Atypical interference control in children with AD/HD with elevated theta/beta ratio

The theta/beta ratio (TBR) is a major area of interest within electroencephalogram (EEG) research in AD/HD. While researchers suggest a prognostic role for TBR in AD/HD, its relationship to behavior remains uncertain. Recent evidence suggests that elevated TBR in AD/HD may be related to atypical inhibition, particularly at an attentional level. This study aimed to examine the performance on three inhibitory tasks of children with AD/HD. Fifty-eight children with AD/HD participated, divided into an elevated TBR (ET) group and a control group (CT). A behavioral disassociation was found − compared to CT, ET showed more difficulty in inhibiting surrounding stimuli but had less day-to-day inhibitory issues measured by BRIEF. There was no significant group difference on response inhibition. The results support the prognostic value of TBR in AD/HD. Elevated TBR may be an inhibitory biomarker; further studies are needed to explore the behavioral implications in patients without elevated TBR

Abnormal Resting-State Functional Connectivity of Insular Subregions and Disrupted Correlation with Working Memory in Adults with Attention Deficit/Hyperactivity Disorder

ObjectivesExecutive function (EF) deficits are major impairments in adults with attention deficit/hyperactivity disorder (ADHD). Previous studies have shown that the insula is involved in cognitive and EFs. However, the insula is highly heterogeneous in function, and few studies have focused on functional networks which related to specific insular subregions in adults with ADHD. We explored the functional networks of the insular subregions [anterior insula (AI), mid-insula (MI), and posterior insula (PI)]. Furthermore, their correlations with self-ratings of ecological EFs, including inhibition, shifting, and working memory were investigated.MethodsResting-state functional magnetic resonance imaging data in 28 adults with ADHD and 30 matched healthy controls (HCs) were analyzed. The seed-based resting-state functional connectivity (RSFC) of the insular subregions was evaluated. We also investigated their associations with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) inhibition, working memory, and shifting factor scores.ResultsCompared with HCs, adults with ADHD showed altered RSFC of the AI, with the precuneus, precentral gyrus, and inferior temporal gyrus extended to the middle temporal gyrus, lingual gyrus, and superior occipital gyrus, respectively. There were no significant differences in RSFC of the MI and PI between the two groups. Within the HC group, working memory scores were associated with the RSFC of AI with precuneus and temporal gyrus. However, there was no correlation between these variables in the ADHD group.ConclusionThe study evaluated RSFC patterns of the insular subregions in adults with ADHD for the first time. Altered RSFC of the AI which is a crucial region of salience network (SN) and part of regions in default mode network (DMN), were detected in adults with ADHD in both results with and without global signal regression (GSR), suggesting that disrupted SN-DMN functional connectivity may be involved in EF impairments in adults with ADHD, especially with respect to working memory. Deficits of the AI which is involved in salient stimuli allocation, might be associated with the pathophysiology of ADHD. The inconsistent results of MI and PI between analyses with and without GSR need further exploration

Profiling surface proteins on individual exosomes using a proximity barcoding assay

Exosomes have been implicated in numerous biological processes, and they may serve as important disease markers. Surface proteins on exosomes carry information about their tissues of origin. Because of the heterogeneity of exosomes it is desirable to investigate them individually, but this has so far remained impractical. Here, we demonstrate a proximity-dependent barcoding assay to profile surface proteins of individual exosomes using antibody-DNA conjugates and next-generation sequencing. We first validate the method using artificial streptavidin-oligonucleotide complexes, followed by analysis of the variable composition of surface proteins on individual exosomes, derived from human body fluids or cell culture media. Exosomes from different sources are characterized by the presence of specific combinations of surface proteins and their abundance, allowing exosomes to be separately quantified in mixed samples to serve as markers for tissue-specific engagement in disease

