121 research outputs found
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The relationship between sensory reactivity differences and mental health symptoms in children with neurodevelopmental conditions and their neurotypical peers
Children with neurodevelopmental conditions (NDC) often have sensory reactivity differences, such as being overwhelmed by sounds, which can elicit distress in their everyday life. Furthermore, children with an NDC often present with a greater frequency of mental health symptoms compared to their typically developing peers. However little research has examined the relationship of these sensory reactivity differences on broader mental health. This study set out to explore the relationship between sensory reactivity and mental health symptoms. Data from parent-reported measures of sensory reactivity and mental health symptoms were collected for 49 children presenting with a neurodevelopmental condition and 42 typically developing (TD) controls. Partial correlational analyses, controlling for IQ, were used to elucidate the relationship between sensory reactivity and mental health symptoms. Children with an NDC were significantly more likely to present with a sensory reactivity difference or mental health symptom. Sensory seeking was found to be the sensory subtype most related to mental health symptoms, especially in externalising conditions. There was evidence also found for a relationship between depression, sensory seeking and sensory hypo-reactivity, and GAD and hyper-reactivity. Findings suggest a relationship between sensory reactivity and mental health symptoms in children with a neurodevelopmental condition. There is also preliminary evidence of unique sensory-based profiles of mental health. Assessment of sensory difficulties as part of more rigorous mental health assessments within mental health services will support more accurate diagnoses and intervention
The Role of Corpus Callosum Development in Functional Connectivity and Cognitive Processing
The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8β12 Hz), beta (12β30 Hz) and gamma (30β55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified
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ARHGEF9 disease: Phenotype clarification and genotype-phenotype correlation.
ObjectiveWe aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations.MethodsPatients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features.ResultsA total of 18 patients (including 5 females) were identified. Six had de novo, 5 had maternally inherited mutations, and 7 had chromosomal disruptions. All females had strongly skewed X-inactivation in favor of the abnormal X-chromosome. Symptoms presented in early childhood with delayed motor development alone or in combination with seizures. Intellectual disability was severe in most and moderate in patients with milder mutations. Males with severe intellectual disability had severe, often intractable, epilepsy and exhibited a particular facial dysmorphism. Patients with mutations in exon 9 affecting the protein's PH domain did not develop epilepsy.ConclusionsARHGEF9 encodes a crucial neuronal synaptic protein; loss of function of which results in severe intellectual disability, epilepsy, and a particular facial dysmorphism. Loss of only the protein's PH domain function is associated with the absence of epilepsy
White Matter Microstructure Associations of Cognitive and Visuomotor Control in Children: A Sensory Processing Perspective
Objective: Recent evidence suggests that co-occurring deficits in cognitive control and visuomotor control are common to many neurodevelopmental disorders. Specifically, children with sensory processing dysfunction (SPD), a condition characterized by sensory hyper/hypo-sensitivity, show varying degrees of overlapping attention and visuomotor challenges. In this study, we assess associations between cognitive and visuomotor control abilities among children with and without SPD. In this same context, we also examined the common and unique diffusion tensor imaging (DTI) tracts that may support the overlap of cognitive control and visuomotor control.Method: We collected cognitive control and visuomotor control behavioral measures as well as DTI data in 37 children with SPD and 25 typically developing controls (TDCs). We constructed regressions to assess for associations between behavioral performance and mean fractional anisotropy (FA) in selected regions of interest (ROIs).Results: We observed an association between behavioral performance on cognitive control and visuomotor control. Further, our findings indicated that FA in the anterior limb of the internal capsule (ALIC), the anterior thalamic radiation (ATR), and the superior longitudinal fasciculus (SLF) are associated with both cognitive control and visuomotor control, while FA in the superior corona radiata (SCR) uniquely correlate with cognitive control performance and FA in the posterior limb of the internal capsule (PLIC) and the cerebral peduncle (CP) tract uniquely correlate with visuomotor control performance.Conclusions: These findings suggest that children who demonstrate lower cognitive control are also more likely to demonstrate lower visuomotor control, and vice-versa, regardless of clinical cohort assignment. The overlapping neural tracts, which correlate with both cognitive and visuomotor control suggest a possible common neural mechanism supporting both control-based processes
Processing Speed Delays Contribute to Executive Function Deficits in Individuals with Agenesis of the Corpus Callosum
