Abnormal effective connectivity of reward network in first-episode schizophrenia with auditory verbal hallucinations.

OBJECTIVE: Auditory verbal hallucinations (AVHs) in schizophrenia is proved to be associated with dysfunction of mesolimbic-cortical circuits, especially during abnormal salient and internal verbal resource monitoring processing procedures. However, the information flow among areas involved in coordinated interaction implicated the pathophysiology of AVHs remains unclear. METHODS: We used spectral dynamic causal modeling (DCM) to quantify connections among eight critical hubs of reward network in 86 first-episode drug-naïve schizophrenia patients with AVHs (AVH), 93 patients without AVHs (NAVH), and 88 matched normal controls (NC) using resting-state functional magnetic resonance imaging. Group-level connection coefficients, between-group differences and correlation analysis between image measures and symptoms were performed. RESULT: DCM revealed weaker effective connectivity (EC) from right ventral striatum (RVS) to ventral tegmental area (VTA) in AVH compared to NAVH. AVH showed stronger EC from left anterior insula (AI) to RVS, stronger EC from RVS to anterior cingulate cortex (ACC), and stronger EC from VTA to posterior cingulate cortex (PCC) compared to NC. The correlation analysis results were mostly visible in the negative correlation between EC from right AI to ACC and positive sub-score, P1 sub-score, and P3 sub-score of PNASS in group-level. CONCLUSION: These findings suggest that neural causal interactions between the reward network associated with AVHs are disrupted, expanding the evidence for potential neurobiological mechanisms of AVHs. Particularly, dopamine-dependent salience attribution and top-down monitoring impairments and compensatory effects of enhanced excitatory afferents to ACC, which may provide evidence for a therapeutic target based on direct in vivo of AVHs in schizophrenia.

Identifying two distinct neuroanatomical subtypes of first-episode depression using heterogeneity through discriminative analysis.

BACKGROUND: Neurobiological heterogeneity in depression remains largely unknown, leading to inconsistent neuroimaging findings. METHODS: Here, we adopted a novel proposed machine learning method ground on gray matter volumes (GMVs) to investigate neuroanatomical subtypes of first-episode treatment-naïve depression. GMVs were obtained from high-resolution T1-weighted images of 195 patients with first-episode, treatment-naïve depression and 78 matched healthy controls (HCs). Then we explored distinct subtypes of depression by employing heterogeneity through discriminative analysis (HYDRA) with regional GMVs as features. RESULTS: Two prominently divergent subtypes of first-episode depression were identified, exhibiting opposite structural alterations compared with HCs but no different demographic features. Subtype 1 presented widespread increased GMVs mainly located in frontal, parietal, temporal cortex and partially located in limbic system. Subtype 2 presented widespread decreased GMVs mainly located in thalamus, cerebellum, limbic system and partially located in frontal, parietal, temporal cortex. Subtype 2 had smaller TIV and longer illness duration than Subtype 1. And TIV in Subtype 1 was positively correlated with age of onset while not in Subtype 2, probably implying the different potential neuropathological mechanisms. LIMITATIONS: Despite results obtained in this study were validated by employing another brain atlas, the conclusions were acquired from a single dataset. CONCLUSIONS: This study revealed two distinguishing neuroanatomical subtypes of first-episode depression, which provides new insights into underlying biological mechanisms of the heterogeneity in depression and might be helpful for accurate clinical diagnosis and future treatment.

Dynamic brain activity states of memory impairment in stroke patients with varying motor outcomes.

Introduction: The objective of this study was to characterize the alteration patterns of dynamic spatiotemporal activity in chronic subcortical stroke patients with varying motor outcomes, while investigating the imaging indicators relevant to the assessment of potential cognitive deficits in these patients. Methods: A total of 136 patients and 88 normal controls were included in the analysis of static and dynamic intrinsic brain activity, determined by amplitude of low-frequency fluctuations. Results: The findings unveiled that subcortical stroke patients exhibited significantly aberrant temporal dynamics of intrinsic brain activity, involving regions within multiple brain networks. These spatiotemporal patterns were found to be contingent upon the side of the lesion. In addition, these aberrant metrics demonstrated potential in discerning cognitive deficits in stroke patients with memory impairment, with the dynamic indices exerting more influence than the static ones. The observe findings may indicate that subcortical stroke can trigger imbalances in the segregation and integration of spatiotemporal patterns across the entire brain with multi-domain networks, especially in patients with poor motor outcomes. Conclusion: It suggests that the temporal dynamics indices of intrinsic brain activity could serve as potential imaging indicators for assessing cognitive impairment in patients with chronic subcortical stroke, which may be associated with the motor outcomes.

