Impaired Ability in Visual-Spatial Attention in Chinese Children With Developmental Dyslexia.

A growing body of evidence suggests that children with dyslexia in alphabetic languages exhibit visual-spatial attention deficits that can obstruct reading acquisition by impairing their phonological decoding skills. However, it remains an open question whether these visual-spatial attention deficits are present in children with dyslexia in non-alphabetic languages. Chinese, with its logographic writing system, offers a unique opportunity to explore this question. The presence of visual-spatial attention deficits in Chinese children with dyslexia remains insufficiently investigated. Therefore, this study aimed to explore whether such deficits exist, employing a visual search paradigm. Three visual search tasks were conducted, encompassing two singleton feature search tasks and a serial conjunction search task. The results indicated that Chinese children with dyslexia performed as well as chronological age-matched control children in color search tasks but less effectively in orientation search, suggesting a difficulty in the rapid visual processing of orientation: a deficit potentially specific to Chinese dyslexia. Crucially, Chinese children with dyslexia also exhibited lower accuracy, longer reaction times, and steeper slopes in the reaction times by set size function in the conjunction search task compared to control children, which is indicative of a visual-spatial attention deficit.

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Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.

Effectiveness of digital game-based trainings in children with neurodevelopmental disorders: A meta-analysis.

Digital game-based training programs have recently been used to train the cognitive abilities of children with neurodevelopmental disorders (NDDs). However, the effects of training remain controversial. The present meta-analysis explored the effectiveness of digital game-based training in children with NDDs and examined the possible moderators of its effects. Twenty-nine studies with cognitive outcomes in 1535 children were included in the present meta-analysis. The results showed that digital game-based training could significantly enhance the core cognitive abilities of children with each type of NDDs and that training could be used remotely. Meanwhile, task content and game features of digital game-based interventions separately make unique and significant contributions to the training effects, suggesting that the combination of training content and game features could efficiently improve children's cognition. Although the present study revealed that the training benefits could be maintained over a period of time, more studies are needed to explore the retention effects of digital game-based training. The present study provides a comprehensive understanding of the training effects of digital game-based interventions and new insights for future cognitive training design and application.

Differences in brain functional networks for audiovisual integration during reading between children and adults.

Building robust letter-to-sound correspondences is a prerequisite for developing reading capacity. However, the neural mechanisms underlying the development of audiovisual integration for reading are largely unknown. This study used functional magnetic resonance imaging in a lexical decision task to investigate functional brain networks that support audiovisual integration during reading in developing child readers (10-12 years old) and skilled adult readers (20-28 years old). The results revealed enhanced connectivity in a prefrontal-superior temporal network (including the right medial frontal gyrus, right superior frontal gyrus, and left superior temporal gyrus) in adults relative to children, reflecting the development of attentional modulation of audiovisual integration involved in reading processing. Furthermore, the connectivity strength of this brain network was correlated with reading accuracy. Collectively, this study, for the first time, elucidates the differences in brain networks of audiovisual integration for reading between children and adults, promoting the understanding of the neurodevelopment of multisensory integration in high-level human cognition.

Functional brain networks underlying the interaction between central and peripheral processes involved in Chinese handwriting in children and adults.

The neural mechanisms that support handwriting, an important mode of human communication, are thought to be controlled by a central process (responsible for spelling) and a peripheral process (responsible for motor output). However, the relationship between central and peripheral processes has been debated. Using functional magnetic resonance imaging, this study examined the neural mechanisms underlying this relationship in Chinese handwriting in 36 children (mean age = 10.40 years) and 56 adults (mean age = 22.36 years) by manipulating character frequency (a central variable). Brain network analysis showed that character frequency reconfigured functional brain networks known to underlie motor processes, including the somatomotor and cerebellar network, in both children and adults, indicating that central processing cascades into peripheral processing. Furthermore, the network analysis characterized the interaction profiles between motor networks and linguistic-cognitive networks, fully mapping the neural architecture that supports the interaction of central and peripheral processes involved in handwriting. Taken together, these results reveal the neural interface underlying the interaction between central and peripheral processes involved in handwriting in a logographic writing system, advancing our understanding of the neural basis of handwriting.

Visual motion processing in Chinese children with developmental dyslexia: An fMRI study.

Dorsal stream is an important pathway for visual information transmission. As a part of the dorsal pathway, the middle temporal visual motion areas (V5/MT+) are mainly responsible for visual motion processing and the ability of visual motion processing is closely related to reading. Compared with alphabetic scripts, the visual structure of Chinese characters is more complex and there are no clear grapheme-phoneme correspondence rules. So the ability of visual analysis plays an important role in Chinese character processing. This study first investigated the brain activation of Chinese dyslexic children and children of the same chronological age when they observed coherent motion stimuli. ROI analysis indicated that only the activation of left V5/MT+ was significantly weaker in dyslexics than that in the control group. The activity of the magnocellular-dorsal stream was closely related to orthographic awareness in the combined data (two groups) and the typical children. In dyslexia group, the stronger the activation of V5/MT+ was, the worse the phonological awareness, rapid naming performance and orthographic awareness were. In short, Chinese dyslexic children were deficient in the activation of the left V5/MT+ and the activity of the magnocellular-dorsal pathway was closely related to orthographic awareness in Chinese pupils.

