Corrigendum to "Default mode network connectivity and social dysfunction in children with attention deficit/hyperactivity disorder" [Int. J. Clin. Health Psychol. 23 (4) (2023) 100393].

[This corrects the article DOI: 10.1016/j.ijchp.2023.100393.].

The underlying neuropsychological and neural correlates of the impaired Chinese reading skills in children with attention deficit hyperactivity disorder.

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

Identifying subgroups of attention-deficit/hyperactivity disorder from the psychopathological and neuropsychological profiles.

The Research Domain Criteria (RDoC) advocates the dimensional approach in characterizing mental disorders. We followed RDoC to characterize children with ADHD using profiling based on the cognitive and psychopathological domains. We aimed to identify and validate ADHD subtypes with different clinical characteristics and functional impairments. We recruited 362 drug-naïve children with ADHD and 103 typically developing controls. The cluster analysis was used to identify subgroups based on the Child Behaviour Checklist (CBCL) and the Behaviour Rating Inventory of Executive Function (BRIEF). The subgroups' clinical characteristics and functional impairments were assessed using the WEISS Functional Impairment Rating Scale-Parent Report (WFIRS-P) and the Conners Parent Symptom Questionnaire (PSQ). The cluster analysis yielded four subgroups: (1) ADHD with severe impairment in psychopathology and executive functions (EF), (2) ADHD with mild executive dysfunctions and normal-level psychopathology, (3) ADHD with severe externalizing problems and (4) ADHD with severe executive dysfunctions. These subgroups showed different clinical characteristics and degrees of functional impairment. The EF impairment group displayed more serious learning problems and worse life skills than the externalizing group. The two groups with externalizing problems (i.e. the severe impairment group and the externalizing group) both exhibited higher rates of the combined subtype of ADHD and higher rates of comorbid ODD. Different subtypes of ADHD displayed different profiles of internalizing and externalizing problems and levels of executive dysfunctions. In particular, the subtype with severe impairment in EF exhibited more learning problems and worse life skills, suggesting EF is a critical target for intervention in children with ADHD.

Default mode network connectivity and social dysfunction in children with Attention Deficit/Hyperactivity Disorder

Objective: Attention Deficit/Hyperactivity Disorder (ADHD) negatively affects social functioning; however, its neurological underpinnings remain unclear. Altered Default Mode Network (DMN) connectivity may contribute to social dysfunction in ADHD. We investigated whether DMN's dynamic functional connectivity (dFC) alterations were associated with social dysfunction in individuals with ADHD. Methods: Resting-state fMRI was used to examine DMN subsystems (dorsal medial prefrontal cortex (dMPFC), medial temporal lobe (MTL)) and the midline core in 40 male ADHD patients (7-10 years) and 45 healthy controls (HCs). Connectivity correlations with symptoms and demographic data were assessed. Group-based analyses compared rsFC between groups with two-sample t-tests and post-hoc analyses. Results: Social dysfunction in ADHD patients was related to reduced DMN connectivity, specifically in the MTL subsystem and the midline core. ADHD patients showed decreased dFC between parahippocampal cortex (PHC) and left superior frontal gyrus, and between ventral medial prefrontal cortex (vMPFC) and right middle frontal gyrus compared to HCs (MTL subsystem). Additionally, decreased dFC between posterior cingulate cortex (PCC), anterior medial prefrontal cortex (aMPFC), and right angular gyrus (midline core) was observed in ADHD patients relative to HCs. No abnormal connectivity was found within the dMPFC. Conclusion: Preliminary findings suggest that DMN connectional abnormalities may contribute to social dysfunction in ADHD, providing insights into the disorder's neurobiology and pathophysiology. (AU)

Specific brain imaging alterations underlying autistic traits in children with attention-deficit/hyperactivity disorder.

