Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns.

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

Barriers and future improvements of workplace-based learning in Korean medicine clinical clerkship: perspectives of graduates.

BACKGROUND: Workplace-based learning (WPBL) has emerged as an essential practice in healthcare education. However, WPBL is rarely implemented in Korean medicine (KM) due to the passive attitude of teachers and possible violation of medical laws that limit the participation of trainees in medical treatment. In this study, we implemented WPBL in the clinical clerkship of Acupuncture and Moxibustion Medicine at a single College of KM and explored the barriers and future improvements of WPBL. METHODS: The WPBL was implemented from January to July 2019. During the clerkship, each senior student was assigned an inpatient at the university hospital. WPBL was conducted as follows: patient presentation by the supervisor, interaction with the patient at the bedside, preparation of medical records, oral case presentation, and discussion with feedback. The student performed a physical examination and review of systems as a clinical task. In addition, six doctors of KM who are currently practicing after three years of WPBL were interviewed in September 2022 to investigate the real-world effects and unmet needs of WPBL in their workplaces. RESULTS: Two major themes identified from the interview were: "the experience of novice doctors of KM with KM practice" and "Current state of KM clinical education." The five subcategories were: "Clinical competency priorities vary according to the KM workplace," "Difficulties faced by doctors of KM immediately after graduation," "WPBL experience of the interviewees," "Necessary but difficult to implement real patient learning," and "Unmet needs for clinical clerkship in KM." CONCLUSION: It is essential to consider the unique characteristics of KM practice and the duties required in various workplaces for successful WPBL. We anticipate our study to be a starting point for improving the WPBL and addressing the unmet needs in KM clinical education.

Paradigm shift required for translational research on the brain.

Biomedical research on the brain has led to many discoveries and developments, such as understanding human consciousness and the mind and overcoming brain diseases. However, historical biomedical research on the brain has unique characteristics that differ from those of conventional biomedical research. For example, there are different scientific interpretations due to the high complexity of the brain and insufficient intercommunication between researchers of different disciplines owing to the limited conceptual and technical overlap of distinct backgrounds. Therefore, the development of biomedical research on the brain has been slower than that in other areas. Brain biomedical research has recently undergone a paradigm shift, and conducting patient-centered, large-scale brain biomedical research has become possible using emerging high-throughput analysis tools. Neuroimaging, multiomics, and artificial intelligence technology are the main drivers of this new approach, foreshadowing dramatic advances in translational research. In addition, emerging interdisciplinary cooperative studies provide insights into how unresolved questions in biomedicine can be addressed. This review presents the in-depth aspects of conventional biomedical research and discusses the future of biomedical research on the brain.

Monophosphoryl lipid A and poly I:C combination enhances immune responses of equine influenza virus vaccine.

Equine influenza is a contagious respiratory disease caused by H3N8 type A influenza virus. Vaccination against equine influenza is conducted regularly; however, infection still occurs globally because of the short immunity duration and suboptimal efficacy of current vaccines. Hence the objective of this study was to investigate whether an adjuvant combination can improve immune responses to equine influenza virus (EIV) vaccines. Seventy-two mice were immunized with an EIV vaccine only or with monophosphoryl lipid A (MPL), polyinosinic-polycytidylic acid (Poly I:C), or MPL + Poly I:C. Prime immunization was followed by boost immunization after 2 weeks. Mice were euthanized at 4, 8, and 32 weeks post-prime immunization, respectively. Sera were collected to determine humoral response. Bone marrow, spleen, and lung samples were harvested to determine memory cell responses, antigen-specific T-cell proliferation, and lung viral titers. MPL + Poly I:C resulted in the highest IgG, IgG1, and IgG2a antibodies and hemagglutination inhibition titers among the groups and sustained their levels until 32 weeks post-prime immunization. The combination enhanced memory B cell responses in the bone marrow and spleen. At 8 weeks post-prime immunization, the combination induced higher CD8+ central memory T cell frequencies in the lungs and CD8+ central memory T cells in the spleen. In addition, the combination group exhibited enhanced antigen-specific T cell proliferation, except for CD4+ T cells in the lungs. Our results demonstrated improved immune responses when using MPL + Poly I:C in EIV vaccines by inducing enhanced humoral responses, memory cell responses, and antigen-specific T cell proliferation.

Anti-thrombotic effects of ginsenoside Rk3 by regulating cAMP and PI3K/MAPK pathway on human platelets.