The influence of temporal asynchrony on character-speech integration in Chinese children with and without dyslexia: An ERP study.

Dyslexic readers have been reported to show abnormal temporal acuity and multisensory integration deficiency. Here, we investigated the influence of temporal intervals on Chinese character-speech integration in children with and without dyslexia. Visual characters were presented synchronously to the onset of speech sounds (AV0) or before speech sound by 300 ms (AV300). Event-related potentials (ERP) evoked by congruent condition (speech sounds presented with congruent Chinese characters) and by baseline condition (speech sounds presented with Korean characters) were compared. Typically developing (TD) children exhibited congruency effect in AV0 condition, whereas dyslexic children exhibited congruency effect in AV300 condition. Moreover, congruency effect in TD children was due to enhanced neural activation to congruent trials, congruency effect in dyslexic children was contributed by neural suppression for baseline trials. These results suggested that different underlying mechanisms were involved in character-speech integration for typical and dyslexic children.

Disruption of Functional Brain Networks Underlies the Handwriting Deficit in Children With Developmental Dyslexia.

Developmental dyslexia (DD) is a neurological-based learning disorder that affects 5-17.5% of children. Handwriting difficulty is a prevailing symptom of dyslexia, but its neural mechanisms remain elusive. Using functional magnetic resonance imaging (fMRI), this study examined functional brain networks associated with handwriting in a copying task in Chinese children with DD (n = 17) and age-matched children (n = 36). We found that dyslexics showed reduced network connectivity between the sensory-motor network (SMN) and the visual network (VN), and between the default mode network (DMN) and the ventral attention network (VAN) during handwriting, but not during drawing geometric figures. Moreover, the connectivity strength of the networks showing group differences was correlated with handwriting speed, reading and working memory, suggesting that the handwriting deficit in DD is linked with disruption of a large-scale brain network supporting motoric, linguistic and executive control processes. Taken together, this study demonstrates the alternations of functional brain networks that underly the handwriting deficit in Chinese dyslexia, providing a new clue for the neural basis of DD.

Spatial and temporal processing difficulties in Chinese children with developmental dyslexia: An ERP study.

Magnocellular (M) deficit theory indicates that individuals with developmental dyslexia (DD) have low sensitivity to stimuli with high temporal frequencies (HTF) and low spatial frequencies (LSF). However, some studies found that temporal processing and spatial processing were correlated with different reading-related skills. Chinese is a logographic language, and visual skills are particularly important for reading in Chinese. It is necessary to investigate the temporal and spatial processing abilities in the M pathway of Chinese children with DD. Using electrophysiological recordings, the present study examined the mean amplitude and latency of P1 during a grating direction judgment task in 13 children with DD and 13 age-matched normal children. Dyslexic children showed a low amplitude and long latency of P1 in the HTF condition and LSF condition compared with age-matched children. In the HTF condition, the amplitude of P1 correlated with phonological awareness, and the latency of P1 correlated with reading fluency and rapid naming of digits. The amplitude of P1 in the LSF condition correlated with reading accuracy. This result suggested that Chinese children with DD had difficulties in both temporal and spatial processing in the M pathway. However, temporal processing and spatial processing played different roles in Chinese reading.

Personality traits modulate the neural responses to handwriting processing.

Handwriting is a vital skill for everyday human activities. It has a wealth of information about writers' characteristics and can hint toward underlying neurological conditions, such as Parkinson's disease, autism, dyslexia, and attention-deficit/hyperactivity disorder (ADHD). Many previous studies have reported a link between personality and individual differences in handwriting, but the evidence for the relationship tends to be anecdotal in nature. Using functional magnetic resonance imaging (fMRI), we examined whether the association between personality traits and handwriting was instantiated at the neural level. Results showed that the personality trait of conscientiousness modulated brain activation in the left premotor cortex and right inferior/middle frontal gyrus, which may reflect the impact of personality on orthography-to-grapheme transformation and executive control involved in handwriting. Such correlations were not observed in symbol-drawing or word-reading tasks, suggesting the specificity of the link between conscientiousness and handwriting in these regions. Moreover, using a connectome-based predictive modeling approach, we found that individuals' conscientiousness scores could be predicted based on handwriting-related functional brain networks, suggesting that the influence of personality on handwriting may occur within a broader network. Our findings provide neural evidence for the link between personality and handwriting processing, extending our understanding of the nature of individual differences in handwriting.