BACKGROUND: Autistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging perspectives. METHODS: We used the Autism Spectrum Screening Questionnaire (ASSQ) to assess and define subjects with and without ATs. For behavioral analyses, 67 children with ADHD and ATs (ADHD + ATs), 105 children with ADHD but without ATs (ADHD - ATs), and 44 typically developing healthy controls without ATs (HC - ATs) were recruited. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the mean amplitude of low-frequency fluctuation (mALFF) values (an approach used to depict different spontaneous brain activities) in a sub-sample. The imaging features that were shared between ATs and ADHD symptoms or that were unique to one or the other set of symptoms were illustrated as a way to explore the "brain-behavior" relationship. RESULTS: Compared to ADHD-ATs, the ADHD + ATs group showed more global impairment in all aspects of autistic symptoms and higher hyperactivity/impulsivity (HI). Partial-correlation analysis indicated that HI was significantly positively correlated with all aspects of ATs in ADHD. Imaging analyses indicated that mALFF values in the left middle occipital gyrus (MOG), left parietal lobe (PL)/precuneus, and left middle temporal gyrus (MTG) might be specifically related to ADHD, while those in the right MTG might be more closely associated with ATs. Furthermore, altered mALFF in the right PL/precuneus correlated with both ADHD and ATs, albeit in diverse directions. CONCLUSIONS: The co-occurrence of ATs in children with ADHD manifested as different behavioral characteristics and specific brain functional alterations. Assessing ATs in children with ADHD could help us understand the heterogeneity of ADHD, further explore its pathogenesis, and promote clinical interventions.

Default mode network connectivity and social dysfunction in children with Attention Deficit/Hyperactivity Disorder.

Objective: Attention Deficit/Hyperactivity Disorder (ADHD) negatively affects social functioning; however, its neurological underpinnings remain unclear. Altered Default Mode Network (DMN) connectivity may contribute to social dysfunction in ADHD. We investigated whether DMN's dynamic functional connectivity (dFC) alterations were associated with social dysfunction in individuals with ADHD. Methods: Resting-state fMRI was used to examine DMN subsystems (dorsal medial prefrontal cortex (dMPFC), medial temporal lobe (MTL)) and the midline core in 40 male ADHD patients (7-10 years) and 45 healthy controls (HCs). Connectivity correlations with symptoms and demographic data were assessed. Group-based analyses compared rsFC between groups with two-sample t-tests and post-hoc analyses. Results: Social dysfunction in ADHD patients was related to reduced DMN connectivity, specifically in the MTL subsystem and the midline core. ADHD patients showed decreased dFC between parahippocampal cortex (PHC) and left superior frontal gyrus, and between ventral medial prefrontal cortex (vMPFC) and right middle frontal gyrus compared to HCs (MTL subsystem). Additionally, decreased dFC between posterior cingulate cortex (PCC), anterior medial prefrontal cortex (aMPFC), and right angular gyrus (midline core) was observed in ADHD patients relative to HCs. No abnormal connectivity was found within the dMPFC. Conclusion: Preliminary findings suggest that DMN connectional abnormalities may contribute to social dysfunction in ADHD, providing insights into the disorder's neurobiology and pathophysiology.

Effects of the SNAP-25 Mnll variant on hippocampal functional connectivity in children with attention deficit/hyperactivity disorder.

