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Attending to heartbeats for interoceptive awareness initiates distinct electrophysiological responses synchronized with the R-peaks of an electrocardiogram (ECG), such as the heartbeat-evoked potential (HEP). Beyond HEP, this study proposes heartbeat-related spectral perturbation (HRSP), a time-frequency map of the R-peak locked electroencephalogram (EEG), and explores its characteristics in identifying interoceptive attention states using a classification approach. HRSPs of EEG brain components specified by independent component analysis (ICA) were used for the offline and online classification of interoceptive states. A convolutional neural network (CNN) designed specifically for HRSP was applied to publicly available data from a binary-state experiment (attending to self-heartbeats and white noise) and data from our four-state classification experiment (attending to self-heartbeats, white noise, time passage, and toe) with diverse input feature conditions of HRSP. From the dynamic state perspective, we evaluated the primary frequency bands of HRSP and the minimal number of averaging epochs required to reflect changing interoceptive attention states without compromising accuracy. We also assessed the utility of group ICA and models for classifying HRSP in new participants. The CNN for trial-by-trial HRSP with actual R-peaks demonstrated significantly higher classification accuracy than HRSP with sham, i.e., randomly positioned, R-peaks. Gradient-weighted class activation mapping highlighted the prominent role of theta and alpha bands between 200-600 ms post-R-peak-features absent in classifications using sham HRSPs. Online classification benefits from employing a group ICA and classification model, ensuring reliable accuracy without individual EEG precollection. These results suggest HRSP's potential to reflect interoceptive attention states, proposing transformative implications for clinical applications.
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In this research, we employed functional magnetic resonance imaging (fMRI) to examine the neurological basis for understanding wh-questions in wh-in-situ languages such as Korean, where wh-elements maintain their original positions instead of moving explicitly within the sentence. Our hypothesis centered on the role of the salience and attention network in comprehending wh-questions in wh-in-situ languages, such as the discernment of wh-elements, the demarcation between interrogative types, and the allocation of cognitive resources towards essential constituents vis-à-vis subordinate elements in order to capture the speaker's communicative intent. We explored subject and object wh-questions and scrambled wh-questions, contrasting them with yes/no questions in Korean. Increased activation was observed in the left anterior insula and bilateral frontal operculum, irrespective of the wh-position or scrambling of wh-element. These results suggest the interaction between the salience and attentional system and the syntactic linguistic system, particularly the left anterior insula and bilateral frontal operculum, in comprehending wh-questions in wh-in-situ languages.
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Compreensão , Idioma , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Compreensão/fisiologia , Adulto , Adulto Jovem , Mapeamento Encefálico , Lobo Frontal/fisiologia , Lobo Frontal/diagnóstico por imagem , República da Coreia , Córtex Insular/fisiologia , Córtex Insular/diagnóstico por imagemRESUMO
The current study investigates the neural correlates when processing prototypicality and simplicity-affecting the preference of product design. Despite its significance, not much is known about how our brain processes these visual qualities of design when forming design preferences. We posit that, although fluency is the perceptual judgment accounting for the positive effects of both prototypicality and simplicity on design preference, the neural substrates for the fluency judgment associated with prototypicality would differ from those associated with simplicity. To investigate these issues, we conducted an fMRI study of preference decisions for actual product designs with different levels of prototypicality and simplicity. The results show a significant functional gradient between the preference processing of simplicity and prototypicality-i.e., involvement of the early ventral stream of visual information processing for simplicity evaluation but recruitment of the late ventral stream and parietal-frontal brain regions for prototypicality evaluation. The interaction between the simplicity and prototypicality evaluations was found in the extrastriate cortex in the right hemisphere. The segregated brain involvements suggest that the fluency judgment for prototypicality and simplicity contribute to preference choice in different levels of cognitive hierarchy in the perceptual mechanism of the design preference.
