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Background Default-mode network (DMN) plays a key role in the pathophysiology of obsessive−compulsive disorder (OCD). However, the network homogeneity (NH) of DMN in OCD remains equivocal. Objective This study aimed to investigate abnormalities in the NH of the DMN at rest and the correlation between the NH of DMN and clinical variables in patients with OCD. Methods This study used the independent component analysis and unbiased hypothesis-driven NH method to analyze the resting-state functional magnetic resonance imaging data of 40 drug-naive patients with OCD and 40 age-, gender-, and education-matched healthy controls (HCs). Results Patients with OCD exhibited decreased NH values in the left ventral medial prefrontal cortex and bilateral posterior cingulate cortex (PCC)/precuneus (PCu) compared with HCs. Furthermore, analyses of receiver operating characteristic curves indicated that the decreased NH values in the right PCC/PCu may be used as a candidate neuroimaging marker to distinguish patients with OCD from HCs. Conclusion These findings contribute new evidence of the participation of the altered NH of the DMN in the pathophysiology of OCD. Trial Registration Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (ChiCTR-COC-17013301).

Background Variation in the CYP2A6 gene alters the rate of nicotine metabolic inactivation and is associated with smoking behaviors and cessation success rates. The underlying neurobiological mechanisms of this genetic influence are unknown. Methods Intrinsic functional connectivity strength, a whole-brain, data-driven, graph theory–based method, was applied to resting-state functional magnetic resonance imaging data in 66 smokers and 92 nonsmokers. A subset of subjects ( n = 23/20; smokers/nonsmokers) performed the monetary incentive delay task, probing reward anticipation, and a go/no-go task, probing response inhibition, on two occasions, in the presence and absence of a nicotine patch. Results A significant CYP2A6 genotype × smoking effect was found in the dorsal anterior cingulate cortex and ventral striatum, such that the normal (vs. slow) genotype individuals showed greater functional connectivity strength among smokers but not nonsmokers. Functional connectivity strength was negatively associated with severity of nicotine dependence in slow metabolizers. Both hubs were biased by inputs from the insula identified from seed-based connectivity. Similar gene × environment interactions were seen in ventral striatum during smoking abstinence when subjects performed the monetary incentive delay task and in dorsal anterior cingulate cortex when they performed the go/no-go task; both reductions were "normalized" in smokers (and increased in nonsmokers) after acute nicotine administration. Conclusions Because the CYP2A6 effect was seen only in smokers, these data suggest that the rate of nicotine metabolism—and thus the concentration of nicotine presented to the brain over the course of nicotine addiction—shapes brain circuits that, among other functions, compute reward and impulsivity processes.

Regional homogeneity (ReHo) quantifies spatially local synchronization of resting state fMRI signal and has been applied to lots of clinic studies. Accumulating evidences demonstrated that the synchronization between spatially distinct brain regions, i.e. functional connectivity, can be remarkably influenced if the global mean time course is regressed out, namely global signal regression (GSR). Very recently, it was reported GSR reduces the test-retest reliability of ReHo, and reduces the positive correlation between ReHo and head motion. In this study, we were interested in two questions: 1) how GSR affects the raw ReHo values and its spatial distribution over the brain; 2) how GSR affects the differences of ReHo between two resting states, eyes open (EO) and eyes closed (EC), in healthy individuals. We found that the ReHo values were reduced by GSR but the spatial distribution of ReHo was not changed remarkably. In addition, split-half reproducibility analysis showed reproducible ReHo difference between EO and EC in some areas (e.g., thalamus and caudate) only with GSR, but showed reproducible ReHo difference in some other area (right temporal pole) only without GSR. The effects of GSR were almost independent of regression of other nuisance covariates. Our results suggest that the influences of GSR on ReHo are remarkable, reliable and complex. For the between-condition comparison, the GSR effects are region specific. We suggest that, for application studies using ReHo approach, it would be helpful to report results both with and without GSR.

