Attention Deficit Hyperactivity Disorder Brain Research Articles

Evaluation of potential alterations related to ADHD in the effective connectivity between the default mode network and cerebellum, hippocampus, thalamus, and primary visual cortex.

Hyperactivity in children with attention-deficit/hyperactivity disorder (ADHD) leads to restlessness and impulse-control impairments. Nevertheless, the relation between ADHD symptoms and brain regions interactions remains unclear. We focused on dynamic causal modeling to study the effective connectivity in a fully connected network comprised of four regions of the default mode network (DMN) (linked to response control behaviors) and four other regions with previously-reported structural alterations due to ADHD. Then, via the parametric empirical Bayes analysis, the most significant connections, with the highest correlation to the covariates ADHD/control, age, and sex were extracted. Our results demonstrated a positive correlation between ADHD and effective connectivity between the right cerebellum and three DMN nodes (intrinsically inhibitory connections). Therefore, an increase in the effective connectivity leads to more inhibition imposition from the right cerebellum to DMN that reduces this network activation. The lower DMN activity makes leaving the resting-state easier, which may be involved in the restlessness symptom. Furthermore, our results indicated a negative correlation between age and these connections. We showed that the difference between the average of effective connectivities of ADHD and control groups in the age-range of 7-11years disappeared after 14years-old. Therefore, aging tends to alleviate ADHD-specific symptoms.

Current Perspectives on Attention-deficit Hyperactivity Disorder.

Attention-deficit hyperactivity disorder (ADHD) is a neurobiological and neurodevelopmental disorder with an idiosyncratic genetic base. ADHD presents various characteristics, such as inattention, hyperactivity, and impulsivity. Over the period, ADHD leads to noticeable functional disability. A five- to ten-fold progressed risk of disorder development is observed in the populations with familial history of ADHD. The abnormal structure of the brain in ADHD results in altered neural mechanisms, such as cognition, attention, and memorial function. The mesolimbic, nigrostriatal, and mesocortical pathways in the brain get affected by the deterioration of the levels of dopamine. The hypothesis of dopamine in ADHD and its etiopathology suggests that detained attention and impaired arousal functions are due to reduced levels of dopamine. The quickest way to improve strategical treatment is by clarifying the etiological aspects of ADHD and identifying the underlying mechanisms of pathophysiology, which will assist in exploring the biomarkers for better diagnosis. The implementation of life course theory is a very important research principle announced by Grand Challenges in Global Health Initiative (GCMHI). Long-term research is needed to define the progression of ADHD. Interdisciplinary collaborations promise a great future for research innovations in ADHD.

Attention-deficit hyperactivity disorder symptoms and brain morphology: Addressing potential selection bias with inverse probability weighting.

The goal of this study was to examine what happens to established associations between attention deficit hyperactivity disorder (ADHD) symptoms and cortical surface and thickness regions once we apply inverse probability of censoring weighting (IPCW) to address potential selection bias. Moreover, we illustrate how different factors that predict participation contribute to potential selection bias. Participants were 9- to 11-year-old children from the Generation R study (N = 2707). Cortical area and thickness were measured with magnetic resonance imaging (MRI) and ADHD symptoms with the Child Behavior Checklist. We examined how associations between ADHD symptoms and brain morphology change when we weight our sample back to either follow-up (ages 9-11), baseline (cohort at birth), or eligible (population of Rotterdam at time of recruitment). Weights were derived using IPCW or raking and missing predictors of participation used to estimate weights were imputed. Weighting analyses to baseline and eligible increased beta coefficients for the middle temporal gyrus surface area, as well as fusiform gyrus cortical thickness. Alternatively, the beta coefficient for the rostral anterior cingulate decreased. Removing one group of variables used for estimating weights resulted in the weighted regression coefficient moving closer to the unweighted regression coefficient. In addition, we found considerably different beta coefficients for most surface area regions and all thickness measures when we did not impute missing covariate data. Our findings highlight the importance of using inverse probability weighting (IPW) in the neuroimaging field, especially in the context of mental health-related research. We found that including all variables related to exposure-outcome in the IPW model and combining IPW with multiple imputations can help reduce bias. We encourage future psychiatric neuroimaging studies to define their target population, collect information on eligible but not included participants and use inverse probability of censoring weighting (IPCW) to reduce selection bias.

