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Background: Inattention is a key characteristic of attention deficit hyperactivity disorder (ADHD). Specific brain abnormalities associated with this symptom form a discernible pattern related with ADHD in children (i.e., ADHD related pattern) in our earlier research. The developmental processes of segregation and integration may be crucial to ADHD. However, how brains reconfigure these processes of the ADHD related pattern in different subtypes of ADHD and across sexes remain unclear., Methods: Nested-spectral partition method was applied to identify effects of subtype and sex on segregation and integration of the ADHD related pattern, using 145 ADHD patients and 135 typically developing controls (TDC) aged 7-14. Relationships between the measures and inattention symptoms were also investigated., Results: Children with ADHD exhibited lower segregation of the ADHD related pattern (p = 1.17 × 10 -8 ) than TDCs. Only the main effect of subtype was significant (p = 1.14 × 10 -5 ). Both ADHD-C (p = 2.16 × 10 -6 ) and ADHD-I (p = 2.87 × 10 -6 ) patients had lower segregation components relative to the TDC. Moreover, segregation components were negatively correlated with inattention scores., Conclusions: This study identified impaired segregation in the ADHD related pattern of children with ADHD and found shared neural bases among different subtypes and sexes., Competing Interests: Declaration of competing interest The authors declare no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hyperactivity is one of the three core symptoms of attention deficit hyperactivity disorder (ADHD) that is a common childhood mental disorder. Objective assessments of hyperactivity are seldom utilized compared with measures of inattention and impulsivity during clinical diagnosis and evaluation. Acceleration-sensitive devices (e.g., Actigraph) and motion tracking systems (e.g., QbTest) are two main groups of devices that can be used to objectively measure hyperactivity. The Actigraph and QbTest have good discriminant validity, convergent validity, and sensitivity to the effects of stimulants. Furthermore, the assessment setting (i.e., research laboratory, school, or home) can greatly influence the presence and severity of hyperactivity. Nevertheless, objective assessments for hyperactivity have poor ability to distinguish ADHD from other disorders, or among the three types of ADHD. Thus, further studies are needed to assess objective measurements of hyperactivity in terms of discriminant and convergent validity, test-retest reliability in different settings, and correlations with brain activity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Neuroimaging studies have independently demonstrated brain anatomical and functional impairments in participants with ADHD. The aim of the current study was to explore the relationship between structural and functional brain alterations in ADHD through an integrated analysis of multimodal neuroimaging data., Methods: We performed a multimodal analysis to integrate resting-state functional magnetic resonance imaging (MRI), structural MRI, and diffusion-weighted imaging data in a large, single-site sample of children with and without diagnosis for ADHD. The inferred subject contributions were fed into regression models to investigate the relationships between diagnosis, symptom severity, gender, and age., Results: Compared with controls, children with ADHD diagnosis showed altered white matter microstructure in widespread white matter fiber tracts as well as greater gray matter volume (GMV) in bilateral frontal regions, smaller GMV in posterior regions, and altered functional connectivity (FC) in default mode and fronto-parietal networks. Age-related growth of GMV of bilateral occipital lobe, FC in frontal regions as well as age-related decline of GMV in medial regions seen in controls appeared reversed in children with ADHD. In the whole group, higher symptom severity was related to smaller GMV in widespread regions in bilateral frontal, parietal, and temporal lobes, as well as greater GMV in intracalcarine and temporal cortices., Conclusions: Through a multimodal analysis approach we show that structural and functional alterations in brain regions known to be altered in subjects with ADHD from unimodal studies are linked across modalities. The brain alterations were related to clinical features of ADHD, including disorder status, age, and symptom severity., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Few studies have investigated verbal working memory-related functional connectivity patterns in participants with attention-deficit/hyperactivity disorder (ADHD). Thus, we aimed to compare working memory-related functional connectivity patterns in healthy children and those with ADHD, and study effects of methylphenidate (MPH)., Method: Twenty-two boys with ADHD were scanned twice, under either MPH (single dose, 10 mg) or placebo, in a randomised, cross-over, counterbalanced placebo-controlled design. Thirty healthy boys were scanned once. We used fMRI during a numerical n-back task to examine functional connectivity patterns in case-control and MPH-placebo comparisons, using independent component analysis., Results: There was no significant difference in behavioural performance between children with ADHD, treated with MPH or placebo, and healthy controls. Compared with controls, participants with ADHD under placebo showed increased functional connectivity within fronto-parietal and auditory networks, and decreased functional connectivity within the executive control network. MPH normalized the altered functional connectivity pattern and significantly enhanced functional connectivity within the executive control network, though in non-overlapping areas., Conclusion: Our study contributes to the identification of the neural substrates of working memory. Single dose of MPH normalized the altered brain functional connectivity network, but had no enhancing effect on (non-impaired) behavioural performance.

