were also examined. Results Both girls and boys with ADHD show atypical FC between vmPFC and subcortical regions including the striatum (stronger positive FC in ADHD) and amygdala (weaker negative FC in ADHD), with the greatest diagnostic effects among girls. In addition, girls with ADHD show atypical intrinsic FC between the striatum and dlPFC components, including stronger positive FC with ACC and stronger negative FC with dlPFC. Further, girls but not boys, with ADHD, show heightened real-time delay discounting. Brain–behavior correlations suggest (1) stronger negative FC between the striatal and dlPFC components correlated with greater money delay discounting across all participants and (2) stronger FC between the amygdala with both the dlPFC and ACC components was differentially related to heightened real-time discounting among girls and boys with and without ADHD. Conclusions Our findings suggest fronto-subcortical functional networks are affected in children with ADHD, particularly girls, and relate to delay discounting. These results also provide preliminary evidence of greater disruptions in fronto-subcortical FC among girls with ADHD that is not due to elevated inattention symptom severity, intellectual reasoning ability, age, or head motion

Beyond Massive Univariate Tests: Covariance Regression Reveals Complex Patterns of Functional Connectivity Related to Attention-Deficit/Hyperactivity Disorder, Age, Sex, and Response Control

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

Characterizing different cognitive and neurobiological profiles in a community sample of children using a non-parametric approach: An fMRI study

Executive Functions (EF) is an umbrella term for a set of mental processes geared towards goal-directed behavior supporting academic skills such as reading abilities. One of the brain’s functional networks implicated in EF is the Default Mode Network (DMN). The current study uses measures of inhibitory control, a main sub-function of EF, to create cognitive and neurobiological ''inhibitory control profiles'' and relate them to reading abilities in a large sample (N = 5055) of adolescents aged 9–10 from the Adolescent Brain Cognitive Development (ABCD) study. Using a Latent Profile Analysis (LPA) approach, data related to inhibitory control was divided into four inhibition classes. For each class, functional connectivity within the DMN was calculated from resting-state data, using a non-parametric algorithm for detecting group similarities. These inhibitory control profiles were then related to reading abilities. The four inhibitory control groups showed significantly different reading abilities, with neurobiologically different DMN segregation profiles for each class versus controls. The current study demonstrates that a community sample of children is not entirely homogeneous and is composed of different subgroups that can be differentiated both behaviorally/cognitively and neurobiologically, by focusing on inhibitory control and the DMN. Educational implications relating these results to reading abilities are noted

sj-docx-1-jad-10.1177_10870547241237242 – Supplemental material for The Impact of Sex on Cognitive Control in ADHD: Girls Slow to Inhibit, Boys Inhibit Less, and Both Show Higher Response Variability

Supplemental material, sj-docx-1-jad-10.1177_10870547241237242 for The Impact of Sex on Cognitive Control in ADHD: Girls Slow to Inhibit, Boys Inhibit Less, and Both Show Higher Response Variability by Beatrice Ojuri, Alyssa DeRonda, Micah Plotkin, Stewart H. Mostofsky and Keri S. Rosch in Journal of Attention Disorders</p

Predicted DRD4 prefrontal gene expression moderates snack intake and stress perception in response to the environment in adolescents.

Body weight is substantially determined by eating behaviors, which are themselves driven by biological factors interacting with the environment. Previous studies in young children suggest that genetic influences on dopamine function may confer differential susceptibility to the environment in such a way that increases behavioral obesity risk in a lower socioeconomic status (SES) environment but decreases it in a higher SES environment. We aimed to test if this pattern of effect could also be observed in adolescence, another critical period for development in brain and behavior, using a novel measure of predicted expression of the dopamine receptor 4 (DRD4) gene in prefrontal cortex. In a sample of 76 adolescents (37 boys and 39 girls from Baltimore, Maryland/US, aged 14-18y), we estimated individual levels of DRD4 gene expression (PredDRD4) in prefrontal cortex from individual genomic data using PrediXcan, and tested interactions with a composite SES score derived from their annual household income, maternal education, food insecurity, perceived resource availability, and receipt of public assistance. Primary outcomes were snack intake during a multi-item ad libitum meal test, and food-related impulsivity assessed using a food-adapted go/no-go task. A linear regression model adjusted for sex, BMI z-score, and genetic ethnicity demonstrated a PredDRD4 by composite SES score interaction for snack intake (p = 0.009), such that adolescents who had lower PredDRD4 levels exhibited greater snack intake in the lower SES group, but lesser snack intake in the higher SES group. Exploratory analysis revealed a similar pattern for scores on the Perceived Stress Scale (p = 0.001) such that the low PredDRD4 group reported higher stress in the lower SES group, but less stress in the higher SES group, suggesting that PredDRD4 may act in part by affecting perceptions of the environment. These results are consistent with a differential susceptibility model in which genes influencing environmental responsiveness interact with environments varying in obesogenicity to confer behavioral obesity risk in a less favorable environment, but behavioral obesity protection in a favorable one