Genome-wide association analyses using machine learning-based phenotyping reveal genetic architecture of occupational creativity and overlap with psychiatric disorders.

Creativity is known to be heritable and exhibits familial aggregation with psychiatric disorders; however, the complex nature of their relationship has not been well-established. In the present study, we demonstrate that using an expanded and validated machine learning (ML)-based phenotyping of occupational creativity (OC) can allow us to further understand the trait of creativity, which was previously difficult to define and study. We conducted the largest genome-wide association study (GWAS) on OC with 241,736 participants from the UK Biobank and identified 25 lead variants that have not yet been reported and three candidate causal genes that were previously associated with educational attainment and psychiatric disorders. We found extensive genetic overlap between OC and psychiatric disorders with mixed effect direction through various post-GWAS analyses, including the bivariate causal mixture model. In addition, we discovered a strongly genetic correlation between our original GWAS and the GWAS adjusted for education years (rg = 0.95). Our GWAS analysis via ML-based phenotyping contributes to the understanding of the genetic architecture of creativity, which may inform genetic discovery and genetic prediction in human cognition and psychiatric disorders.

Facial Expressions Track Depressive Symptoms in Old Age.

Facial expressions play a crucial role in the diagnosis of mental illnesses characterized by mood changes. The Facial Action Coding System (FACS) is a comprehensive framework that systematically categorizes and captures even subtle changes in facial appearance, enabling the examination of emotional expressions. In this study, we investigated the association between facial expressions and depressive symptoms in a sample of 59 older adults without cognitive impairment. Utilizing the FACS and the Korean version of the Beck Depression Inventory-II, we analyzed both "posed" and "spontaneous" facial expressions across six basic emotions: happiness, sadness, fear, anger, surprise, and disgust. Through principal component analysis, we summarized 17 action units across these emotion conditions. Subsequently, multiple regression analyses were performed to identify specific facial expression features that explain depressive symptoms. Our findings revealed several distinct features of posed and spontaneous facial expressions. Specifically, among older adults with higher depressive symptoms, a posed face exhibited a downward and inward pull at the corner of the mouth, indicative of sadness. In contrast, a spontaneous face displayed raised and narrowed inner brows, which was associated with more severe depressive symptoms in older adults. These findings suggest that facial expressions can provide valuable insights into assessing depressive symptoms in older adults.

3D Printing-Enabled Design and Manufacturing Strategies for Batteries: A Review.

Lithium-ion batteries (LIBs) have significantly impacted the daily lives, finding broad applications in various industries such as consumer electronics, electric vehicles, medical devices, aerospace, and power tools. However, they still face issues (i.e., safety due to dendrite propagation, manufacturing cost, random porosities, and basic & planar geometries) that hinder their widespread applications as the demand for LIBs rapidly increases in all sectors due to their high energy and power density values compared to other batteries. Additive manufacturing (AM) is a promising technique for creating precise and programmable structures in energy storage devices. This review first summarizes light, filament, powder, and jetting-based 3D printing methods with the status on current trends and limitations for each AM technology. The paper also delves into 3D printing-enabled electrodes (both anodes and cathodes) and solid-state electrolytes for LIBs, emphasizing the current state-of-the-art materials, manufacturing methods, and properties/performance. Additionally, the current challenges in the AM for electrochemical energy storage (EES) applications, including limited materials, low processing precision, codesign/comanufacturing concepts for complete battery printing, machine learning (ML)/artificial intelligence (AI) for processing optimization and data analysis, environmental risks, and the potential of 4D printing in advanced battery applications, are also presented.

The efficacy of memory load on speech-based detection of Alzheimer's disease.