Clinical phenotype of familial amyotrophic lateral sclerosis with SOD1 gene mutation mimicking proximal myopathy: A case report and literature review.

Amyotrophic lateral sclerosis (ALS) is a disorder with strong clinical and genetic heterogeneity, and its pathogenic mechanism has not been completely clarified. Proximal myopathy is rare in clinical manifestations of ALS. Here, we describe a 34-year-old woman with a 1-year history of symmetrical, proximal limb weakness, and muscle atrophy, with slow progression and no upper motor neuron (UMN) signs. The clinical phenotype was similar to myopathy and was initially misdiagnosed as proximal myopathy. Electromyography (EMG) and muscle and nerve biopsy were performed. The genomic DNA from the patient's peripheral blood lymphocytes was analyzed. The EMG and pathologic examinations revealed chronic neurogenic changes and mild mixed peripheral neuropathy. DNA analysis revealed a heterozygous missense mutation in exon 1 at codon 50 (c.50>C) of SOD1, and a heterozygous missense mutation in exon 11 at codon 1013 (c.1013G>A) of CPT1C that has not been reported previously. The patient was diagnosed as familial ALS (FALS) type 1, and the patient had a family history of autosomal dominant (AD) pattern. This report expands the knowledge of the clinical phenotype of FALS. For patients with clinical manifestations mimicking proximal myopathy, the possibility of underlying ALS should be considered.

Chan-Lam Reaction and Lewis Acid Promoted 1,3-Rearrangement of N-O Bonds to Prepare N-(2-Hydroxyaryl)pyridin-2-ones.

We describe the difunctionalization of arylboronic acids to prepare various N-(2-hydroxyaryl)pyridin-2-ones in good yields using N-hydroxypyridin-2-ones as the oxygen and nitrogen sources through a copper(II)-catalyzed Chan-Lam reaction and subsequent BF3-promoted selective 1,3-rearrangement of N-O bond in a one-pot procedure. Mechanistic studies reveal that the 1,3-rearrangement selectivity is controlled by the formation of the key aryloxypyridinium salt. The obtained products are easily converted to various useful pyridin-2-one scaffolds.

Comparative research on neural dysfunction in children with dyslexia under different writing systems: A meta-analysis study.

Developmental dyslexia is a special learning disorder which is prevalent in all languages. A central question in dyslexia is whether the neural mechanism of their defects is universal or distinct in different writing systems. Using meta-analytic approach, we created meta-images using activation abnormalities in Chinese and alphabetic children with dyslexia to find convergence and divergence under different writing systems. The results revealed that dyslexic children have a universal attention-related dysfunction with hypoactivation in the left inferior frontal cortex (IFC) and the anterior cingulate cortex (ACC) under different writing systems, in spite of differences of degree and spatial extent in those regions. Alphabetic dyslexic children additionally showed hypoactivation in the left occipito-temporo-parietal regions. Chinese dyslexic children showed specific hyperactivation in the right postcentral gyrus, the left rectus, and the right middle temporal gyrus. The present meta-analysis for the first time showed both shared and distinct abnormalities in children with dyslexia under Chinese and alphabetic writing systems.

Cholesterol crystals activate NLRP3 inflammasomes and promote gallstone formation by increasing mucin secretion.

Cholesterol crystals participate in cholesterol nucleation; however, the role of cholesterol crystals in gallstone development is unknown. Mucin secretion contributes to increased size of gallstones. Cholesterol crystals activate inflammasomes and participate in many sterile inflammation related human diseases. We investigated the role of cholesterol crystals and mucins in sterile inflammation and gallstone enlargement. We found that expression of mucin 5AC (MUC5AC), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and interleukin-1b (IL-1b) was increased significantly in tissues adjacent to gallstones. Experiments in vitro showed that cholesterol crystals promote MUC5AC secretion; they also increase expression of NLRP3, NLR family CARD domain-containing 4 (NLRC4), apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and cleaved caspase-1 in biliary epithelial cells. Inhibition of Inflammasomes by NLRP3, ASC or caspase-1 small interfering RNAs reduced MUC5AC secretion. Also, the IL-1 receptor antagonist, IL1RA, and caspase-1 inhibitor, Ac-YVAD, both inhibited MUC5AC secretion induced by cholesterol crystals. We found that inflammasome activation participates in cholesterol crystal induced mucin secretion and gallstone development.

The brain basis of handwriting deficits in Chinese children with developmental dyslexia.

Abundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown; however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age-matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory-motor processing (including supplementary motor area and postcentral gyrus) and visual-orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual-orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory-motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual-orthographic processing, and cognitive control, providing important implications for the diagnosis and treatment of dyslexia.