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is one of the most widespread and highly heritable neurodevelopmental disorders affecting children worldwide. Although synaptosomal-associated protein 25 (SNAP-25) is a possible gene hypothesized to be associated with working memory deficits in ADHD, little is known about its specific impact on the hippocampus. The goal of the current study was to determine how variations in ADHD's SNAP-25 Mnll polymorphism (rs3746544) affect hippocampal functional connectivity (FC). Methods: A total of 88 boys between the ages of 7 and 10 years were recruited for the study, including 60 patients with ADHD and 28 healthy controls (HCs). Data from resting-state functional magnetic resonance imaging (rs-fMRI) and clinical information were acquired and assessed. Two single nucleotide polymorphisms (SNP) in the SNAP-25 gene were genotyped, according to which the study's findings separated ADHD patients into two groups: TT homozygotes (TT = 35) and G-allele carriers (TG = 25). Results: Based on the rs-fMRI data, the FC of the right hippocampus and left frontal gyrus was evaluated using group-based comparisons. The corresponding sensitivities and specificities were assessed. Following comparisons between the patient groups, different hippocampal FCs were identified. When compared to TT patients, children with TG had a lower FC between the right precuneus and the right hippocampus, and a higher FC between the right hippocampus and the left middle frontal gyrus. Conclusion: The fundamental neurological pathways connecting the SNAP-25 Mnll polymorphism with ADHD via the FC of the hippocampus were newly revealed in this study. As a result, the hippocampal FC may further serve as an imaging biomarker for ADHD.

The clinical, neuropsychological, and brain functional characteristics of the ADHD restrictive inattentive presentation.

Objectives: There is an ongoing debate about the restrictive inattentive (RI) presentation of attention deficit hyperactivity disorder (ADHD). The current study aimed to systematically investigate the clinical, neuropsychological, and brain functional characteristics of children with ADHD restrictive inattentive presentation. Methods: A clinical sample of 789 children with or without ADHD participated in the current study and finished clinical interviews, questionnaires, and neuropsychological tests. Those individuals with a diagnosis of ADHD were further divided into three subgroups according to the presentation of inattentive and/or hyperactive/impulsive symptoms, the ADHD-RI, the ADHD-I (inattentive), and the ADHD-C (combined) groups. Between-group comparisons were carried out on each clinical and neuropsychological measure using ANCOVA, with age and sex as covariates. Bonferroni corrections were applied to correct for multiple comparisons. Two hundred twenty-seven of the subjects also went through resting-state functional magnetic resonance imaging scans. Five ADHD-related brain functional networks, including the default mode network (DMN), the dorsal attention network (DAN), the ventral attention network, the executive control network, and the salience network, were built using predefined regions of interest (ROIs). Voxel-based group-wise comparisons were performed. Results: Compared with healthy controls, all ADHD groups presented more clinical problems and weaker cognitive function. Among the ADHD groups, the ADHD-C group had the most clinical problems, especially delinquent and aggressive behaviors. Regarding cognitive function, the ADHD-RI group displayed the most impaired sustained attention, and the ADHD-C group had the worst response inhibition function. In terms of brain functional connectivity (FC), reduced FC in the DMN was identified in the ADHD-C and the ADHD-I groups but not the ADHD-RI group, compared to the healthy controls. Subjects with ADHD-I also presented decreased FC in the DAN in contrast to the control group. The ADHD-RI displayed marginally significantly lower FC in the salience network compared to the ADHD-I and the control groups. Conclusion: The ADHD-RI group is distinguishable from the ADHD-I and the ADHD-C groups. It is characterized by fewer externalizing behaviors, worse sustained attention, and better response inhibition function. The absence of abnormally high hyperactive/impulsive symptoms in ADHD-RI might be related to less impaired brain function in DMN, but potentially more impairment in the salience network.

Computer-based multiple component cognitive training in children with ADHD: a pilot study.

BACKGROUND: ADHD is associated with deficits in executive functions. Cognitive training is a promising nonpharmacological intervention for ADHD, however, there is insufficient evidence to guide the selection of training for individuals with ADHD. This pilot study aims to investigate the efficacy of executive function training targeting key executive dysfunctions in ADHD, compared with general executive function training which targets other executive functions. METHODS: A total of 127 subjects (6-12 years) diagnosed with ADHD were allocated to receive one of two different cognitive trainings. ADHD symptoms and cognitive functions were evaluated using parent-rated scales and CANTAB cognitive assessments. All participants were required to complete 48 training sessions within a two-month period. RESULTS: 94 out of 127 children completed the required training and assessments. Both ADHD executive function training group and general executive function training group showed significant improvement in ADHD symptoms on the ADHD Rating Scale and in executive function on the assessment of CANTAB. There was no significant difference in improvements between the two groups. Subgroup analysis suggested that children who had ADHD-RS total scores less than or equal to 28 at baseline showed greater improvement following ADHD executive function training. CONCLUSIONS: This study indicates that cognitive training can improve ADHD symptoms and executive function, with no difference in efficacy between targeted and generalized cognitive training. In addition, individuals with lower symptom severity may benefit more from training targeting key ADHD executive dysfunctions.