Introduction: The study aims to test whether an increase in memory load could improve the efficacy in detection of Alzheimer's disease and prediction of the Mini-Mental State Examination (MMSE) score. Methods: Speech from 45 mild-to-moderate Alzheimer's disease patients and 44 healthy older adults were collected using three speech tasks with varying memory loads. We investigated and compared speech characteristics of Alzheimer's disease across speech tasks to examine the effect of memory load on speech characteristics. Finally, we built Alzheimer's disease classification models and MMSE prediction models to assess the diagnostic value of speech tasks. Results: The speech characteristics of Alzheimer's disease in pitch, loudness, and speech rate were observed and the high-memory-load task intensified such characteristics. The high-memory-load task outperformed in AD classification with an accuracy of 81.4% and MMSE prediction with a mean absolute error of 4.62. Discussion: The high-memory-load recall task is an effective method for speech-based Alzheimer's disease detection.

Leveraging genetic overlap between irritability and psychiatric disorders to identify genetic variants of major psychiatric disorders.

Irritability is a heritable core mental trait associated with several psychiatric illnesses. However, the genomic basis of irritability is unclear. Therefore, this study aimed to 1) identify the genetic variants associated with irritability and investigate the associated biological pathways, genes, and tissues as well as single-nucleotide polymorphism (SNP)-based heritability; 2) explore the relationships between irritability and various traits, including psychiatric disorders; and 3) identify additional and shared genetic variants for irritability and psychiatric disorders. We conducted a genome-wide association study (GWAS) using 379,506 European samples (105,975 cases and 273,531 controls) from the UK Biobank. We utilized various post-GWAS analyses, including linkage disequilibrium score regression, the bivariate causal mixture model (MiXeR), and conditional and conjunctional false discovery rate approaches. This GWAS identified 15 independent loci associated with irritability; the total SNP heritability estimate was 4.19%. Genetic correlations with psychiatric disorders were most pronounced for major depressive disorder (MDD) and bipolar II disorder (BD II). MiXeR analysis revealed polygenic overlap with schizophrenia (SCZ), bipolar I disorder (BD I), and MDD. Conditional false discovery rate analyses identified additional loci associated with SCZ (number [n] of additional SNPs = 105), BD I (n = 54), MDD (n = 107), and irritability (n = 157). Conjunctional false discovery rate analyses identified 85, 41, and 198 shared loci between irritability and SCZ, BD I, and MDD, respectively. Multiple genetic loci were associated with irritability and three main psychiatric disorders. Given that irritability is a cross-disorder trait, these findings may help to elucidate the genomics of psychiatric disorders.

Erratum: A Comparison Between the Performances of Verbal and Nonverbal Fluency Tests in Discriminating Between Mild Cognitive Impairments and Alzheimer's Disease Patients and Their Brain Morphological Correlates.

[This corrects the article on p. 17 in vol. 21, PMID: 35154337.].

Shared genetic architectures of subjective well-being in East Asian and European ancestry populations.

Subjective well-being (SWB) has been explored in European ancestral populations; however, whether the SWB genetic architecture is shared across populations remains unclear. We conducted a cross-population genome-wide association study for SWB using samples from Korean (n = 110,919) and European (n = 563,176) ancestries. Five ancestry-specific loci and twelve cross-ancestry significant genomic loci were identified. One novel locus (rs12298541 near HMGA2) associated with SWB was also identified through the European meta-analysis. Significant cross-ancestry genetic correlation for SWB between samples was observed. Polygenic risk analysis in an independent Korean cohort (n = 22,455) demonstrated transferability between populations. Significant correlations between SWB and major depressive disorder, and significant enrichment of central nervous system-related polymorphisms heritability in both ancestry populations were found. Hence, large-scale cross-ancestry genome-wide association studies can advance our understanding of SWB genetic architecture and mental health.

Effect of active learning and online discussions on the academic performances of dental students.