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin αIIbß3 using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B2 secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP3R). In the presence of G-Rk3, dense tubular system Ca2+ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/ß3 and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA2. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

Dimensional emotions are represented by distinct topographical brain networks

The ability to recognize others’ facial emotions has become increasingly important after the COVID-19 pandemic, which causes stressful situations in emotion regulation. Considering the importance of emotion in maintaining a social life, emotion knowledge to perceive and label emotions of oneself and others requires an understanding of affective dimensions, such as emotional valence and emotional arousal. However, limited information is available about whether the behavioral representation of affective dimensions is similar to their neural representation. To explore the relationship between the brain and behavior in the representational geometries of affective dimensions, we constructed a behavioral paradigm in which emotional faces were categorized into geometric spaces along the valence, arousal, and valence and arousal dimensions. Moreover, we compared such representations to neural representations of the faces acquired by functional magnetic resonance imaging. We found that affective dimensions were similarly represented in the behavior and brain. Specifically, behavioral and neural representations of valence were less similar to those of arousal. We also found that valence was represented in the dorsolateral prefrontal cortex, frontal eye fields, precuneus, and early visual cortex, whereas arousal was represented in the cingulate gyrus, middle frontal gyrus, orbitofrontal cortex, fusiform gyrus, and early visual cortex. In conclusion, the current study suggests that dimensional emotions are similarly represented in the behavior and brain and are presented with differential topographical organizations in the brain. (AU)

Elucidating the Correlation between Bone Mineral Density and Multifidus Muscle Characteristics: A Cross-Modal Study with Dual-Energy X-ray Absorptiometry and Spinal Computed Tomography Texture Analysis.

BACKGROUND: Recent research underscores the clinical relevance of muscle conditions such as sarcopenia and their links to bone mineral density (BMD), yet notable gaps persist in the understanding of their interconnections. Our study addresses this by introducing a novel approach to decipher the correlation between BMD and the texture of the multifidus muscle, utilizing spinal computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) to evaluate muscle texture, BMD, and bone mineral content (BMC) at the total lumbar vertebra and total hip. METHODS: Our single-institution study examined 395 cases collected from 6 May 2012 to 30 November 2021. Each patient underwent a spinal CT scan and a DXA scan within a one-month interval. BMD and BMC at the total lumbar vertebra and total hip were measured. The texture features of the multifidus muscle from the axial cuts of T12 to S1 vertebrae were assessed via gray-level co-occurrence matrices. CT texture analysis values at angles of 45 + 45 and 90 degrees were calculated and correlated with BMD and BMC. A regression model was then constructed to predict BMD values, and the precision of these correlations was evaluated using mean square error (MSE) analysis. RESULTS: Total lumbar BMC showed a correlation of 0.583-0.721 (MSE 1.568-1.842) and lumbar BMD of 0.632-0.756 (MSE 0.068-0.097). Total hip BMC had a correlation of 0.556-0.690 (MSE 0.448-0.495), while hip BMD ranged from 0.585 to 0.746 (MSE 0.072-0.092). CONCLUSIONS: The analysis of spinal CT texture alongside BMD and BMC measures provides a new approach to understanding the relationship between bone and muscle health. The strong correlations expected from our research affirm the importance of integrating bone and muscle measures in the prevention, diagnosis, and management of conditions such as sarcopenia and osteoporosis.

Immunostimulatory effects of marine algae extracts on in vitro antigen-presenting cell activation and in vivo immune cell recruitment.

Marine algae are photosynthetic eukaryotic organisms that are widely used as sources of food, cosmetics, and drugs. However, their biological and immunological effects on immune cells have not been fully elucidated. To unravel their immunological activity and broaden their application, we generated antigen-presenting cells (APCs), including dendritic cells (DCs) and macrophages, from mouse bone marrow cells and treated them with six different marine algae extracts (MAEs). We evaluated cell viability, activation marker expression, and pro-inflammatory cytokine production by APCs after 2 days of MAE treatment. All six MAEs significantly induced cytokine production of APCs, among which Pyropia yezoensis (PY), Peyssonnelia caulifera (PC), and Meristotheca papulosa (MP) extracts exhibited the strongest effect. Cladophora wrightiana var. minor (CW) extract moderately upregulated cytokine levels but increased the expression of activation markers on DCs. Moreover, PY, PC, MP, Sargassum pectinifera (SP), and Caulerpa okamurae (CO) pre-treated APCs effectively stimulated T-cell proliferation and cytokine production. Furthermore, the mice injected with MAEs exhibited higher cytokine (TNF-α, IL-6, and IL-1ß) production as well as enhanced innate immune cell recruitment capacities (DCs, monocytes, neutrophils, and natural killer cells) in the peritoneal cavity of the mice compared to those of the non-treated mice. Therefore, all MAEs exhibited immunostimulatory potential, with PY, PC, CW, and MP extracts being the most effective in stimulating immune responses and cell activation. To the best of our knowledge, this is the first study to determine the immunomodulatory activities of six MAEs both in vitro and in vivo.