The effect of physical activity on quality of life and parenting stress in children with attention-deficit/hyperactivity disorder: A randomized controlled trial.

BACKGROUND: Poorer quality of life (QoL) is commonly observed in children with Attention-deficit/Hyperactivity Disorder (ADHD). Parents of children with ADHD also perceived elevated levels of parenting stress. Previous research has documented the positive effects of physical activity (PA) on managing ADHD symptoms. It is critical to implement ADHD management with broader functioning from both children's and parents' perspectives. OBJECTIVE: This study aimed to examine whether PA would exert an influence on the QoL of children with ADHD and parenting stress of their parents. METHODS: Forty-three children with ADHD (6-12 years) were randomly assigned to the PA intervention and waitlist control groups. Children in the intervention group participated in a 12-week PA program. Parent-reported QoL and parenting stress were assessed before and immediately after the intervention. Analysis of covariance with a mixed factorial design of 2 (time: before vs. after intervention) × 2 (group: PA intervention vs. waitlist control) was conducted to examine changes in QoL and parenting stress over the 12 weeks. RESULTS: Compared to the control group, parents of children in the intervention group reported significant reduced overall parenting stress (p = .021, η2 = 0.142) and child domain of parenting stress (p = .024, η2 = 0.138) after the intervention. No significant improvement in QoL was documented in either group. CONCLUSIONS: The participation of PA intervention positively impacts parenting stress perceived by parents of children with ADHD, which provides further evidence of the family-wide benefits of the PA intervention.

Behavioral and brain functional characteristics of children with Attention-Deficit/Hyperactivity disorder and anxiety trait.

The current study aimed to explore the behavioral, daily-life executive functional, and brain functional connectivity patterns in children with attention-deficit/hyperactivity disorder (ADHD) and anxiety. A total of 246 children with non-comorbid ADHD and 91 healthy controls (HCs) participated in the current study, among whom 175 subjects went through resting-state functional magnetic resonance imaging (fMRI) scans. The ADHD participants were divided into two subgroups: ADHD with a high level of anxiety (ADHD + ANX) and ADHD with a low level of anxiety (ADHD-ANX). The Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF) were used to capture the behavioral and daily-life executive functional characteristics. Independent component analysis with dual regression models was applied to the fMRI data. All statistical models were estimated with age and sex as covariates. Compared with the ADHD-ANX group, the ADHD + ANX group showed more withdrawn, somatic, social, thought, attention, delinquent, and aggressive problems (all corrected p < 0.05). The ADHD + ANX group also displayed more impaired emotional control and working memory than the ADHD-ANX (all corrected p < 0.05). The ADHD-ANX group, but not the ADHD + ANX group, showed elevated functional connectivity within the default mode network compared with the HC group. The mean function connectivity within the default mode network significantly mediated the correlation between anxiety level and attention problems. In sum, anxiety in children with ADHD was associated with more social, emotional, and behavioral problems, more impaired daily-life executive function, and altered brain function. Our work provides important information on the heterogeneity of ADHD.