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Cognição , Percepção Visual , Lobo Parietal , Encéfalo , Julgamento , Mapeamento Encefálico , Imageamento por Ressonância MagnéticaRESUMO
Previous studies have reported that collagen tripeptide (CTP) derived from collagen hydrolysate has various beneficial effects on health by protecting against skin aging and improving bone formation and cartilage regeneration. Collagen-Tripep20TM (CTP20), which is a low-molecular-weight CTP derived from fish skin, contains a bioactive CTP, Gly-Pro-Hyp >3.2% with a tripeptide content >20%. Herein, we investigated the osteogenic effects and mechanisms of CTP20 (<500 Da) on MG-63 osteoblast-like cells and SW1353 chondrocytes. And we measured promoting ratio of the longitudinal bone growth in childhood rats. First, CTP20 at 100 µg/mL elevated the proliferation (15.0% and 28.2%), alkaline phosphatase activity (29.3% and 32.0%), collagen synthesis (1.25- and 1.14-fold), and calcium deposition (1.18- and 1.15-fold) in MG-63 cells and SW1353, respectively. In addition, we found that CTP20 could promote the longitudinal growth and height of the growth plate of the tibia in childhood rats. CTP20 enhanced the protein expression of insulin-like growth factor-1 (IGF-1) in MG-63 and SW1353 cells, and in the growth plate of childhood rats, along with Janus Kinase 2, and signal transducer and activator of transcription 5 activation in MG-63 and SW1353 cells. CTP20 also elevated the expression levels of bone morphogenetic proteins (BMPs) in MG-63 and SW1353 cells and in the growth plates of childhood rats. These results indicate that CTP20 may promote the endochondral ossification and longitudinal bone growth, through enhancing of IGF-1 and BMPs. (Clinical Trial Registration number: smecae 19-09-01).
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Desenvolvimento Ósseo , Fator de Crescimento Insulin-Like I , Humanos , Ratos , Animais , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/farmacologia , Osteogênese , Colágeno/farmacologiaRESUMO
Artificial intelligence (AI) using deep learning approaches the capabilities of human experts in medical image diagnosis. However, due to liability issues in medical decisions, AI is often relegated to an assistant role. Based on this responsibility constraint, the effective use of AI to assist human intelligence in real-world clinics remains a challenge. Given the significant inter-individual variations in clinical decisions among physicians based on their expertise, AI needs to adapt to individual experts, complementing weaknesses and enhancing strengths. For this adaptation, AI should not only acquire domain knowledge but also understand the specific human experts it assists. This study introduces a meta-model for human-machine cooperation that first evaluates each expert's class-specific diagnostic tendencies using conditional probability, based on which the meta-model adjusts the AI's predictions. This meta-model was applied to ear disease diagnosis using otoendoscopy, highlighting improved performance when incorporating individual diagnostic characteristics, even with limited evaluation data. The highest accuracy was achieved by combining each expert's conditional probabilities with machine classification probability, using optimal weights specific to each individual's overall classification accuracy. This tailored model aims to mitigate potential misjudgments due to psychological effects caused by machine suggestions and to capitalize on the unique expertise of individual clinicians.
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Inteligência Artificial , Médicos , Humanos , Inteligência , Conhecimento , ProbabilidadeRESUMO
The speed-accuracy tradeoff (SAT) often makes psychophysical data difficult to interpret. Accordingly, the SAT experimental procedure and model were proposed for an integrated account of the speed and accuracy of responses. However, the extensive data collection for a SAT experiment has blocked its popularity. For a quick estimation of SAT function (SATf), we previously developed a Bayesian adaptive SAT method, including an online stimulus selection strategy. By simulations, the method was proved efficient with high accuracy and precision with minimal trials, adequate for practically applying a single condition task. However, it calls for extensions to more general designs with multiple conditions and should be revised to achieve improved estimation performance. It also demands real experimental validation with human participants. In the current study, we suggested an improved method to measure SATfs for multiple task conditions concurrently and to enhance robustness in general designs. The performance was evaluated with simulation studies and a psychophysical experiment using a flanker task. Simulation results revealed that the proposed method with the adaptive stimulus selection strategy efficiently estimated multiple SATfs and improved performance even for cases with an extreme parameter value. In the psychophysical experiment, SATfs estimated by minimal adaptive trials (1/8 of conventional trials) showed high agreement with those by conventional trials required for reliably estimating multiple SATfs. These results indicate that the Bayesian adaptive SAT method is reliable and efficient in estimating SATfs in most experimental settings and may apply to SATf estimation in general behavioral research designs.