BACKGROUND: COVID-19 caused significant confusion around the world, and dental education was no exception. Therefore, in line with the demands of the times, this study sought to determine the applicability of online active learning to dental education. METHODS: This study was conducted in the second semester of 2020 at a school of dentistry in a selective university in Korea. A total of 114 dental students were recruited. Participants were assigned to four different groups (lecture and discussion [LD], lecture and discussion with instructor's worksheet [LW], self-study and discussion [SSD], and self-study and discussion with instructor's worksheet [SW]) using the random breakout room function in the Zoom video conference application. Their final test scores were then analyzed using analysis of variance and the online active learning results were compared with the offline learning results. RESULTS: The scores were highest for the transfer type items in the SSD group, followed by the SW group and the two lecture groups, which had no significant differences. These scores and pattern differences between the groups were similar for all items. The results suggested that studying by oneself rather than simply listening to lectures enhanced the effects of the discussions and led to higher learning outcomes. In addition, the effect of the instructor's intervention in the middle of the discussion varied depending on the pre-learning activities of discussion. As with previous offline experiments, self-study followed by group discussion had higher learning outcomes for both the verbatim and transfer type items. CONCLUSIONS: In agreement with the Interactive, Constructive, Active, and Passive (ICAP) framework and other active learning theories, the findings clearly indicated that online active learning was applicable to dental students, and when self-study precedes discussion, the learning is richer and the learning outcomes are better.

Association between Residential Greenness and Incidence of Parkinson's Disease: A Population-Based Cohort Study in South Korea.

It is widely known that exposure to residential greenness is beneficial for health. However, few studies have analyzed the association between greenery and Parkinson's disease (PD). We selected 313,355 participants who matched the inclusion criteria from the National Health Insurance Service-National Sample Cohort, followed up from 2007 to 2015. Residential greenness, represented by the normalized difference vegetation index (NDVI), was obtained from satellite measurements. We estimated hazard ratios of PD associated with a 0.1-unit increase in long-term greenness exposure at the district level for the previous 1 year of each year until a censoring/event occurred, using time-varying Cox proportional hazard models, adjusted for individual- and area-level characteristics. During the 2,745,389 person-years of follow-up, 2621(0.8%) participants developed PD. Exposure to higher levels of residential greenness was found to be associated with a decreased risk of PD incidence (21% per 0.1-unit increase, 95% confidence interval (CI): 0.74-0.84). In subgroup analyses, stronger protective effects were observed in participants aged over 50 years, females, overweight/obese participants, non-urban residents, non-smokers, alcoholics, and those with comorbidities. Long-term exposure to greenness was beneficial to incident PD, and our findings could aid in the development of public-health strategies.

A Comparison Between the Performances of Verbal and Nonverbal Fluency Tests in Discriminating Between Mild Cognitive Impairments and Alzheimer's Disease Patients and Their Brain Morphological Correlates.

BACKGROUND AND PURPOSE: Verbal and nonverbal fluency tests are the conventional methods for examining executive function in the elderly population. However, differences in impairments result in fluency tests in patients with mild cognitive impairments (MCIs) and Alzheimer's disease (AD) and in neural correlates underlying the tests still necessitate concrete evidence. METHODS: We compared the test performances in 27 normal controls, 28 patients with MCI, and 20 with AD, and investigated morphological changes in association with the test performances using structural magnetic imaging. RESULTS: Patients with AD performed poorly across all the fluency tests, and a receiver operating characteristics curve analysis revealed that only category fluency test discriminated all the 3 groups. Association, category, and design fluency tests involved temporal and frontal regions, while letter fluency involved the cerebellum and caudate. CONCLUSIONS: Category fluency is a reliable measure for screening patients with AD and MCI, and this efficacy might be related to morphological correlates that underlie semantic and executive processing.

Multiple Cognitive and Behavioral Factors Link Association Between Brain Structure and Functional Impairment of Daily Instrumental Activities in Older Adults.

