The language network of the human brain has core components in the inferior frontal cortex and superior/middle temporal cortex, with left-hemisphere dominance in most people. Functional specialization and interconnectivity of these neocortical regions is likely to be reflected in their molecular and cellular profiles. Excitatory connections between cortical regions arise and innervate according to layer-specific patterns. Here, we generated a gene expression dataset from human postmortem cortical tissue samples from core language network regions, using spatial transcriptomics to discriminate gene expression across cortical layers. Integration of these data with existing single-cell expression data identified 56 genes that showed differences in laminar expression profiles between the frontal and temporal language cortex together with upregulation in layer II/III and/or layer V/VI excitatory neurons. Based on data from large-scale genome-wide screening in the population, DNA variants within these 56 genes showed set-level associations with interindividual variation in structural connectivity between the left-hemisphere frontal and temporal language cortex, and with the brain-related disorders dyslexia and schizophrenia which often involve affected language. These findings identify region-specific patterns of laminar gene expression as a feature of the brain\'s language network.

BACKGROUND: Developmental dyslexia, a complex neurodevelopmental disorder, not only affects children\'s academic performance but is also associated with increased healthcare costs, lower employment rates, and reduced productivity. The pathogenesis of dyslexia remains unclear and it is generally considered to be caused by the overlap of genetic and environmental factors. Systematically exploring the close relationship between exposure to environmental compounds and susceptibility genes in the development of dyslexia is currently lacking but high necessary.
METHODS: In this study, we systematically compiled 131 publicly reported susceptibility genes for dyslexia sourced from DisGeNET, OMIM, and GeneCards databases. Comparative Toxicogenomics Database database was used to explore the overlap between susceptibility genes and 95 environmental compounds, including metals, persistent organic pollutants, polycyclic aromatic hydrocarbons, and pesticides. Chemical bias towards the dyslexia risk genes was taken into account in the observation/expectation ratios > 1 and the corresponding P value obtained by hypergeometric probability test.
RESULTS: Our study found that the number of dyslexia risk genes targeted by each chemical varied from 1 to 109. A total of 35 chemicals were involved in chemical reactions with dyslexia-associated genes, with significant enrichment values (observed/expected dyslexia risk genes) ranging from 1.147 (Atrazine) to 66.901 (Dibenzo(a, h)pyrene).
CONCLUSIONS: The results indicated that dyslexia-associated genes were implicated in certain chemical reactions. However, these findings are exploratory, and further research involving animal or cellular experiments is needed.

BACKGROUND: Morphological awareness (MA) deficit is strongly associated with Chinese developmental dyslexia (DD). However, little is known about the white matter substrates underlying the MA deficit in Chinese children with DD.
METHODS: In the current study, 34 Chinese children with DD and 42 typical developmental (TD) children were recruited to complete a diffusion magnetic resonance imaging scan and cognitive tests for MA. We conducted linear regression to test the correlation between MA and DTI metrics, the structural abnormalities of the tracts related to MA, and the interaction effect of DTI metrics by group on MA.
RESULTS: First, MA was significant related to the right inferior occipito-frontal fascicle (IFO) and inferior longitudinal fsciculus (ILF), the bilateral thalamo-occipital (T_OCC) and the left arcuate fasciculus (AF); second, compared to TD children, Chinese children with DD had lower axial diffusivity (AD) in the right IFO and T_OCC; third, there were significant interactions between metrics (fractional anisotropy (FA) and radial diffusivity (RD)) of the right IFO and MA in groups. The FA and RD of the right IFO were significantly associated with MA in children with DD but not in TD children.
CONCLUSIONS: In conclusion, compared to TD children, Chinese children with DD had axonal degeneration not only in the ventral tract (the right IFO) but also the visuospatial tract (the right T_OCC) which were associated with their MA deficit. And Chinese MA involved not only the ventral tracts, but also the visuospatial pathway and dorsal tracts.