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The hierarchical characteristics of the brain are prominent in the pharmacological treatment of psychiatric diseases, primarily targeting cellular receptors that extend upward to intrinsic connectivity within a region, interregional connectivity, and, consequently, clinical observations such as an electroencephalogram (EEG). To understand the long-term effects of neuropharmacological intervention on neurobiological properties at different hierarchical levels, we explored long-term changes in neurobiological parameters of an N-methyl-D-aspartate canonical microcircuit model (CMM-NMDA) in the default mode network (DMN) and auditory hallucination network (AHN) using dynamic causal modeling of longitudinal EEG in clozapine-treated patients with schizophrenia. The neurobiological properties of the CMM-NMDA model associated with symptom improvement in schizophrenia were found across hierarchical levels, from a reduced membrane capacity of the deep pyramidal cell and intrinsic connectivity with the inhibitory population in DMN and intrinsic and extrinsic connectivity in AHN. The medication duration mainly affects the intrinsic connectivity and NMDA time constant in DMN. Virtual perturbation analysis specified the contribution of each parameter to the cross-spectral density (CSD) of the EEG, particularly intrinsic connectivity and membrane capacitances for CSD frequency shifts and progression. It further reveals that excitatory and inhibitory connectivity complements frequency-specific CSD changes, notably the alpha frequency band in DMN. Positive and negative synergistic interactions exist between neurobiological properties primarily within the same region in patients treated with clozapine. The current study shows how computational neuropharmacology helps explore the multiscale link between neurobiological properties and clinical observations and understand the long-term mechanism of neuropharmacological intervention reflected in clinical EEG.
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Clozapina , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Clozapina/farmacologia , Clozapina/uso terapêutico , N-Metilaspartato , Neurofarmacologia , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Alucinações , Mapeamento Encefálico , Imageamento por Ressonância Magnética , Rede NervosaRESUMO
AIM: In our pilot study, we found an increase in tyrosine hydroxylase (Th) mRNA expression in the prefrontal cortex of 72-h REM sleep-deprived (SD) rats, a mania model. Additionally, the expression levels of miR-325-3p, miR-326-3p, and miR-330-5p, the predicted target miRNAs on TH, were significantly decreased. Based on these results, in this study, we investigated whether miRNA-325-3p, miR-326-3p, and miR-330-5p modulate TH and manic-like behaviors in SD rats. METHODS: Manic-like behaviors were assessed using the open field test (OFT) and elevated plus-maze (EPM) test. The direct binding activity of miRNAs to the 3'-untranslated region (3'-UTR) of the Th gene was measured in HEK-293 cells using a luciferase reporter system. We also examined mRNA and protein expression of TH after intracerebroventricular (ICV) injection of miR-330-5p agomir to SD rats, along with manic-like behaviors. RESULTS: We observed an upregulation in mRNA and protein expression of TH and downregulation in miRNA-325-3p, miR-326-3p, and miR-330-5p expressions in the prefrontal cortex of SD rats, together with increased manic-like behaviors. The luciferase reporter assay showed that miR-330-5p could repress TH expression through direct binding to its target site in the 3'-UTR of Th, whereas miR-326-3p and miR-330-5p could not. In addition, ICV injection of miR-330-5p agomir alleviated the increase in TH expression in the prefrontal cortex of SD rats and manic-like behaviors. CONCLUSIONS: TH expression regulation through miR-330-5p may be implicated in the pathophysiology of mania in SD rats.
