Altered asymmetries of diffusion and volumetry in basal ganglia of schizophrenia.

Basal ganglia, which include the striatum and thalamus, have key roles in motivation, emotion, motor function, also contribute to higher-order cognitive function. Previous researches have documented structural and functional alterations in basal ganglia in schizophrenia. While few studies have assessed asymmetries of these characters in basal ganglia of schizophrenia. The current study investigated this issue by using diffusion tensor imaging, anatomic T1-weight image and resting-state functional data from 88 chronic schizophrenic subjects and 92 healthy controls. The structural characteristic, including fractional anisotropy, mean diffusivity (MD) and volume, were extracted and quantified from the subregions of basal ganglia, including caudate, putamen, pallidum and thalamus, through automated atlas-based method. The resting-state functional maps of these regions were also calculated through seed-based functional connectivity. Then, the laterality indexes of structural and functional features were calculated. Compared with healthy controls, schizophrenic subjects showed increased left laterality of volume in striatum and reduced left laterality of volume in thalamus. Furthermore, the difference of laterality of subregions in thalamus is compensatory in schizophrenic subjects. Importantly, the severity of patients' positive symptom was negative corelated with reduced left laterality of volume in thalamus. Our findings provide preliminary evidence demonstrating that the possibility of aberrant laterality in neural pathways and connectivity patterns related to the basal ganglia in schizophrenia.

Evaluation of functional connectivity in subdivisions of the thalamus in schizophrenia.

BACKGROUND: Previous studies in schizophrenia revealed abnormalities in the cortico-cerebellar-thalamo-cortical circuit (CCTCC) pathway, suggesting the necessity for defining thalamic subdivisions in understanding alterations of brain connectivity.AimsTo parcellate the thalamus into several subdivisions using a data-driven method, and to evaluate the role of each subdivision in the alterations of CCTCC functional connectivity in patients with schizophrenia. METHOD: There were 54 patients with schizophrenia and 42 healthy controls included in this study. First, the thalamic structural and functional connections computed, based on diffusion magnetic resonance imaging (MRI, white matter tractography) and resting-state functional MRI, were clustered to parcellate thalamus. Next, functional connectivity of each thalamus subdivision was investigated, and the alterations in thalamic functional connectivity for patients with schizophrenia were inspected. RESULTS: Based on the data-driven parcellation method, six thalamic subdivisions were defined. Loss of connectivity was observed between several thalamic subdivisions (superior-anterior, ventromedial and dorsolateral part of the thalamus) and the sensorimotor system, anterior cingulate cortex and cerebellum in patients with schizophrenia. A gradual pattern of dysconnectivity was observed across the thalamic subdivisions. Additionally, the altered connectivity negatively correlated with symptom scores and duration of illness in individuals with schizophrenia. CONCLUSIONS: The findings of the study revealed a wide range of thalamic functional dysconnectivity in the CCTCC pathway, increasing our understanding of the relationship between the CCTCC pathway and symptoms associated with schizophrenia, and further indicating a potential alteration pattern in the thalamic nuclei in people with schizophrenia.Declaration of interestNone.

Aberrant Prefrontal-Thalamic-Cerebellar Circuit in Schizophrenia and Depression: Evidence From a Possible Causal Connectivity.

Neuroimaging studies have suggested the presence of abnormalities in the prefrontal-thalamic-cerebellar circuit in schizophrenia (SCH) and depression (DEP). However, the common and distinct structural and causal connectivity abnormalities in this circuit between the two disorders are still unclear. In the current study, structural and resting-state functional magnetic resonance imaging (fMRI) data were acquired from 20 patients with SCH, 20 depressive patients and 20 healthy controls (HC). Voxel-based morphometry analysis was first used to assess gray matter volume (GMV). Granger causality analysis, seeded at regions with altered GMVs, was subsequently conducted. To discover the differences between the groups, ANCOVA and post hoc tests were performed. Then, the relationships between the structural changes, causal connectivity and clinical variables were investigated. Finally, a leave-one-out resampling method was implemented to test the consistency. Statistical analyses showed the GMV and causal connectivity changes in the prefrontal-thalamic-cerebellar circuit. Compared with HC, both SCH and DEP exhibited decreased GMV in middle frontal gyrus (MFG), and a lower GMV in MFG and medial prefrontal cortex (MPFC) in SCH than DEP. Compared with HC, both patient groups showed increased causal flow from the right cerebellum to the MPFC (common causal connectivity abnormalities). And distinct causal connectivity abnormalities (increased causal connectivity from the left thalamus to the MPFC in SCH than HC and DEP, and increased causal connectivity from the right cerebellum to the left thalamus in DEP than HC and SCH). In addition, the structural deficits in the MPFC and its causal connectivity from the cerebellum were associated with the negative symptom severity in SCH. This study found common/distinct structural deficits and aberrant causal connectivity patterns in the prefrontal-thalamic-cerebellar circuit in SCH and DEP, which may provide a potential direction for understanding the convergent and divergent psychiatric pathological mechanisms between SCH and DEP. Furthermore, concomitant structural and causal connectivity deficits in the MPFC may jointly contribute to the negative symptoms of SCH.

