A Potential Mechanism of Neurological Impairment in Children With Infantile Spasm: Based on Microanatomic Structure Analysis Employing Voxel-Based Morphometry and Surface-Based Morphometry.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) would accompany with severe neurological impairment. Our study aimed to explore the potential mechanism by employing voxel-based and surface-based morphometry to detect brain microwould accompany with severe neurological impairment. Our study aimed to explore the potential mechanism by employing voxel-based and surface-based morphometry to detect brain microanatomic structure alteration. METHODS: The IESS group had 21 males and 13 females (mean age: 17.7 ± 15.6 months), whereas the healthy controls group had 22 males and 10 females (mean age: 29.4 ± 18.7 months). High-resolution 3D T1WI was performed. Computational Anatomy Toolbox implemented in Statistical Parametric Mapping 12 was used to measure the gray matter and white matter volume, and the cortical thickness separately. Independent sample t test was used to assess between-group differences. IESS group was assessed using the Bayley Scales of Infant Development. RESULTS: The IESS group showed a significantly decreased volume of gray matter in right middle temporal gyrus, inferior temporal gyrus, superior temporal gyrus, right fusiform, and bilateral precuneus (P < 0.001). There were no significant between-group differences with respect to white matter volume or cortical thickness (P > 0.001). The results of Bayley Scales of Infant Development showed that the Mental Development Index (MDI) and Psychomotor Development Index scores of children with IESS were almost concentrated in the range of <70. MDI score showed a positive correlation with gray matter reduction area in IESS group. CONCLUSION: Children with IESS had impaired cognitive and delayed motor development. And the decreased gray matter in the right temporal lobe, fusiform, and bilateral precuneus could be the potential anatomic basis for impaired function, such as hearing, visual, and language.

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.

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.

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.

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.

Dynamic Functional Connectivity Reveals Abnormal Variability in the Amygdala Subregions of Children With Attention-Deficit/Hyperactivity Disorder.

Objective: This study investigates whether the dynamic functional connectivity (dFC) of the amygdala subregions is altered in children with attention-deficit/hyperactivity disorder (ADHD). Methods: The dFC of the amygdala subregions was systematically calculated using a sliding time window method, for 75 children with ADHD and 20 healthy control (HC) children. Results: Compared with the HC group, the right superficial amygdala exhibited significantly higher dFC with the right prefrontal cortex, the left precuneus, and the left post-central gyrus for children in the ADHD group. The dFC of the amygdala subregions showed a negative association with the cognitive functions of children in the ADHD group. Conclusion: Functional connectivity of the amygdala subregions is more unstable among children with ADHD. In demonstrating an association between the stability of functional connectivity of the amygdala and cognitive functions, this study may contribute by providing a new direction for investigating the internal mechanism of ADHD.

Effects of the DRD4 -521 C/T SNP on Local Neural Activity and Functional Connectivity in Children With ADHD.

Objective: The present study aimed to investigate the effects of the dopamine receptor D4 (DRD4) -521 C/T single-nucleotide polymorphism on brain function among children with attention deficit hyperactivity disorder (ADHD) and to evaluate whether brain function is associated with behavioral performance among this demographic. Methods: Using regional homogeneity, fractional amplitude low-frequency fluctuation, and functional connectivity as measurement indices, we compared differences in resting-state brain function between 34 boys with ADHD in the TT homozygous group and 37 boys with ADHD in the C-allele carrier group. The Conners' Parent Rating Scale, the SNAP-IV Rating Scale, the Stroop Color Word Test, the go/no-go task, the n-back task, and the working memory index within the Wechsler Intelligence Scale for Children-Fourth Edition were selected as comparative indicators in order to test effects on behavioral performance. Results: We found that TT homozygotes had low behavioral performance as compared with C-allele carriers. The regional homogeneity for TT homozygotes decreased in the right middle occipital gyrus and increased in the right superior frontal gyrus as compared with C-allele carriers. In addition, the right middle occipital gyrus and the right superior frontal gyrus were used as the seeds of functional connectivity, and we found that the functional connectivity between the right middle occipital gyrus and the right cerebellum decreased, as did the functional connectivity between the right superior frontal gyrus and the angular gyrus. No statistically significant differences were observed in the respective brain regions when comparing the fractional amplitudes for low-frequency fluctuation between the two groups. Correlation analyses demonstrated that the fractional amplitude low-frequency fluctuation in the precentral gyrus for TT homozygotes were statistically significantly correlated with working memory. Conclusions: We found differing effects of DRD4 -521 C/T polymorphisms on brain function among boys with ADHD. These findings promote our understanding of the genetic basis for neurobiological differences observed among children with ADHD, but they must be confirmed in larger samples.

Effectiveness of High-Speed T2-Corrected Multiecho MR Spectroscopic Method for Quantifying Thigh Muscle Fat Content in Boys With Duchenne Muscular Dystrophy.

