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Objective: The symptom-related neurobiology characteristic of schizophrenia in the brain from a network perspective is still poorly understood, leading to a lack of potential biologically-based markers and difficulty identifying therapeutic targets. We aim to test the dysregulated cross-network interactions among the Salience Network (SN), Central Executive Network (CEN) and Default Mode Network (DMN) and how they contributed to different symptoms in schizophrenia patients.Methods: We examined network interactions among the SN, CEN and DMN in 76 patients with schizophrenia vs. 80 well-matched controls using dynamic causal modeling (DCM). We further analyzed the relation between network dynamics and Positive and Negative Syndrome Scale (PANSS).Results: We observed that the DMN, CEN and SN across healthy controls and schizophrenia patients showed several similarities within or between-network pattern in the resting state. Comparing schizophrenia to controls, SN-centered cross-network interactions were most significantly reduced. Crucially, the strength of connections from CEN subnetwork 1 to DMN subnetwork 1 was positively correlated with the Positive Score of PANSS. The connection from the DMN subnetwork 2 to CEN subnetwork 2 was negatively correlated with the Negative Score of PANSS.Conclusions: Our study provides strong evidence for the dysregulation among SN, CEN and DMN in a triple-network perspective in schizophrenia. The connection between DMN and CEN could be clinically-relevant neurobiological signature of schizophrenia symptoms. Our study indicated that the description of brain triple network hypothesis could be a novel and possible bio-marker for schizophrenia. [ABSTRACT FROM AUTHOR]

Background and Purpose: Conventional magnetic resonance imaging (MRI) is sometimes difficult to distinguish primary central nervous system lymphoma (PCNSL) from other malignant brain tumors effectively. The study aimed to evaluate the diagnostic performance of arterial spin labeling (ASL) and dynamic contrast-enhanced (DCE)-derived permeability parameters to differentiate PCNSL from high-grade glioma (HGG) and brain metastasis.Materials and Methods: Eight patients with PCNSL, twenty one patients with HGG and six brain metastasis underwent preoperative 3.0-T MR imaging including conventional, ASL and DCE. Quantitative parameters including relative cerebral blood flow (rCBF), extravascular extracellular volume fraction (Ve) and the volume transfer constant (Ktrans) among PCNSL, HGG and metastasis were compared with a one-way analysis of variance. In addition, the area under the receiver-operating characteristic (ROC) curve (AUC) was constructed to evaluate the differentiation diagnostic performance of each parameter and the combination.Results: The PCNSL demonstrated significantly lower rCBF, higher Ktrans and Ve compared with HGG and metastasis. For the ROC analyses, both Ktrans and rCBF had good diagnostic performance for discriminating PCNSL from HGG and metastasis, with the AUC of 0.880 and 0.889. With the combination of rCBF and Ktrans, the diagnostic ability for PCNSL was improved with AUC of 0.986.Conclusion: rCBF and Ktrans are useful parameters for differentiating PCNSL from HGG and brain metastasis. The combination of rCBF and Ktrans further helps to improve the diagnostic performance of PCNSL. [ABSTRACT FROM AUTHOR]

Heterogeneous findings across studies of structural abnormality in schizophrenia (SZ) have impeded the development a unified theory of white matter pathology. As a cardinal symptom of SZ, auditory verbal hallucination (AVH) has been suspected to be associated with improper communication among several brain regions, which might indicated white matter pathology. Participants comprised 25 first-episode (FE) patients with AVH, 25 patients without AVH and 25 healthy subjects. Diffusion tensor imaging (DTI) measures were calculated using the TBSS of FSL. Voxel-based ANOVA tests were performed among the three groups and threshold-free cluster enhancement (TFCE) method correction was used for multiple comparisons. Voxel-based one-way ANOVA showed significant group effects for fractional anisotropy (FA) and radial diffusivity (RD) values. Post-hoc t -tests indicated that schizophrenia patients had lower FA and higher RD values in the internal capsule and anterior corona radiata than control subjects. Post-hoc analyses exhibited more widespread fiber disruptions in AVH patients than non-AVH patients. These results hinted on the important role of projection fiber disruption in schizophrenia patients. In addition, the current study also suggested that direct comparison between studies using patients with different symptom profiles should be interpreted with caution. [ABSTRACT FROM AUTHOR]

