Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording; this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
Animals ; CA1 Region, Hippocampal/physiology* ; Male ; Association Learning/physiology* ; Neuronal Plasticity/physiology* ; Cues ; Memory/physiology* ; Synapses/physiology* ; Conditioning, Classical/physiology* ; Excitatory Postsynaptic Potentials/physiology* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Rats ; Optogenetics

PURPOSE: The aim of this study was to investigate the safety and the effects of elevated doses of solifenacin and trospium on cognitive function and health-related quality of life (HRQoL) in elderly women receiving treatment for urinary incontinence. METHODS: The study included 312 women aged 60–83 years (mean age, 69.4 years). All participants had scored at least 24 points on the Mini-Mental State Examination (MMSE) scale, and all of them had been diagnosed with urge urinary incontinence (UUI) or mixed urinary incontinence (MUI). The women were randomly assigned to 3 groups: group A, individuals who were simultaneously administered solifenacin at a high dosage of 20 mg per day and trospium at a high dosage of 60 mg per day; group B, persons taking solifenacin and trospium at the usual dosage of 10 and 30 mg per day, respectively; and group C, persons who received a placebo. Participants’ cognitive status was assessed by the MMSE, Controlled Oral Word Association Test, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale III, Colour Trails Test, and California Verbal Learning Test scales. The HRQoL assessment was performed using the Medical Outcomes Study 36-Item Health Survey. RESULTS: The cognitive function parameters did not differ at the start and end of the study across the groups (P>0.05). Additionally, the cognitive function parameters did not differ significantly within each group between the start and end of the study (P>0.05). The values of most HRQoL parameters regarding the functional state of the lower urinary tract (LUT) after the termination of treatment significantly improved in groups A and B (P < 0.05). A significant correlation between cognitive status and HRQoL or LUT parameters was absent (r < 0.3), while the correlations between HRQoL and LUT parameters were r=0.31–0.83, P < 0.05. CONCLUSIONS: The use of elevated doses of solifenacin and trospium did not increase the risk of cognitive impairment in women with UUI and MUI. The combination of solifenacin and trospium at a double dosage may be recommended to elderly women with treatment-resistant symptoms of UUI and MUI. However, the safety of combining antimuscarinic drugs in women with an increased volume of residual urine requires further study.
Adult ; Aged ; California ; Cognition Disorders ; Cognition* ; Female ; Health Surveys ; Humans ; Intelligence ; Memory ; Muscarinic Antagonists ; Quality of Life* ; Solifenacin Succinate* ; Urinary Incontinence* ; Urinary Tract ; Verbal Learning ; Weights and Measures ; Word Association Tests

The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate (NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies (GWAS) have uncovered dozens of single nucleotide polymorphism (SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants in Han and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations. Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.
Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Genome-Wide Association Study ; Humans ; Infant ; Logistic Models ; Machine Learning ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide ; Retinol-Binding Proteins, Plasma ; genetics ; Risk Assessment

With the success of the genome-wide association studies (GWASs), many candidate loci for complex human diseases have been reported in the GWAS catalog. Recently, many disease prediction models based on penalized regression or statistical learning methods were proposed using candidate causal variants from significant single-nucleotide polymorphisms of GWASs. However, there have been only a few systematic studies comparing existing methods. In this study, we first constructed risk prediction models, such as stepwise linear regression (SLR), least absolute shrinkage and selection operator (LASSO), and Elastic-Net (EN), using a GWAS chip and GWAS catalog. We then compared the prediction accuracy by calculating the mean square error (MSE) value on data from the Korea Association Resource (KARE) with body mass index. Our results show that SLR provides a smaller MSE value than the other methods, while the numbers of selected variables in each model were similar.
Body Mass Index* ; Decision Support Techniques ; Genome-Wide Association Study ; Humans ; Korea ; Learning ; Linear Models