Dimensional emotions are represented by distinct topographical brain networks.

The ability to recognize others' facial emotions has become increasingly important after the COVID-19 pandemic, which causes stressful situations in emotion regulation. Considering the importance of emotion in maintaining a social life, emotion knowledge to perceive and label emotions of oneself and others requires an understanding of affective dimensions, such as emotional valence and emotional arousal. However, limited information is available about whether the behavioral representation of affective dimensions is similar to their neural representation. To explore the relationship between the brain and behavior in the representational geometries of affective dimensions, we constructed a behavioral paradigm in which emotional faces were categorized into geometric spaces along the valence, arousal, and valence and arousal dimensions. Moreover, we compared such representations to neural representations of the faces acquired by functional magnetic resonance imaging. We found that affective dimensions were similarly represented in the behavior and brain. Specifically, behavioral and neural representations of valence were less similar to those of arousal. We also found that valence was represented in the dorsolateral prefrontal cortex, frontal eye fields, precuneus, and early visual cortex, whereas arousal was represented in the cingulate gyrus, middle frontal gyrus, orbitofrontal cortex, fusiform gyrus, and early visual cortex. In conclusion, the current study suggests that dimensional emotions are similarly represented in the behavior and brain and are presented with differential topographical organizations in the brain.

Chronic allergic asthma induces T-cell exhaustion and impairs virus clearance in mice.

BACKGROUND: Allergic asthma, one of the most common types of asthma, is thought to be highly susceptible to respiratory viral infections; however, its pathological mechanism needs to be elucidated. Recent studies have found impaired T-cell function in asthmatic mice. Therefore, we aimed to investigate the way by which asthma induction affects T-cell exhaustion in the lungs and assess the relationship between T-cell exhaustion and influenza viral infection. METHODS: Chronic allergic asthma mice were induced by intranasal injection of ovalbumin for 6 weeks and asthmatic features and T cell populations in lung or airway were assessed. To determine the influenza virus susceptibility, control and asthma mice were challenged with the human influenza virus strain A/Puerto Rico/8/1934 H1N1 and evaluated the survival rate, lung damage, and virus titer. RESULTS: Six weeks of OVA sensitization and challenge successfully induced chronic allergic asthma in a mouse model showing significant increase of sera IgE level and broncho-pathological features. A significant decrease in interferon-γ-producing T-cell populations and an increase in exhausted T-cell populations in the lungs of OVA-induced asthmatic mice were observed. Asthmatic mice were more susceptible to influenza virus infection than control mice showing lower survival rate and higher virus titer in lung, and a positive correlation existed between T-cell exhaustion in the lung and virus titer. CONCLUSIONS: Asthma induction in mice results in the exhaustion of T-cell immunity, which may contribute to the defective capacity of viral protection. This study demonstrates a correlation between asthma conditions and viral susceptibility by investigating the functional characteristics of T-cells in asthma. Our results provide insights into the development of strategies to overcome the dangers of respiratory viral disease in patients with asthma.

Adjuvant effects of combination monophosphoryl lipid A and poly I:C on antigen-specific immune responses and protective efficacy of influenza vaccines.

Toll-like receptor (TLR) agonists improve vaccine immunogenicity and efficacy, but they are currently unlicensed as adjuvants in influenza vaccines. This study aimed to investigate whether a combination of monophosphoryl lipid A (MPL, a TLR4 agonist) and polyriboinosinic polyribocytidylic acid (poly I:C, a TLR3 agonist) can enhance the protective efficacy of an inactivated A/Puerto Rico/8/1934 (A/PR8) H1N1 influenza vaccine against homologous influenza infection and minimize illness outcomes. Results showed that combination MPL and poly I:C adjuvanted influenza vaccination increased the production of antigen-specific antibodies, decreased the levels of cytokines and cellular infiltrates at the infection sites, and induced significant memory T and B cell responses in mice. The results of this study suggest that the combination of MPL and poly I:C can be developed into a possible adjuvant for enhancing the efficacy of influenza vaccines.

In vitro effects of monophosphoryl lipid A and Poly I:C combination on equine cells.

BACKGROUND: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. OBJECTIVES: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). METHODS: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. RESULTS: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1ß, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. CONCLUSIONS: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.