• We were first to investigate the functional connectivity (FC) of cerebellar dentate nucleus (DN) with whole-brain and its association with cognitive impairments as well psychotic symptoms in patients with drug-naïve and first-episode schizophrenia. • The DN showed increased FC with the bilateral postcentral gyrus and decreased FC with the right inferior temporal gyrus and regional cerebellum (e.g., Vermis 4-5 and Crus I). • These abnormal DN FC correlated with cognitive impairments (e.g., working memory and processing speed) and symptom severity (e.g., negative symptom). Cognitive impairments are the hallmark of schizophrenia and prominent in the early episode stage. However, the underlying pathological mechanisms of cognitive impairments are not fully understood. This study aimed to investigate the abnormal functional connectivity (FC) of the cerebellar dentate nucleus (DN) and its correlation with cognitive impairments in patients with drug-naive and first-episode schizophrenia. Resting-state functional magnetic resonance imaging data were acquired in 47 patients and 43 healthy controls. Cognitive functions were assessed by number sequence span, verbal category fluency, digit-symbol coding tests. The results showed that the patients had deficits in all three cognitive tests compared to the controls. Furthermore, the increased FC of DN with the bilateral postcentral gyrus and decreased FC of DN with the right inferior temporal gyrus and regional cerebellum (e.g., Vermis 4-5 and Crus I) were observed in the patient group compared to the control group. Importantly, these abnormal DN FC significantly correlated with cognitive tests (e.g., number sequence span and digit-symbol coding) and clinical symptoms (e.g., negative symptom) in the patient group. The results suggested that abnormal FC of DN with cortical and subcortical regions was associated with cognitive impairments and symptom severity and might be an underlying neural mechanism in schizophrenia. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) has been shown to be effective in schizophrenia, particularly when rapid symptom reduction is needed or in cases of resistance to drug treatment. However, there are no markers available to predict response to ECT. Here, we examine whether multi-parametric magnetic resonance imaging (MRI)-based radiomic features can predict response to ECT for individual patients. A total of 57 treatment-resistant schizophrenia patients, or schizophrenia patients with an acute episode or suicide attempts were randomly divided into primary (42 patients) and test (15 patients) cohorts. We collected T1-weighted structural MRI and diffusion MRI for 57 patients before receiving ECT and extracted 600 radiomic features for feature selection and prediction. To predict a continuous improvement in symptoms (ΔPANSS), the prediction process was performed with a support vector regression model based on a leave-one-out cross-validation framework in primary cohort and was tested in test cohort. The multi-parametric MRI-based radiomic model, including four structural MRI feature from left inferior frontal gyrus, right insula, left middle temporal gyrus and right superior temporal gyrus respectively and six diffusion MRI features from tracts connecting frontal or temporal gyrus possessed a low root mean square error of 15.183 in primary cohort and 14.980 in test cohort. The Pearson's correlation coefficients between predicted and actual values were 0.671 and 0.777 respectively. These results demonstrate that multi-parametric MRI-based radiomic features may predict response to ECT for individual patients. Such features could serve as prognostic neuroimaging biomarkers that provide a critical step toward individualized treatment response prediction in schizophrenia. [ABSTRACT FROM AUTHOR]

Background and Purpose: The detection and characterization of functional activities in the gray matter of schizophrenia (SZ) have been widely explored. However, the relationship between resting‐state functional signals in the white matter of first‐episode SZ and short‐term treatment response remains unclear. Methods: Thirty‐six patients with first‐episode SZ and 44 matched healthy controls were recruited in this study. Patients were classified as nonresponders and responders based on response to antipsychotic medication during a single hospitalization. The fractional amplitude of low‐frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) of white matter were calculated. The relationships between functional changes and clinical features were analyzed. In addition, voxel‐based morphometry was performed to analyze the white matter volume. Results: One‐way analysis of variance showed significant differences of fALFF and ReHo in the left posterior thalamic radiation and left cingulum (hippocampus) in the patient group, and the areas were regarded as seeds. The FC was calculated between seeds and other white matter networks. Compared with responders, nonresponders showed significantly increased FC between the left cingulum (hippocampus) and left posterior thalamic radiation, splenium of corpus callosum, and left tapetum, and were associated with the changes of clinical assessment. However, there was no difference in white matter volume between groups. Conclusion: Our work provides a novel insight that psycho‐neuroimaging‐based white matter function holds promise for influencing the clinical diagnosis and treatment of SZ. [ABSTRACT FROM AUTHOR]