Controllability in attention deficit hyperactivity disorder brains.

The online version contains supplementary material available at 10.1007/s11571-023-10063-z.

Temporal Alpha Dissimilarity of ADHD Brain Network in Comparison With CPT and CATA.

Attention deficit hyperactivity disorder (ADHD) is a chronic neurological and psychiatric disorder that affects children during their development. To find neural patterns for ADHD and provide subjective features as decision references to assist specialists and physicians. Many studies have been devoted to investigating the neural dynamics of the brain through resting-state or continuous performance tests (CPT) with EEG or functional magnetic resonance imaging (fMRI). The present study used coherence, which is one of the functional connectivity (FC) methods, to analyze the neural patterns of children and adolescents (8-16 years old) under CPT and continuous auditory test of attention (CATA) task. In the meantime, electroencephalography (EEG) oscillations were recorded by a wireless brain-computer interface (BCI). 72 children were enrolled, of which 53 participants were diagnosed with ADHD and 19 presented to be typical developing (TD). The experimental results exhibited a higher difference in alpha and theta bands between the TD group and the ADHD group. While the differences between the TD group and the ADHD group in all four frequency domains were greater than under CPT conditions. Statistically significant differences ( [Formula: see text]) were observed between the ADHD and TD groups in the alpha rhythm during the CATA task in the short-range of coherence. For the temporal lobe FC during the CATA task, the TD group exhibited statistically significantly FC ( [Formula: see text]) in the alpha rhythm compared to the ADHD group. These findings offering new possibilities for more techniques and diagnostic methods in finding more ADHD features. The differences in alpha and beta frequencies were more pronounced in the ADHD group during the CPT task compared to the CATA task. Additionally, the disparities in brain activity were more evident across delta, theta, alpha and beta frequency domains when the task given was a CATA as opposed to a CPT. The findings presented the underlying mechanisms of the FC differences between children and adolescents with ADHD. Moreover, these findings should extend to use machine learning approaches to assist the ADHD classification and diagnosis.

Altered morphological characteristics and structural covariance connectivity associated with verbal working memory performance in ADHD children.

Deficits in verbal working memory (VWM) observed in attention deficit hyperactivity disorder (ADHD)children can persist into adulthood. Although previous studies have identified brain regions that are activated during VWM tasks, the neural mechanisms underlying the relationship between VWM deficits remain unclear. The objective of this study was to investigate the structural covariance network connectivity and brain morphology changes that are associated with VWM performance in ADHD children. For this study, we selected 26 ADHD children and 26 healthy control (HC) participants. Participants were instructed to perform a n-back VWM task and their accuracy and response times were subsequently recorded. This research utilized voxel-based morphometry to measure the grey matter (GM) volume, and conducted structural covariance connectivity network analysis to explore the changes of brain in ADHD. Voxel-based morphometry analysis showed that lower GM volume in the right cerebellum lobule VI and the left parahippocampal gryus in ADHD children. Moreover, a positive correlation was found between the GM volume in the right cerebellum lobule VI and the accuracy of 2-back VWM task with verbal, small reward, and delayed feedback (VSD). Structural covariance network analysis found decreased structural connectivity between right cerebellum lobule VI and right precentral gyrus, right postcentral gyrus, left paracentral lobule, right superior parietal gyrus, left hippocampus in ADHD children. The low GM volume and altered structural covariance connectivity in the right cerebellum lobule VI might potentially affect VWM performance in ADHD children. The innovation of this study lies in its more focused discussion on the morphological characteristics and structural covariance connectivity of verbal working memory deficits in ADHD children, and the innovative finding of a positive correlation between gray matter volume in the right cerebellum lobule VI and accuracy in completing the 2-back VWM task with verbal instructions, small reward, and delayed feedback(VSD). This expands upon previous research by elucidating the specific brain structures involved in verbal working memory deficits in ADHD children and highlights the potential importance of the cerebellum in this cognitive process. Overall, these innovative findings advance our understanding of the neural basis of ADHD and may have important implications for the development of targeted interventions for verbal working memory deficits.