Elucidation of Phytochemicals Affecting Platelet Responsiveness in Dangguisu-san: Active Ingredient Prediction and Experimental Research Using Network Pharmacology.

Plant-derived phytochemicals are emerging as novel agents for protection against chronic disorders. Dangguisu-san is a herbal prescription to invigorate the blood and relieve pain. Among the numerous active constituents of Dangguisu-san, those expected to be effective at inhibiting platelet aggregation were predicted using a network pharmacological method, and their efficacy was experimentally demonstrated. All four identified chemical components, namely chrysoeriol, apigenin, luteolin, and sappanchalcone, suppressed the aggregation of platelets to a certain extent. However, we report, for the first time, that chrysoeriol acts as a strong inhibitor of platelet aggregation. Although additional in vivo studies are needed, among the complex constituents of herbal medicines, the components that exert an inhibitory effect on platelet aggregation were predicted using a network pharmacological method and experimentally confirmed with human platelets.

Comparative study of lumbar bone mineral content using DXA and CT Hounsfield unit values in chest CT.

BACKGROUND: Bone mineral content (BMC) values in certain bones and changes in BMC over time are key features for diagnosing osteoporosis. This study examined those features using morphometric texture analysis in chest computational tomography (CT) by comparing a dual-energy X-ray absorptiometry (DXA)-based BMC. An accessible approach for screening osteoporosis was suggested by accessing BMC using only Hounsfield units (HU). METHODOLOGY: The study included a total of 510 cases (255 patients) acquired between May 6, 2012, and June 30, 2020, at a single institution. Two cases were associated with two chest CT scans from one patient with a scan interval of over two years, and each scan was followed soon after by a DXA scan. Axial cuts of the first lumbar vertebra in CT and DXA-based L1 BMC values were corrected for each case. The maximum trabecular area was selected from the L1 spine body, and 45 texture features were extracted from the region using gray-level co-occurrence matrices. A regression model was employed to estimate the absolute BMC value in each case using 45 features. Also, an additional regression model was used to estimate the change in BMC between two scans for each patient using 90 features from the corresponding cases. RESULTS: The correlation coefficient (CC) and mean absolute error (MAE) between estimates and DXA references were obtained for the evaluation of regressors. In the case of the BMC estimation, CC and MAE were 0.754 and 1.641 (g). In the case of the estimation of change in BMC, CC and MAE were 0.680 and 0.528 (g). CONCLUSION: The modality using morphometric texture analysis with CT HUs can indirectly help screening osteoporosis because it provides estimates of BMC and BMC change that show moderate positive correlations with DXA measures.

Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Optimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation. METHODS: In this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels. RESULTS: Of all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7-22.2) and MPD involvement (OR 16.8, 95% CI 1.6-174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy. CONCLUSIONS: This combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.

Effects of transcranial direct current stimulation on neural activity and functional connectivity during fear extinction

Background/Objective: Anxiety disorders are highly prevalent and negatively impact daily functioning and quality of life. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), especially in the right hemisphere impacts extinction learning; however, the underlying neural mechanisms are elusive. Therefore, we aimed to investigate the effects of cathodal tDCS stimulation to the right dlPFC on neural activity and connectivity patterns during delayed fear extinction in healthy participants. Methods: We conducted a two-day fear conditioning and extinction procedure. On the first day, we collected fear-related self-reports, clinical questionnaires, and skin conductance responses during fear acquisition. On the second day, participants in the tDCS group (n = 16) received 20-min offline tDCS before fMRI and then completed the fear extinction session during fMRI. Participants in the control group (n = 18) skipped tDCS and directly underwent fMRI to complete the fear extinction procedure. Whole-brain searchlight classification and resting-state functional connectivity analyses were performed. Results: Whole-brain searchlight classification during fear extinction showed higher classification accuracy of threat and safe cues in the left anterior dorsal and ventral insulae and hippocampus in the tDCS group than in the control group. Functional connectivity derived from the insula with the dlPFC, ventromedial prefrontal cortex, and inferior parietal lobule was increased after tDCS. Conclusion: tDCS over the right dlPFC may function as a primer for information exchange among distally connected areas, thereby increasing stimulus discrimination. The current study did not include a sham group, and one participant of the control group was not randomized. Therefore, to address potential allocation bias, findings should be confirmed in the future with a fully randomized and sham controlled study. (AU)

Functional Connectivity in the Mouse Brainstem Represents Signs of Recovery from Concussion.