Objectives: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive–compulsive disorder (OCD), the treatment mechanisms remain poorly understood. This study aimed to investigate the effects of CBT on changes in the intrinsic whole-brain functional network of OCD patients. Materials and Methods: Twenty drug-naive and noncomorbid OCD patients were recruited, and resting-state functional magnetic resonance imaging was performed before and after 12 weeks of CBT. Moreover, 20 healthy controls were scanned twice with a 12-week interval. A graph-theory degree centrality (DC) approach and functional connectivity method were used to analyze the whole-brain functional network hub and connectivity changes in OCD patients before and after CBT treatment. Results: A significant group × time interaction on DC was found in the left dorsolateral prefrontal cortex (DLPFC); the DC in the left DLPFC was significantly reduced after CBT treatment. Resting-state functional connectivity (RSFC) between the left DLPFC and right orbitofrontal cortex was increased in the OCD patients at baseline, and normalized after CBT treatment. RSFC changes between the left DLPFC and default mode network (DMN) positively correlated with changes in clinical symptoms in OCD patients. Conclusions: These findings suggest that CBT can modulate changes in intrinsic functional network hubs in the cortico–striato–thalamo-cortical circuit in OCD patients. Cognitive control network and DMN connectivity may be a potential imaging biomarker for evaluating CBT treatment for OCD.

The changes of spontaneous activity from before and after a memory or learning task had been considered to be related to off-line memory consolidation process in human brain by using resting-state functional connectivity (RSFC) MRI (fMRI). However, RSFC reflects temporal synchronization of timecourses of spatially distinct brain regions and therefore could not determine which specific brain region is involved in the memory consolidation process. Here we used regional homogeneity (ReHo), a method for measuring local synchronization, to link the local spontaneous activity change to off-line episodic memory consolidation. We hypothesized that the spontaneous activity change would be different between people with better memory performance and those with worse performance in memory-related regions. All participants completed two resting-state sessions, that is, before (REST-1) and after (REST-2) an episodic memory encoding task (picture indoor or outdoor judgment). Then, based on the d' of a later surprise memory retrieval test, a high-performance group and a low-performance group, each consisting of 16 participants, were chosen from whole 58 participants. We defined a ReHo ratio, that is, ReHo of REST-2 divided by ReHo of REST-1, as a change induced by memory consolidation. The high-performance group showed a significant higher ReHo ratio than low-performance group in medial temporal lobe (MTL) including parahippocampal and anterior temporal regions. The current results provide neuroimaging evidence supporting that the MTL is involved in off-line memory consolidation of episodic memory. Moreover, this study may provide a paradigm for understanding of episodic memory deficit in Alzheimer's disease.

We examined resting state brain activity in the depressive phase of bipolar disorder (BD) by measuring the amplitude of low-frequency fluctuations (ALFF) in the functional magnetic resonance imaging (fMRI) signal. Unlike functional connectivity, the ALFF approach reflects local properties in specific regions and provides direct information about impaired foci. Groups of 26 patients with BD depression and 26 gender-, age-, and education-matched healthy subjects participated in fMRI scans. We examined group differences in ALFF findings as well as correlations between clinical measurements and ALFF in the regions showing significant group differences. Our results showed that patients with BD depression had significantly increased ALFF in the left insula, the right caudate nucleus, the temporal gyrus, the bilateral inferior frontal gyrus, and the posterior lobe of the cerebellum. They also had decreased ALFF in the left postcentral gyrus, the left parahippocampal gyrus, and the cerebellum. Moderate negative correlations were found between the Hamilton Depression Rating Scale score and ALFF in the left insular cortex in the patient group. These results support a model of BD that involves dysfunction in the prefrontal-limbic networks and associated striatal systems. We also demonstrated the feasibility of ALFF as a technique to investigate persistent cerebral dysfunction in BD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to assess the safety of fenofibrate-statin combination therapy.Medline, Cochrane Library, Web of Knowledge and CNKI were searched for 2184 randomized controlled trials. Finally, twenty-six studies with a total of 9494 participants were included in this analysis.Compared with statins group, the fenofibrate-statin group had significantly higher incidence of aminotransferase elevations (OR 1.67, 95%CI 1.22-2.30, P0.05) . The two groups had identical incidence of creatin kinase elevations (OR 0.86, 95%CI 0.62-1.20, P0.05) , muscle-associated adverse events (OR 0.98, 95%CI 0.88-1.09, P0.05) and withdrawals due to hepatotoxicity or muscle toxicity. The safety of fenofibrate + standard-dose statin regimens were similar to those in fenofibrate-statin group.Combined fenofibrate-statin treatment is generally safe and well tolerated, liver function should be monitored before and during and after therapy.

Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years.The clinical data of 3498 patients hospitalized in Peking University People's Hospital with AMI from 1991 to 2010 were used. Information was collected regarding to patients' demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia and current smoking). To assess trends over time in the prevalence of risk factors, we categorized patients into four groups (1991 to 1995, 1996 to 2000, 2001 to 2005 and 2006 to 2010).Highly significant increases were observed in the prevalence of hypertension from 40.8% to 55.6% for males and from 58.0% to 69.0% for females; and diabetes mellitus from 12.9% to 30.8% for males and from 23.0% to 42.3% for females. Similarly, the prevalence of hypercholesterolaemia decreased from 53.1% to 30.7% for males and from 57.0% to 44.0% for females. The prevalence of current smoking decreased in females from 29.0% to 11.1%, but remained unchanged in males. In addition, the proportion of patients with more than three modifiable risk factors increased from 19.0% to 27.1% and the age at onset of AMI extended to younger as well as older individuals.The prevalence of hypertension and diabetes mellitus are still increasing in patients with AMI in Beijing and although the prevalence of hypercholesterolaemia and current smoking decreased, high clustering of risk factors were commonly present. These adverse trends show a compelling need for more effective management of cardiovascular risk factors.

Aims The contraction of a heart cell is controlled by Ca2+-induced Ca2+ release between L-type Ca2+ channels (LCCs) in the cell membrane/T-tubules (TTs) and ryanodine receptors (RyRs) in the junctional sarcoplasmic reticulum (SR). During heart failure, LCC–RyR signalling becomes defective. The purpose of the present study was to reveal the ultrastructural mechanism underlying the defective LCC–RyR signalling and contractility. Methods and results In rat models of heart failure produced by transverse aortic constriction surgery, stereological analysis of transmission electron microscopic images showed that the volume density and the surface area of junctional SRs and those of SR-coupled TTs were both decreased in failing heart cells. The TT–SR junctions were displaced or missing from the Z-line areas. Moreover, the spatial span of individual TT–SR junctions was markedly reduced in failing heart cells. Numerical simulation and junctophilin-2 knockdown experiments demonstrated that the decrease in junction size (and thereby the constitutive LCC and RyR numbers) led to a scattered delay of Ca2+ release activation. Conclusions The shrinking and eventual absence of TT–SR junctions are important mechanisms underlying the desynchronized and inhomogeneous Ca2+ release and the decreased contractile strength in heart failure. Maintaining the nanoscopic integrity of TT–SR junctions thus represents a therapeutic strategy against heart failure and related cardiomyopathies.

In this study, we explored different spontaneous functional connectivity patterns between the anterior prefrontal cortex and other brain regions in nonmedicated patients with obsessive-compulsive disorder in a resting state, and examined the relationship between the abnormal spontaneous functional connectivity patterns of the anterior prefrontal cortex and clinical symptoms in patients with obsessive-compulsive disorder. Twenty nonmedicated patients with obsessive-compulsive disorder and 20 sex-matched and age-matched healthy individuals underwent resting state functional MRI scanning. Compared with the healthy controls, significantly increased positive functional connectivity with the right anterior prefrontal cortex was observed in the right insula and the middle cingulate cortex in patients with obsessive-compulsive disorder. Our findings suggest that abnormal intrinsic or spontaneous functional connectivity in the cognitive control system in a resting state may underlie the pathophysiology of obsessive-compulsive disorder.

