Claudin-5, occludin, zonulin and tricellulin levels of children with attention-deficit/hyperactivity disorder

Background and objectives Accumulating studies have pointed out that gut-blood and blood-brain barrier dysfunctions due to the alterations in permeability may play a role in the pathophysiology of neurodevelopmental disorders. Tight junctions are crucial components of these barriers and some peptides including claudin-5, occludin, zonulin and tricellulin are important components of these structures. This study aimed to investigate the relationship between these molecules and attention deficit hyperactivity disorder (ADHD) in children and adolescents. Methods A total of 57 children with ADHD and 60 controls aged between 6 and 12 years were included in the study. The severity of ADHD symptoms was assessed through a parent-rated questionnaire, and Conner's Continuous Performance Test was administered to the study group. Serum levels of biochemical variables were measured using enzyme-linked immunosorbent assay kits. Biochemical parameter levels and scale scores were compared using Mann-Whitney U or Student's t tests. In addition, a multivariate analysis of covariance (MANCOVA) and a one-way analysis of covariance (ANCOVA) was performed on the outcome variables. Finally, a hierarchical regression model was conducted on the study group. Results Serum claudin-5 and tricellulin levels were significantly lower in the ADHD group compared to the control group. The difference between the groups in terms of serum claudin-5 and tricellulin levels remained significant after controlling for confounding factors such as age, gender and autistic characteristics. There was no significant difference between the groups in terms of serum zonulin and occludin levels.Conclusion These results reveal that claudin-5 and tricellulin levels vary in patients with ADHD. Alterations in these peptides may affect the brain by leading to a dysregulation in intestinal or blood-brain barrier permeability. The causal relationship between these peptides and ADHD requires further ... (AU)

Properties of white matter tract diffusivity in children with developmental dyslexia and comorbid attention deficit/hyperactivity disorder.

BACKGROUND: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored. METHODS: Participants were 3rd and 4th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants. RESULTS: DD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found. CONCLUSIONS: Findings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD.

Neuropsychological and Symptom Predictors of Diagnostic Persistence in ADHD: A 25-Year Follow-up Study.

BACKGROUND: This study extends long-term predictive research on ADHD by including both neuropsychological and symptom measures at baseline in adolescence as predictors of diagnostic persistence 25 years later. METHODS: Nineteen males with ADHD and 26 healthy controls (HC; M/F = 13/13), were assessed in adolescence and 25 years later. Measurements at baseline included a comprehensive test battery measuring eight neuropsychological domains, an IQ estimate, the Child Behavior Checklist (CBCL), and the Global Assessment Scale of Symptoms. Differences between ADHD Retainers, Remitters, and HC were calculated with ANOVAs, and potential predictions of differences in the ADHD group by linear regression analyses. RESULTS: Eleven (58%) participants retained their ADHD diagnoses at follow-up. Motor Coordination and Visual perception at baseline predicted diagnosis at follow-up. CBCL Attention problems at baseline in the ADHD group predicted variance in diagnostic status. CONCLUSION: Lower-order neuropsychological functions related to motor function and perception are important long-time predictors of persistence of ADHD.

Time-frequency neural dynamics of ADHD children and adolescents during a Working Memory task.

The present report analyzed the time-frequency changes in Event-Related Spectral perturbations (ERSP) in a sample of ADHD children and adolescents compared to a normodevelopment (ND) sample. A delayed match-to-sample (DMTS) test of working memory (WM) was presented to a group of ADHD subjects (N = 29) and compared with ND group (N = 34) with ages between 6 and 17 years old. Time-frequency decomposition was computed through wavelets. ADHD subjects presented higher Reaction Time (RT), Standard Deviation of RT (Std of RT), and a reduced percentage of correct responses. The results showed a complex pattern of oscillatory bursts during the encoding, maintenance, and recognition phases with similar dynamics in both groups. ADHD children presented a reduced Event-Related Synchronization (ERS) in the Theta range during the encoding phase, and also a reduced Alpha ERS during the late period of the maintenance phase. S1 Early theta ERS was positively correlated with Std of RT. Behavioral data, early Theta, and late Alpha ERS classified correctly above 70 % of ADHD and ND subjects when a linear discriminant analysis was applied. The reduced encoding and maintenance impaired brain dynamics of ADHD subjects would justify the poorer performance of this group of subjects.