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MicroRNAs , Tirosina 3-Mono-Oxigenase , Animais , Humanos , Ratos , Regulação para Baixo , Células HEK293 , Mania , MicroRNAs/metabolismo , Projetos Piloto , RNA Mensageiro , Sono REM , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
OBJECTIVE: Thalamotomy at the nucleus ventralis intermedius using MR-guided focused ultrasound has been an effective treatment method for essential tremor (ET). However, this is not true for all cases, even for successful ablation. How the brain differs in patients with ET between those with long-term good and poor outcomes is not clear. To analyze the functional connectivity difference between patients in whom thalamotomy was effective and those in whom thalamotomy was ineffective and its prognostic role in ET treatment, the authors evaluated preoperative resting-state functional MRI in thalamotomy-treated patients. METHODS: Preoperative resting-state functional MRI data in 85 patients with ET, who were experiencing tremor relief at the time of treatment and were followed up for a minimum of 6 months after the procedure, were collected for the study. The authors conducted a graph independent component analysis of the functional connectivity matrices of tremor-related networks. The patients were divided into thalamotomy-effective and thalamotomy-ineffective groups (thalamotomy-effective group, ≥ 50% motor symptom reduction; thalamotomy-ineffective group, < 50% motor symptom reduction at 6 months after treatment) and the authors compared network components between groups. RESULTS: Seventy-two (84.7%) of the 85 patients showed ≥ 50% tremor reduction from baseline at 6 months after thalamotomy. The network analysis shows significant suppression of functional network components with connections between the areas of the cerebellum and the basal ganglia and thalamus, but enhancement of those between the premotor cortex and supplementary motor area in the noneffective group compared to the effective group. CONCLUSIONS: The present study demonstrates that patients in the noneffective group have suppressed functional subnetworks in the cerebellum and subcortex regions and have enhanced functional subnetworks among motor-sensory cortical networks compared to the thalamotomy-effective group. Therefore, the authors suggest that the functional connectivity pattern might be a possible predictive factor for outcomes of MR-guided focused ultrasound thalamotomy.
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Tremor Essencial , Humanos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Tremor , Imageamento por Ressonância Magnética/métodos , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Núcleos Ventrais do Tálamo , Resultado do TratamentoRESUMO
The correlation matrix is a typical representation of node interactions in functional brain network analysis. The analysis of the correlation matrix to characterize brain networks observed in several neuroimaging modalities has been conducted predominantly in the Euclidean space by assuming that pairwise interactions are mutually independent. One way to take account of all interactions in the network as a whole is to analyze the correlation matrix under some geometric structure. Recent studies have focused on the space of correlation matrices as a strict subset of symmetric positive definite (SPD) matrices, which form a unique mathematical structure known as the Riemannian manifold. However, mathematical operations of the correlation matrix under the SPD geometry may not necessarily be coherent (i.e., the structure of the correlation matrix may not be preserved), necessitating a post-hoc normalization. The contribution of the current paper is twofold: (1) to devise a set of inferential methods on the correlation manifold and (2) to demonstrate its applicability in functional network analysis. We present several algorithms on the correlation manifold, including measures of central tendency, cluster analysis, hypothesis testing, and low-dimensional embedding. Simulation and real data analysis support the application of the proposed framework for brain network analysis.
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Algoritmos , Encéfalo , Encéfalo/diagnóstico por imagem , Simulação por ComputadorRESUMO
Prior experiences of successful and failed treatments are known to influence the efficacy of a newly applied treatment. However, whether that carry-over effect applies to non-pharmacological treatments is unknown. This study investigated how a failed treatment history with placebo analgesic cream affected the therapeutic outcomes of cold-pack treatment. The neural correlates underlying those effects were also explored using functional magnetic resonance imaging. The effect of the placebo analgesic cream was induced using placebo conditioning with small (44.5 °C to 43.7 °C, negative experience) and large (44.5 °C to 40.0 °C, positive experience) thermal stimuli changes. After the placebo conditioning, brain responses and self-reported evaluations of the effect of subsequent treatment with a cold-pack were contrasted between the two groups. The negative experience group reported less pain and lower anxiety scores in the cold-pack condition than the positive experience group and exhibited significantly greater activation in the right inferior parietal lobule (IPL), which is known to be involved in pain relief. These findings suggest that an unsatisfying experience with an initial pain-relief treatment could increase the expectations for the complementary treatment outcome and improve the analgesic effect of the subsequent treatment. The IPL could be associated with this expectation-induced pain relief process.
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Analgésicos , Hipotermia Induzida , Analgésicos/uso terapêutico , Humanos , Dor/tratamento farmacológico , Manejo da Dor , Lobo Parietal/diagnóstico por imagemRESUMO
We explore potential cross-informant discrepancies between child- and parent-report measures with an example of the Child Behavior Checklist (CBCL) and the Youth Self Report (YSR), parent- and self-report measures on children's behavioral and emotional problems. We propose a new way of examining the parent- and child-report differences with an interaction map estimated using a Latent Space Item Response Model (LSIRM). The interaction map enables the investigation of the dependency between items, between respondents, and between items and respondents, which is not possible with the conventional approach. The LSIRM captures the differential positions of items and respondents in the latent spaces for CBCL and YSR and identifies the relationships between each respondent and item according to their dependent structures. The results suggest that the analysis of item response in the latent space using the LSIRM is beneficial in uncovering the differential structures embedded in the response data obtained from different perspectives in children and their parents. This study also argues that the differential hidden structures of children and parents' responses should be taken together to evaluate children's behavioral problems.