OBJECTIVE: Functional impairment in daily activity is a cornerstone in distinguishing the clinical progression of dementia. Multiple indicators based on neuroimaging and neuropsychological instruments are used to assess the levels of impairment and disease severity; however, it remains unclear how multivariate patterns of predictors uniquely predict the functional ability and how the relative importance of various predictors differs. METHOD: In this study, 881 older adults with subjective cognitive complaints, mild cognitive impairment (MCI), and dementia with Alzheimer's type completed brain structural magnetic resonance imaging (MRI), neuropsychological assessment, and a survey of instrumental activities of daily living (IADL). We utilized the partial least square (PLS) method to identify latent components that are predictive of IADL. RESULTS: The result showed distinct brain components (gray matter density of cerebellar, medial temporal, subcortical, limbic, and default network regions) and cognitive-behavioral components (general cognitive abilities, processing speed, and executive function, episodic memory, and neuropsychiatric symptoms) were predictive of IADL. Subsequent path analysis showed that the effect of brain structural components on IADL was largely mediated by cognitive and behavioral components. When comparing hierarchical regression models, the brain structural measures minimally added the explanatory power of cognitive and behavioral measures on IADL. CONCLUSION: Our finding suggests that cerebellar structure and orbitofrontal cortex, alongside with medial temporal lobe, play an important role in the maintenance of functional status in older adults with or without dementia. Moreover, the significance of brain structural volume affects real-life functional activities via disruptions in multiple cognitive and behavioral functions.

Genome-wide association study of occupational attainment as a proxy for cognitive reserve.

Occupational attainment, which represents middle-age cognitive activities, is a known proxy marker of cognitive reserve for Alzheimer's disease. Previous genome-wide association studies have identified numerous genetic variants and revealed the genetic architecture of educational attainment, another marker of cognitive reserve. However, the genetic architecture and heritability for occupational attainment remain elusive. We performed a large-scale genome-wide association study of occupational attainment with 248 847 European individuals from the UK Biobank using the proportional odds logistic mixed model method. In this analysis, we defined occupational attainment using the classified job levels formulated in the UK Standard Occupational Classification system considering the individual professional skill and academic level. We identified 30 significant loci (P < 5 × 10-8); 12 were novel variants, not associated with other traits. Among them, four lead variants were associated with genes expressed in brain tissues by expression quantitative trait loci mapping from 10 brain regions: rs13002946, rs3741368, rs11654986 and rs1627527. The single nucleotide polymorphism-based heritability was estimated to be 8.5% (standard error of the mean = 0.004) and partitioned heritability was enriched in the CNS and brain tissues. Genetic correlation analysis showed shared genetic backgrounds between occupational attainment and multiple traits, including education, intelligence, leisure activities, life satisfaction and neuropsychiatric disorders. In two-sample Mendelian randomization analysis, we demonstrated that high occupation levels were associated with reduced risk for Alzheimer's disease [odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.65-0.92 in inverse variance weighted method; OR = 0.73, 95% CI = 0.57-0.92 in the weighted median method]. This causal relationship between occupational attainment and Alzheimer's disease was robust in additional sensitivity analysis that excluded potentially pleiotropic single nucleotide polymorphisms (OR = 0.72, 95% CI = 0.57-0.91 in the inverse variance weighted method; OR = 0.72, 95% CI = 0.53-0.97 in the weighted median method). Multivariable Mendelian randomization confirmed that occupational attainment had an independent effect on the risk for Alzheimer's disease even after taking educational attainment into account (OR = 0.72, 95% CI = 0.54-0.95 in the inverse variance weighted method; OR = 0.68, 95% CI = 0.48-0.97 in the weighted median method). Overall, our analyses provide insights into the genetic architecture of occupational attainment and demonstrate that occupational attainment is a potential causal protective factor for Alzheimer's disease as a proxy marker of cognitive reserve.

Changes in Computer-Analyzed Facial Expressions with Age.

Facial expressions are well known to change with age, but the quantitative properties of facial aging remain unclear. In the present study, we investigated the differences in the intensity of facial expressions between older (n = 56) and younger adults (n = 113). In laboratory experiments, the posed facial expressions of the participants were obtained based on six basic emotions and neutral facial expression stimuli, and the intensities of their faces were analyzed using a computer vision tool, OpenFace software. Our results showed that the older adults expressed strong expressions for some negative emotions and neutral faces. Furthermore, when making facial expressions, older adults used more face muscles than younger adults across the emotions. These results may help to understand the characteristics of facial expressions in aging and can provide empirical evidence for other fields regarding facial recognition.