UNASSIGNED: Despite an increasing amount of research on the relationship between parenting styles and neurodevelopmental disorders, there has been minimal focus on how parenting styles impact children\'s reading abilities. The aim of this study was to investigate the potential mediating role of the home literacy environment in the connection between parenting styles and dyslexia.
UNASSIGNED: A total of 212 primary school students from grade 2-5 were recruited for this study. The Chinese Reading Ability Test was used to screen children with dyslexia. The home literacy environment was evaluated using a structured questionnaire that measured the frequency and quality of reading-related activities between parents and children. Egna Minnen Beträffande Uppfostran questionnaire was used to assess the parenting style, including emotional warmth, rejection, overprotection, and anxious rearing. It is a self-report tool filled out by the children themselves, used to assess their perceptions of their parents\' parenting styles. The structural equation modeling was carried out to evaluate the direct, indirect, and total effects of parenting styles on dyslexia.
UNASSIGNED: Compared to control group, male children with dyslexia had lower scores in parenting styles characterized by emotional warmth, overprotecting and anxious rearing (p < 0.05), while female children with dyslexia only showed lower scores in anxious rearing (p < 0.05). Children with dyslexia lacked regular reading time (OR = 2.69, 95%CI: 1.04-6.97, p < 0.05), and have higher homework pressure compared to normal children (OR = 7.41, 95%CI: 1.45-37.82, p < 0.05). Additionally, emotional warmth, paternal overprotection and anxious rearing were negatively associated with dyslexia in children (all p < 0.05). Our findings indicate a strong correlation between dyslexia, home literacy environment, and parenting styles. In a structural equation model, the home literacy environment was identified as an independent mediator between parenting styles and dyslexia. The total effect of parenting styles on dyslexia is 0.55, with an indirect effect of 0.68 mediated by the home literacy environment.
UNASSIGNED: The findings of this study indicate that home literacy environment serves as a mediator between parenting styles and dyslexia in children. This study highlights how parenting styles influence dyslexia, offering key insights for aiding dyslexic children and guiding effective interventions.

UNASSIGNED: We examined the neurocognitive bases of lexical morphology in children of varied reading abilities to understand the role of meaning-based skills in learning to read with dyslexia.
UNASSIGNED: Children completed auditory morphological and phonological awareness tasks during functional near-infrared spectroscopy neuroimaging. We first examined the relation between lexical morphology and phonological processes in typically developing readers (Study 1, N = 66, Mage = 8.39), followed by a more focal inquiry into lexical morphology processes in dyslexia (Study 2, N = 50, Mage = 8.62).
UNASSIGNED: Typical readers exhibited stronger engagement of language neurocircuitry during the morphology task relative to the phonology task, suggesting that morphological analyses involve synthesizing multiple components of sublexical processing. This effect was stronger for more analytically complex derivational affixes (like + ly) than more semantically transparent free base morphemes (snow + man). In contrast, children with dyslexia exhibited stronger activation during the free base condition relative to derivational affix condition. Taken together, the findings suggest that although children with dyslexia may struggle with derivational morphology, they may also use free base morphemes\' semantic information to boost word recognition.
UNASSIGNED: This study informs literacy theories by identifying an interaction between reading ability, word structure, and how the developing brain learns to recognize words in speech and print.
UNASSIGNED: https://doi.org/10.23641/asha.25944949.

Different tasks have been used in examining the neural functional differences associated with developmental dyslexia (DD), and consequently, different findings have been reported. However, very few studies have systematically compared multiple tasks in understanding what specific task differences each brain region is associated with. In this study, we employed an auditory rhyming task, a visual rhyming task, and a visual spelling task, in order to investigate shared and task-specific neural differences in Chinese children with DD. First, we found that children with DD had reduced activation in the opercular part of the left inferior frontal gyrus (IFG) only in the two rhyming tasks, suggesting impaired phonological analysis. Children with DD showed functional differences in the right lingual gyrus/inferior occipital gyrus only in the two visual tasks, suggesting deficiency in their visuo-orthographic processing. Moreover, children with DD showed reduced activation in the left dorsal inferior frontal gyrus and increased activation in the right precentral gyrus across all of the three tasks, suggesting neural signatures of DD in Chinese. In summary, our study successfully separated brain regions associated with differences in orthographic processing, phonological processing, and general lexical processing in DD. It advances our understanding about the neural mechanisms of DD.