Reconfiguration of Dynamic Functional Connectivity in Sensory and Perceptual System in Schizophrenia.

Schizophrenia is thought as a self-disorder with dysfunctional brain connectivity. This self-disorder is often attributed to high-order cognitive impairment. Yet due to the frequent report of sensorial and perceptual deficits, it has been hypothesized that self-disorder in schizophrenia is dysfunctional communication between sensory and cognitive processes. To further verify this assumption, the present study comprehensively examined dynamic reconfigurations of resting-state functional connectivity (rsFC) in schizophrenia at voxel level, region level, and network levels (102 patients vs. 124 controls). We found patients who show consistently increased rsFC variability in sensory and perceptual system, including visual network, sensorimotor network, attention network, and thalamus at all the three levels. However, decreased variability in high-order networks, such as default mode network and frontal-parietal network were only consistently observed at region and network levels. Taken together, these findings highlighted the rudimentary role of elevated instability of information communication in sensory and perceptual system and attenuated whole-brain integration of high-order network in schizophrenia, which provided novel neural evidence to support the hypothesis of disrupted perceptual and cognitive function in schizophrenia. The foci of effects also highlighted that targeting perceptual deficits can be regarded as the key to enhance our understanding of pathophysiology in schizophrenia and promote new treatment intervention.

Reduction in gray matter of cerebellum in schizophrenia and its influence on static and dynamic connectivity.

Pathophysiological and atrophic changes in the cerebellum have been well-documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was confirmed across cognitive and motor cerebellar modules in schizophrenia. Such abnormalities in the cerebellum could potentially have widespread effects on both sensorimotor and cognitive symptoms. In this study, we investigated how reduction change in the cerebellum affects the static and the dynamic functional connectivity (FC) between the cerebellum and cortical/subcortical networks in schizophrenia. Reduction of GM in the cerebellum was confirmed across the cognitive and motor cerebellar modules in schizophrenic subjects. Results from this study demonstrates that the extent of reduction of GM within cerebellum correlated with increased static FCs between the cerebellum and the cortical/subcortical networks, including frontoparietal network (FPN), and thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also associated with a declined dynamic FC between the cerebellum and the FPN in schizophrenic subjects. The severity of patients' positive symptom was related to these structural-functional coupling score of cerebellum. These findings identified potential cerebellar driven functional changes associated with positive symptom deficits. A post hoc analysis exploring the effect of changed FC within cerebellum, confirmed that a significant positive relationship, between dynamic FCs of cerebellum-thalamus and intracerebellum existed in patients, but not in controls. The reduction of GM within the cerebellum might be associated with modulation of cerebellum-thalamus, and contributes to the dysfunctional cerebellar-cortical communication in schizophrenia. Our results provide a new insight into the role of cerebellum in understanding the pathophysiological of schizophrenia.

The Effects of Music Intervention on Functional Connectivity Strength of the Brain in Schizophrenia.

Schizophrenia is often associated with behavior abnormality in the cognitive and affective domain. Music intervention is used as a complementary treatment for improving symptoms in patients with schizophrenia. However, the neurophysiological correlates of these remissions remain poorly understood. Here, we investigated the effects of music intervention in neural circuits through functional magnetic resonance imaging (fMRI) study in schizophrenic subjects. Under the standard care, patients were randomly assigned to music and non-music interventions (MTSZ, UMTSZ) for 1 month. Resting-state fMRI were acquired over three time points (baseline, 1 month, and 6 months later) in patients and analyzed using functional connectivity strength (FCS) and seed-based functional connection (FC) approaches. At baseline, compared with healthy controls, decreased FCS in the right middle temporal gyrus (MTG) was observed in patients. However, after music intervention, the functional circuitry of the right MTG, which was related with the function of emotion and sensorimotor, was improved in MTSZ. Furthermore, the FC increments were significantly correlated with the improvement of symptoms, while vanishing 6 months later. Together, these findings provided evidence that music intervention might positively modulate the functional connectivity of MTG in patients with schizophrenia; such changes might be associated with the observed therapeutic effects of music intervention on neurocognitive function. This trial is registered with ChiCTR-OPC-14005339.

Progressive Reduction in Gray Matter in Patients with Schizophrenia Assessed with MR Imaging by Using Causal Network Analysis.

Purpose To investigate the temporal and causal relationships of structural changes in the brain in patients with schizophrenia. Materials and Methods T1-weighted magnetic resonance (MR) images of 97 patients with schizophrenia (29 women; mean ± standard deviation age, 41 years ± 11.5; range, 16-66 years; illness duration, 16.3 years ± 10.9; range, 0-50 years) and 126 age- and sex-matched (38 years ± 14.9; range, 18-68 years; 42 women) healthy control subjects were evaluated. The causal network of structural covariance was used to assess the causal relationships of structural changes in patients with schizophrenia. This was accomplished by applying Granger causality analysis to the morphometric T1-weighted images ranked according to duration of disease. Results With greater disease duration, reduction in gray matter volume began in the thalamus and progressed to the frontal lobe, and then to the temporal and occipital cortices as well and the cerebellum (P < .00001, false discovery rate corrected). The thalamus was shown to be the primary hub of the directional network and exhibited positive causal effects on the frontal, temporal, and occipital regions as well as on the cerebellum (P < .05, false discovery rate corrected). The frontal regions, which were identified to be transitional points, projected causal effects to the occipital lobe, temporal regions, and the cerebellum and received causal effects from the thalamus (P < .05, false discovery rate corrected). Conclusion Schizophrenia shows progression of gray matter abnormalities over time, with the thalamus as the primary hub and the frontal regions as prominent nodes. © RSNA, 2018 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 5, 2018.

