Functional Abnormalities In Children Research Articles

Structural and functional changes in drug-naïve benign childhood epilepsy with centrotemporal spikes and their associated gene expression profiles.

Benign epilepsy with centrotemporal spikes (BECTS) is a common pediatric epilepsy syndrome that has been widely reported to show abnormal brain structure and function. However, the genetic mechanisms underlying structural and functional changes remain largely unknown. Based on the structural and resting-state functional magnetic resonance imaging data of 22 drug-naïve children with BECTS and 33 healthy controls, we conducted voxel-based morphology (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) analyses to compare cortical morphology and spontaneous brain activity between the 2 groups. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial correlation analyses were applied to explore gene expression profiles associated with gray matter volume (GMV) and fALFF changes in BECTS. VBM analysis demonstrated significantly increased GMV in the right brainstem and right middle cingulate gyrus in BECTS. Moreover, children with BECTS exhibited significantly increased fALFF in left temporal pole, while decreased fALFF in right thalamus and left precuneus. These brain structural and functional alterations were closely related to behavioral and cognitive deficits, and the fALFF-linked gene expression profiles were enriched in voltage-gated ion channel and synaptic activity as well as neuron projection. Our findings suggest that brain morphological and functional abnormalities in children with BECTS involve complex polygenic genetic mechanisms.

A multi-parameter resting-state functional magnetic resonance imaging study of brain intrinsic activity in attention deficit hyperactivity disorder children

A great number of studies have demonstrated functional abnormalities in children with attention-deficit/hyperactivity disorder (ADHD), although conflicting results have also been reported. And few studies analyzed homotopic functional connectivity between hemispheres. In this study, resting-state functional magnetic resonance imaging (MRI) data were recorded from 45 medication-naïve ADHD children and 26 healthy controls. The regional homogeneity (ReHo), degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) values were compared between the two groups to depict the intrinsic brain activities. We found that ADHD children exhibited significantly lower ReHo and DC values in the right middle frontal gyrus and the two values correlated with each other; moreover, lower VMHC values were found in the bilateral occipital lobes of ADHD children, which was negatively related with anxiety scores of Conners' Parent Rating Scale (CPRS-R) and positively related with completed categories of Wisconsin Card Sorting Test (WCST). Our results might suggest that less spontaneous neuronal activities of the right middle frontal gyrus and the bilateral occipital lobes in ADHD children.

Structural and Functional Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder: A Focus on Subgenual Anterior Cingulate Cortex.

Attention-deficit/hyperactivity disorder (ADHD), characterized by developmentally inappropriate inattention, hyperactivity/impulsivity, or a combination of both, is a major public health problem. Neuroimaging studies have revealed associations of these cognitive impairments with structural and functional deficits all over the brain. Existing findings are not fully consistent because of the heterogeneity of study samples and diversity of research techniques. In this study, we propose to utilize a multimodal magnetic resonance imaging (MRI) approach to study the structural and functional brain networks in children with ADHD-combined type (ADHD-C) with a focus on the subgenual anterior cingulate cortex (sgACC). Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) data from 32 children with ADHD-C and 32 group-matched controls were involved. Network-based statistic analysis of the rs-fMRI data revealed a disconnected functional network between the sgACC and multiple regions in the occipital lobe and cerebellum, whereas the DTI data showed disrupted white matter integrity in the subgenual cingulum bundle (sgCB). Post hoc region of interest (ROI)-based analyses showed significantly increased fluctuation of the spontaneous brain activity in the sgACC and higher radial diffusivity in the sgCB in the ADHD group. Both the rs-fMRI and DTI ROI-based measures were significantly correlated with clinical measures that examine behavioral capacities of attention and inhibitory control. Findings of this study suggest that functional alterations in the sgACC and white matter under development in the sgCB may impact each other, and together contribute to impaired attention and inhibitory control function in children with ADHD.

Cortical gyrification is abnormal in children with prenatal alcohol exposure.

ObjectivesPrenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined.Experimental designIncluded were 92 children with PAE and 83 controls ages 9–16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure.Principal observationsWhole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ).ConclusionsAbnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.

EN

The aim of the present study was to map the pathophysiology of resting state functional connectivity accompanying structural and functional abnormalities in children with bipolar disorder. Children with bipolar disorder and demographically matched healthy controls underwent resting-state functional magnetic resonance imaging. A model-free independent component analysis was performed to identify intrinsically interconnected networks. We included 34 children with bipolar disorder and 40 controls in our analysis. Three distinct resting state networks corresponding to affective, executive and sensorimotor functions emerged as being significantly different between the pediatric bipolar disorder (PBD) and control groups. All 3 networks showed hyperconnectivity in the PBD relative to the control group. Specifically, the connectivity of the dorsal anterior cingulate cortex (ACC) differentiated the PBD from the control group in both the affective and the executive networks. Exploratory analysis suggests that greater connectivity of the right amygdala within the affective network is associated with better executive function in children with bipolar disorder, but not in controls. Unique clinical characteristics of the study sample allowed us to evaluate the pathophysiology of resting state connectivity at an early state of PBD, which led to the lack of generalizability in terms of comorbid disorders existing in a typical PBD population. Abnormally engaged resting state affective, executive and sensorimotor networks observed in children with bipolar disorder may reflect a biological context in which abnormal task-based brain activity can occur. Dual engagement of the dorsal ACC in affective and executive networks supports the neuroanatomical interface of these networks, and the amygdala's engagement in moderating executive function illustrates the intricate interplay of these neural operations at rest.