Studies of brain alterations in children with attention-deficit/hyperactivity disorder (ADHD) have shown heterogeneous results. The aims of the current study were to investigate white matter microstructure in children using both categorical and dimensional definitions of ADHD and to determine the functional consequences of observed alterations. In a large single-site sample of children (aged 8-15 years) with ADHD (n=83) and healthy controls (n=122), we used tract-based spatial statistics on diffusion tensor imaging data to investigate whole-skeleton differences of fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD), and mode of anisotropy related to ADHD status (categorical) and symptom severity (dimensional). For categorical differences observed, we analyzed their association with cognitive functioning in working memory and inhibition. Compared with healthy controls, children with ADHD showed decreased FA and increased RD in widespread, overlapping brain regions, mainly in corpus callosum (CC) and major tracts in the left hemisphere. Decreased FA was associated with inhibition performance in the participants with ADHD. Using dimensional definitions, greater hyperactivity/impulsivity symptom severity was associated with higher FA also in widespread regions, mainly in CC and major tracts in the right hemisphere. Our study showed white matter alterations to be related to ADHD status and symptom severity in patients. The coexistence of decreased FA and increased RD in the absence of alterations in MD or AD might indicate altered myelination as a pathophysiological factor in ADHD.

Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF) are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging (RS-fMRI) data. Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder (ADHD) remains unknown. In this study, we applied ReHo and ALFF to 23 medication-naïve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis. Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD. We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipito-cerebellar circuitry, while the ALFF method showed a difference only in the right occipital area. When a larger smoothing kernel and a more lenient threshold were used for ALFF, more overlapped regions were found between ALFF and ReHo, and ALFF even found some new regions with group differences. The ADHD symptom scores were correlated with the ReHo values in the right cerebellum, dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group, while no correlation was detected between ALFF and ADHD symptoms. In conclusion, ReHo may be more sensitive to regional abnormalities, at least in boys with ADHD, than ALFF. And ALFF may be complementary to ReHo in measuring local spontaneous activity. Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.

Attention-deficit/hyperactivity disorder (ADHD), which is characterized by core symptoms of inattention and hyperactivity/impulsivity, is one of the most common neurodevelopmental disorders of childhood. Neuroimaging studies have suggested that these behavioral disturbances are associated with abnormal functional connectivity among brain regions. However, the alterations in the structural connections that underlie these behavioral and functional deficits remain poorly understood. Here, we used diffusion magnetic resonance imaging and probabilistic tractography method to examine whole-brain white matter (WM) structural connectivity in 30 drug-naive boys with ADHD and 30 healthy controls. The WM networks of the human brain were constructed by estimating inter-regional connectivity probability. The topological properties of the resultant networks (e.g., small-world and network efficiency) were then analyzed using graph theoretical approaches. Nonparametric permutation tests were applied for between-group comparisons of these graphic metrics. We found that both the ADHD and control groups showed an efficient small-world organization in the whole-brain WM networks, suggesting a balance between structurally segregated and integrated connectivity patterns. However, relative to controls, patients with ADHD exhibited decreased global efficiency and increased shortest path length, with the most pronounced efficiency decreases in the left parietal, frontal, and occipital cortices. Intriguingly, the ADHD group showed decreased structural connectivity in the prefrontal-dominant circuitry and increased connectivity in the orbitofrontal-striatal circuitry, and these changes significantly correlated with the inattention and hyperactivity/impulsivity symptoms, respectively. The present study shows disrupted topological organization of large-scale WM networks in ADHD, extending our understanding of how structural disruptions of neuronal circuits underlie behavioral disturbances in patients with ADHD.

We used resting-state functional magnetic resonance imaging (RS-fMRI) to investigate the acute effects of methylphenidate hydrochloride (MPH) on spontaneous brain activity in children with attention deficit hyperactivity disorder (ADHD). In all, 23 boys with ADHD were scanned twice, under either 10 mg dose of MPH or placebo, in a randomized, cross-over, counterbalanced placebo-controlled design. 32 Matched healthy controls were scanned once for comparison. Seven of the 23 ADHD boys participated in a follow-up 8-week MPH treatment. A regional homogeneity (ReHo) method was applied to characterize the local synchronization of spontaneous brain activity. ADHD boys under placebo compared with controls showed decreased ReHo in bilateral dorsolateral prefrontal cortices and increased ReHo in bilateral sensorimotor and parieto-visual cortices. Relative to placebo, MPH upregulated ReHo in bilateral ventral prefrontal cortices and cerebellar vermis, and downregulated ReHo in right parietal and visual areas that overlapped with the abnormally enhanced activities. When under MPH, ReHo differences between patients and controls were no longer observed. The preliminary prediction analysis revealed that the decreased ReHo in right parietal cortex after the acute MPH was positively correlated with the decreased symptom scores after the 8-week MPH treatment in the seven patients. We show that an acute dose of MPH normalized all fronto-parieto-cerebellar dysfunctions in boys with ADHD during the resting state. Preliminary findings furthermore suggest the potential of RS-fMRI as a prognostic imaging tool to identify response to MPH treatment.

