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Chen, C.-L. W.

Publications and source records attributed to Chen, C.-L. W..

2 recordsLinked to original sources

A longitudinal naturalistic fMRI study of trait anxiety and cross-phase consistency in subjective fear signature expression

Persistent fear is a central feature of anxiety, but it remains unclear whether this persistence is more closely related to the consistency of conditioned-threat processing or to the consistency of subjectively experienced fear. Using a longitudinal naturalistic viewing fMRI paradigm, the present study examined whether trait anxiety was associated with cross-phase consistency in the expression of two validated fear-related neural signatures. Forty-two participants completed two fMRI phases separated by approximately three months, viewing the same sequence of 18 naturalistic videos followed by a post-viewing resting-state segment, resulting in 19 corresponding analysis segments for all cross-phase analyses. We applied pre-trained subjective-fear and threat-conditioning signatures to estimate their expression over time and examined how consistently each signature was reexpressed across phases within each participant. We found that higher trait anxiety was significantly associated with greater cross-phase consistency in subjective-fear signature expression, whereas no significant association was observed for threat-conditioning signature expression. This association became more prominent over longer temporal windows and was not detected in the average time series of the amygdala, ventro-medial prefrontal cortex, insula, or hippocampus. These findings suggest that individual differences in trait anxiety are more closely associated with the consistent cross-phase reexpression of distributed neural patterns related to subjective fear than with the stability of conditioned-threat processing or regional neural dynamics. Taken together, this study shows how predictive brain models combined with longitudinal naturalistic viewing provide a new approach for examining individual differences in trait anxiety across repeated experiences of the same naturalistic contexts. HighlightsO_LIHigher trait anxiety predicted greater cross-phase subjective-fear consistency. C_LIO_LINo association emerged for the threat-conditioning neural signature. C_LIO_LIThe subjective-fear effect strengthened over longer temporal windows. C_LIO_LIThe effect was not detected in amygdala, vmPFC, insula, or hippocampus. C_LIO_LILongitudinal naturalistic fMRI tracked fear signatures across three months. C_LI

neuroscience↗

Mechanism of the Switch from NO to H2O2 in Endothelium-Dependent Vasodilation in Diabetes

Coronary microvascular dysfunction is prevalent among diabetics and is correlated with cardiac mortality. Compromised endothelial-dependent dilation (EDD) is an early event in the progression of diabetes, but the mechanisms remain incompletely understood. Nitric oxide (NO) is the major endothelium-dependent vasodilatory metabolite in the healthy coronary circulation, but switches to hydrogen peroxide (H2O2) in coronary artery disease (CAD) patients. Because diabetes is a major risk factor for CAD we hypothesized that a similar switch from NO-to-H2O2 occurs in diabetes. Methods: Vasodilation was measured ex vivo in isolated coronary arteries from wild type (WT) and microRNA-21 (miR-21) null mice fed chow or high fat and sugar diet, and LepR null (db/db) mice using myography. Myocardial blood flow (MBF), blood pressure, and heart rate were measured in vivo using contrast echocardiography and a solid-state pressure sensor catheter. RNA from coronary arteries, endothelial cells and hearts were analyzed via qPCR for gene expression and protein expression was assessed via Western-Blot analyses. Superoxide was detected via electron paramagnetic resonance (EPR). Results: 1) Ex vivo coronary EDD and in vivo MBF was impaired in diabetes. 2) L-NAME (NO-synthase inhibitor) inhibited ex vivo coronary EDD and in vivo MBF in WT, while PEG-catalase (H2O2 scavenger) inhibited diabetic EDD ex vivo and MBF in vivo. 5) miR-21 deficiency blocked the NO-to-H2O2 switch and prevented diabetic vasodilation impairments. 6) Diabetic mice displayed increased serum NO and H2O2, upregulated mRNA expression of Sod1, Sod2, iNos, and Cav-1, and downregulated Pgc-1. Deficiency of miR-21 reversed these changes. 7) miR-21 deficiency increased PGC1, PPAR and eNOS protein and reduced detection of endothelial superoxide. Conclusions: Diabetics exhibit an NO-to-H2O2 switch in the mediator of EDD coronary dilation, which contributed to microvascular dysfunction and is mediated by miR-21. This study represents the first mouse model recapitulating the NO-to-H2O2 switch seen in CAD patients.

physiology↗