Time Effects on Resting EEG in Children With/Without AD/HD

In this study we extend on behavioural evidence to examine the effect of time on EEG measures related to arousal and emotion/motivation in children with/without AD/HD. Thirty children with AD/HD and 30 age- and sex-matched controls participated. EEG was recorded during an eyes-closed resting condition and divided into three 2.5 min blocks after pre-processing. Time effects for absolute and relative alpha activity were found in healthy controls; these effects did not interact with AD/HD status. Interactions between time and AD/HD status were found for absolute theta, relative theta, and theta/beta ratio (TBR), with these EEG indices increasing over time in children with AD/HD. Moreover, IQ played a role in the interaction between time and AD/HD status. These results are consistent with predictions from both the optimal stimulation model and the delay aversion model, and suggest important methodological considerations for future EEG research in children with/without AD/HD

Roles of obesity in mediating the causal effect of attention-deficit/hyperactivity disorder on diabetes

Abstract Aims Previous observational studies have reported potential associations among attention-deficit/hyperactivity disorder (ADHD), obesity, and diabetes (including type 1 and type 2 diabetes mellitus [T1DM/T2DM]). However, whether the association between ADHD and diabetes is mediated by obesity is unknown. Methods With two-sample Mendelian randomization, we analysed the causal effect of ADHD on T1DM and T2DM and six obesity-related traits [including body mass index, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat percentage and basal metabolic rate] and the causal effect of these obesity-related traits on T1DM/T2DM. Finally, with multivariable Mendelian randomization, we explored and quantified the possible mediation effects of obesity-related traits on the causal effect of ADHD on T1DM/T2DM. Results Our results showed that ADHD increased the risk of T2DM by 14% [odds ratio (OR) = 1.140, 95% confidence interval (CI) = 1.005–1.293] but with no evidence of an effect on T1DM (OR = 0.916, 95% CI = 0.735–1.141, P = 0.433.). In addition, ADHD had a 6.1% increased causal effect on high WC (OR = 1.061, 95% CI = 1.024–1.099, P = 0.001) and an 8.2% increased causal effect on high WHR (OR = 1.082, 95% CI = 1.035–1.131, P = 0.001). In addition, a causal effect of genetically predicted high WC (OR = 1.870, 95% CI = 1.594–2.192, P < 0.001) on a higher risk of T2DM was found. In further analysis, WC mediated approximately 26.75% (95% CI = 24.20%–29.30%) of the causal association between ADHD and T2DM. Conclusions WC mediates a substantial proportion of the causal effect of ADHD on the risk of T2DM, which indicated that the risk of T2DM induced by ADHD could be indirectly reduced by controlling WC as a main risk factor

Network analysis of 18 attention-deficit/hyperactivity disorder symptoms suggests the importance of “Distracted” and “Fidget” as central symptoms: Invariance across age, gender, and subtype presentations

The network theory of mental disorders conceptualizes psychiatric symptoms as networks of symptoms that causally interact with each other. Our present study aimed to explore the symptomatic structure in children with attention-deficit/hyperactivity disorder (ADHD) using network analyses. Symptom network based on 18 items of ADHD Rating Scale-IV was evaluated in 4,033 children and adolescents with ADHD. The importance of nodes was evaluated quantitatively by examining centrality indices, including Strength, Betweenness and Closeness, as well as Predictability and Expected Influence (EI). In addition, we compared the network structure across different subgroups, as characterized by ADHD subtypes, gender and age groups to evaluate its invariance. A three-factor-community structure was identified including inattentive, hyperactive and impulsive clusters. For the centrality indices, the nodes of “Distracted” and “Fidget” showed high closeness and betweenness, and represented a bridge linking the inattentive and hyperactive/impulsive domains. “Details” and “Fidget” were the most common endorsed symptoms in inattentive and hyperactive/impulsive domains respectively. On the contrary, the “Listen” item formed a peripheral node showing weak links with all other items within the inattentive cluster, and the “Loss” item as the least central node by all measures of centrality and with low predictability value. The network structure was relatively invariant across gender, age and ADHD subtypes/presentations. The 18 items of ADHD core symptoms appear not equivalent and interchangeable. “Distracted” and “Fidget” should be considered as central, or core, symptoms for further evaluation and intervention. The network-informed differentiation of these symptoms has the potentials to refine the phenotype and reduce heterogeneity

Electroencephalogram Theta/Beta Ratio and Spectral Power Correlates of Executive Functions in Children and Adolescents With AD/HD