Corpus callosum malformation and dysfunction are increasingly recognized causes of cognitive and behavioral disability. Individuals with agenesis of the corpus callosum (AgCC) offer unique insights regarding the cognitive skills that depend specifically upon callosal connectivity. We examined the impact of AgCC on cognitive inhibition, flexibility, and processing speed using the Color-Word Interference Test (CWIT) and Trail Making Test (TMT) from the Delis-Kaplan Executive Function System. We compared 36 individuals with AgCC and IQs within the normal range to 56 matched controls. The AgCC cohort was impaired on timed measures of inhibition and flexibility; however, group differences on CWIT Inhibition, CWIT Inhibition/Switching and TMT Number-Letter Switching appear to be largely explained by slow performance in basic operations such as color naming and letter sequencing. On CWIT Inhibition/Switching, the AgCC group was found to commit significantly more errors which suggests that slow performance is not secondary to a cautious strategy. Therefore, while individuals with agenesis of the corpus callosum show real deficits on tasks of executive function, this impairment appears to be primarily a consequence of slow cognitive processing. Additional studies are needed to investigate the impact of AgCC on other aspects of higher order cortical function
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White matter connectome correlates of auditory over-responsivity: edge density imaging and machine-learning classifiers
Sensory over-responsivity (SOR) commonly involves auditory and/or tactile domains, and can affect children with or without additional neurodevelopmental challenges. In this study, we examined white matter microstructural and connectome correlates of auditory over-responsivity (AOR), analyzing prospectively collected data from 39 boys, aged 8β12 years. In addition to conventional diffusion tensor imaging (DTI) maps β including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD); we used DTI and high-resolution T1 scans to develop connectome Edge Density (ED) maps. The tract-based spatial statistics was used for voxel-wise comparison of diffusion and ED maps. Then, stepwise penalized logistic regression was applied to identify independent variable (s) predicting AOR, as potential imaging biomarker (s) for AOR. Finally, we compared different combinations of machine learning algorithms (i.e., naΓ―ve Bayes, random forest, and support vector machine (SVM) and tract-based DTI/connectome metrics for classification of children with AOR. In direct sensory phenotype assessment, 15 (out of 39) boys exhibited AOR (with or without neurodevelopmental concerns). Voxel-wise analysis demonstrates extensive impairment of white matter microstructural integrity in children with AOR on DTI maps β evidenced by lower FA and higher MD and RD; moreover, there was lower connectome ED in anterior-superior corona radiata, genu and body of corpus callosum. In stepwise logistic regression, the average FA of left superior longitudinal fasciculus (SLF) was the single independent variable distinguishing children with AOR (p = 0.007). Subsequently, the left SLF average FA yielded an area under the curve of 0.756 in receiver operating characteristic analysis for prediction of AOR (p = 0.008) as a region-of-interest (ROI)-based imaging biomarker. In comparative study of different combinations of machine-learning models and DTI/ED metrics, random forest algorithms using ED had higher accuracy for AOR classification. Our results demonstrate extensive white matter microstructural impairment in children with AOR, with specifically lower connectomic ED in anterior-superior tracts and associated commissural pathways. Also, average FA of left SLF can be applied as ROI-based imaging biomarker for prediction of SOR. Finally, machine-learning models can provide accurate and objective image-based classifiers for identification of children with AOR based on white matter tracts connectome ED
Hemispheric lateralization of white matter microstructure in children and its potential role in sensory processing dysfunction
Diffusion tensor imaging (DTI) studies have demonstrated white matter microstructural differences between the left and right hemispheres of the brain. However, the basis of these hemispheric asymmetries is not yet understood in terms of the biophysical properties of white matter microstructure, especially in children. There are reports of altered hemispheric white matter lateralization in ASD; however, this has not been studied in other related neurodevelopmental disorders such as sensory processing disorder (SPD). Firstly, we postulate that biophysical compartment modeling of diffusion MRI (dMRI), such as Neurite Orientation Dispersion and Density Imaging (NODDI), can elucidate the hemispheric microstructural asymmetries observed from DTI in children with neurodevelopmental concerns. Secondly, we hypothesize that sensory over-responsivity (SOR), a common type of SPD, will show altered hemispheric lateralization relative to children without SOR. Eighty-seven children (29 females, 58 males), ages 8β12βyears, presenting at a community-based neurodevelopmental clinic were enrolled, 48 with SOR and 39 without. Participants were evaluated using the Sensory Processing 3 Dimensions (SP3D). Whole brain 3βT multi-shell multiband dMRI (bβ=β0, 1,000, 2,500βs/mm2) was performed. Tract Based Spatial Statistics were used to extract DTI and NODDI metrics from 20 bilateral tracts of the Johns Hopkins University White-Matter Tractography Atlas and the lateralization Index (LI) was calculated for each leftβright tract pair. With DTI metrics, 12 of 20 tracts were left lateralized for fractional anisotropy and 17/20 tracts were right lateralized for axial diffusivity. These hemispheric asymmetries could be explained by NODDI metrics, including neurite density index (18/20 tracts left lateralized), orientation dispersion index (15/20 tracts left lateralized) and free water fraction (16/20 tracts lateralized). Children with SOR served as a test case of the utility of studying LI in neurodevelopmental disorders. Our data demonstrated increased lateralization in several tracts for both DTI and NODDI metrics in children with SOR, which were distinct for males versus females, when compared to children without SOR. Biophysical properties from NODDI can explain the hemispheric lateralization of white matter microstructure in children. As a patient-specific ratio, the lateralization index can eliminate scanner-related and inter-individual sources of variability and thus potentially serve as a clinically useful imaging biomarker for neurodevelopmental disorders
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