In this study, a resting-state fMRI based classifier, for the first time, was proposed and applied to discriminate children with attention-deficit/hyperactivity disorder (ADHD) from normal controls. On the basis of regional homogeneity (ReHo), a mapping of brain function at resting state, PCA-based Fisher discriminative analysis (PC-FDA) was trained to build a linear classifier. Permutation test was then conducted to identify the brain areas with the most significant contribution to the final discrimination. Experimental results showed a correct classification rate of 85% using a leave-one-out cross-validation. Moreover, some highly discriminative brain regions, like the prefrontal cortex and anterior cingulate cortex, well confirmed the previous findings on ADHD. Interestingly, some important but less reported regions such as the thalamus were also identified. We conclude that the classifier, using resting-state brain function as classification feature, has potential ability to improve current diagnosis and treatment evaluation of ADHD.

Objective: To study the differences of brain functions between children with attention deficit hyperactivity disorder (ADHD) predominantly inattentive (ADHD-I) and combined (ADHD-C) subtypes in resting state using functional magnetic resonance imaging (fMRI)., Methods: A newly reported regional homogeneity (ReHo) approach was used to analyze blood oxygen level-dependent fMRI (BOLD-fMRI) data in resting state among 6 ADHDj C, 9 ADHD-I and 15 normal control boys., Results: The brain regions showing differences among the three groups included bilateral frontal lobe, right cuneus and right inferior temporal gyrus. Compared with the normal controls, ADHD-C showed decreased ReHo in left frontal lobe and right inferior temporal gyrus, ADHD-I showed decreased ReHo in bilateral frontal and temporal lobe and right cerebellum and increased ReHo in bilateral occipital lobe and right inferior parietal gyrus. There were no brain regions showing different ReHo between ADHD-C and ADHD-I., Conclusion: Although both ADHD-C and ADHD-I showed abnormal neural activity in resting state compared with the normal controls, there were no differences for brain functions in resting state between ADHD-C and ADHD-I.

In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

Using proton magnetic resonance spectroscopy ((1)H-MRS) to investigate possible neurometabolic differences between the predominantly inattentive subtype (ADHD-I), the combined subtype (ADHD-C) and normal controls. Proton spectra were acquired bilaterally on the lenticular nucleus in 20 schoolboys having ADHD and 10 matched controls. The boys with ADHD were divided into ADHD-C subtype (n=10) and ADHD-I subtype (n=10) according to DSM-IV criteria. The peaks of N-acetylaspartate (NAA), Choline moieties (Cho), myo-inositol (mI), creatine (Cr) and alpha-Glx were measured and their ratios to Cr were calculated. One-way ANOVA and post-hoc Bonferroni tests were used to detect the difference of the peak-area ratios of NAA, Cho, mI, and alpha-Glx to Cr among the three groups. There was a significant overall group difference in the NAA/Cr ratio both in the right and left lenticular nucleus (right: P=0.002; left: P=0.003). Only the ADHD-C subtype group showed a significant difference with controls (right: P=0.001; left: P=0.003) the right lenticular nucleus, the NAA/Cr ratio in the ADHD-C group was significantly lower than that in the ADHD-I group (P=0.012). In the left lenticular nucleus, the NAA/Cr ratio in the ADHD-C group showed a significant trend compared to the ADHD-I group (P=0.06). This study demonstrated the existence of measurable difference between children with ADHD-C and ADHD-I using (1)H-MRS.

In this work, a discriminative model of attention deficit hyperactivity disorder (ADHD) is presented on the basis of multivariate pattern classification and functional magnetic resonance imaging (fMRI). This model consists of two parts, a classifier and an intuitive representation of discriminative pattern of brain function between patients and normal controls. Regional homogeneity (ReHo), a measure of brain function at resting-state, is used here as a feature of classification. Fisher discriminative analysis (FDA) is performed on the features of training samples and a linear classifier is generated. Our initial experimental results show a successful classification rate of 85%, using leave-one-out cross validation. The classifier is also compared with linear support vector machine (SVM) and Batch Perceptron. Our classifier outperforms the alternatives significantly. Fisher brain, the optimal projective-direction vector in FDA, is used to represent the discriminative pattern. Some abnormal brain regions identified by Fisher brain, like prefrontal cortex and anterior cingulate cortex, are well consistent with that reported in neuroimaging studies on ADHD. Moreover, some less reported but highly discriminative regions are also identified. We conclude that the discriminative model has potential ability to improve current diagnosis and treatment evaluation of ADHD.

Twelve previously untreated boys suffering from attention-deficit hyperactivity disorder (ADHD) were investigated by using proton magnetic resonance spectroscopy (1H MRS) before and after one dose (10 mg) of methylphenidate. Pre- and post-methylphenidate spectra were acquired bilaterally in the globus pallidus. Peaks of N-acetylaspartate (NAA), choline (Cho), myo-inositol, glutamate and creatine (Cr) were measured and the ratios of the peaks were calculated and compared with data from ten matched controls. In children having ADHD, NAA/Cr ratio decreased significantly in the bilateral striatum while Cho/Cr ratio showed a mild unilateral increase. One oral dose of methylphenidate did not affect the ratios significantly. These findings suggest that the striatum was bilaterally involved in pediatric ADHD patients. Approximately 20-25% of neurons may have died or may be severely dysfunctional. There seems to be a mild hyperactivity of the cholinergic system.