OBJECTIVE: The electroencephalogram (EEG) has been widely used in AD/HD research. The current study firstly aimed to replicate a recent trend related to EEG theta/beta ratio (TBR) in children and adolescents. Also, the study aimed to examine the value of resting EEG activity as biomarkers for executive function (EF) in participants with AD/HD. METHOD: Fifty-three participants with AD/HD and 37 healthy controls were recruited. Resting EEG was recorded with eyes closed. Participants with AD/HD additionally completed EF tasks via the Cambridge Neuropsychological Test Automated Battery. RESULTS: TBR did not differ between groups; however, TBR was positively correlated with inattentive symptoms in AD/HD. Other correlations were found between EEG activity and neuropsychological functions including spatial planning and decision making in the AD/HD group. CONCLUSION: The results do not support the diagnostic value of TBR. Instead, given the heterogeneous features, the results support the prognostic value of EEG in AD/HD

Shared and distinct resting functional connectivity in children and adults with attention-deficit/hyperactivity disorder

2020, The Author(s). Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, with a shift of symptoms including less hyperactivity/impulsivity and more co-morbidity of affective disorders in ADHDadult. Many studies have questioned the stability in diagnosing of ADHD from childhood to adulthood, and the shared and distinct aberrant functional connectivities (FCs) between ADHDchild and ADHDadult remain unidentified. We aim to explore shared and distinct FC patterns in ADHDchild and ADHDadult, and further investigated the cross-cohort predictability using the identified FCs. After investigating the ADHD-discriminative FCs from healthy controls (HCs) in both child (34 ADHDchild, 28 HCs) and adult (112 ADHDadult,77 HCs) cohorts, we identified both shared and distinct aberrant FC patterns between cohorts and their association with clinical symptoms. Moreover, the cross-cohort predictability using the identified FCs were tested. The ADHD-HC classification accuracies were 84.4% and 81.0% for children and male adults, respectively. The ADHD-discriminative FCs shared in children and adults lie in the intra-network within default mode network (DMN) and the inter-network between DMN and ventral attention network, positively correlated with total scores of ADHD symptoms. Particularly, inter-network FC between somatomotor network and dorsal attention network was uniquely impaired in ADHDchild, positively correlated with hyperactivity index; whereas the aberrant inter-network FC between DMN and limbic network exhibited more adult-specific ADHD dysfunction. And their cross-cohort predictions were 70.4% and 75.6% between each other. This work provided imaging evidence for symptomatic changes and pathophysiological continuity in ADHD from childhood to adulthood, suggesting that FCs may serve as potential biomarkers for ADHD diagnosis

Network analysis of 18 attention-deficit/hyperactivity disorder symptoms suggests the importance of "Distracted" and "Fidget" as central symptoms: Invariance across age, gender, and subtype presentations

The network theory of mental disorders conceptualizes psychiatric symptoms as networks of symptoms that causally interact with each other. Our present study aimed to explore the symptomatic structure in children with attention-deficit/hyperactivity disorder (ADHD) using network analyses. Symptom network based on 18 items of ADHD Rating Scale-IV was evaluated in 4,033 children and adolescents with ADHD. The importance of nodes was evaluated quantitatively by examining centrality indices, including Strength, Betweenness and Closeness, as well as Predictability and Expected Influence (EI). In addition, we compared the network structure across different subgroups, as characterized by ADHD subtypes, gender and age groups to evaluate its invariance. A three-factor-community structure was identified including inattentive, hyperactive and impulsive clusters. For the centrality indices, the nodes of "Distracted" and "Fidget" showed high closeness and betweenness, and represented a bridge linking the inattentive and hyperactive/impulsive domains. "Details" and "Fidget" were the most common endorsed symptoms in inattentive and hyperactive/impulsive domains respectively. On the contrary, the "Listen" item formed a peripheral node showing weak links with all other items within the inattentive cluster, and the "Loss" item as the least central node by all measures of centrality and with low predictability value. The network structure was relatively invariant across gender, age and ADHD subtypes/presentations. The 18 items of ADHD core symptoms appear not equivalent and interchangeable. "Distracted" and "Fidget" should be considered as central, or core, symptoms for further evaluation and intervention. The network-informed differentiation of these symptoms has the potentials to refine the phenotype and reduce heterogeneity