Background Major depressive disorder (MDD) is a highly heritable psychiatric disease, and the existing literature is not robust enough to allow us to evaluate whether MDD-associated biomarkers are state-independent heritable endophenotypes or state markers related to depression per se. Methods Twenty two patients diagnosed with MDD, 22 siblings, as well as 26 gender-, age-, and education-matched healthy subjects, participated in the resting-state functional magnetic resonance imaging (fMRI) analysis. We compared the differences in the fractional amplitude of low-frequency fluctuation (fALFF) among the three groups and investigated the correlation between clinical measurements and fALFF in the regions displaying significant group differences. Results Both the MDD and siblings groups showed an increased fALFF in the left middle frontal gyrus (l-MFG, Brodmann Area, BA 10) compared to the healthy controls. The MDD groups demonstrated an increased fALFF in the right dorsal medial frontal gyrus (r-DMFG, BA 9) and a decreased fALFF in the bilateral lingual gyrus relative to siblings and healthy controls. Limitations Medication effects, an inability to control subjects' thoughts during imaging. Conclusions Our results suggest that the dysfunction in the l-MFG may represent an imaging endophenotype which may indicate a risk for MDD. The r-DMFG may play a critical role in depressive symptomatology and may reveal therapeutic target for MDD.

Previous case-control and family-based association studies have implicated the SLC6A4 gene in obsessive-compulsive disorder (OCD). Little research, however, has examined this gene's role in obsessive-compulsive symptoms (OCS) in community samples. The present study genotyped seven tag SNPs and two common functional tandem repeat polymorphisms (5-HTTLPR and STin2), which together cover the whole SLC6A4 gene, and investigated their associations with OCS in normal Chinese college students (N = 572). The results revealed a significant gender main effect and gender-specific genetic effects of the SLC6A4 gene on OCS. Males scored significantly higher on total OCS and its three dimensions than did females (ps

Spontaneous brain activity or off-line activity after memory encoding is associated with memory consolidation. A few recent resting-state functional magnetic resonance imaging (RS-fMRI) studies indicate that the RS-fMRI could map off-line memory consolidation effects. However, the gene effects on memory consolidation process remain largely unknown. Here we collected two RS-fMRI sessions, one before and another after an episodic memory encoding task, from two groups of healthy young adults, one with apolipoprotein E (APOE) e2/e3 and the other with APOE e3/e4. The ratio of regional homogeneity (ReHo), a measure of local synchronization of spontaneous RS-fMRI signal, of the two sessions was used as an index of memory-consolidation. APOE e3/e4 group showed greater ReHo ratio within the medial temporal lobe (MTL). The ReHo ratio in MTL was significantly correlated with the recognition memory performance in the APOE e3/e4 group but not in e2/e3 group. Additionally, APOE e3/e4 group showed lower ReHo ratio in the occipital and parietal picture-encoding areas. Our results indicate that APOE e3/e4 group may have a different off-line memory consolidation process compared to e2/e3 group. These results may help generate future hypotheses that the off-line memory consolidation might be impaired in Alzheimer’s disease.

BACKGROUND: Prior research has shown that the amygdala of carriers of the short allele (s) of the serotonin transporter (5-HTT) gene (5-HTTLPR) have a larger response to negative emotional stimuli and higher spontaneous activity during the resting state than non-carriers. However, recent studies have suggested that the effects of 5-HTTLPR may be specific to different ethnic groups. Few studies have been conducted to address this issue. METHODOLOGY/PRINCIPAL FINDINGS: Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was conducted on thirty-eight healthy Han Chinese subjects (l/l group, n = 19; s/s group, n = 19) during the resting state and during an emotional processing task. Compared with the s/s group, the l/l group showed significantly increased regional homogeneity or local synchronization in the right amygdala during the resting state (|t|>2.028, p