Role of SNAP-25 MnlI variant in impaired working memory and brain functions in attention deficit/hyperactivity disorder.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) is a hereditary neurodevelopmental disorder characterized by working memory (WM) deficits. The MnlI variant (rs3746544) of the synaptosomal-associated protein 25 (SNAP-25) gene is associated with ADHD. In this study, we investigated the role and underlying mechanism of SNAP-25 MnlI variant in cognitive impairment and brain functions in boys with ADHD. METHOD: We performed WM capacity tests using the fourth version of the Wechsler Intelligence Scale for Children (WISC-IV) and regional homogeneity (ReHo) analysis for the resting-state functional magnetic resonance imaging data of 56 boys with ADHD divided into two genotypic groups (TT homozygotes and G-allele carriers). Next, Spearman's rank correlation analysis between the obtained ReHo values and the WM index (WMI) calculated for each participant. RESULTS: Compared with G-allele carrier group, there were higher ReHo values for the left medial prefrontal cortex (mPFC) and higher WM capacity in TT homozygote group. Contrary to TT homozygote group, the WM capacity was negatively correlated with the peak ReHo value for the left mPFC in G-allele carrier group. CONCLUSION: These findings suggest that SNAP-25 MnlI variant may underlie cognitive and brain function impairments in boys with ADHD, thus suggesting its potential as a new target for ADHD treatment.

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OBJECTIVES: To study the association between oppositional defiant disorder (ODD) and parenting style in children with attention deficit hyperactivity disorder (ADHD). METHODS: A case-control study was performed on 482 children with ADHD, among whom 322 did not have ODD (simple ADHD group) and 160 had ODD (ADHD+ODD group). General demographic data and the Parenting Style Scale assessment scores were collected from the two groups. A multivariate logistic regression analysis was used to identify the association between parenting style and ODD in children with ADHD. RESULTS: There was no significant difference in parenting style scores (including rejection factor, emotional warmth factor, overprotection factor, and preference factor) and general demographic data between the simple ADHD and ADHD+ODD groups (P>0.05). Among the children with the predominantly inattentive type of ADHD, the older the child or the lower the father's educational level, the higher the risk of ODD (P<0.05), while there was no significant association between parenting style and the development of ODD (P>0.05). CONCLUSIONS: Parenting style is not significantly associated with the development of ODD in children with ADHD. In clinical practice, it is necessary to eliminate the stereotype that the parents of children with ADHD and comorbid ODD have a poor parenting style and look for the causes of development of ODD from multiple perspectives, so as to provide reasonable intervention recommendations.

Abnormal Degree Centrality in Children with Low-Function Autism Spectrum Disorders: A Sleeping-State Functional Magnetic Resonance Imaging Study.

Purpose: This study used the graph-theory approach, degree centrality (DC) to analyze whole-brain functional networks at the voxel level in children with ASD, and investigated whether DC changes were correlated with any clinical variables in ASD children. Methods: The current study included 86 children with ASD and 54 matched healthy subjects Aged 2-5.5 years. Next, chloral hydrate induced sleeping-state functional magnetic resonance imaging (ss-fMRI) datasets were acquired from these ASD and healthy subjects. For a given voxel, the DC was calculated by calculating the number of functional connections with significantly positive correlations at the individual level. Group differences were tested using two-sample t-tests (p < 0.01, AlphaSim corrected). Finally, relationships between abnormal DCs and clinical variables were investigated via Pearson's correlation analysis. Results: Children with ASD exhibited low DC values in the right middle frontal gyrus (MFG) (p < 0.01, AlphaSim corrected). Furthermore, significantly negative correlations were established between the decreased average DC values within the right MFG in ASD children and the total ABC scores, as well as with two ABC subscales measuring highly relevant impairments in ASD (ie, stereotypes and object-use behaviors and difficulties in language). Conclusion: Taken together, the results of our ss-fMRI study suggest that abnormal DC may represent an important contribution to elucidation of the neuropathophysiological mechanisms of preschoolers with ASD.

Abnormal Insular Dynamic Functional Connectivity and Its Relation to Social Dysfunctioning in Children With Attention Deficit/Hyperactivity Disorder.