The Effects of Aqueous Extract from Nardostachys chinensis Batalin on Blood Pressure and Cardiac Hypertrophy in Two-Kidney One-Clip Hypertensive Rats.

AIMS: The aim of this study was to investigate the effects of the aqueous extract of Nardostachys chinensis Batalin (NCBAE) on blood pressure and cardiac hypertrophy using two-kidney one-clip (2K1C) hypertensive rats. METHODS: 2K1C rat models were set up by clipping the left renal artery. Sham-operated rats underwent the same surgical procedure except for renal arterial clipping. 2K1C hypertensive rats were orally given NCBAE at doses of 210, 420, and 630 mg·kg-1·d-1 for 6 weeks. Twelve weeks after surgery, rat SBP and echocardiographic parameters were measured, cardiac histopathology was assessed, serum NO and LDH were detected, and the expression of Bcl-2 and caspase-3 of left ventricular tissue was assessed by western blot. RESULTS: Treatment with NCBAE resulted in a decrease of SBP, LVPWd, LVPWs, IVSd, IVSs, LVW/BW ratio, and cardiomyocyte CSA, an increase of LVEF, and inhibition of 2K1C-induced reduction in serum NO and elevation of LDH compared with 2K1C group. NCBAE intervention also showed a significant increase of Bcl-2 expression and reduction of cleaved caspase-3 level dose-dependently in left ventricular tissue. CONCLUSION: Our data demonstrate that NCBAE has an antihypertensive property and protective effect on 2K1C-induced cardiac hypertrophy especially at the dose of 630 mg·kg-1·d-1.

Music Intervention Leads to Increased Insular Connectivity and Improved Clinical Symptoms in Schizophrenia.

Schizophrenia is a syndrome that is typically accompanied by delusions and hallucinations that might be associated with insular pathology. Music intervention, as a complementary therapy, is commonly used to improve psychiatric symptoms in the maintenance stage of schizophrenia. In this study, we employed a longitudinal design to assess the effects of listening to Mozart music on the insular functional connectivity (FC) in patients with schizophrenia. Thirty-six schizophrenia patients were randomly divided into two equal groups as follows: the music intervention (MTSZ) group, which received a 1-month music intervention series combined with antipsychotic drugs, and the no-music intervention (UMTSZ) group, which was treated solely with antipsychotic drugs. Resting-state functional magnetic resonance imaging (fMRI) scans were performed at the following three timepoints: baseline, 1 month after baseline and 6 months after baseline. Nineteen healthy participants were recruited as controls. An FC analysis seeded in the insular subregions and machine learning techniques were used to examine intervention-related changes. After 1 month of listening to Mozart music, the MTSZ showed increased FC in the dorsal anterior insula (dAI) and posterior insular (PI) networks, including the dAI-ACC, PI-pre/postcentral cortices, and PI-ACC connectivity. However, these enhanced FCs had vanished in follow-up visits after 6 months. Additionally, a support vector regression on the FC of the dAI-ACC at baseline yielded a significant prediction of relative symptom remission in response to music intervention. Furthermore, the validation analyses revealed that 1 month of music intervention could facilitate improvement of the insular FC in schizophrenia. Together, these findings revealed that the insular cortex could potentially be an important region in music intervention for patients with schizophrenia, thus improving the patients' psychiatric symptoms through normalizing the salience and sensorimotor networks.

Functional abnormalities of the right posterior insula are related to the altered self-experience in schizophrenia.

The insula is involved in detecting the salience of internal and external stimuli, and it plays a critical role in psychosis. Previous studies have demonstrated the structural and functional alterations of the insula in schizophrenia. To acquire a full picture of the functional alterations of the insula in schizophrenia, the resting-state fMRI data of 46 patients with schizophrenia and 46 healthy control subjects were collected. We used clustering analysis to divide the insula into three subregions: the dorsal anterior insula (dAI), ventral anterior insula (vAI) and posterior insula (PI). Then, whole-brain functional connectivity analysis was conducted based on these subregions. The results showed that the right dAI and PI in patients exhibited altered functional connections with the primary sensorimotor area. In addition, the right PI of the patients exhibited increased functional correlations with the thalamus. More importantly, the altered functional properties of the right PI were significantly correlated with the severity of the delusion and poor insight in schizophrenia. The results suggested that the right PI might play an important role in self-experience processing in schizophrenia. Accordingly, the right PI should be considered very important in the pathological mechanism of schizophrenia.

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats.

AIM: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. METHODS: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17ß-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. RESULTS: Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects. CONCLUSION: ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.