Pain hypersensitivity in a pharmacological mouse model of attention-deficit/hyperactivity disorder.

Clinical evidence suggests that pain hypersensitivity develops in patients with attention-deficit/hyperactivity disorder (ADHD). However, the mechanisms and neural circuits involved in these interactions remain unknown because of the paucity of studies in animal models. We previously validated a mouse model of ADHD obtained by neonatal 6-hydroxydopamine (6-OHDA) injection. Here, we have demonstrated that 6-OHDA mice exhibit a marked sensitization to thermal and mechanical stimuli, suggesting that phenotypes associated with ADHD include increased nociception. Moreover, sensitization to pathological inflammatory stimulus is amplified in 6-OHDA mice as compared to shams. In this ADHD model, spinal dorsal horn neuron hyperexcitability was observed. Furthermore, ADHD-related hyperactivity and anxiety, but not inattention and impulsivity, are worsened in persistent inflammatory conditions. By combining in vivo electrophysiology, optogenetics, and behavioral analyses, we demonstrated that anterior cingulate cortex (ACC) hyperactivity alters the ACC-posterior insula circuit and triggers changes in spinal networks that underlie nociceptive sensitization. Altogether, our results point to shared mechanisms underlying the comorbidity between ADHD and nociceptive sensitization. This interaction reinforces nociceptive sensitization and hyperactivity, suggesting that overlapping ACC circuits may be targeted to develop better treatments.

Towards high-accuracy classifying attention-deficit/hyperactivity disorders using CNN-LSTM model.

Objective. The neurocognitive attention functions involve the cooperation of multiple brain regions, and the defects in the cooperation will lead to attention-deficit/hyperactivity disorder (ADHD), which is one of the most common neuropsychiatric disorders for children. The current ADHD diagnosis is mainly based on a subjective evaluation that is easily biased by the experience of the clinicians and lacks the support of objective indicators. The purpose of this study is to propose a method that can effectively identify children with ADHD.Approach. In this study, we proposed a CNN-LSTM model to solve the three-class problems of classifying ADHD, attention deficit disorder (ADD) and healthy children, based on a public electroencephalogram (EEG) dataset that includes event-related potential (ERP) EEG signals of 144 children. The convolution visualization and saliency map methods were used to observe the features automatically extracted by the proposed model, which could intuitively explain how the model distinguished different groups.Main results. The results showed that our CNN-LSTM model could achieve an accuracy as high as 98.23% in a five-fold cross-validation method, which was significantly better than the current state-of-the-art CNN models. The features extracted by the proposed model were mainly located in the frontal and central areas, with significant differences in the time period mappings among the three different groups. The P300 and contingent negative variation (CNV) in the frontal lobe had the largest decrease in the healthy control (HC) group, and the ADD group had the smallest decrease. In the central area, only the HC group had a significant negative oscillation of CNV waves.Significance. The results of this study suggest that the CNN-LSTM model can effectively identify children with ADHD and its subtypes. The visualized features automatically extracted by this model could better explain the differences in the ERP response among different groups, which is more convincing than previous studies, and it could be used as more reliable neural biomarkers to help with more accurate diagnosis in the clinics.

A Systematic Review on Feature Extraction in Electroencephalography-Based Diagnostics and Therapy in Attention Deficit Hyperactivity Disorder.

A systematic review on electroencephalographic (EEG)-based feature extraction strategies to diagnosis and therapy of attention deficit hyperactivity disorder (ADHD) in children is presented. The analysis is realized at an executive function level to improve the research of neurocorrelates of heterogeneous disorders such as ADHD. The Quality Assessment Tool for Quantitative Studies (QATQS) and field-weighted citation impact metric (Scopus) were used to assess the methodological rigor of the studies and their impact on the scientific community, respectively. One hundred and one articles, concerning the diagnostics and therapy of ADHD children aged from 8 to 14, were collected. Event-related potential components were mainly exploited for executive functions related to the cluster inhibition, whereas band power spectral density is the most considered EEG feature for executive functions related to the cluster working memory. This review identifies the most used (also by rigorous and relevant articles) EEG signal processing strategies for executive function assessment in ADHD.