Anomalies in large-scale cognitive control networks impacting social attention abilities are hypothesized to be the cause of attention deficit hyperactivity disorder (ADHD). The precise nature of abnormal brain functional connectivity (FC) dynamics including other regions, on the other hand, is unknown. The concept that insular dynamic FC (dFC) among distinct brain regions is dysregulated in children with ADHD was evaluated using Insular subregions, and we studied how these dysregulations lead to social dysfunctioning. Data from 30 children with ADHD and 28 healthy controls (HCs) were evaluated using dynamic resting state functional magnetic resonance imaging (rs-fMRI). We evaluated the dFC within six subdivisions, namely both left and right dorsal anterior insula (dAI), ventral anterior insula (vAI), and posterior insula (PI). Using the insular sub-regions as seeds, we performed group comparison between the two groups. To do so, two sample t-tests were used, followed by post-hoc t-tests. Compared to the HCs, patients with ADHD exhibited decreased dFC values between right dAI and the left middle frontal gyrus, left postcentral gyrus and right of cerebellum crus, respectively. Results also showed a decreased dFC between left dAI and thalamus, left vAI and left precuneus and left PI with temporal pole. From the standpoint of the dynamic functional connectivity of insular subregions, our findings add to the growing body of evidence on brain dysfunction in ADHD. This research adds to our understanding of the neurocognitive mechanisms behind social functioning deficits in ADHD. Future ADHD research could benefit from merging the dFC approach with task-related fMRI and non-invasive brain stimulation, which could aid in the diagnosis and treatment of the disorder.

Neuropsychological characteristics of children with Attention-Deficit/Hyperactivity Disorder and Sluggish Cognitive Tempo.

OBJECTIVE: The present study aims to explore the neuropsychological features of children with Attention-Deficit/Hyperactivity Disorder (ADHD) and Sluggish Cognitive Tempo (SCT). METHODS: Fifty-eight children with ADHD+SCT, 480 children with ADHD-SCT, and 105 healthy controls (HC) were recruited. Neuropsychological tests and the Behavior Rating Inventory of Executive Function (BRIEF) were used. RESULTS: The ADHD+SCT group performed worse than the HC in processing speed (p = .005), set-shifting (p = .0003), interference control (p = .00014), and visual memory (p = .007), while the ADHD-SCT group performed worse than the HC in sustained attention measurements (all p < .0001). The ADHD+SCT group scored higher than the ADHD-SCT group in the following factors from BRIEF: plan/organize (p = .00083), working memory (p < .001), and shift (p = .0054). CONCLUSION: Our results indicated that SCT symptoms are associated with worse executive function in children with ADHD except for sustained attention.

An observational MRI study of methotrexate-treated children with acute lymphoblastic leukemia in remission and subtle cognitive decline.