Impaired large-scale cortico-hippocampal network connectivity, including the anterior temporal and posterior medial systems, and its associations with cognition in patients with first-episode schizophrenia.

Background and objective: The cortico-hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico-hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition. Methods: A total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico-hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores. Results: Compared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico-hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico-hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC). Conclusion: Schizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico-hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia.

Identification of shared and distinct patterns of brain network abnormality across mental disorders through individualized structural covariance network analysis.

BACKGROUND: Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders. METHODS: Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed. RESULTS: Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network. CONCLUSIONS: These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.

Altered static and dynamic functional connectivity of habenula in first-episode, drug-naïve schizophrenia patients, and their association with symptoms including hallucination and anxiety.

Background and objective: The pathogenesis of schizophrenia (SCH) is related to the dysfunction of monoamine neurotransmitters, and the habenula participates in regulating the synthesis and release of dopamine. We examined the static functional connectivity (sFC) and dynamic functional connectivity (dFC) of habenula in first-episode schizophrenia patients using resting state functional magnetic resonance imaging (rs-fMRI) in this study. Methods: A total of 198 first-Episode, drug-Naïve schizophrenia patients and 199 healthy controls (HC) underwent rs-fMRI examinations. The sFC and dFC analysis with habenula as seed was performed to produce a whole-brain diagram initially, which subsequently were compared between SCH and HC groups. Finally, the correlation analysis of sFC and dFC values with the Positive and Negative Symptom Scale (PANSS) were performed. Results: Compared with the HC groups, the left habenula showed increased sFC with the bilateral middle temporal gyrus, bilateral superior temporal gyrus, and right temporal pole in the SCH group, and the right habenula exhibited increased sFC with the left middle temporal gyrus, left superior temporal gyrus, and left angular gyrus. Additionally, compared with the HC group, the left habenula showed decreased dFC with the bilateral cuneus gyrus and bilateral calcarine gyrus in the SCH group. The PANSS negative sub-scores were positively correlated with the sFC values of the bilateral habenula with the bilateral middle temporal gyrus, superior temporal gyrus and angular gyrus. The PANSS general sub-scores were positively correlated with the sFC values of the right habenula with the left middle temporal gyrus and left superior temporal gyrus. The hallucination scores of PANSS were negatively correlated with the sFC values of the left habenula with the bilateral cuneus gyrus and bilateral calcarine gyrus; The anxiety scores of PANSS were positively correlated with the dFC values of the left habenula with the right temporal pole. Conclusion: This study provides evidence that the habenula of the first-episode schizophrenia patients presented abnormal static functional connectivity with temporal lobe and angular gyrus, and additionally showed weakened stability of functional connectivity in occipital lobe. This abnormality is closely related to the symptoms of hallucination and anxiety in schizophrenia, which may indicate that the habenula involved in the pathophysiology of schizophrenia by affecting the dopamine pathway.

The interaction between first-episode drug-naïve schizophrenia and age based on gray matter volume and its molecular analysis: a multimodal magnetic resonance imaging study.