Development of coordination and muscular fitness in children and adolescents with parent-reported ADHD in the German longitudinal MoMo Study.

This study examined the development of muscular fitness and coordination in children and adolescents with and without attention deficit hyperactivity disorder (ADHD) over a period of 11 years. Data was collected in three measurement waves as part of the longitudinal, representative Motorik-Modul (MoMo) study in Germany (2003-2006, 2009-2012, 2014-2017). The overall sample comprised 2988 participants (253 with ADHD, 65% males; 2735 non-ADHD, 47% males; mean age 9 years). Structural equation modeling was conducted, and the estimated models had a good fit. No differences in muscular fitness were observed between participants with and without ADHD. Participants with ADHD had a lower coordinative performance at first measurement than those without ADHD. The difference in coordinative performance persisted throughout the study period.

Auditory time thresholds in the range of milliseconds but not seconds are impaired in ADHD.

The literature on time perception in individuals with ADHD is extensive but inconsistent, probably reflecting the use of different tasks and performances indexes. A sample of 40 children/adolescents (20 with ADHD, 20 neurotypical) was engaged in two identical psychophysical tasks measuring auditory time thresholds in the milliseconds (0.25-1 s) and seconds (0.75-3 s) ranges. Results showed a severe impairment in ADHD for milliseconds thresholds (Log10BF = 1.9). The deficit remained strong even when non-verbal IQ was regressed out and correlation with age suggests a developmental delay. In the seconds range, thresholds were indistinguishable between the two groups (Log10BF = - 0.5) and not correlated with milliseconds thresholds. Our results largely confirm previous evidence suggesting partially separate mechanisms for time perception in the ranges of milliseconds and seconds. Moreover, since the evidence suggests that time perception of milliseconds stimuli might load relatively less on cognitive control and working memory, compared to longer durations, the current results are consistent with a pure timing deficit in individuals with ADHD.

Brain activity in the prefrontal cortex during cancelation tasks: Effects of the stimulus array.

Cancelation tasks have been widely used to neurologically assess selective attention and visual search in various clinical and research settings. However, there is still a lack of evidence regarding the effect of differences in array conditions on brain activity in the prefrontal cortex (PFC) and its association with developmental characteristics. This study employed cancelation tasks to investigate the effects of varying array conditions on oxygenated hemoglobin (oxy-Hb) concentrations. Data from 24 healthy adults were analyzed based on performance during two-block-design type of cancelation tasks with different array conditions (i.e., structured array vs. random array). Performance was assessed based on the number of correct responses, incorrect responses, hit ratios, and performance scores (PS); while PFC activity was examined using near-infrared spectroscopy. In addition, characteristics of attention-deficit/hyperactivity disorder (ADHD) were assessed using the ADHD-Rating Scale-IV (ADHD-RS-IV). Results revealed that the numbers of correct responses and PS were higher in the random array, but there was no difference in the incorrect responses and hit ratio. Similarly, we observed that the oxy-Hb concentration in the PFC significantly increased during the task. Additionally, in the structured array, a significant relationship between task performance and characteristics of ADHD was found but not in the random array. Our results regarding the above-mentioned changes in oxy-Hb concentration suggest that the PFC region is involved in selective attention. We also found that cancelation tasks in a structured array may be useful in evaluating the characteristics of ADHD.

Manual dexterity and strength and in young adults with and without Attention-Deficit/Hyperactivity Disorder (ADHD).

Manual motor deficits are common in children with attention deficit/hyperactivity disorder (ADHD); however, it is unclear whether these impairments persist into adulthood. The aim of this study was to examine manual dexterity and strength in young adults with ADHD aged 18-25 years. Sixty-one individuals with confirmed ADHD and 56 adults without ADHD completed Purdue Pegboard tasks for manual dexterity and maximal hand- and pinch-grip tests for strength. In the Purdue Pegboard task, participants placed pins using the right, left, and both-hands, respectively. In addition, participants built assemblies using pins, washers, and collars with alternating hand movements. The results demonstrated that women without ADHD out-performed the other three groups in the right-hand, bimanual, and assembly PPB tasks. Both maximal hand strength tests demonstrated that men were stronger than women, but no differences were observed between adults with and without ADHD. The current findings suggest that adults with ADHD may have deficits in manual dexterity and tasks requiring bimanual coordination.

