Test-retest reliability of mismatch negativity and gamma-band auditory steady-state response in patients with schizophrenia.

Patients with schizophrenia show widespread impairments in clinical, cognitive and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are two neurophysiological biomarkers widely used to inform diagnosis, guide treatments and track response to interventions in schizophrenia. However, evidence for the test-retest reliability of these indices across multiple sessions in schizophrenia patients remains scarce. In the present study, we included 34 schizophrenia patients (17 females) and obtained duration MMN (dMMN), frequency MMN (fMMN) and 40-Hz ASSR data across three sessions with intervals of 2 days. Event-related spectrum perturbation (ERSP) and inter-trial coherence (ITC) were calculated following Morlet wavelet time-frequency decomposition of ASSR data. The intra-class correlation coefficient (ICC) was used to quantify the reliability of MMN and ASSR measures among the three sessions. We found fair to good reliability for dMMN amplitudes but poor reliability for fMMN amplitudes. For the ASSR measures, ERSP showed good to excellent test-retest reliability while ITC had poor to fair test-retest reliability. In addition, the average of dMMN amplitudes was significantly correlated with that of ERSP across the three sessions. In summary, we established for the first time the short-term test-retest reliability of MMN and ASSR measures in schizophrenia patients. These findings demonstrate that dMMN amplitudes and ERSP of ASSR are reliable indices which may be used in longitudinal observational studies.

Test-retest reliability of duration-related and frequency-related mismatch negativity.

OBJECTIVES: -Mismatch negativity (MMN) has been demonstrated as a potential biomarker for pre-attentive processing and prognosis in patients with psychosis. However, previous studies mainly evaluated the reliability of MMN across only two repeated sessions, which is inadequate to draw a convincing conclusion. The current study aimed to assess multi-session test-retest reliability in duration-related MMN (dMMN) and frequency-related MMN (fMMN). METHODS: -We recorded four repeated sessions of electroencephalography (EEG) from 16 healthy participants in an oddball task. MMNs were extracted and their reliability was evaluated by intra-class coefficient (ICC). We also analyzed the correlation between fMMN and dMMN. RESULTS: -Both dMMN and fMMN amplitudes exhibited good test-retest reliability, and fMMN had better reliability (average ICC = 0.7279) than dMMN (average ICC = 0.6974). Moreover, dMMN and fMMN showed more than moderate linear correlation in amplitudes (r = 0.598, CI: [0.100, 0.857]). CONCLUSION: -Both the duration- and frequency-related MMN amplitudes were highly reliable across four-session experiments. These results provide further evidence for the potential utility of MMNs as biomarkers in research into brain function, and prognosis in psychotic illness.

The lateralization and reliability of spatial mismatch negativity elicited by auditory deviants with virtual spatial location.

Mismatch negativity (MMN) is an intensively studied event-related potential component that reflects pre-attentive auditory processing. Existing spatial MMN (sMMN) studies usually use loud-speakers in different locations or deliver sound with binaural localization cues through earphones to elicit MMN, which either was practically complicated or sounded unnatural to the subjects. In the present study, we generated head related transfer function (HRTF)-based spatial sounds and verified that the HRTF-based sounds retained the left and the right spatial localization cues. We further used them as deviants to elicit sMMN with conventional oddball paradigm. Results showed that sMMN was successfully elicited by the HRTF-based deviants in 18 of 21 healthy subjects in two separate sessions. Furthermore, the left deviants elicited higher sMMN amplitudes in the right hemisphere compared to the left hemisphere, while the right deviants elicited sMMN with similar amplitudes in both hemispheres, which supports a combination of contralateral and right-hemispheric dominance in spatial auditory information processing. In addition, the sMMN in response to the right deviants showed good test-retest reliability, while the sMMN in response to the left deviants had weak test-retest reliability. These findings implicate that HRTF-based sMMN could be a robust paradigm to investigate spatial localization and discrimination abilities.

Guanxintai Exerts Protective Effects on Ischemic Cardiomyocytes by Mitigating Oxidative Stress.