Pioglitazone enhances brain mitochondrial biogenesis and phase II detoxification capacity in neonatal rats with 6-OHDA-induced unilateral striatal lesions.

The psychostimulant methylphenidate (MPH) is the first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), but has numerous adverse side effects. The PPARγ receptor agonist pioglitazone (PIO) is known to improve mitochondrial bioenergetics and antioxidant capacity, both of which may be deficient in ADHD, suggesting utility as an adjunct therapy. Here, we assessed the effects of PIO on ADHD-like symptoms, mitochondrial biogenesis and antioxidant pathways in multiple brain regions of neonate rats with unilateral striatal lesions induced by 6-hydroxydopamine (6-OHDA) as an experimental ADHD model. Unilateral striatal injection of 6-OHDA reduced ipsilateral dopaminergic innervation by 33% and increased locomotor activity. This locomotor hyperactivity was not altered by PIO treatment for 14 days. However, PIO increased the expression of proteins contributing to mitochondrial biogenesis in the striatum, hippocampus, cerebellum and prefrontal cortex of 6-OHDA-lesioned rats. In addition, PIO treatment enhanced the expression of the phase II transcription factor Nrf2 in the striatum, prefrontal cortex and cerebellum. In contrast, no change in the antioxidant enzyme catalase was observed in any of the brain regions analyzed. Thus, PIO may improve mitochondrial biogenesis and phase 2 detoxification in the ADHD brain. Further studies are required to determine if different dose regimens can exert more comprehensive therapeutic effects against ADHD neuropathology and behavior.

Synchronization in functional brain networks of children suffering from ADHD based on Hindmarsh-Rose neuronal model

Attention Deficit Hyperactivity Disorder (ADHD) is one of the common psychological disorders in children, which causes improper recognition of others' emotions. These children often have very poor social interaction and a lack of self-confidence. Brain disorders are typically studied by investigating the functional connectivity of different areas in the brain networks of individuals and measuring synchronization. This study investigates synchronization in the simulated functional brain networks of 22 boys with ADHD and 22 healthy boys using electroencephalogram (EEG) signals during angry, happy, neutral, and sad emotions. In these simulated networks, a Hindmarsh-Rose neuronal model is considered for each network node. The edges' weights connecting these nodes represent the synchronization level between the EEG electrode pairs. By changing the coupling strength between the network nodes, different synchronization patterns in the ADHD and healthy brain networks can be observed in all four types of facial emotions. This study shows a higher synchronization, especially in happiness emotion in the frontal and occipital brain lobes of the ADHD group, responsible for human emotional and visual processing, respectively. Results also indicate the chimera phenomenon in both of the brain networks of ADHD and healthy individuals. However, this phenomenon occurs in the ADHD group at a lower coupling strength. These findings may represent a deficit in the brain's emotional and visual processing centers in the ADHD group, especially during the happy emotional stimuli.

Investigation of phase synchronization in functional brain networks of children with ADHD using nonlinear recurrence measure

Measuring the phase synchronization between different brain regions in functional brain networks is a common approach to investigate many psychological disorders such as Attention Deficit Hyperactivity Disorder (ADHD). The emotional processing deficit in ADHD children is one of the main obstacles in their social interactions. In this study, the nonlinear Correlation between Probability of Recurrences (CPR) method is used for the first time to construct functional brain networks of 22 boys with ADHD and 22 healthy ones during watching four visual-emotional stimuli types. Topological features of brain networks, including shortest path length, clustering coefficient, and nodes strengths, are investigated in groups of ADHD and healthy. The results indicate a significantly (P-Values < 0.01) greater average clustering coefficient and lower shortest path length in the brain networks of ADHD individuals than the healthy ones. Accordingly, in the ADHD brain networks, the information exchange in both local and global scales is abnormally more than the healthy ones, leading to a hyper-synchronization in this group. The topological alterations of ADHD brain networks are mainly observed in the brain's frontal and occipital lobes, indicating impaired brain function of this group in emotional and visual processing. This survey demonstrates that the CPR method can be a good candidate for distinguishing the phase interactions of ADHD and healthy brain networks. Therefore, this study can contribute to further insights into the nonlinear dynamics analysis of brain networks in ADHD individuals.