Background: For children diagnosed with acute lymphoblastic leukemia (ALL), methotrexate (MTX) treatment carries the risk of leukoencephalopathy and other treatment-related brain damage. However, earlier and more sensitive evaluation is needed to elucidate the specific effects of MTX treatment in this group. This study aimed to evaluate changes in brain metabolites, diffusion and anisotropy features, and cognitive performance in children with ALL after MTX treatment. Methods: In this observational study conducted from December 2013 to December 2015, 30 children with ALL and 30 healthy children were recruited and evaluated using baseline magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and neurocognitive tests. After MTX treatment and ALL remission, the children with ALL underwent MR examination and neurocognitive tests again. Quantitative alterations of MR and cognitive test results from the baseline data were calculated. Results: At baseline, the ALL group (age 6.9±3.3 years; 14 boys) and the healthy controls (age 6.0±3.1 years, 14 boys) had comparable neurocognitive performance and MR results. After MTX treatment, 6.7% (2/30) of children with ALL showed abnormalities on diffusion- and T1- and T2-weighted images. The N-acetylaspartate/creatine and N-acetylaspartate/choline values of children with ALL decreased, whereas their choline/creatine values increased significantly. The fractional anisotropy (FA) values decreased in the frontal lobe (P=0.03) and the genu of the corpus callosum (P=0.01). The FA values in the genu of the internal capsule (P=0.08), the occipital lobe (P=0.20) and the splenium of the corpus callosum (P=0.30) did not change from baseline. The apparent diffusion coefficient (ADC) values decreased in the frontal lobe (P=0.03). The ADC values in the genu of the corpus callosum (P=0.11), the genu of the internal capsule (P=0.93), and the occipital lobe (P=0.65) did not change from baseline. Due to the presence of outliers and the small sample, the ADC values in the splenium of the corpus callosum were discarded. Neurocognitive performance decreased slightly after MTX treatment, with noticeable declines in working memory and processing speed. Changes in FA values were positively correlated with the reduction in the N-acetylaspartate/creatine ratio at the genu of the corpus callosum of children with ALL aged above 6 years. Conclusions: MTX treatment causes subtle cognitive decline in children with ALL in remission and dramatically affects their brain metabolites, but changes in white matter diffusion features are limited to the frontal lobe and corpus callosum.

ADHD-inattentive versus ADHD-Combined subtypes: A severity continuum or two distinct entities? A comprehensive analysis of clinical, cognitive and neuroimaging data.

The current study aimed to explore the multimodal differences between the inattentive ADHD (ADHD-I) subtype and the combined ADHD (ADHD-C) subtype. A large sample of medication-naïve children with pure ADHD (i.e., without any comorbidity) (145 with ADHD-I, 132 with ADHD-C) and healthy controls (n = 98) were recruited. A battery of multiple scales and cognitive tests were utilized to assess the clinical and cognitive profiles of each individual. In addition, structural and diffusion magnetic resonance imaging (MRI) were acquired for 120 subjects with ADHD and 85 controls. Regional gray matter volume, white matter volume, and diffusion tensors, e.g., axial diffusivity (AD), were compared among the three groups in a whole-brain voxel-wise manner. Compared with healthy controls, both ADHD groups exhibited elevated levels of behavioral and emotional problems. The ADHD-C group had more behavioral problems and emotional liability, as well as less anxiety, than the ADHD-I group. The two ADHD groups were equally impaired in most cognitive domains, with the exception of sustained attention. Compared with healthy controls, the ADHD-C group showed a high gray matter volume (GMV) in the bilateral thalamus and a high white matter volume in the body of the corpus callosum, while the ADHD-I group presented an elevated GMV mainly in the left precentral gyrus and posterior cingulate cortex. Compared with participants with ADHD-C and healthy controls, subjects with ADHD-I showed increased AD in widespread brain regions. Our study has revealed a distinct, interconnected pattern of behavioral, cognitive, and brain structural characteristics in children with different ADHD subtypes.

Effects of the SNAP25 on Integration Ability of Brain Functions in Children With ADHD.

OBJECTIVE: The present study aimed to examine the effects of SNAP25 on the integration ability of intrinsic brain functions in children with ADHD, and whether the integration ability was associated with working memory (WM). METHODS: A sliding time window method was used to calculate the spatial and temporal concordance among five rs-fMRI regional indices in 55 children with ADHD and 20 healthy controls. RESULTS: The SNAP25 exhibited significant interaction effects with ADHD diagnosis on the voxel-wise concordance in the right posterior central gyrus, fusiform gyrus and lingual gyrus. Specifically, for children with ADHD, G-carriers showed increased voxel-wise concordance in comparison to TT homozygotes in the right precentral gyrus, superior frontal gyrus, postcentral gyrus, and middle frontal gyrus. The voxel-wise concordance was also found to be related to WM. CONCLUSION: Our findings provided a new insight into the neural mechanisms of the brain function of ADHD children.