Work of breathing in children with diffuse parenchymal lung disease

Respiratory mechanics have been poorly studied in children with chronic diffuse parenchymal lung disease (DPLD). The aim of the study was to assess the usefulness of respiratory mechanics to monitor lung function alteration in children with DPLD. Respiratory mechanics, total (WOBt), elastic (WOBe) and resistive (WOBr) work of breathing, gas exchange, lung function and respiratory muscle strength were measured in 10 children, aged 1.8–18.4 years old, who were followed in our national reference centre. Mean tidal volume (Vt) was normal (11±4mL/kg) but respiratory rate (fr, 32±19breaths/min), fr/Vt (118±75breaths/min/L) and total lung resistance (10.2±4.8cmH2OL−1s) were increased. Mean WOBt was increased mainly due to WOBe. Dynamic lung compliance (Cldyn) was severely reduced (26±24mL/cmH2O). Cldyn and the oesophageal pressure-time product strongly correlated with vital capacity and functional residual capacity. Respiratory muscle strength was within the normal range. In conclusion, lung mechanics may be considered as useful complementary or alternative markers of functional abnormalities in children with DPLD.

Prevalence and Predictors of Renal Functional Abnormalities of High Grade Vesicoureteral Reflux

The association of vesicoureteral reflux, febrile urinary tract infections and renal parenchymal damage is well recognized. We determined the prevalence and predictors of renal functional abnormalities in children with high grade vesicoureteral reflux. We retrospectively reviewed the medical records and dimercapto-succinic acid scans of 774 consecutive children with primary high grade vesicoureteral reflux (grade IV-V) seen at our institution between 1998 and 2011. For multivariate analysis we analyzed variables associated with renal functional abnormalities, such as presentation history, age, gender and reflux grade, in a logistic regression model. Of the children 698 (90%) and 76 (10%) had grade IV and V reflux, respectively. Dimercapto-succinic acid scans revealed renal functional abnormalities in 291 children (37.6%), including 240 (34%) with grade IV and 51 (67%) with grade V reflux. Univariate analysis showed that age greater than 1 year (OR 2.95, p <0.001), grade V reflux (OR 4.09, p <0.001) and preoperative bladder/bowel dysfunction (OR 2.94, p = 0.026) were significant predictors of renal functional abnormalities. Multivariate analysis showed that age greater than 1 year (OR 3.45, p = 0.001) and grade V reflux (OR 5.89, p <0.001) were the most significant independent predictors of such abnormalities. There is an increased risk of renal functional abnormalities in children older than 1 year and those with grade V vesicoureteral reflux. Patients with a history of bladder/bowel dysfunction are also at greater risk for such abnormalities. The early detection and treatment of high grade vesicoureteral reflux may prevent acquired renal parenchymal damage and limit the progression of renal damage in patients with congenital reflux nephropathy.

Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults — A functional magnetic resonance imaging (fMRI) study

Attention deficit hyperactivity disorder (ADHD) is a common, genetically transmitted common childhood-onset disorder with a high rate of persistence in adulthood. Although many studies have shown anatomical and functional abnormalities in children and adolescents, studies with adult patients are rare. Nineteen adults with ADHD (11 ADHD, combined type; 8 ADHD, partially remitted) and 17 controls were included in this functional magnetic resonance imaging (fMRI) study. Brain activation was investigated with a continuous performance test (CPT). Impaired activation of a fronto-striatal and a parietal attentional network was observed during the NoGo condition in ADHD subjects. Correlations of reduced activity of the caudate nuclei, the anterior cingulate cortex, and parietal cortical structures, as well as increased activity in the insular cortex, with inattention and impulsivity symptom scores were found. The activation patterns were similar to those known from children and adolescents with ADHD. In conclusion we found not only a widespread dysfunction of brain regions that are involved in cognitive processing in adults with ADHD compared with controls, but also correlations between symptom severity and dysfunction of neuronal systems across adult subjects with a history of ADHD in childhood but whose symptoms did (persistent ADHD) and did not (not persistent ADHD) qualify for a full diagnosis of ADHD in adulthood.

Immunoregulatory Functional Abnormalities in Children Affected by HBsAg‐Positive Chronic Active Hepatitis

SummarySuppressor cell function was evaluated in children affected by HBsAg‐positive chronic active hepatitis. Circulating concanavalin A‐ (ConA) precultured lymphocytes failed to suppress the proliferative response of autologous responder cells to a mitogen. In four of eight patients with a failure of ConA‐induced suppressor activity, indomethacin added during the induction phase of T suppressor cells abolished the defect, indicating that prostaglandin‐producing adherent cells may influence ConA‐induced suppressor activity. An inverse relation ship between suppressor cell activity and the number of suppressor/cytotoxic subsets defined by the OK T8 monoclonal antibody was found. Our findings strongly support the hypothesis that an abnormality in the immunoregulatory system plays a role in the pathogenesis of HBsAg‐related chronic active hepatitis. It is also suggested that non‐T regulatory cells are implicated in the immunological abnormality in chronic active hepatitis.

Immunoregulatory functional abnormalities in children affected by HBsAg-positive chronic active hepatitis: role of prostaglandins in T-mediated suppression.

Suppressor cell function was evaluated in children affected by HBsAg-positive chronic active hepatitis. Circulating concanavalin A- (ConA) precultured lymphocytes failed to suppress the proliferative response of autologous responder cells to a mitogen. In four of eight patients with a failure of ConA-induced suppressor activity, indomethacin added during the induction phase of T suppressor cells abolished the defect, indicating that prostaglandin-producing adherent cells may influence ConA-induced suppressor activity. An inverse relationship between suppressor cell activity and the number of suppressor/cytotoxic subsets defined by the OK T8 monoclonal antibody was found. Our findings strongly support the hypothesis that an abnormality in the immunoregulatory system plays a role in the pathogenesis of HBsAg-related chronic active hepatitis. It is also suggested that non-T regulatory cells are implicated in the immunological abnormality in chronic active hepatitis.