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Pais , Comportamento Problema , Adolescente , Lista de Checagem , Humanos , Pais/psicologia , Comportamento Problema/psicologia , AutorrelatoRESUMO
BACKGROUND/AIM: Sleep loss is proposed as a trigger for manic episodes in bipolar disorder in humans. It has been shown that sleep and wakefulness can affect changes in mitochondrial gene expression, oxidative phosphorylation (OXPHOS) activity, and morphology in the brain. In this study, we investigated alterations in mitochondrial bioenergetic function in the brain of rats after 72-h rapid eye movement sleep deprivation (REM-SD). MATERIALS AND METHODS: Alterations in the mitochondrial DNA (mtDNA) copy number were detected in the prefrontal cortex and hippocampus through amplification of mitochondrially encoded NADH dehydrogenase 1 (mt-Nd1) gene using quantitative real-time polymerase chain reaction. The expression levels of mitochondrial biogenesis-related proteins such as peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), cytochrome c oxidase subunit 4I1 (COX4I1) and sirtuin 3 (SIRT3) were assessed using western blot analysis and immunohistochemistry. RESULTS: We found that REM-SD significantly increased the mtDNA copy number in the hippocampus but not in the prefrontal cortex. In addition, REM-SD increased the protein expression of COX4I1 in the hippocampus. Furthermore, we observed manic-like behaviors in rats exposed to 72-h REM-SD. REM-SD increased locomotion in the open-field test and the time spent in open arms in the elevated plus-maze test. CONCLUSION: REM-SD may induce mitochondrial dysfunction in the brain, which may be involved in the induction of mania.
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Biogênese de Organelas , Privação do Sono , Animais , Encéfalo , DNA Mitocondrial/genética , Hipocampo/metabolismo , Ratos , Privação do Sono/metabolismoRESUMO
The white matter in the brain is composed of neural fibers that wire the cortical and subcortical brain systems. Considering the complexity in terms of interconnections of many neural populations within the narrow space surrounded by the folding walls of the gray matter, the brain requires a certain way of structured wiring. To explore the three-dimensional organization of wiring in an accessible manner, we focused on voxel-level wiring patterns in the white matter according to cortical distributions in which each voxel mediates the wiring. We constructed a voxel-wise connection distribution map from the whole white matter voxels to 360 cortical regions using probabilistic tractography of the 100 diffusion imaging data in the Human Connectome Project. We then explored the spatial organization of the fiber bundles at the white matter voxels in terms of the maximal and second maximal cortical connection labels and the local gradient and entropy of cortical connection density using the population connection distribution map. We presented dominant cortical connection labels, local gradient, and connection entropy for the most representative white matter regions, including the internal capsule, external capsule, corpus callosum, cingulum bundle, and uncinate fascicles, most of which were introduced in the current study. Those major tracts showed a gradient organization of connection distributions for individual voxels. This organized pattern, as reflected in the whole brain connection distribution map, could be established to optimize wiring in the entire brain within the physical space of the white matter.