Neuroanatomical correlates of self-awareness of highly practiced visuomotor skills.

Metacognition is the ability to introspect and control ongoing cognitive processes. Despite the extensive investigation of the brain architectures supporting metacognition for perception and memory, little is known about the neural basis of metacognitive capacity for motor function, a vital aspect of human behavior. Here, using functional and structural magnetic resonance imaging (MRI), we examined the brain substrates underlying self-awareness of handwriting, a highly practiced visuomotor skill. Results showed that experienced adult writers generally overestimated their handwriting quality, and such overestimation was more pronounced in men relative to women. Individual variations in self-awareness of handwriting quality were positively correlated with gray matter volume in the left fusiform gyrus, right middle frontal gyrus and right precuneus. The left fusiform gyrus and right middle frontal gyrus are thought to represent domain-specific brain mechanisms for handwriting self-awareness, while the right precuneus that has been reported in other domains likely represents a domain-general brain mechanism for metacognition. Furthermore, the activity of these structurally related regions in a handwriting task was not correlated with self-awareness of handwriting, suggesting the correlation with metacognition was independent of task performance. Together, this study reveals that metacognition for practiced motor skills relies on both domain-general and domain-specific brain systems, extending our understanding about the neural basis of human metacognition.

Functional brain networks underlying automatic and controlled handwriting in Chinese.

This study aimed to identify the functional brain networks underlying the distinctions between automatic and controlled handwriting in Chinese. Network-based analysis was applied to functional magnetic resonance imaging data collected while adult participants performed a copying task under automatic and speed-controlled conditions. We found significant differences between automatic and speed-controlled handwriting in functional connectivity within and between the frontoparietal network, default mode network, dorsal attention network, somatomotor network and visual network; these differences reflect the variations in general attentional control and task-relevant visuomotor operations. However, no differences in brain activation were detected between the two handwriting conditions, suggesting that the reorganization of functional networks, rather than the modulation of local brain activation, underlies the dissociations between automatic and controlled handwriting in Chinese. Our findings illustrate the brain basis of handwriting automaticity, shedding new light on how handwriting automaticity may be disrupted in individuals with neurological disorders.

Auditory processing deficit in individuals with dyslexia: A meta-analysis of mismatch negativity.

Several previous studies have used mismatch negativity (MMN) to examine the auditory processing deficit in individuals with dyslexia. However, researchers have not clearly determined whether the deficit is general or specific and how it potentially changes with age. Meta-analysis was adopted to quantitatively identify the auditory processing deficit in individuals with dyslexia. By analysing 81 results within 25 publications that employed passive oddball paradigms to explore auditory processing in individuals with dyslexia, we identified that MMN impairment in auditory processing of speech was observed in children (Cohen's d = 0.296) and adults with dyslexia (Cohen's d = 0.486). Besides, adults with dyslexia showed atypical auditory processing of non-speech (Cohen's d = 0.409), which appeared to be related to the types of stimuli. Based on these findings, for individuals with dyslexia, the auditory processing deficit in speech will persist into adulthood, and the auditory processing deficit is general in adults with dyslexia. Because few studies used appropriate non-speech stimuli to examine the auditory processing in children with dyslexia, future studies should focus more on this area.

Visual Dysfunction in Chinese Children With Developmental Dyslexia: Magnocellular-Dorsal Pathway Deficit or Noise Exclusion Deficit?

Many studies have suggested that children with developmental dyslexia (DD) not only show phonological deficit but also have difficulties in visual processing, especially in non-alphabetic languages such as Chinese. However, mechanisms underlying this impairment in vision are still unclear. Visual magnocellular deficit theory suggests that the difficulties in the visual processing of dyslexia are caused by the dysfunction of the magnocellular system. However, some researchers have pointed out that previous studies supporting the magnocellular theory did not control for the role of "noise". The visual processing difficulties of dyslexia might be related to the noise exclusion deficit. The present study aims to examine these two possible explanations via two experiments. In experiment 1, we recruited 26 Chinese children with DD and 26 chronological age-matched controls (CA) from grades 3 to 5. We compared the Gabor contrast sensitivity between the two groups in high-noise and low-noise conditions. Results showed a significant between-group difference in contrast sensitivity in only the high-noise condition. In experiment 2, we recruited another 29 DD and 29 CA and compared the coherent motion/form sensitivity in the high- and low-noise conditions. Results also showed that DD exhibited lower coherent motion and form sensitivities than CA in the high-noise condition, whereas no evidence was observed that the group difference was significant in the low-noise condition. These results suggest that Chinese children with dyslexia have noise exclusion deficit, supporting the noise exclusion hypothesis. The present study provides evidence for revealing the visual dysfunction of dyslexia from the Chinese perspective. The nature of the perceptual noise exclusion and the relationship between the two theoretical hypotheses are discussed.