Exploring a Cost-Efficient Model for Predicting Cerebral Aß Burden Using MRI and Neuropsychological Markers in the ADNI-2 Cohort.

Many studies have focused on the early detection of Alzheimer's disease (AD). Cerebral amyloid beta (Aß) is a hallmark of AD and can be observed in vivo via positron emission tomography imaging using an amyloid tracer or cerebrospinal fluid assessment. However, these methods are expensive. The current study aimed to identify and compare the ability of magnetic resonance imaging (MRI) markers and neuropsychological markers to predict cerebral Aß status in an AD cohort using machine learning (ML) approaches. The prediction ability of candidate markers for cerebral Aß status was examined by analyzing 724 participants from the ADNI-2 cohort. Demographic variables, structural MRI markers, and neuropsychological test scores were used as input in several ML algorithms to predict cerebral Aß positivity. Out of five combinations of candidate markers, neuropsychological markers with demographics showed the most cost-efficient result. The selected model could distinguish abnormal levels of Aß with a prediction ability of 0.85, which is the same as that for MRI-based models. In this study, we identified the prediction ability of MRI markers using ML approaches and showed that the neuropsychological model with demographics can predict Aß positivity, suggesting a more cost-efficient method for detecting cerebral Aß status compared to MRI markers.

Analyzing Facial and Eye Movements to Screen for Alzheimer's Disease.

Brain disease can be screened using eye movements. Degenerative brain disorders change eye movement because they affect not only memory and cognition but also the cranial nervous system involved in eye movement. We compared the facial and eye movement patterns of patients with mild Alzheimer's disease and cognitively normal people to analyze the neurological signs of dementia. After detecting the facial landmarks, the coordinate values for the movements were extracted. We used Spearman's correlation coefficient to examine associations between horizontal and vertical facial and eye movements. We analyzed the correlation between facial and eye movements without using special eye-tracking equipment or complex conditions in order to measure the behavioral aspect of the natural human gaze. As a result, we found differences between patients with Alzheimer's disease and cognitively normal people. Patients suffering from Alzheimer's disease tended to move their face and eyes simultaneously in the vertical direction, whereas the cognitively normal people did not, as confirmed by a Mann-Whitney-Wilcoxon test. Our findings suggest that objective and accurate measurement of facial and eye movements can be used to screen such patients quickly. The use of camera-based testing for the early detection of patients showing signs of neurodegeneration can have a significant impact on the public care of dementia.

Differences in Facial Expressions between Spontaneous and Posed Smiles: Automated Method by Action Units and Three-Dimensional Facial Landmarks.

Research on emotion recognition from facial expressions has found evidence of different muscle movements between genuine and posed smiles. To further confirm discrete movement intensities of each facial segment, we explored differences in facial expressions between spontaneous and posed smiles with three-dimensional facial landmarks. Advanced machine analysis was adopted to measure changes in the dynamics of 68 segmented facial regions. A total of 57 normal adults (19 men, 38 women) who displayed adequate posed and spontaneous facial expressions for happiness were included in the analyses. The results indicate that spontaneous smiles have higher intensities for upper face than lower face. On the other hand, posed smiles showed higher intensities in the lower part of the face. Furthermore, the 3D facial landmark technique revealed that the left eyebrow displayed stronger intensity during spontaneous smiles than the right eyebrow. These findings suggest a potential application of landmark based emotion recognition that spontaneous smiles can be distinguished from posed smiles via measuring relative intensities between the upper and lower face with a focus on left-sided asymmetry in the upper region.

Cognitive Profiling Related to Cerebral Amyloid Beta Burden Using Machine Learning Approaches.