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Conectoma , Substância Branca , Encéfalo/diagnóstico por imagem , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Substância Cinzenta , Humanos , Substância Branca/diagnóstico por imagemRESUMO
ABSTRACT: Accumulating evidence indicates that the autophagy process is involved in the pathogenesis of schizophrenia. Autophagy plays a fundamental role in neuronal survival and function, and autophagy-related genes have been suggested to be associated with the pathogenesis of schizophrenia. The Unc-51-like autophagy activating kinase 2 (ULK2) gene has been implicated in autophagy regulation; therefore, we hypothesized that ULK2 polymorphisms may be associated with schizophrenia susceptibility.This study explored the association between polymorphisms of ULK2 and schizophrenia.Two single nucleotide polymorphisms (SNPs) (rs55730189 and rs150122) of ULK2 were genotyped in 279 patients with schizophrenia and 403 healthy individuals using Fluidigm SNPtype assays. We analyzed the genotype distribution of 2 SNPs and haplotypes between patients with schizophrenia and control subjects.The T allele frequency of rs55730189 showed a significant association between patients with schizophrenia and control subjects (Pâ=â.003). Genotype frequencies of rs55710189 were found to be significantly different between patients with schizophrenia and control subjects (odds ratioâ=â6.89, 95% confidence intervalâ=â1.91-24.90, Pâ<â.001 in the dominant model [C/Tâ+âT/T vs C/C], ORâ=â6.50, 95% confidence intervalâ=â1.83-23.01, Pâ<â.001 in the log-additive model (C/T vs T/T vs C/C)]. In haplotype analysis, the TT haplotype for these 2 SNPs was significantly associated with schizophrenia (Pâ<â.001, χ2â=â12.231).Our findings suggest that specific ULK2 polymorphisms may be associated with susceptibility to schizophrenia in the Korean population.
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Predisposição Genética para Doença , Proteínas Serina-Treonina Quinases/genética , Esquizofrenia , Autofagia , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , República da Coreia , Esquizofrenia/genéticaRESUMO
OBJECTIVES: To evaluate the association of three single-nucleotide polymorphisms (SNPs) of growth hormone receptor (GHR) gene with mandibular prognathism (MP) and relationships between mandibular morphology and GHR gene SNPs in the Korean population. MATERIALS AND METHODS: A total of 325 subjects were divided into two groups based on sagittal maxillomandibular relationship by the lateral cephalography: the MP and control groups. From the SNPs in the GHR gene, three SNPs (rs6180, rs6182 and rs6184) were selected. SNP genotyping was performed using direct sequencing. The craniofacial measurements of lateral cephalography were analysed. RESULTS: We found a lack of association between GHR and MP. However, in the analysis according to the values of cephalometric measurements, rs6180 was significantly associated with ANB, SNB, effective mandibular length and SNMP in females. Additionally, rs6182 and rs6184 were significantly associated with ramal height in males. CONCLUSION: Growth hormone receptor SNPs may affect not only the sagittal development of mandible but also the vertical development of ramal height, and GHR SNPs may gender-differently influence mandibular morphology. This finding supports that the GHR might be susceptible on mandibular morphogenesis in the Korean population.
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Má Oclusão Classe III de Angle , Prognatismo , Cefalometria , Feminino , Genótipo , Humanos , Masculino , Má Oclusão Classe III de Angle/genética , Mandíbula/anatomia & histologia , Polimorfismo de Nucleotídeo Único , Prognatismo/genética , Receptores da Somatotropina/genética , República da CoreiaRESUMO
The heterogeneous presentation of inattentive and hyperactive-impulsive core symptoms in attention deficit hyperactivity disorder (ADHD) warrants further investigation into brain network connectivity as a basis for subtype divisions in this prevalent disorder. With diffusion and resting-state functional magnetic resonance imaging data from the Healthy Brain Network database, we analyzed both structural and functional network efficiency and structure-functional network (SC-FC) coupling at the default mode (DMN), executive control (ECN), and salience (SAN) intrinsic networks in 201 children diagnosed with the inattentive subtype (ADHD-I), the combined subtype (ADHD-C), and typically developing children (TDC) to characterize ADHD symptoms relative to TDC and to test differences between ADHD subtypes. Relative to TDC, children with ADHD had lower structural connectivity and network efficiency in the DMN, without significant group differences in functional networks. Children with ADHD-C had higher SC-FC coupling, a finding consistent with diminished cognitive flexibility, for all subnetworks compared to TDC. The ADHD-C group also demonstrated increased SC-FC coupling in the DMN compared to the ADHD-I group. The correlation between SC-FC coupling and hyperactivity scores was negative in the ADHD-I, but not in the ADHD-C group. The current study suggests that ADHD-C and ADHD-I may differ with respect to their underlying neuronal connectivity and that the added dimensionality of hyperactivity may not explain this distinction.