Risk Behaviors in Youth With and Without Tourette Syndrome.

BACKGROUND: Specific health-risk behaviors are present in older adolescents and young adults wtih Tourette syndrome (TS), but little is known about health-risk behaviors in youth with TS. METHODS: We compared responses on the Youth Risk Behavior Surveillance System (YRBS) in youth with TS with those in a concurrent community control group. The YRBS evaluates risk behaviors most closely associated with morbidity and mortality in young people. Tic severity, presence of comorbid attention-deficit/hyperactivity disorder (ADHD), measures of ADHD symptom severity, and whether or not the individual had been bullied in school were also compared between the groups. RESULTS: Data from 52 youth with TS and 48 control youth were included. We did not detect any differences between control youth and youth with TS in the reporting of risky behaviors. Tic severity was not significantly associated with high-risk behavior. However, ADHD was significantly more common in youth with TS (P < 0.0002), and youth with TS who identified themselves as victims of bullying had significantly higher ADHD symptom severity scores (P = 0.04) compared with those who were not bullied. CONCLUSIONS: Risk behaviors are not reliably or clinically different in youth with TS compared with control youth. ADHD severity, but not tic severity, was associated with being bullied in youth with TS.

A dynamic graph convolutional neural network framework reveals new insights into connectome dysfunctions in ADHD.

The pathological mechanism of attention deficit hyperactivity disorder (ADHD) is incompletely specified, which leads to difficulty in precise diagnosis. Functional magnetic resonance imaging (fMRI) has emerged as a common neuroimaging technique for studying the brain functional connectome. Most existing methods that have either ignored or simply utilized graph structure, do not fully leverage the potentially important topological information which may be useful in characterizing brain disorders. There is a crucial need for designing novel and efficient approaches which can capture such information. To this end, we propose a new dynamic graph convolutional network (dGCN), which is trained with sparse brain regional connections from dynamically calculated graph features. We also develop a novel convolutional readout layer to improve graph representation. Our extensive experimental analysis demonstrates significantly improved performance of dGCN for ADHD diagnosis compared with existing machine learning and deep learning methods. Visualizations of the salient regions of interest (ROIs) and connectivity based on informative features learned by our model show that the identified functional abnormalities mainly involve brain regions in temporal pole, gyrus rectus, and cerebellar gyri from temporal lobe, frontal lobe, and cerebellum, respectively. A positive correlation was further observed between the identified connectomic abnormalities and ADHD symptom severity. The proposed dGCN model shows great promise in providing a functional network-based precision diagnosis of ADHD and is also broadly applicable to brain connectome-based study of mental disorders.

Boys with attention-deficit/hyperactivity disorder perform wider and fewer finger tapping than typically developing boys - Peer comparisons and the effects of methylphenidate from an exploratory perspective.

AIM: This study aimed to investigate the differences in fine motor and coordination skills between boys with attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) boys and the effect of methylphenidate (MPH) in boys with ADHD. METHODS: Fourteen boys aged 7-12 years who were diagnosed with ADHD and previously treated with MPH were instructed to tap their thumbs and index fingers together repetitively for 10 s after attaching magnetic sensors. The participants executed "in-phase" and "anti-phase" tapping. A two-way analysis of variance for comparing boys with ADHD and TD boys and the paired t-test to investigate the effect of MPH between sessions with and without MPH were performed. RESULTS: Boys with ADHD showed a significantly lower "number of taps" and a significantly higher "average of local maximum distance" than TD boys. "Energy balance" was significantly lower in ADHD boys than in TD boys. MPH caused a significant difference in the "standard deviation (SD) of phase difference" in "anti-phase tapping." CONCLUSION: Our studies indicated that finger-tapping movements in boys with ADHD tended to be significantly wider and fewer than those in TD boys, and MPH may improve the phase difference of bimanual fine motor coordination skills in boys with ADHD who are above 1.0 SD. The results should be interpreted with caution because we conducted statistical tests for many outcomes and groups without considering the multiplicity factor from an exploratory perspective.

Altered single-subject gray matter structural networks in drug-naïve attention deficit hyperactivity disorder children.