Objective: To explore the optimization of the standardized assessment tool for clinical diagnosis of Chinese developmental dyslexia (DD). Methods: A cross-sectional study was conducted from May to December 2023, in which 130 primary school children in grades 1 to 3 with clinical signs of literacy lag and positive screening results on the screening scales were recruited from the outpatient clinic of Child Health Care Medical Division, Shanghai Children\'s Hospital, Shanghai Jiao Tong University School of Medicine. Chinese dyslexia screening behavior checklist for primary students (CDSBC) was used as the screening scales, and supplemented by dyslexia checklist for Chinese children. Referring to the standard procedure of the\"expert advice on diagnosis and intervention of Chinese developmental dyslexia\", the developmental dyslexia scale for standard mandarin (DDSSM) was used to evaluate the children\'s literacy-related cognitive abilities and conduct the diagnostic assessment, and divided the children into learning backward group and the DD group. The t-test and χ2 test were used to compare the differences in the distribution of intelligence, literacy and attention deficit hyperactivity disorder between the two groups. Spearman\'s correlation was used to analyze the correlation between the scores for each cognitive ability in the DDSSM and the CDSBC. Results: Of the 130 children, 90 were male, aged (8.3±1.0) years; 40 were female, aged (8.1±0.9) years. A final diagnosis of DD was made in 59 cases, of which 41 were males. There was no statistically significant difference in operational intelligence quotient (101±15 vs.100±15, t=0.53, P>0.05) and statistically significant difference in literacy of DDSSM (32±5 vs.21±4, t=11.56, P<0.001) between the learning backward group and the DD group. Eighteen cases (25.4%) of the learning backward group were children with attention deficit subtype attention deficit hyperactivity disorder (ADHD-I), and 16 cases (27.1%) in DD group, the difference in incidence between the two groups was not statistically significant (χ2=0.05, P>0.05). There were correlations between the DDSSM (for oral vocabulary, morphological awareness and orthographic awareness) and the CDSBC total score (r=-0.42, -0.32, -0.35, all P<0.01), but the correlations for visuospatial perception and rapid automatized naming with CDSBC total score were not statistically significant (r=-0.09 and -0.20,both P>0.05). Conclusion: For literacy-related cognitive abilities, screening scales CDSBC are not sufficiently useful for assessment, so the introduction of standardized assessment tools DDSSM is an optimization of the clinical diagnosis of Chinese DD, which is crucial for achieving accurate diagnosis and intervention.
目的： 探讨引入标准化评估工具对汉语发展性阅读障碍（DD）临床诊断的优化作用。 方法： 采用横断面研究，于2023年5至12月从上海交通大学医学院附属儿童医院儿童保健科门诊招募130名存在语文成绩明显落后临床表现且筛查性量表筛查阳性的小学一至三年级儿童作为研究对象。筛查性量表采用中国小学生阅读障碍行为筛查量表（CDSBC），以儿童汉语阅读障碍筛查量表作为辅助。参照“汉语发展性阅读障碍诊断与干预的专家意见”的标准流程，对研究对象使用现代汉语发展性读写障碍评估工具（DDSSM）进行读写相关认知能力评价及诊断性评估，分为学习落后表现组和DD组。采用t检验和χ2检验对比两组在智力、读写能力和注意缺陷多动障碍分布方面的差异。采用Spearman相关性分析分析DDSSM中各项认知能力得分与CDSBC得分的相关性。 结果： 130名研究对象中男90名，年龄（8.3±1.0）岁；女40名，年龄（8.1±0.9）岁。最终诊断DD 59例，其中男41例。学习落后表现组与DD组的操作智商差异无统计学意义（101±15比100±15，t=0.53，P>0.05），DDSSM中字词读写能力差异有统计学意义（32±5比21±4，t=11.56，P<0.001）。学习落后表现组（71名）和DD组注意缺陷亚型注意缺陷多动障碍发生率差异无统计学意义［18名（25.4%）比16例（27.1%），χ2=0.05，P>0.05］。DDSSM中口语词汇量、语素意识和正字法意识与CDSBC总分均负相关（r=-0.42、-0.32、-0.35，均P<0.01），但视觉空间知觉和快速自动化命名与CDSBC总分的相关性均无统计学意义（r=-0.09、-0.20，均P>0.05）。 结论： 针对读写相关认知能力，CDSBC的评估作用不足，因此引入标准化DDSSM是对汉语DD临床诊断的优化，对实现精准诊断和干预具有至关重要的作用。.