Different functional alteration in attention-deficit/hyperactivity disorder across developmental age groups: A meta-analysis and an independent validation of resting-state functional connectivity studies.

Attention-deficit/hyperactivity disorder (ADHD) is a highly complex and heterogeneous disorder. Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. However, the developmental patterns and mechanisms of ADHD brain connectivity remain to be fully uncovered. In the present study, we searched PubMed, Scopus, Web of Science, and Embase for seed-based whole-brain resting-state functional connectivity studies of ADHD published through October 12th, 2020. The seeds meeting inclusion criteria were categorized into the cortex group and subcortex group, as previous studies suggested that the cortex and subcortex have different temporal patterns of development. Activation likelihood estimation meta-analysis was performed to investigate the abnormal connectivity in different age groups (all-age group, younger: <12 years, older: ≥12 years). Moreover, significant convergence of reported foci was used as seeds for validation with our independent dataset. As with previous studies, scarce results were found in the all-age group. However, we found that the younger group consistently exhibited hyper-connectivity between different parts of the cortex and left middle frontal gyrus, and hypo-connectivity between different parts of the cortex and left putamen/pallidus/amygdala. Whereas, the older group (mainly for adults) showed hyper-connectivity between the cortex and right precuneus/sub-gyral/cingulate gyrus. Besides, the abnormal cortico-cortical and cortico-subcortical functional connectivity in children, and the abnormal cortico-cortical functional connectivity in adults were verified in our independent dataset. Our study emphasizes the importance of developmental age effects on the study of brain networks in ADHD. Further, we proposed that cortico-cortical and cortico-subcortical connectivity might play an important role in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for adults with ADHD. This work provided a potential new insight to understand the neurodevelopmental mechanisms and possible clinical application of ADHD.

Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan.

For decades, psychostimulants have been the gold standard pharmaceutical treatment for attention-deficit/hyperactivity disorder (ADHD). In the United States, an astounding 9% of all boys and 4% of girls will be prescribed stimulant drugs at some point during their childhood. Recent meta-analyses have revealed that individuals with ADHD have reduced brain volume loss later in life (>60 y.o.) compared to the normal aging brain, which suggests that either ADHD or its treatment may be neuroprotective. Crucially, these neuroprotective effects were significant in brain regions (e.g., hippocampus, amygdala) where severe volume loss is linked to cognitive impairment and Alzheimer’s disease. Historically, the ADHD diagnosis and its pharmacotherapy came about nearly simultaneously, making it difficult to evaluate their effects in isolation. Certain evidence suggests that psychostimulants may normalize structural brain changes typically observed in the ADHD brain. If ADHD itself is neuroprotective, perhaps exercising the brain, then psychostimulants may not be recommended across the lifespan. Alternatively, if stimulant drugs are neuroprotective, then this class of medications may warrant further investigation for their therapeutic effects. Here, we take a bottom-up holistic approach to review the psychopharmacology of ADHD in the context of recent models of attention. We suggest that future studies are greatly needed to better appreciate the interactions amongst an ADHD diagnosis, stimulant treatment across the lifespan, and structure-function alterations in the aging brain.

Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder.