Altered topological organization of brain structural covariance networks has been observed in attention deficit hyperactivity disorder (ADHD). However, results have been inconsistent, potentially related to confounding medication effects. In addition, since structural networks are traditionally constructed at the group level, variabilities in individual structural features remain to be well characterized. Structural brain imaging with MRI was performed on 84 drug-naïve children with ADHD and 83 age-matched healthy controls. Single-subject gray matter (GM) networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared using nonparametric permutation testing. Compared with healthy subjects, GM networks in ADHD patients demonstrated significantly altered topological characteristics, including higher global and local efficiency and clustering coefficient, and shorter path length. In addition, ADHD patients exhibited abnormal centrality in corticostriatal circuitry including the superior frontal gyrus, orbitofrontal gyrus, medial superior frontal gyrus, precentral gyrus, middle temporal gyrus, and pallidum (all p < .05, false discovery rate [FDR] corrected). Altered global and nodal topological efficiencies were associated with the severity of hyperactivity symptoms and the performance on the Stroop and Wisconsin Card Sorting Test tests (all p < .05, FDR corrected). ADHD combined and inattention subtypes were differentiated by nodal attributes of amygdala (p < .05, FDR corrected). Alterations in GM network topologies were observed in drug-naïve ADHD patients, in particular in frontostriatal loops and amygdala. These alterations may contribute to impaired cognitive functioning and impulsive behavior in ADHD.

Effect of sex chromosome number variation on attention-deficit/hyperactivity disorder symptoms, executive function, and processing speed.

AIM: To study sex differences in attention-deficit/hyperactivity disorder (ADHD) symptoms, we explored whether X chromosome absence or excess is independently associated with deficits in attention and hyperactivity, executive function, and processing speed. METHOD: We assessed 116 children (ages 3y 10mo-11y 11mo, mean 8y 5mo, SD 1y 11mo) with a variable number of sex chromosomes: 36 females with Turner syndrome (45, X0), 20 males with Klinefelter syndrome (47, XXY), 37 typically developing females (XX), and 23 typically developing males (XY). RESULTS: X chromosome absence was associated with increased attention problems, hyperactivity, and deficits in inhibitory control, compared with female children with XX (all p<0.003). Conversely, X chromosome excess was associated with weakness in working memory (p=0.018) and approached significance for attention problems (p=0.071) but not with hyperactivity, or weakness in inhibitory control relative to male children with XY. Using non-parametric effect size to quantify the clinical effect revealed that X chromosome absence affected attention, hyperactivity, executive function, and processing speed (all r>0.4), while X excess affected in-laboratory as well as parent-reported working memory (all r>0.4). INTERPRETATION: Our observations provide compelling evidence that the absence or excess of an X chromosome distinctly affects cognition and behaviors associated with ADHD.

Artificial food coloring affects EEG power and ADHD symptoms in college students with ADHD: a pilot study.

Objectives: Removing artificial food coloring (AFC) is a common dietary intervention for children with Attention-Deficit/Hyperactivity Disorder (ADHD), but has not been tested in young adults. This pilot study examined the effects of AFC on ADHD symptoms and electroencephalography (EEG) in college students with and without ADHD.Methods: At baseline, control and ADHD participants completed the Adult ADHD Self-Report Scale (ASRS), simple and complex attention measures, and resting-state EEG recordings. ADHD participants (n = 18) and a subset of controls (extended control group or EC, n = 11) avoided AFC in their diet for 2 weeks and then were randomized to a double-blind, placebo-controlled crossover challenge. Subjects received either 225 mg AFC disguised in chocolate cookies or placebo chocolate cookies for 3 days each week, with testing on the third day each week. Baseline comparisons were made using Student's t-test or Wilcoxon rank sum tests and challenge period analyses were run using General Linear Modeling.Results: The ADHD group had significantly greater scores on the ASRS (p < 0.001), confirming a symptom differential between groups; however, there were no differences in attentional measures or EEG at baseline. The AFC challenge resulted in an increase in posterior mean gamma power (p = 0.05), a decrease in posterior relative alpha power (p = 0.04), and a marginal increase in inattentive symptoms (p = 0.08) in the ADHD group. There were no effects of AFC in the EC group.Discussion: This study indicates that AFC exposure may affect brainwave activity and ADHD symptoms in college students with ADHD. Larger studies are needed to confirm these findings.