Reading disorders (RD) are human-specific neuropsychological conditions associated with decoding printed words and/or reading comprehension. So far only a handful of candidate genes segregated in families and 42 loci from genome-wide association study (GWAS) have been identified that jointly provided little clues of pathophysiology. Leveraging human-specific genomic information, we critically assessed the RD candidates for the first time and found substantial human-specific features within. The GWAS candidates (i.e., population signals) were distinct from the familial counterparts and were more likely pleiotropic in neuropsychiatric traits and to harbor human-specific regulatory elements (HSREs). Candidate genes associated with human cortical morphology indeed showed human-specific expression in adult brain cortices, particularly in neuroglia likely regulated by HSREs. Expression levels of candidate genes across human brain developmental stages showed a clear pattern of uplifted expression in early brain development crucial to RD development. Following the new insights and loci pleiotropic in cognitive traits, we identified four novel genes from the GWAS sub-significant associations (i.e., FOXO3, MAPT, KMT2E and HTT) and the Semaphorin gene family with functional priors (i.e., SEMA3A, SEMA3E and SEMA5B). These novel genes were related to neuronal plasticity and disorders, mostly conserved the pattern of uplifted expression in early brain development and had evident expression in cortical neuroglial cells. Our findings jointly illuminated the association of RD with neuroglia regulation-an emerging hotspot in studying neurodevelopmental disorders, and highlighted the need of improving RD phenotyping to avoid jeopardizing future genetic studies of RD.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are ubiquitous in the environment, and all of them can cause neurotoxicity. However, the association between BTEX exposure and dyslexia, a disorder with language network-related regions in left hemisphere affected, remains unclear. We aimed to assess the relationship between BTEX exposure and dyslexic odds among school-aged children. A case-control study, including 355 dyslexics and 390 controls from three cities in China, was conducted. Six BTEX metabolites were measured in their urine samples. Logistic regression model was used to explore the association between the BTEX metabolites and the dyslexic odds. Urinary trans,trans-muconic acid (MU: a metabolite of benzene) was significantly associated with an increased dyslexic odds [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.01, 1.50], and the adjusted OR of the dyslexic odds in the third tertile was 1.72 (95% CI: 1.06, 2.77) compared to that in the lowest tertile regarding urinary MU concentration. Furthermore, the association between urinary MU level and the dyslexic odds was more pronounced among children from low-income families based on stratified analyses. Urinary metabolite levels of toluene, ethylbenzene, and xylene were not found to be associated with the dyslexic odds. In summary, elevated MU concentrations may be associated with an increased dyslexic odds. We should take measures to reduce MU related exposure among children, particularly those with low family income.

Previous studies have shown associations between children\'s exposure to phthalates and neurodevelopmental disorders. Whereas the impact of exposure to phthalate alternatives is understudied. This study aimed to evaluate the association of exposure to phthalates/their alternatives with the risk of dyslexia. We recruited 745 children (355 dyslexia and 390 non-dyslexia) via the Tongji Reading Environment and Dyslexia Research Project, and their urine samples were collected. A total of 26 metabolites of phthalates/their alternatives were measured. Multivariate logistic regression and quantile-based g-computation were used to estimate the associations of exposure to the phthalates/their alternatives with dyslexia. More than 80% of the children had 17 related metabolites detected in their urine samples. After adjustment, the association between mono-2-(propyl-6-hydroxy-heptyl) phthalate (OH-MPHP) with the risk of dyslexia was observed. Compared with the lowest quartile of OH-MPHP levels, the odds of dyslexia for the third quartile was 1.93 (95% CI 1.06, 3.57). Regarding mixture analyses, it was found that OH-MPHP contributed the most to the association. Further analyses stratified by sex revealed that this association was only observed in boys. Our results suggested a significantly adverse association of di-2-propylheptyl phthalate exposure with children\'s language abilities. It highlights the necessity to prioritize the protection of children\'s neurodevelopment by minimizing their exposure to endocrine-disrupting chemicals like di-2-propylheptyl phthalate.