Attention-Deficit Hyperactivity Disorder (ADHD) is a highly prevalent childhood psychiatric disorder. In general, a child with ADHD has significant attention problems with difficulty concentrating on a subject and is generally associated with impulsivity and excessive activity. The etiology of ADHD in most patients is unknown, although it is considered to be a multifactorial disease caused by a combination of genetics and environmental factors. Diverse factors, such as the existence of mental, nutritional, or general health problems during childhood, as well as smoking and alcohol drinking during pregnancy, are related to an increased risk of ADHD. Behavioral and psychological characteristics of ADHD include anxiety, mood disorders, behavioral disorders, language disorders, and learning disabilities. These symptoms affect individuals, families, and communities, negatively altering educational and social results, strained parent-child relationships, and increased use of health services. ADHD may be associated with deficits in inhibitory frontostriatal noradrenergic neurons on lower striatal structures that are predominantly driven by dopaminergic neurons. Phosphoinositide 3-kinases (PI3Ks) are a conserved family of lipid kinases that control a number of cellular processes, including cell proliferation, differentiation, migration, insulin metabolism, and apoptosis. Since PI3K plays an important role in controlling the noradrenergic neuron, it opens up new insights into research on ADHD and other developmental brain diseases. This review presents evidence for the potential usefulness of PI3K and its modulators as a potential treatment for ADHD.

Whither the ADHD Brain? Waning Structural Brain Differences in a Sample of Thousands

Background: Structural neuroimaging studies, including meta-analyses, have identified a variety of differences across cortical and subcortical structures associated with Attention deficit hyperactivity disorder (ADHD) among children. However, studies to date have not employed large, representative samples, complete with data on potential confounders. Here, we compared brain measures among 9- and 10-year-old children with and without ADHD using data from the Adolescent Brain and Cognitive Development (ABCD) Study, the largest longitudinal study of brain development in the United States. Methods: We used baseline demographic, clinical, and neuroimaging data from the ABCD Study. Neuroimaging data underwent centralized quality control, harmonization, and processing by the ABCD Team. Mixed effects models were used to estimate effect sizes (Cohen’s d) associated with ADHD. We used a novel simulation strategy to assess our ability to detect significant effects despite misclassification. Outcomes: Our sample included 949 participants with ADHD and 9,787 without. In the full model, which included a priori selected potential confounders, we found only 11 significant differences across 79 brain regions using a false discovery rate correction. Significant effect sizes ranged from -0.07 to -0.05. Effect sizes remained essentially unchanged using alternative diagnostic instruments. Simulations indicated that we were well powered to detect differences even if there was substantial misclassification in the sample. Interpretation: We found fewer and smaller differences than previous studies, consistent with the trend towards smaller effects in larger samples. Our results suggest that there are few meaningful and specific structural differences associated with ADHD among children in the general population. Funding: We thank the Adolescent Brain and Cognitive Development Study Team. JB was supported by Grant No. T32 MH016434-41, by the AACAP Pilot Research Award for Attention Disorders, and by the Bender-Fishbein Award in Child Psychiatry Research. JP was supported by the Edwin S Webster Foundation, Suzanne Crosby Murphy Endowment and by NIH (UH3 OD023328). Declaration of Interest: JP has received research support from Takeda (formerly Shire) and Aevi Genomics, and consultancy fees from Innovative Science Solutions. JB, AL, LC, EB, and JD declare no competing interests. Ethical Approval: Institutional review boards at each site approved the study procedures. Written consent was obtained from all parents, and children gave verbal assent.

Atypical sulcal pattern in boys with attention-deficit/hyperactivity disorder.

Neurodevelopmental disorders, such as attention‐deficit/hyperactivity disorder (ADHD), are often accompanied by disrupted cortical folding. We applied a quantitative sulcal pattern analysis technique using graph structures to study the atypical cortical folding at the lobar level in ADHD brains in this study. A total of 183 ADHD patients and 167 typical developmental controls matched according to age and gender were enrolled. We first constructed sulcal graphs at the brain lobar level and then investigated their similarity to the typical sulcal patterns. The within‐group variability and interhemispheric similarity in sulcal patterns were also compared between the ADHD and TDC groups. The results showed that, compared with controls, the left frontal, right parietal, and temporal lobes displayed altered similarities to the typical sulcal patterns in patients with ADHD. Moreover, the sulcal patterns in ADHD seem to be more heterogeneous than those in controls. The results also identified the disruption of the typical asymmetric sulcal patterns in the frontal lobe between the ADHD and control groups. Taken together, our results revealed the atypical sulcal pattern in boys with ADHD and provide new insights into the neuroanatomical mechanisms of ADHD.

