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.

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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.

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.

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.

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.

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.

Men and women differ in the neural basis of handwriting.

There is an ongoing debate about whether, and to what extent, males differ from females in their language skills. In the case of handwriting, a composite language skill involving language and motor processes, behavioral observations consistently show robust sex differences but the mechanisms underlying the effect are unclear. Using functional magnetic resonance imaging (fMRI) in a copying task, the present study examined the neural basis of sex differences in handwriting in 53 healthy adults (ages 19-28, 27 males). Compared to females, males showed increased activation in the left posterior middle frontal gyrus (Exner's area), a region thought to support the conversion between orthographic and graphomotor codes. Functional connectivity between Exner's area and the right cerebellum was greater in males than in females. Furthermore, sex differences in brain activity related to handwriting were independent of language material. This study identifies a novel neural signature of sex differences in a hallmark of human behavior, and highlights the importance of considering sex as a factor in scientific research and clinical applications involving handwriting.

Nickel(II)-Catalyzed [5 + 1] Annulation of 2-Carbonyl-1-propargylindoles with Hydroxylamine To Synthesize Pyrazino[1,2-a]indole-2-oxides in Water.

An atom-economical and practical method for the efficient synthesis of various pyrazino[1,2-a]indole-2-oxides was developed through a nickel(II)-catalyzed [5 + 1] annulation of 2-carbonyl-1-propargylindoles with hydroxylamine in water without using an organic solvent. The reaction involved an initial condensation of 2-carbonyl-1-propargylindoles with hydroxylamine to afford oxime intermediates, which then underwent a nickel(II)-catalyzed 6-exo-dig cyclization. Preliminary studies showed that (n-Bu)4NI served as a phase transfer catalyst and promoted the formation of active nickel(II) species. More importantly, the nickel(II) salt and phase transfer catalyst-in-water could be recycled seven times, and a gram scalable product was easily obtained in good yields through a filtration and washing protocol.

Development of neural basis for chinese orthographic neighborhood size effect.

The brain activity of orthographic neighborhood size (N size) effect in Chinese character naming has been studied in adults, meanwhile behavioral studies have revealed a developmental trend of Chinese N-size effect in developing readers. However, it is unclear whether and how the neural mechanism of N-size effect changes in Chinese children along with development. Here we address this issue using functional magnetic resonance imaging. Forty-four students from the 3(rd) , 5(th) , and 7(th) grades were scanned during silent naming of Chinese characters. After scanning, all participants took part in an overt naming test outside the scanner, and results of the naming task showed that the 3(rd) graders named characters from large neighborhoods faster than those from small neighborhoods, revealing a facilitatory N-size effect; the 5(th) graders showed null N-size effect while the 7(th) graders showed an inhibitory N-size effect. Neuroimaging results revealed that only the 3(rd) graders exhibited a significant N-size effect in the left middle occipital activity, with greater activation for large N-size characters. Results of 5(th) and 7(th) graders showed significant N-size effects in the left middle frontal gyrus, in which 5(th) graders induced greater activation in large N-size condition than in small N-size condition, while 7(th) graders exhibited an opposite effect which was similar to the adult pattern reported in a previous study. The current findings suggested the transition from broadly tuned to finely tuned orthographic representation with reading development, and the inhibition from neighbors' phonology for higher graders. Hum Brain Mapp 37:632-647, 2016. © 2015 Wiley Periodicals, Inc.

Synthesis of N-(2-Hydroxyaryl)benzotriazoles via Metal-Free O-Arylation and N-O Bond Cleavage.

A metal-free method for synthesis of N-(2-hydroxyaryl)benzotriazoles via O-arylation of N-hydroxybenzotriazoles with readily available diaryliodonium salts and sequential N-O bond cleavage under mild conditions has been developed. The [3,3]-rearrangement of N-O bond cleavage could take place on the N instead of C atom. The reaction was compatible with diverse functional groups and a new type of P,N-ligand was synthesized in three steps.

Verbal Short-Term Memory Deficits in Chinese Children with Dyslexia may not be a Problem with the Activation of Phonological Representations.

This study explored the underlying mechanism of the verbal short-term memory deficit in Chinese children with developmental dyslexia. Twenty-four children with dyslexia and 28 age-matched normal readers participated in the study. They were required to memorize a visually presented series of six Chinese characters and identify them from a list also including code-specific distracters and non-code-specific distracters. Error rates were recorded and were higher for code-specific distracters in all three conditions, revealing phonological, visual, and semantic similarity effects respectively. Group comparisons showed a stronger phonological similarity effect in dyslexic group, suggesting intact activation of phonological representations of target characters. Children with dyslexia also exhibited a greater semantic similarity effect, revealing stronger activation of semantic representations, while visual similarity effects were equivalent to controls. These results suggest that the verbal short-term memory deficit in Chinese dyslexics might not stem from insufficient activation of phonological information. Based the semantic activation of target characters in dyslexics is greater than in controls, it is possible that the memory deficit of dyslexia is related with deficient inhibition of target semantic representations in short-term memory.

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.

Evidence for cerebellar dysfunction in Chinese children with developmental dyslexia: an fMRI study.

Numerous studies reported that developmental dyslexia in alphabetic languages was associated with a wide range of sensorimotor deficits, including balance, motor skill and time estimation, explained by skill automatization deficit hypothesis. Neural correlates of skill automatization deficit point to cerebellar dysfunction. Recently, a behavioral study revealed an implicit motor learning deficit in Chinese children with developmental dyslexia in their left hands, indicating left cerebellar dysfunction. Using functional magnetic resonance imaging (fMRI), our study examined the brain activation during implicit motor learning in 9 Chinese dyslexic and 12 age-matched children. Dyslexic children showed abnormal activations in the left cerebellum, left middle/medial temporal lobe and right thalamus compared with age-matched children during implicit motor learning. These findings provide evidence of cerebellar abnormality in Chinese dyslexic people. Furthermore, dysfunction of the left cerebellum in Chinese dyslexia is inconsistent with the right cerebellum abnormalities that were reported by studies on alphabetic-language dyslexia, suggesting that neurobiological abnormalities of impaired reading are probably language specific.

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.

Neural basis of phonological processing in second language reading: an fMRI study of Chinese regularity effect.

The present study examined the neural basis of phonological processing in Chinese later acquired as a second language (L2). The regularity effect of Chinese was selected to elucidate the addressed phonological processing. We recruited a group of alphabetic language speakers who had been learning Chinese as L2 for at least one year, and a control group of native Chinese speakers. Participants from both groups exhibited a regularity effect in a pilot behavioral test. Neuroimaging results revealed that L2 learners exhibited stronger activation than native Chinese speakers in the right occipitotemporal region (i.e. right lingual gyrus and right fusiform gyrus). Moreover, L2 learners exhibited greater activations in the ventral aspects of the left inferior parietal lobule (LIPL) and the left inferior frontal gyrus (LIFG) for irregular character reading minus regular character reading. In contrast, native Chinese speakers exhibited more dorsal activations in the LIPL and LIFG. According to the "accommodation/assimilation" hypothesis of second language reading, the current findings suggest that native speakers of alphabetic languages utilized an accommodation pattern for the specific requirements of the visual form of Chinese characters, and an assimilation pattern for orthography-to-phonology transformation in Chinese reading.

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.

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.

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.