Oxidative stress participates in numerous myocardial pathophysiological processes and is considered a therapeutic target for myocardial ischemia and heart failure. Guanxintai (GXT), a traditional Chinese medicine, is commonly used to treat cardiovascular disease on account of its numerous beneficial physiological activities, such as dilating coronary arteries, inhibiting platelet aggregation, and reducing the serum lipid content. However, the antioxidative properties of GXT and potential underlying mechanisms remain to be established. In the present study, we investigated the protective effects of GXT on ischemic cardiomyocytes and the associated antioxidative mechanisms, both in vivo and in vitro. Notably, GXT treatment reduced the degree of cardiomyocyte injury, myocardial apoptosis, and fibrosis and partially improved cardiac function after myocardial infarction. Furthermore, GXT suppressed the level of ROS as well as expression of NADPH oxidase (NOX) and phospho-p38 mitogen-activated protein kinase (MAPK) proteins. Our results collectively suggest that the protective effects of GXT on ischemic cardiomyocytes are exerted through its antioxidative activity of NOX inhibition.

QishenYiqi Dripping Pill Improves Heart Failure by Up-Regulation of ß2-Adrenergic Receptor Expression.

BACKGROUND: QishenYiqi Dripping Pill (QYDP) is a Chinese herbal medicine that originally was used for the treatment of coronary artery disease. Recently, QYDP was used as a complementary treatment for heart failure (HF) in China. METHODS: An HF rat model was used to clarify the possible therapeutic effects of QYDP on HF. The HF rats were allocated to two groups, HF and HF+QYDP, while normal rats served as a negative control. Cardiac functions were evaluated echocardiographically and hemodynamically. Cardiac apoptosis and the expression of ß-adrenergic receptors were also investigated. RESULTS: Compared to the HF group, rats in the HF+QYDP group had a significantly higher fraction shortening (p<0.05), ejection fraction (p<0.05), left ventricular systolic pressure (p<0.05), maximum positive derivatives of left ventricular pressure (p<0.05), maximum negative derivatives of left ventricular pressure (p<0.05), and ß2-adrenergic receptor expression (p<0.05), and lower left ventricular end-diastolic pressure (p<0.05) and apoptotic index (p<0.05). CONCLUSIONS: The study results indicated that QYDP could efficiently improve HF, possibly by an inhibition of cardiac apoptosis via the ß2-adrenergic receptor signaling pathway. Hence, QYDP might be a promising candidate drug for HF therapy.

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction.

Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.

Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia.

The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycorticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hyporesponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsiveness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.

Motor imagery cognitive network after left ischemic stroke: study of the patients during mental rotation task.

Although motor imagery could improve motor rehabilitation, the detailed neural mechanisms of motor imagery cognitive process of stroke patients, particularly from functional network perspective, remain unclear. This study investigated functional brain network properties in each cognitive sub-stage of motor imagery of stroke patients with ischemic lesion in left hemisphere to reveal the impact of stroke on the cognition of motor imagery. Both stroke patients and control subjects participated in mental rotation task, which includes three cognitive sub-stages: visual stimulus perception, mental rotation and response cognitive process. Event-related electroencephalograph was recorded and interdependence between two different cortical areas was assessed by phase synchronization. Both global and nodal properties of functional networks in three sub-stages were statistically analyzed. Phase synchronization of stroke patients significantly reduced in mental rotation sub-stage. Longer characteristic path length and smaller global clustering coefficient of functional network were observed in patients in mental rotation sub-stage which implied the impaired segregation and integration. Larger nodal clustering coefficient and betweenness in contralesional occipitoparietal and frontal area respectively were observed in patients in all sub-stages. In addition, patients also showed smaller betweenness in ipsilesional central-parietal area in response sub-stage. The compensatory effects on local connectedness and centrality indicated the neuroplasticity in contralesional hemisphere. The functional brain networks of stroke patients demonstrated significant alterations and compensatory effects during motor imagery.

Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells.

Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)-derived splenic CD11b(+)CD8α(-)Esam(high) DCs and the developmentally related CD11b(+)CD103(+) subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC-derived CD11b(-)CD8α(+) and CD11b(-)CD103(+) nor monocyte-derived CD11b(+)CD8α(-)Esam(low) or CD11b(+)CD103(-) DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b(+)CD8α(-) subset, whereas transfer into vitamin A-deficient (VAD) hosts caused diversion to the CD11b(-)CD8α(+) lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II-restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC-derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation.