Analysis of Dynamic Network Reconfiguration in Adults with Attention-Deficit/Hyperactivity Disorder Based Multilayer Network.

Attention-deficit/hyperactivity disorder (ADHD) has been reported exist abnormal topology structure in the brain network. However, these studies often treated the brain as a static monolithic structure, and dynamic characteristics were ignored. Here, we investigated how the dynamic network reconfiguration in ADHD patients differs from that in healthy people. Specifically, we acquired resting-state functional magnetic resonance imaging data from a public dataset including 40 ADHD patients and 50 healthy people. A novel model of a "time-varying multilayer network" and metrics of recruitment and integration were applied to describe group differences. The results showed that the integration scores of ADHD patients were significantly lower than those of controls at every level. The recruitment scores were lower than healthy people except for the whole-brain level. It is worth noting that the subcortical network and the thalamus in ADHD patients exhibited reduced alliance preference both within and between functional networks. In addition, we also found that recruitment and integration coefficients showed a significant correlation with symptom severity in some regions. Our results demonstrate that the capability to communicate within or between some functional networks is impaired in ADHD patients. These evidences provide a new opportunity for studying the characteristics of ADHD brain networks.

Task-generic and task-specific connectivity modulations in the ADHD brain: an integrated analysis across multiple tasks

Attention-deficit/hyperactivity disorder (ADHD) is associated with altered functioning in multiple cognitive domains and neural networks. This paper offers an overarching biological perspective across these. We applied a novel strategy that extracts functional connectivity modulations in the brain across one (Psingle), two (Pmix) or three (Pall) cognitive tasks and compared the pattern of modulations between participants with ADHD (n-89), unaffected siblings (n = 93) and controls (n = 84; total N = 266; age range = 8–27 years). Participants with ADHD had significantly fewer Pall connections (modulated regardless of task), but significantly more task-specific (Psingle) connectivity modulations than the other groups. The amplitude of these Psingle modulations was significantly higher in ADHD. Unaffected siblings showed a similar degree of Pall connectivity modulation as controls but a similar degree of Psingle connectivity modulation as ADHD probands. Pall connections were strongly reproducible at the individual level in controls, but showed marked heterogeneity in both participants with ADHD and unaffected siblings. The pattern of reduced task-generic and increased task-specific connectivity modulations in ADHD may be interpreted as reflecting a less efficient functional brain architecture due to a reduction in the ability to generalise processing pathways across multiple cognitive domains. The higher amplitude of unique task-specific connectivity modulations in ADHD may index a more “effortful” coping strategy. Unaffected siblings displayed a task connectivity profile in between that of controls and ADHD probands, supporting an endophenotype view. Our approach provides a new perspective on the core neural underpinnings of ADHD.

A mixed herbal extract as an adjunctive therapy for attention deficit hyperactivity disorder: A randomized placebo-controlled trial

BackgroundMethylphenidate improves clinical symptoms and brain activity in attention deficit hyperactivity disorder (ADHD) patients through the attention-regulation network's dopamine system. Additionally, water-soluble extracts (HX106) of four plants (Gastrodia elata Blume, Liriope platyphylla Wang et Tang, Salvia miltiorrhiza Bunge, and Dimocarpus longan Lour) improve cognitive function. We hypothesized that the combination of HX106 and methylphenidate would improve ADHD symptoms and brain activity of the attention network more effectively than the combination of placebo and methylphenidate. MethodsTwenty-seven patients with ADHD were administered a herbal mixture and methylphenidate (n=13), or placebo and methylphenidate (n=14) during a 4-week, randomized, double-blind, placebo-controlled clinical trial. Changes in ADHD symptoms (K-ARS scores), as well as brain activity and functional connectivity, were assessed at baseline and 4 weeks later. ResultsThe HX106 group showed a greater improvement in total attention (16.8%) and inattention (17.2%) scores than the placebo group. The HX106 group showed increased brain activity within the left precuneus compared to the placebo group. The HX106 group also showed increased functional connectivity from the precuneus seed to the left middle temporal gyrus compared with the placebo group. In all participants, the changes in K-ARS scores were negatively correlated with changes in brain activity in the left middle temporal gyrus. ConclusionsHX106 enhanced the effect of methylphenidate on ADHD symptoms and increased brain activity in the attention-regulation network. Therefore, HX106 may be an effective adjunctive therapy for patients with ADHD.