Background: Cerebral amyloid beta (Aß) is a hallmark of Alzheimer's disease (AD). Aß can be detected in vivo with amyloid imaging or cerebrospinal fluid assessments. However, these technologies can be both expensive and invasive, and their accessibility is limited in many clinical settings. Hence the current study aims to identify multivariate cost-efficient markers for Aß positivity among non-demented individuals using machine learning (ML) approaches. Methods: The relationship between cost-efficient candidate markers and Aß status was examined by analyzing 762 participants from the Alzheimer's Disease Neuroimaging Initiative-2 cohort at baseline visit (286 cognitively normal, 332 with mild cognitive impairment, and 144 with AD; mean age 73.2 years, range 55-90). Demographic variables (age, gender, education, and APOE status) and neuropsychological test scores were used as predictors in an ML algorithm. Cerebral Aß burden and Aß positivity were measured using 18F-florbetapir positron emission tomography images. The adaptive least absolute shrinkage and selection operator (LASSO) ML algorithm was implemented to identify cognitive performance and demographic variables and distinguish individuals from the population at high risk for cerebral Aß burden. For generalizability, results were further checked by randomly dividing the data into training sets and test sets and checking predictive performances by 10-fold cross-validation. Results: Out of neuropsychological predictors, visuospatial ability and episodic memory test results were consistently significant predictors for Aß positivity across subgroups with demographic variables and other cognitive measures considered. The adaptive LASSO model using out-of-sample classification could distinguish abnormal levels of Aß. The area under the curve of the receiver operating characteristic curve was 0.754 in the mild change group, 0.803 in the moderate change group, and 0.864 in the severe change group, respectively. Conclusion: Our results showed that the cost-efficient neuropsychological model with demographics could predict Aß positivity, suggesting a potential surrogate method for detecting Aß deposition non-invasively with clinical utility. More specifically, it could be a very brief screening tool in various settings to recruit participants with potential biomarker evidence of AD brain pathology. These identified individuals would be valuable participants in secondary prevention trials aimed at detecting an anti-amyloid drug effect in the non-demented population.

Active learning through discussion: ICAP framework for education in health professions.

BACKGROUND: The ICAP framework based on cognitive science posits four modes of cognitive engagement: Interactive, Constructive, Active, and Passive. Focusing on the wide applicability of discussion as interactive engagement in medical education, we investigated the effect of discussion when it was preceded by self-study and further investigated the effect of generating questions before discussions. METHODS: This study was conducted in the second semester of 2018 and was participated in by 129 students majoring in health professions, including medicine, dentistry, veterinary medicine, and nursing. The students were assigned to four different trial groups and were asked to fill out a Subjective Mental Effort Questionnaire after completing each session. Their performance in posttest scores was analyzed using Bonferroni test, and mental effort was analyzed using mediation analysis. RESULTS: These results indicated that the self-study and question group had the highest performance and that the lecture and summary group had the lowest performance when comparing the total score. Using the analysis of mental effort, it was confirmed that the relationship between different study conditions and post-test performance was mediated by mental effort during test. CONCLUSIONS: Our findings support the ICAP framework and provide practical implications for medical education, representing the fact that students learn more when they are involved in active learning activities, such as self-study and question generation, prior to discussions.

Differential effects of blood insulin and HbA1c on cerebral amyloid burden and neurodegeneration in nondiabetic cognitively normal older adults.

We tested the hypothesis that lower insulin or higher glycated hemoglobin (HbA1c) levels in blood are associated with increased cerebral beta amyloid (Aß) deposition and neurodegeneration in nondiabetic cognitively normal (CN) older adults. A total of 205 nondiabetic CN older adults underwent comprehensive clinical assessment, [11C]Pittsburgh compound B (PiB)-positron emission tomography (PET), [18F]fluorodeoxyglucose-PET, magnetic resonance imaging, and blood sampling for fasting insulin and HbA1c measurement. Lower blood insulin was significantly associated with increased Aß positivity rates and decreased cerebral glucose metabolism in the AD-signature region. In contrast, higher HbA1c levels were not associated with Aß positivity rates but were significantly associated with higher rates of having neurodegeneration in the AD-signature regions. Our results suggest different roles of insulin and HbA1c in AD pathogenesis, in that decreased blood insulin below optimal levels may contribute to increasing cerebral Aß deposition and neurodegeneration whereas impaired glycemic control may aggravate neurodegeneration through a nonamyloid mechanism in nondiabetic CN older adults.