Functional brain networks for sensory maintenance in top-down selective attention to audiovisual inputs.

Sensory maintenance in top-down selective attention to audiovisual inputs involves distributed cortical activations, while the connectivity between the widespread cortical regions has not been well understood. Graph theory has been demonstrated to be a useful tool in the analysis of brain networks. In this study, we used graph theoretical analysis to investigate the functional brain networks for sensory maintenance in top-down selective attention to audiovisual inputs. Electroencephalograms (EEGs) of 30 channels were recorded from 13 young healthy subjects during a passive view task and a top-down intersensory selective attention task. Phase synchronization indices of EEG signals in pair were computed to construct weighted brain networks. We found small-world properties of the brain networks during both passive view state and top-down selective attentional state in α, ß, and γ bands. In addition, the significantly increased clustering coefficient and decreased characteristic path length were observed for brain networks during attentional state compared with passive view state in both ß band and γ band. Our results suggest that functional brain networks in higher frequency bands, i.e., ß band and γ band, are integrated in different ways during attentional state compared with passive view state.

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia.

PURPOSE: The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock. METHODS: Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist, and dexamethasone (DEX), a glucocorticoid agonist, or with placebo for 96 h. Oxacillin (30 mg/kg every 8 h) was started 4 h after infection onset. Bacterial dose was titrated to achieve 80-90 % lethality (n = 20) using an adaptive design; additional animals (n = 18) were investigated using the highest bacterial dose. RESULTS: Initial analysis of all animals (n = 38) demonstrated that the effects of DOC + DEX were significantly altered by bacterial dose (p = 0.04). The treatment effects of DOC + DEX were different in animals administered high or relatively lower bacterial doses in terms of survival (p = 0.05), shock reversal (p = 0.02), interleukin-6 levels (p = 0.02), and temperature (p = 0.01). DOC + DEX significantly improved the above parameters (p ≤ 0.03 for all) and lung injury scores (p = 0.02) after high-dose bacterial challenges, but not after lower challenges (p = not significant for all). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC + DEX increased the frequency of persistent staphylococcal bacteremia (odds ratio 3.09; 95 % confidence interval 1.05-9.11; p = 0.04). CONCLUSIONS: Stress-dose corticosteroids were only beneficial in cases of sepsis with high risk for death and even short courses may interfere with host mechanisms of bacterial clearance.

Cognitive alterations in motor imagery process after left hemispheric ischemic stroke.

BACKGROUND: Motor imagery training is a promising rehabilitation strategy for stroke patients. However, few studies had focused on the neural mechanisms in time course of its cognitive process. This study investigated the cognitive alterations after left hemispheric ischemic stroke during motor imagery task. METHODOLOGY/PRINCIPAL FINDINGS: Eleven patients with ischemic stroke in left hemisphere and eleven age-matched control subjects participated in mental rotation task (MRT) of hand pictures. Behavior performance, event-related potential (ERP) and event-related (de)synchronization (ERD/ERS) in beta band were analyzed to investigate the cortical activation. We found that: (1) The response time increased with orientation angles in both groups, called "angle effect", however, stoke patients' responses were impaired with significantly longer response time and lower accuracy rate; (2) In early visual perceptual cognitive process, stroke patients showed hypo-activations in frontal and central brain areas in aspects of both P200 and ERD; (3) During mental rotation process, P300 amplitude in control subjects decreased while angle increased, called "amplitude modulation effect", which was not observed in stroke patients. Spatially, patients showed significant lateralization of P300 with activation only in contralesional (right) parietal cortex while control subjects showed P300 in both parietal lobes. Stroke patients also showed an overall cortical hypo-activation of ERD during this sub-stage; (4) In the response sub-stage, control subjects showed higher ERD values with more activated cortical areas particularly in the right hemisphere while angle increased, named "angle effect", which was not observed in stroke patients. In addition, stroke patients showed significant lower ERD for affected hand (right) response than that for unaffected hand. CONCLUSIONS/SIGNIFICANCE: Cortical activation was altered differently in each cognitive sub-stage of motor imagery after left hemispheric ischemic stroke. These results will help to understand the underlying neural mechanisms of mental rotation following stroke and may shed light on rehabilitation based on motor imagery training.