Neuroimaging in Attention-Deficit/Hyperactivity Disorder: Recent Advances.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that leads to impaired attention and impulsive behaviors diagnosed in, but not limited to, children. ADHD can cause symptoms throughout life. This article summarizes the structural (conventional, volumetric, and diffusion tensor imaging) and functional (task-based functional MRI [fMRI], resting-state fMRI, PET, and MR spectroscopy) brain findings in patients with ADHD. Consensus is lacking regarding altered anatomic or functional imaging findings of the brain in children with ADHD, likely because of the heterogeneity of the disorder. Most anatomic studies report abnormalities in the frontal lobes, basal ganglia, and corpus callosum; decreased surface area in the left ventral frontal and right prefrontal cortex; thinner medial temporal lobes; and smaller caudate nuclei. Using fMRI, researchers have focused on the prefrontal and temporal regions, reflecting perception-action mapping alterations. Artificial intelligence models evaluating brain anatomy have highlighted changes in cortical thickness and the shape of the inferior frontal cortex, bilateral sensorimotor cortex, left temporal lobe, and insula. Early intervention and/or normal brain maturation can alter imaging patterns and convert functional imaging studies to a normal pattern. Although imaging findings provide insight into the neuropathophysiology of the disease, no definitive structural or functional pattern defines the disorder from a neuroradiologic perspective.

Effects of substance misuse on inhibitory control in patients with attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) are often diagnosed with comorbid substance misuse (SM), which is associated with poor treatment efficacy. Although literature indicates similar inhibitory control deficits in both conditions, it is unclear whether SM in ADHD exaggerates pre-existing deficits, with additive or distinct impairments in patients. Our aim was to examine SM effects on inhibitory control in ADHD. Behavioural and functional magnetic resonance imaging (fMRI) data from a stop-signal task were compared across ADHD patients with and without SM (ADHD + SM and ADHD-only, respectively) and controls (n = 33/group; 79 males, mean age 18.02 ± 2.45). To limit substance use disorder (SUD) trait effects, groups were matched for parental SUD. Overall, we found worse performance for ADHD-only and/or ADHD + SM compared with controls but no difference between the ADHD groups. Moreover, the ADHD groups showed decreased frontostriatal and frontoparietal activity during successful and failed stop trials. There were no differences between the ADHD groups in superior frontal nodes, but there was more decreased activation in temporal/parietal nodes in ADHD-only compared with ADHD + SM. During go-trials, ADHD + SM showed decreased activation in inferior frontal nodes compared with ADHD-only and controls. Findings during response inhibition showed deficits in inhibition and attentional processes for ADHD patients with and without SM. Despite no evidence for SM effects during response inhibition, results during go-trials suggest distinct effects on nodes that are associated with several executive functions. Future studies should investigate whether distinct deficits in ADHD + SM relate to poor treatment results and can direct development of distinct ADHD treatment strategies for these patients.

Enhancing neural markers of attention in children with ADHD using a digital therapeutic.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by diminished attentional control. Critically, these difficulties are related to negative consequences in real-life functioning both during development and into adulthood. There is now growing evidence that modulating the underlying neural circuits related to attention can improve behavior and brain function in children with ADHD. We have previously shown that game-based digital therapeutics targeting a key neural marker of attention-midline frontal theta (MFT)-yield positive effects on attentional control in several populations. However, the effects of such digital therapeutics in children with ADHD and no other comorbidities has not been yet examined. To address this gap, we assessed a sample of 25 children with ADHD (8-12 years old) on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention on an iPad targeting MFT circuitry. We found that children showed enhancements on a neural measure of attention (MFT power), as well as on objective behavioral measures of attention and parent reports of clinical ADHD symptoms. Importantly, we observed relationships between the neural and behavioral cognitive improvements, demonstrating that those children who showed the largest intervention-related neural gains were also those that improved the most on the behavioral tasks indexing attention. These findings provide support for using targeted, digital therapeutics to enhance multiple features of attentional control in children with ADHD. Study registration: ClinicalTrials.gov registry (NCT03844269) https://clinicaltrials.gov/ct2/show/NCT03844269.