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Conectoma , Transtorno do Deficit de Atenção com Hiperatividade/classificação , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Cognição , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: Deep learning (DL)-based artificial intelligence may have different diagnostic characteristics than human experts in medical diagnosis. As a data-driven knowledge system, heterogeneous population incidence in the clinical world is considered to cause more bias to DL than clinicians. Conversely, by experiencing limited numbers of cases, human experts may exhibit large interindividual variability. Thus, understanding how the 2 groups classify given data differently is an essential step for the cooperative usage of DL in clinical application. OBJECTIVE: This study aimed to evaluate and compare the differential effects of clinical experience in otoendoscopic image diagnosis in both computers and physicians exemplified by the class imbalance problem and guide clinicians when utilizing decision support systems. METHODS: We used digital otoendoscopic images of patients who visited the outpatient clinic in the Department of Otorhinolaryngology at Severance Hospital, Seoul, South Korea, from January 2013 to June 2019, for a total of 22,707 otoendoscopic images. We excluded similar images, and 7500 otoendoscopic images were selected for labeling. We built a DL-based image classification model to classify the given image into 6 disease categories. Two test sets of 300 images were populated: balanced and imbalanced test sets. We included 14 clinicians (otolaryngologists and nonotolaryngology specialists including general practitioners) and 13 DL-based models. We used accuracy (overall and per-class) and kappa statistics to compare the results of individual physicians and the ML models. RESULTS: Our ML models had consistently high accuracies (balanced test set: mean 77.14%, SD 1.83%; imbalanced test set: mean 82.03%, SD 3.06%), equivalent to those of otolaryngologists (balanced: mean 71.17%, SD 3.37%; imbalanced: mean 72.84%, SD 6.41%) and far better than those of nonotolaryngologists (balanced: mean 45.63%, SD 7.89%; imbalanced: mean 44.08%, SD 15.83%). However, ML models suffered from class imbalance problems (balanced test set: mean 77.14%, SD 1.83%; imbalanced test set: mean 82.03%, SD 3.06%). This was mitigated by data augmentation, particularly for low incidence classes, but rare disease classes still had low per-class accuracies. Human physicians, despite being less affected by prevalence, showed high interphysician variability (ML models: kappa=0.83, SD 0.02; otolaryngologists: kappa=0.60, SD 0.07). CONCLUSIONS: Even though ML models deliver excellent performance in classifying ear disease, physicians and ML models have their own strengths. ML models have consistent and high accuracy while considering only the given image and show bias toward prevalence, whereas human physicians have varying performance but do not show bias toward prevalence and may also consider extra information that is not images. To deliver the best patient care in the shortage of otolaryngologists, our ML model can serve a cooperative role for clinicians with diverse expertise, as long as it is kept in mind that models consider only images and could be biased toward prevalent diseases even after data augmentation.
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The human brain at rest exhibits intrinsic dynamics transitioning among the multiple metastable states of the inter-regional functional connectivity. Accordingly, the demand for exploring the state-specific functional connectivity increases for a deeper understanding of mental diseases. Functional connectivity, however, lacks information about the directed causal influences among the brain regions, called effective connectivity. This study presents the dynamic causal modeling (DCM) framework to explore the state-dependent effective connectivity using spectral DCM for the resting-state functional MRI (rsfMRI). We established the sequence of brain states using the hidden Markov model with the multivariate autoregressive coefficients of rsfMRI, summarizing the functional connectivity. We decomposed the state-dependent effective connectivity using a parametric empirical Bayes scheme that models the effective connectivity of consecutive windows with the time course of the discrete states as regressors. We showed the plausibility of the state-dependent effective connectivity analysis in a simulation setting. To test the clinical applicability, we applied the proposed method to characterize the state- and subtype-dependent effective connectivity of the default mode network in children with combined-type attention deficit hyperactivity disorder (ADHD-C) compared with age-matched, typically developed children (TDC). All 88 children were subtyped according to the occupation times (i.e., dwell times) of the three dominant functional connectivity states, independently of clinical diagnosis. The state-dependent effective connectivity differences between ADHD-C and TDC according to the subtypes and those between the subtypes of ADHD-C were expressed mainly in self-inhibition, magnifying the importance of excitation inhibition balance in the subtyping. These findings provide a clear motivation for decomposing the state-dependent dynamic effective connectivity and state-dependent analysis of the directed coupling in exploring mental diseases.