Mild traumatic brain injury (mTBI) is one of the most frequent neurological disorders. Diagnostic criteria for mTBI are based on cognitive or neurological symptoms without fully understanding the neuropathological basis for explaining behaviors. From the neuropathological perspective of mTBI, recent neuroimaging studies have focused on structural or functional differences in motor-related cortical regions but did not compare topological network properties between the post-concussion days in the brainstem. We investigated temporal changes in functional connectivity and evaluated network properties of functional networks in the mouse brainstem. We observed a significantly decreased functional connectivity and global and local network properties on post-concussion day 7, which normalized on post-concussion day 14. Functional connectivity and local network properties on post-concussion day 2 were also significantly decreased compared with those on post-concussion day 14, but there were no significant group differences in global network properties between days 2 and 14. We also observed that the local efficiency and clustering coefficient of the brainstem network were significantly correlated with anxiety-like behaviors on post-concussion days 7 and 14. This study suggests that functional connectivity in the mouse brainstem provides vital recovery signs from concussion through functional reorganization.

Estimation of Bone Mineral Density in the Femoral Neck and Lumbar Spine using Texture Analysis of Chest and Pelvis Computed Tomography Hounsfield Unit.

OBJECTIVE: This study aimed to establish an academic basis for using a computed tomography (CT) model for predicting osteoporosis in the clinical setting by illustrating the effectiveness of morphometric texture analysis. We introduce texture analysis and quantitative approaches using CT Hounsfield units (HU) to screen osteoporosis. METHODS: From March 6th, 2013, to August 11th, 2020, a total of 4,333 cases (1,766 patients) were included in the study. After applying exclusion criteria concerning the patient status and scan interval between CT and DXA, we selected only 1,647 samples (736 patients) and analyzed both their CT and DXA bone mineral density (BMD) results. BMD was measured in the femoral neck and L1 spine body. A region of interest (ROI) was extracted from each patient's CT as the maximum trabecular area of the L1 spine body and femoral neck. A total of 45 texture features were extracted from every ROI using gray-level co-occurrence matrices. Machine-learning techniques, including linear regression (LR) and artificial neural network (ANN), were applied to predict BMD. RESULTS: We assigned samples to (1) Set 1 (857 lumbar spine samples in chest model, L1 spine DXA BMD), (2) Set 2 (392 lumbar spine samples in lumbar spine CT model, L1 spine DXA BMD), (3) Set 3 (1,249 lumbar spine samples in both chest and lumbar spine CT model, L1 spine DXA BMD), (4) Set 4 (398 femoral neck samples in hip and pelvis CT model, femoral neck DXA BMD), and (5) Set 5 (a total of 1,647 samples). When we applied LR, the correlation coefficients between estimated and reference values for Sets 1, 2, 3, and 4 were 0.783, 0.784, 0.757, and 0.652, respectively. For total samples (Set 5), LR and ANN provided correlation coefficients of 0.707 and 0.782, respectively. CONCLUSION: The modality using morphometric texture analysis with CT HU can be an additional diagnostic tool for osteoporosis and an alternative for DXA.

Effects of transcranial direct current stimulation on neural activity and functional connectivity during fear extinction.

Background/Objective: Anxiety disorders are highly prevalent and negatively impact daily functioning and quality of life. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), especially in the right hemisphere impacts extinction learning; however, the underlying neural mechanisms are elusive. Therefore, we aimed to investigate the effects of cathodal tDCS stimulation to the right dlPFC on neural activity and connectivity patterns during delayed fear extinction in healthy participants. Methods: We conducted a two-day fear conditioning and extinction procedure. On the first day, we collected fear-related self-reports, clinical questionnaires, and skin conductance responses during fear acquisition. On the second day, participants in the tDCS group (n = 16) received 20-min offline tDCS before fMRI and then completed the fear extinction session during fMRI. Participants in the control group (n = 18) skipped tDCS and directly underwent fMRI to complete the fear extinction procedure. Whole-brain searchlight classification and resting-state functional connectivity analyses were performed. Results: Whole-brain searchlight classification during fear extinction showed higher classification accuracy of threat and safe cues in the left anterior dorsal and ventral insulae and hippocampus in the tDCS group than in the control group. Functional connectivity derived from the insula with the dlPFC, ventromedial prefrontal cortex, and inferior parietal lobule was increased after tDCS. Conclusion: tDCS over the right dlPFC may function as a primer for information exchange among distally connected areas, thereby increasing stimulus discrimination. The current study did not include a sham group, and one participant of the control group was not randomized. Therefore, to address potential allocation bias, findings should be confirmed in the future with a fully randomized and sham controlled study.