Evidence from behavioral, electrophysiological and diffusion-weighted imaging studies suggest that schizophrenia patients suffer from deficiencies in bilateral brain communication, and this disruption may be related to the occurrence of auditory verbal hallucinations (AVH). To increase our understanding of aberrant inter-hemispheric communication in relation to AVH, we recruited two groups of first-episode schizophrenia patients: one group with AVH (N = 18 AVH patients) and one without hallucinations (N = 18 Non-AVH patients), and 20 healthy controls. All participants received T1 structural imaging and resting-state fMRI scanning. We adopted a newly developed index, voxel-mirrored homotopic connectivity (VMHC), to quantitatively describe bilateral functional connectivity. The whole-brain VMHC measure was compared among the three groups and correlation analyses were conducted between symptomology scores and neurological measures. Our findings suggest all patients shared abnormalities in parahippocampus and striatum. Aberrant bilateral connectivity of default mode network (DMN), inferior frontal gyrus and cerebellum only showed in AVH patients, whereas aberrances in superior temporal gyrus and precentral gyrus were specific to Non-AVH patients. Meanwhile, inter-hemispheric connectivity of DMN correlated with patients' symptomatology scores. This study corroborates that schizophrenia is characterized by inter-hemispheric dysconnectivity, and suggests the localization of such abnormalities may be crucial to whether auditory verbal hallucinations develop. [ABSTRACT FROM AUTHOR]

Attempts to determine why some patients respond to electroconvulsive therapy (ECT) are valuable in schizophrenia. Schizophrenia is associated with aberrant dynamic functional architecture, which might impact the efficacy of ECT. We aimed to explore the relationship between pre‐treatment temporal variability and ECT acute efficacy. Forty‐eight patients with schizophrenia and 30 healthy controls underwent functional magnetic resonance imaging to examine whether patterns of temporary variability of functional architecture differ between high responders (HR) and low responders (LR) at baseline. Compared with LR, HR exhibited significantly abnormal temporal variability in right inferior front gyrus (IFGtriang.R), left temporal pole (TPOsup.L) and right middle temporal gyrus (MTG.R). In the pooled patient group, ∆PANSS was correlated with the temporal variability of these regions. Patients with schizophrenia with a distinct dynamic functional architecture appear to reveal differential response to ECT. Our findings provide not only an understanding of the neural functional architecture patterns that are found in schizophrenia but also the possibility of using these measures as moderators for ECT selection. [ABSTRACT FROM AUTHOR]

Multimodal neuroimaging features provide opportunities for accurate classification and personalized treatment options in the psychiatric domain. This study aimed to investigate whether brain features predict responses to the overall treatment of schizophrenia at the end of the first or a single hospitalization. Structural and functional magnetic resonance imaging (MRI) data from two independent samples (N = 85 and 63, separately) of schizophrenia patients at baseline were included. After treatment, patients were classified as responders and non‐responders. Radiomics features of gray matter morphology and functional connectivity were extracted using Least Absolute Shrinkage and Selection Operator. Support vector machine was used to explore the predictive performance. Prediction models were based on structural features (cortical thickness, surface area, gray matter regional volume, mean curvature, metric distortion, and sulcal depth), functional features (functional connectivity), and combined features. There were 12 features after dimensionality reduction. The structural features involved the right precuneus, cuneus, and inferior parietal lobule. The functional features predominately included inter‐hemispheric connectivity. We observed a prediction accuracy of 80.38% (sensitivity: 87.28%; specificity 82.47%) for the model using functional features, and 69.68% (sensitivity: 83.96%; specificity: 72.41%) for the one using structural features. Our model combining both structural and functional features achieved a higher accuracy of 85.03%, with 92.04% responder and 80.23% non‐responders to the overall treatment to be correctly predicted. These results highlight the power of structural and functional MRI‐derived radiomics features to predict early response to treatment in schizophrenia. Prediction models of the very early treatment response in schizophrenia could augment effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Despite evidence of structural brain abnormalities in schizophrenia, the current study aimed to explore the effects of antipsychotic treatment on gray matter (GM) volume using structural magnetic resonance imaging (MRI) and investigate the relationship between brain structure and treatment response. The GM volumes of 33 patients with first-episode schizophrenia were calculated with voxel-based morphometry (VBM), with 33 matched healthy controls. Longitudinal volume changes within subjects after 4-month antipsychotic treatment were also evaluated. Correlation between volumetric changes and clinical symptoms derived from the Positive and Negative Syndrome Scale (PANSS) were further investigated. Compared with healthy controls, decreased GM volumes in the frontal gyrus were observed in schizophrenia patients. After 4-month treatment, patients showed significantly decreased GM volume primarily in the bilateral frontal, temporal and left parietal brain regions. In addition, the GM volume changes of the left postcentral gyrus was positively correlated with negative symptoms improvement, and the correlation analysis revealed the total PANSS scores changes were associated with GM volume changes in the right inferior frontal gyrus and the right superior temporal gyrus. Besides, non-responders had reduced GM volume in the bilateral middle frontal gyrus and the right superior frontal gyrus compared with responders and healthy controls. Our results suggest that the abnormality in the right frontal gyrus exists in the early stage of schizophrenia. Moreover, the relationship between antipsychotics and structural changes was identified. The GM volume might have the potential to reflect the symptom improvement in schizophrenia patients. And MRI may assist in predicting the antipsychotic treatment response in first-episode schizophrenia patients. [ABSTRACT FROM AUTHOR]