Cognitive behavioural therapy in groups for medicated adults with attention deficit hyperactivity disorder: protocol for a randomised controlled trial

IntroductionCognitive behavioural therapy (CBT) is an evidence-based treatment for adults with attention deficit hyperactivity disorder (ADHD). However, it is still inconsistent whether a combination of CBT would have additive effects...

Inter-hemispheric Asymmetry Patterns in the ADHD Brain: A Neuroimaging Replication Study.

Attention-deficit/ hyperactivity disorder (ADHD) is the most common neurodevelopment disorder in children, and many genetic markers have been linked to the behavioral phenotypes of this highly heritable disease. The neuroimaging correlates are similarly complex, with multiple combinations of structural and functional alterations associated with the disease presentations of hyperactivity and inattentiveness. Thus far, neuroimaging studies have provided mixed results in ADHD patients, particularly with respect to the laterality of findings. It is possible that hemispheric asymmetry differences may help reconcile the variability of these findings. We recently reported that inter-hemispheric asymmetry differences were more sensitive descriptors for identifying differences between ADHD and typically developing (TD) brains (n=849) across volumetric, morphometric, and white matter neuroimaging metrics. Here, we examined the replicability of these findings across a new data set (n=202) of TD and ADHD subjects at the time of diagnosis (medication naive) and after a six week course of either stimulant drugs, non-stimulant medications, or combination therapy. Our findings replicated our earlier work across a number of volumetric and white matter measures confirming that asymmetry is more robust at detecting differences between TD and ADHD brains. However, the effects of medication failed to produce significant alterations across either lateralized or symmetry measures. We suggest that the delay in brain volume maturation observed in ADHD youths may be hemisphere dependent. Future work may investigate the extent to which these inter-hemispheric asymmetry differences are causal or compensatory in nature.

Applicable features of electroencephalogram for ADHD diagnosis

Attention-deficit/hyperactivity disorder (ADHD) is a neuro-developmental and psychiatric disorder, which affects 11% of children around the world. Several linear and nonlinear biomarkers from electroencephalogram (EEG) signals have been proposed for diagnosis of ADHD to date. However, the determination of which type of analysis gives us the best feature and biomarker to diagnose ADHD is still controversial. In this study, we aimed to evaluate and compare several categories of features, extracted from EEG signals, for diagnosis of ADHD. Thirty 7–12-year-old children fulfilling the DSM5 criteria for ADHD and thirty healthy children underwent a noninvasive EEG evaluation at resting-state. After preprocessing, five categories of features including morphological, time, frequency, time-frequency, and nonlinear features were extracted from EEGs. The efficacy of each feature category in ADHD diagnosis was determined using statistical analysis, receiver operating characteristic (ROC) curves, and evidential K-nearest neighbor (EKNN) classifier. Statistical analyses showed that 13.15, 13.68, 14.47, 14.03, and 34.73% of extracted features were significant (p < 0.05) in morphological, time, frequency, time-frequency, and nonlinear domains, respectively. The largest AUC values for the five morphological, time, frequency, time-frequency, and nonlinear feature categories, were 0.870, 0.796, 0.824, 0.806, and 0.899, respectively. We obtained the accuracies of 77.43% using morphological features, 74.09% using time features, 80.44% using frequency features, 78.50% using time-frequency features, and 86.40% using nonlinear features. Our results showed that EEG nonlinear analysis is a good quantitative tool to detect the abnormalities of the electrical activity of the brain in ADHD. This result was expected due to the complexity of the brain and the nonlinear nature of the EEG signal. Therefore, better outcomes may be expected in early diagnosis of diseases, especially psychiatric disorders, by increasing the use of nonlinear methods.