BACKGROUND AND PURPOSE: Although the 15-item Geriatric Depression Scale (GDS15) is a widely used depression screening questionnaire, the implications of the GDS15 in patients with Alzheimer's disease (AD) are questionable. We designed this study to explore the GDS15 factor structure and the relationships between these factors and cognitive-behavioral aspects. METHODS: The GDS15, cognitive function tests, and the Korean-Neuropsychiatry Inventory were administered to 310 patients with probable AD, who were not medicated before visiting the hospital. Three factors were identified by principal components analysis. A bivariate correlation analysis was conducted to determine the relationships between factors and neurocognitive and behavior symptoms. RESULTS: Factor 2 was correlated with the Korean Boston Naming Test, calculating ability, the go-no-go test, the Controlled Oral Word Association Test (COWAT), the Color Word Stroop Test (CWST; words and color), aggression, depression, and apathy. Factor 3 was correlated with calculating ability, the Seoul Verbal Learning Test, immediate recall, copy, and delayed recall on the Rey-Osterieth Complex Figure Test, contrasting on the COWAT, and words and delusion on the CWST. We identified three factors and revealed that the GDS15 may be comprised of a heterogeneous scale. CONCLUSIONS: These results suggest that the GDS15 may be comprised of a heterogeneous scale and suggest multi-dimensional properties of the GDS15 in patients with AD.
Aggression ; Alzheimer Disease* ; Apathy ; Delusions ; Depression* ; Factor Analysis, Statistical ; Humans ; Mass Screening ; Memory, Short-Term ; Seoul ; Stroop Test ; Verbal Learning ; Word Association Tests ; Surveys and Questionnaires

Bardet-Biedl syndrome (BBS) is a rare ciliopathy generally inherited with an autosomal recessive pattern. BBS is characterized by 6 primary features namely retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction, learning difficulties, and hypogonadism and a wide range of secondary features. To date, mutations in 16 genes have been identified as causative factors for BBS. Among them, the BBS1 and BBS10 genes are major disease-causing genes, and each of these gene mutations presents in more than 20% of all BBS patients. Genotype-phenotype correlations have not been observed in BBS, and there can be phenotypic overlap between BBS and other ciliopathies. In Korea, no molecular, genetically confirmed case of BBS has been reported to date. Herein, we describe the case of the first Korean siblings with BBS resulting from 2 BBS10 gene mutations who showed typical clinical phenotypes, including retinal dystrophy, obesity, intellectual disability, cystic tubular disease, and postaxial polydactyly.
Bardet-Biedl Syndrome* ; Genetic Association Studies ; Humans ; Hypogonadism ; Intellectual Disability ; Korea ; Learning ; Obesity ; Phenotype ; Polycystic Kidney Diseases ; Polydactyly ; Retinal Dystrophies ; Retinitis Pigmentosa ; Siblings*

OBJECTIVES: The purpose of this study was to find risk factors that are associated with complications of cerebral infarction in patients with atrial fibrillation (AF) and to discover useful association rules among these factors. METHODS: The risk factors with respect to cerebral infarction were selected using logistic regression analysis with the Wald's forward selection approach. The rules to identify the complications of cerebral infarction were obtained by using the association rule mining (ARM) approach. RESULTS: We observed that 4 independent factors, namely, age, hypertension, initial electrocardiographic rhythm, and initial echocardiographic left atrial dimension (LAD), were strong predictors of cerebral infarction in patients with AF. After the application of ARM, we obtained 4 useful rules to identify complications of cerebral infarction: age (>63 years) and hypertension (Yes) and initial ECG rhythm (AF) and initial Echo LAD (>4.06 cm); age (>63 years) and hypertension (Yes) and initial Echo LAD (>4.06 cm); hypertension (Yes) and initial ECG rhythm (AF) and initial Echo LAD (>4.06 cm); age (>63 years) and hypertension (Yes) and initial ECG rhythm (AF). CONCLUSIONS: Among the induced rules, 3 factors (the initial ECG rhythm [i.e., AF], initial Echo LAD, and age) were strongly associated with each other.
Arm ; Association Learning ; Atrial Fibrillation ; Cerebral Infarction ; Data Mining ; Electrocardiography ; Humans ; Hypertension ; Logistic Models ; Mining ; Risk Factors