Diffuse midline glioma H3 K27M mutant is a new tumor entity described in the revised 2016 World Health Organization classification. It is most frequently observed in children and develops in midline structures, including the brainstem, thalamus, and spine. We describe a rare diffuse midline glioma with an H3 K27M mutation arising in the hypothalamus of an adult. A 27-year-old woman was admitted to our department complaining of amenorrhea, polydipsia, and diuresis for the previous 3 months, and headache and lethargy for approximately 10 days. Computed tomography scan showed an oval isodense solid mass extending from the pituitary toward the suprasellar cistern. A gadolinium-enhanced magnetic resonance imaging (MRI) showed a strongly heterogeneous enhanced solid lesion and nonenhanced cystic lesion. The patient underwent surgery and chemoradiotherapy with temozolomide. Histologic and immunohistochemical analyses revealed H3 K27M–mutant diffuse midline glioma. The patient underwent another resection for a recurrent tumor 5 months after the first surgery. Three months after the second operation, the patient relapsed, with MRI revealing spinal cord and meningeal metastases; she died shortly afterward. Diffuse midline glioma with an H3 K27M mutation occurring in the hypothalamus of an adult is rare but should be considered in differential diagnoses. Because histone H3 K27M mutations are associated with aggressive clinical behavior and poor prognosis, molecular analyses should be used to determine the clinical and histopathologic features of such tumors. This will contribute to developing targeted drugs and gene therapy going forward. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the functional network properties in first-episode schizophrenia (SZ) patients at baseline and after 4-months treatment with second-generation antipsychotic drugs.Methods: Resting-state functional magnetic resonance imaging and graph theory approaches were utilized to evaluate the functional integration and segregation of brain networks in 36 first-episode patients (20 male/16 female) with SZ and 36 age and sex matched healthy controls (20 male/16 female).Results: Compared with healthy controls, SZ at baseline showed lower clustering coefficient (Cp) and local network efficiency (Eloc), and this abnormal pattern was modulated with treatment of antipsychotic drugs at follow-up. Longitudinally, the increase of Cp was associated with the improvement of negative symptom. We found that the strength of functional connectivity between brain regions were significantly increased in three connections after treatment, mainly involving the frontal, parietal and occipital lobes.Conclusion: The current study suggested that antipsychotic drugs could modulate the faulty local clustering of the functional connectome in SZ. Furthermore, Cp, the parameter that reflects local clustering of topological organization, demonstrated the potential to be a connectome-based biomarker of treatment response to second-generation antipsychotics in patients with SZ. [ABSTRACT FROM AUTHOR]

Summary: Background: Disturbances in emotion regulation are the hallmarks of major depressive disorder (MDD). The incapacity to control negative emotion in patients has been associated with abnormal hyperactivation of the limbic system and hypoactivation of the frontal cortex. The amygdala and orbital frontal cortex (OFC) are two critical regions of the emotion regulation neural systems. Methods: This study investigated the anatomical basis of abnormal emotion regulation by tracking the fiber tracts connecting the amygdala and OFC. In addition, using dynamic casual modeling on resting‐state fMRI data of 20 MDD patients and equivalent controls, we investigated the exact neural mechanism through which abnormal communications between these two nodes were mediated in MDD. Key Results: The results revealed disrupted white matter integrity of fiber tracts in MDD, suggesting that functional abnormalities were accompanied by underlying anatomical basis. We also detected a failure of inhibition of the OFC on the activity of the amygdala in MDD, suggesting dysconnectivity was mediated through "top‐down" influences from the frontal cortex to the amygdala. Following 8 weeks of antidepressant treatment, the patients showed significant clinical improvement and normalization of the abnormal OFC‐amygdala structural and effective connectivity in the left hemisphere. Conclusions & Inferences: Our findings suggest that pathways connecting these two nodes may be core targets of the antidepressant treatment. In particular, it raised the intriguing question: Does the reversal of structural markers of connectivity reflect a response to antidepressant medication or activity‐dependent myelination following a therapeutic restoration of effective connectivity? [ABSTRACT FROM AUTHOR]

