RESUMO
AIMS: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro-micro-molecular perspective from in vivo neuroimaging data. METHODS: The "ADHD-200 initiative" repository provided multi-site high-quality resting-state functional connectivity (rsfc-) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient-transcriptional signatures of AHBA enrichment and meta-analytic decoding. RESULTS: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition-involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5-HT2A receptors (all pBH <0.01) and co-varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient-transcriptional variants indicated the risk of both cell-specific and chromosome- dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). CONCLUSIONS: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5-HT systems as well brain-derived enrichment of specific cellular/chromosomal expressions.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Conectoma , Transcriptoma , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Criança , Masculino , Feminino , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Córtex Cerebral/patologia , Adolescente , Neurotransmissores/metabolismoRESUMO
Pentatricopeptide repeat (PPR) proteins were identified as site-specific recognition factors for RNA editing in plant mitochondria and plastids. In this study, we characterized maize (Zea mays) kernel mutant defective kernel 53 (dek53), which has an embryo lethal and collapsed endosperm phenotype. Dek53 encodes an E-subgroup PPR protein, which possesses a short PLS repeat region of only seven repeats. Subcellular localization analysis indicated that DEK53 is localized in the mitochondrion. Strand- and transcript-specific RNA-seq analysis showed that the dek53 mutation affected C-to-U RNA editing at more than 60 mitochondrial C targets. Biochemical analysis of mitochondrial protein complexes revealed a significant reduction in the assembly of mitochondrial complex III in dek53. Transmission electron microscopic examination showed severe morphological defects of mitochondria in dek53 endosperm cells. In addition, yeast two-hybrid and luciferase complementation imaging assays indicated that DEK53 can interact with the mitochondrion-targeted non-PPR RNA editing factor ZmMORF1, suggesting that DEK53 might be a functional component of the organellar RNA editosome.
Assuntos
Regulação da Expressão Gênica de Plantas , Zea mays , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Mitocondrial , Sementes/genética , Sementes/metabolismo , Zea mays/genética , Zea mays/metabolismoRESUMO
Procrastination has adverse effects on personal growth and social development. Behavior research has found reward sensitivity is positively correlated with procrastination. However, it remains unclear that the neural substrates underlie the relationship between reward sensitivity and procrastination. To address this issue, the present study used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analyses to investigate the neural substrates underlying the association with reward sensitivity and procrastination in two independent samples (N1 = 388, N2 = 330). In Sample 1, the behavioral result indicated reward sensitivity was positively correlated with procrastination. Moreover, the VBM analysis showed that reward sensitivity was positively associated with the gray matter volume (GMV) of the right parahippocampal gyrus. Furthermore, the RSFC result found reward sensitivity was negatively associated with the functional connectivity of the right parahippocampal gyrus-precuneus. Crucially, the mediation analysis revealed that functional connectivity of the right parahippocampal gyrus-precuneus mediated the relationship between reward sensitivity and procrastination. To verify the robustness of the results, confirmatory analysis was carried out in Sample 2. The results of Sample 1 (i.e., the behavioral, VBM, RSFC, and mediation results) can be verified in Sample 2. In brief, these findings suggested that the functional connectivity of the right parahippocampal gyrus-precuneus involved in reward impulsive control could modulate the relationship between reward sensitivity and procrastination, which is the first to reveal the neural underpinning of the association between reward sensitivity and procrastination.
Assuntos
Córtex Pré-Frontal , Procrastinação , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Giro Para-Hipocampal/diagnóstico por imagem , Substância Cinzenta , Lobo Parietal/diagnóstico por imagemRESUMO
Procrastination has adverse consequences across cultural contexts. Behavioral research found a positive correlation between punishment sensitivity and procrastination. However, little is known about the neural substrates underlying the association between them. We employed voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) methods to address this issue with two independent samples. In Sample 1, behavioral results found that punishment sensitivity was positively related to procrastination. The VBM analysis showed that punishment sensitivity was negatively correlated with gray matter volume in left putamen. Subsequently, the RSFC results revealed that left putamen - left middle temporal gyrus (MTG) connectivity was positively associated with punishment sensitivity. More crucially, mediation analysis indicated that left putamen - left MTG connectivity mediated the relationship between punishment sensitivity and procrastination. The aforementioned results were validated in Sample 2. Altogether, left putamen - left MTG connectivity might be the neural signature of the association between punishment sensitivity and procrastination.
Assuntos
Mapeamento Encefálico , Procrastinação , Mapeamento Encefálico/métodos , Putamen/diagnóstico por imagem , Punição , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta , Lobo Temporal/diagnóstico por imagemRESUMO
Effective behavior monitoring, including internal monitoring/error detection and external monitoring/feedback, is very pivotal for reinforcement learning. However, less attention has been paid to internal monitoring and the dynamic learning performance in reinforcement learning, and there is still a heated debate on which kind of external feedback is relied on in the reinforcement learning. In order to address these questions, an adaption probabilistic selection task was used to examine the effect of the internal monitoring, external feedback and the relationship between them for approach learners and avoidance learners during dynamic learning process of reinforcement learning and behavior adaption. Error-related negativity (ERN), feedback-related negativity (FRN) and feedback-related P300 are three ERPs components, which can be used as the indexes of internal monitoring, external feedback and behavior adaption. For our results, the ERN effect of avoidance learners become large in block 3, which is earlier than approach learners (block 4). This phenomenon suggests that avoidance learners learned faster than approach learners. In addition, the FRN amplitude of avoidance learners in block 4 was significantly smaller than the other three blocks. The aforementioned results demonstrated a tradeoff relationship between the ERN and FRN effects.