PURPOSE: The success of cardiopulmonary resuscitation (CPR) depends on how soon after a heart attack the intervention is done and on how the quality of the CPR is. Although in Korea there are several CPR education courses, CPR done by bystanders to an attack remains very low. This might be related to different causes such as the complexity of the CPR sequence and the difficulty of learning CPR, specifically ventilation maneuvers. The American Heart Association (AHA) has recently recommended 'Hands Only(TM) CPR', without ventilation, for bystander rescuers. In the present study, we investigated the educational effects of 'Hands Only(TM) CPR' in elementary school students. We further analyzed the effects of this variable on CPR skill learning and retention for a 3 months period. METHODS: We selected two groups of 5th grade elementary school students to perform this study. One group received CPR education with ventilation (CPR with ventilation group); the other received 'Hands Only(TM) CPR' education ('Hands Only(TM) CPR' group). The Laerdal PC Skill Reporting system was used for both education sessions and for evaluation immediately after the sessions. Skill performance data, together with ventilation data and compression data were recorded for further comparisons. RESULTS: There were no differences between the two groups regarding chest compression (average rate, average duty cycle, registered with no error, average depth, etc.). The average chest compression count per minute was 118+/-12/min in the 'Hands Only(TM) CPR' group and 85+/-13/min in the CPR with ventilation group (p=0.001). Registered adequate compression depth was 23+/-29% in the 'Hands Only(TM) CPR' group and 23+/-31% in the CPR with ventilation group (p=0.962). The total hands off time was 18+/-7 seconds in the 'Hands Only(TM) CPR' group and 40+/-11 seconds in the CPR with ventilation group. After 3 months there were still no differences in chest compression between the two groups. The average count per minute at 3 months was 109+/-15/min in the 'Hands Only(TM) CPR' group and 83+/-17/min in the CPR with ventilation group (p=0.001). Registered adequate compression depth was 26+/-31% in the 'Hands Only(TM) CPR' group and 31+/-35% in the CPR with ventilation group (p=0.334). The total hands off time was 12+/-5 seconds in the 'Hands Only(TM) CPR' group and 31+/-12 seconds in the CPR with ventilation group (p=0.001). CONCLUSION: The 'Hands Only(TM) CPR' program in elementary school children increased the chest compression rate. However, there was no between groups difference in adequate compression depth. We were unable to demonstrate that the 'Hands Only(TM) CPR' education program in elementary school children led to a better effect.
American Heart Association ; Cardiopulmonary Resuscitation ; Child ; Hand ; Heart ; Humans ; Korea ; Learning ; Retention (Psychology) ; School Health Services ; Thorax ; Ventilation

OBJECTIVE: This study was conducted to evaluate effects of sertraline treatment on symptoms and memory function of posttraumatic stress disorder (PTSD). METHODS: Thirty Vietnam veterans were collected for this study, among whom fifteen were PTSD patients and fifteen were combat control subjects. We used Mississippi Scale for Combat-Related PTSD, Combat Exposure Scale (CES), Hamilton Depression Rating Scale (HDRS) and Clinician Administered PTSD Scale (CAPS). Digit Span, Paired Association Learning Test (PALT) and Rey- Osterreith Complex Figure Test (CFT) were assessed for memory function. We evaluated HDRS, CAPS and memory function tests at baseline, 2-week and 6-week intervals with each subjects. RESULTS: There were significant differences between PTSD and Non-PTSD veterans in Mississippi Scale for Combat-Related PTSD, CES, HDRS and CAPS. Significant difference was found in memory function tests between PTSD and Non-PTSD veterans. PTSD veterans showed significant improvement in HDRS and CAPS at 2-week and 6-week and in memory function tests at 6-week of sertraline treatment. There was no significant correlation between symptoms and memory function. CONCLUSION: These results suggest that sertraline improve symptoms and memory function of PTSD. There was no significant correlation between PTSD sysmtoms and memory function.
Association Learning ; Depression ; Humans ; Memory* ; Mississippi ; Sertraline* ; Stress Disorders, Post-Traumatic* ; Veterans ; Vietnam

OBJECTIVE: This study was conducted to evaluate efficacy on symptoms and memory function of mirtazapine treatment of posttraumatic stress disorder. METHODS: Thirty Vietnam veterans were collected for this study, among whom fifteen were PTSD patients and fifteen were combat control subjects. We used Mississippi Scale for CombatRelated PTSD, Combat Exposure Scale (CES), Hamilton Depression Rating Scale (HDRS) and Clinician Administered PTSD Scale (CAPS). Digit Span, Paired Association Learning Test (PALT) and Rey-Osterrith Complex Figure Test (CFT) were assessed for memory function. We also evaluate HDRS, CAPS and memory function tests intervals of baseline, 2 week and 6 week in PTSD patients during mirtazapine treatment. RESULTS: There were significant differences between PTSD and Non-PTSD veterans in Mississippi Scale for Combat-Related PTSD, CES, HDRS and CAPS. Significant difference was found in memory function tests between PTSD and Non-PTSD veterans. PTSD veterans showed significant improvement in HDRS and CAPS at 2 week and 6 week during mirtazapine treatment and in memory function tests at 6 week during mirtazapine treatment. There was no significant correlation between symptoms and memory function. CONCLUSION: These results suggest that mirtazapine improve symptoms and memory function of PTSD. There was no significant correlation between PTSD sysmtoms and memory function.
Association Learning ; Depression ; Humans ; Memory* ; Mississippi ; Stress Disorders, Post-Traumatic* ; Veterans ; Vietnam