The goal of the study was to investigate cerebral blood flow (CBF) and its connectivity (an across-subject covariance measure) patterns of schizophrenia (SZ) patients with auditory verbal hallucinations (AVHs). A total of demographically matched 25 SZ patients with AVHs, 25 without AVHs, and 25 healthy controls (HCs) underwent resting state perfusion imaging using a pulsed arterial spin labeling sequence. CBF and its connectivity were analyzed and then CBF topological properties were calculated. AVHs patients exhibited decreased CBF in the bilateral superior and middle frontal gyri and postcentral gyri, and right supplementary motor area compared with SZ patients without AVHs. SZ patients without AVHs showed reduced CBF in the left middle frontal gyrus relative to HCs. Moreover, AVHs groups showed distinct connectivity pattern, an intermediate level between HCs and patients without AVHs in the global efficiency. Our study demonstrates aberrant CBF in the brain regions associated with inner speech monitoring and language processing in SZ patients with AVHs. The complex network measures showed by CBF-derived functional connectivity indicate dysconnectivity between different functional units within the network of AVHs in SZ. Our findings might shed light on the neural underpinnings behind AVHs in this devastating disease at the level of CBF and its connectivity. [ABSTRACT FROM AUTHOR]

Objective: Auditory verbal hallucinations (AVHs) are one of the cardinal symptoms of schizophrenia (SZ). Cerebral dysfunction may represent pathophysiological underpinnings behind AVHs in SZ. However, regional and network functional deficits for AVHs in SZ remain to be identified. Methods: Seventeen medication-naïve first-episode SZ patients with AVHs, 15 without AVHs, and 19 healthy controls (HCs) were studied using resting-state functional magnetic resonance imaging. We compared the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) among these subjects. Areas with both ALFF and ReHo alterations were used as seeds in functional connectivity (FC) analysis. Then we performed correlation analysis between image measures and symptoms and receiver operating characteristic analysis. Results: One-way analysis of variance showed significant differences of ALFF and ReHo in the bilateral putamen, thereby being used as seeds. SZ patients with AVHs showed decreased ALFF in the left putamen, increased ReHo in the right dorsolateral prefrontal cortex (DLPFC), and increased right putamen-seeded FC with the left DLPFC and Broca's area relative to those without AVHs. Furthermore, the increased strength of the connectivity between the right putamen and left Broca's area correlated with the severity of SZ symptoms. Both patient groups demonstrated hypoconnectivity within frontal/parietal/temporal cortico-striatal-cerebellar networks compared with HCs. Conclusion: AVHs in SZ may be caused by abnormal regional function in the putamen and prefrontal cortex, as well as hyperconnectivity between them. The putamen-related regional and network functional deficits may reflect imbalance in neuromodulation of AVHs in SZ. Furthermore, dysconnectivity within cortico-striatal-cerebellar networks might subserve the pathogenesis of SZ. [ABSTRACT FROM AUTHOR]

Introduction: Treatment response at an early stage of schizophrenia is of considerable value with regard to future management of the disorder; however, there are currently no biomarkers that can inform physicians about the likelihood of response. Objects: We aim to develop and validate regional brain activity derived from functional magnetic resonance imaging (fMRI) as a potential signature to predict early treatment response in schizophrenia. Methods: Amplitude of low‐frequency fluctuation (ALFF) was measured at the start of the first/single episode resulting in hospitalization. Inpatients were included in a principal dataset (n = 79) and a replication dataset (n = 44). Two groups of healthy controls (n = 87; n = 106) were also recruited for each dataset. The clinical response was assessed at discharge from the hospital. The predictive capacity of normalized ALFF in patients by healthy controls, ALFFratio, was evaluated based on diagnostic tests and clinical correlates. Results: In the principal dataset, responders exhibited increased baseline ALFF in the left postcentral gyrus/inferior parietal lobule relative to non‐responders. ALFFratio of responders before treatment was significantly higher than that of non‐responders (p < 0.001). The area under the receiver operating characteristic curve was 0.746 for baseline ALFFratio to distinguish responders from non‐responders, and the sensitivity, specificity, and accuracy were 72.7%, 68.6%, and 70.9%, respectively. Similar results were found in the independent replication dataset. Conclusions: Baseline regional activity of the brain seems to be predictive of early response to treatment for schizophrenia. This study shows that psycho‐neuroimaging holds promise for influencing the clinical treatment and management of schizophrenia. The amplitude of low‐frequency fluctuation (ALFF) was measured at the beginning of hospitalization. Baseline regional activity of the brain seems to be able to predict early response to treatment for schizophrenia. [ABSTRACT FROM AUTHOR]