OBJECTIVE. The purpose of this study was to investigate the potential of high-speed T2-corrected multiecho (HISTO) MR spectroscopy (MRS) for rapidly quantifying the fat content of thigh muscles in children with Duchenne muscular dystrophy (DMD). SUBJECTS AND METHODS. This study prospectively enrolled 58 boys with DMD (mean age, 7.5 years; range, 4-11 years) and 30 age-matched healthy boys (mean age, 7.2 years; range, 4-11 years) at one institution over a 1-year period. T1- and T2-weighted, multiecho Dixon, and HISTO sequences were performed on the right adductor magnus and vastus lateralis muscles. The fat fractions of these muscles were acquired from HISTO and multiecho Dixon images. An experienced radiologist graded the degree of fat infiltration of the adductor magnus and vastus lateralis muscles on axial T1-weighted images. The Bland-Altman method was used to assess the consistency and repeatability of the HISTO sequence. Pearson linear correlation analysis was used to determine the correlation coefficient relating HISTO fat fraction to multiecho Dixon fat fraction values. Spearman rank correlation analysis was used to assess the relation between the HISTO fat fraction values and T1-weighted image fat infiltration grades. The independent t test was used to compare the HISTO fat fraction values of the boys with DMD with those of the healthy control subjects. RESULTS. Bland-Altman analysis showed that 95.5% of the HISTO fat fraction values of the adductor magnus were within the 95% CI. HISTO fat fraction and multiecho Dixon fat fraction values of the adductor magnus and vastus lateralis muscles were highly positively correlated (adductor magnus, r = 0.983; vastus lateralis, r = 0.967; p < 0.0001). HISTO fat fraction values were also highly positively correlated with the grades of fat infiltration on T1-weighted images (adductor magnus, r = 0.911; vastus lateralis, r = 0.937; p < 0.0001). The HISTO fat fraction of the adductor magnus muscle was 33.3% ± 22.6% and of the vastus lateralis muscle was 25.6% ± 20.3% in patients with DMD. The corresponding values were 2.9% ± 2.1% and 2.3% ± 1.9% in the control group. The differences were statistically significant (p < 0.0001). CONCLUSION. The HISTO sequence is a rapid and feasible noninvasive MRS technique for quantifying the fat infiltration of thigh muscles in children with known or suspected DMD. It is useful for diagnosis and for assessment of disease activity and prognosis.

The impact of SNAP25 on brain functional connectivity density and working memory in ADHD.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopment disorder. The deficit in working memory is a central cognitive impairment in ADHD. The SNAP-25 is a neurotransmitter vesicular docking protein whose MnlI polymorphism (rs3746544) is located in the 3'-untranslated region (3'-UTR) and known to be linked to ADHD, but the underlying mechanism of this polymorphism remains unclear. Using a functional connectivity density (FCD) mapping method based on resting-state functional magnetic resonance imaging in a sample of male children diagnosed with ADHD, we first investigated the correlation between SNAP-25 rs3746544 and FCD hubs. Compared with rs3746544 G-allele carriers, TT homozygous, which confers a high risk for ADHD, exhibited significantly decreased local and long-range FCD in anterior cingulate cortex, and decreased local FCD in the dorsal lateral prefrontal cortex. Moreover, both higher local and long-range FCD could predict better WM capacity. The current findings provide new insights into the underlying neural mechanisms linking SNAP-25 rs3746544 with the risk for ADHD via the endophenotype of brain functional connectivity.

Relationship between renal apparent diffusion coefficient values and glomerular filtration rate in infants with congenital hydronephrosis.

The aim was to investigate the relationship between apparent diffusion coefficient (ADC) values measured by diffusion-weighted magnetic resonance imaging (DW MRI) and the split glomerular filtration rate (GFR) in infants with congenital hydronephrosis. Diffusion-weighted imaging (DWI) (b = 0 and 700 seconds/mm(2)) was performed with a General Electric Company (GE) Signa 1.5T MR unit in 46 infants suffering single congenital hydronephrosis and in 30 healthy infants as normal control group. The ADCs were calculated with regions of interest (ROIs) positioned in the renal parenchyma. The 46 obstructed kidneys were classified into four groups according to the GFR level: renal dysfunction compensated group, renal dysfunction decompensated group, renal failure group, and uremia group. The renal ADCs in six groups (normal kidneys in control group, contralateral kidneys, and four groups of hydronephrotic kidneys) were compared statistically using analysis of variance (ANOVA), and the correlative relationship between ADCs and GFR was examined by Pearson's correlation test. There were statistically significant differences in renal ADCs among the six groups. The ADCs of hydronephrotic kidneys were lower than that of the normal kidneys. There was a moderate positive correlation between the ADCs of hydronephrotic kidneys and split GFR (r = 0.744). This study indicated that the ADCs of congenital hydronephrotic kidneys were lower than that of normal renal parenchyma, and there was a positive correlation between the ADCs and split renal GFR, which demonstrates that the ADCs can reflect the filtration function of hydronephrotic kidneys and may provide some reference to help clinical physician to explore a novel noninvasive approach to evaluate the single renal function.