OBJECTIVES: Schizophrenia is a neurodevelopmental disorder characterized by progressive and widespread gray matter (GM) atrophy. Studies have shown that normal brain development has an impact on schizophrenia-induced GM alterations. However, the neuropathology and underlying molecular mechanisms of interaction between age and schizophrenia are unclear. METHODS: This study enrolled 66/84 first-episode drug-naïve patients with early-onset/adult-onset schizophrenia ((EOS)/(AOS)) and matched normal controls (NC) (46 adolescents/73 adults), undergoing T1-weighted high-resolution magnetic resonance imaging. Gray matter volume (GMV) in four groups was detected using 2-way analyses of variance with diagnosis and age as factors. Then, factors-related volume maps and neurotransmitter maps were spatially correlated using JuSpace to determine the relationship to molecular structure. RESULTS: Compared to AOS, EOS and adult NC had larger GMV in right middle frontal gyrus. Compared to adolescent NC, EOS and adult NC had smaller GMV in right lingual gyrus, right fusiform gyrus, and right cerebellum_6. Disease-induced GMV reductions were mainly distributed in frontal, parietal, thalamus, visual, motor cortex, and medial temporal lobe structures. Age-induced GMV alterations were mainly distributed in visual and motor cortex. The changed GMV induced by schizophrenia, age, and their interaction was related to dopaminergic and serotonergic receptors. Age is also related to glutamate receptors, and schizophrenia is also associated with GABAaergic and noradrenergic receptors. CONCLUSIONS: Our results revealed the multimodal neural mechanism of interaction between disease and age. We emphasized age-related GM abnormalities of ventral stream of visual perceptual pathways and high-level cognitive brain in EOS, which may be affected by imbalance of excitatory and inhibitory neurotransmitters.

Convergent molecular and structural neuroimaging signatures of first-episode depression.

BACKGROUND: Convergent studies have demonstrated morphological abnormalities in various brain regions in depression patients. However, the molecular underpinnings of the structural impairments remain largely unknown, despite a pressing need for treatment targets and mechanisms. Here, we investigated the gray matter volume (GMV) alteration in patients with depression and its underlying molecular architecture. METHODS: We recruited 195 first-episode, treatment-naïve depression patients and 78 gender-, age-, and education level-matched healthy controls (HCs) who underwent high-resolution T1-weighted magnetic resonance scans. Voxel-based morphometry (VBM) was adopted to calculate the GMV differences between two groups. Then we analyzed the spatial correlation between depression-induced alteration in GMV and density maps of 10 receptors/transporters deriving from prior molecular imaging in healthy people. RESULTS: Compared to HCs, the depression group had significantly increased GMV in the left ventral portions of the ventral medial prefrontal cortex, parahippocampal gyrus, amygdala, the right superior parietal lobule and precuneus while decreased GMV in the bilateral hippocampus extending to the thalamus and cerebellum. The GMV alteration introduced by depression was spatially correlated with serotonin receptors (5-HT1a, 5-HT1b, and 5-HT2a), dopamine receptors (D1 and D2) and GABAergic receptor (GABAa) densities. LIMITATIONS: The conclusions drawn in this study were obtained from a single dataset. CONCLUSIONS: This study reveals abnormal GMV alteration and provides a series of neurotransmitters receptors possibly related to GMV alteration in depression, which facilitates an integrative understanding of the molecular mechanism underlying the structural abnormalities in depression and may provide clues to new treatment strategies.

Altered dynamic functional connectivity of auditory cortex and medial geniculate nucleus in first-episode, drug-naïve schizophrenia patients with and without auditory verbal hallucinations.

Background and objective: As a key feature of schizophrenia, auditory verbal hallucination (AVH) is causing concern. Altered dynamic functional connectivity (dFC) patterns involving in auditory related regions were rarely reported in schizophrenia patients with AVH. The goal of this research was to find out the dFC abnormalities of auditory related regions in first-episode, drug-naïve schizophrenia patients with and without AVH using resting state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 107 schizophrenia patients with AVH, 85 schizophrenia patients without AVH (NAVH) underwent rs-fMRI examinations, and 104 healthy controls (HC) were matched. Seed-based dFC of the primary auditory cortex (Heschl's gyrus, HES), auditory association cortex (AAC, including Brodmann's areas 22 and 42), and medial geniculate nucleus (MGN) was conducted to build a whole-brain dFC diagram, then inter group comparison and correlation analysis were performed. Results: In comparison to the NAVH and HC groups, the AVH group showed increased dFC from left ACC to the right middle temporal gyrus and right middle occipital gyrus, decreased dFC from left HES to the left superior occipital gyrus, left cuneus gyrus, left precuneus gyrus, decreased dFC from right HES to the posterior cingulate gyrus, and decreased dFC from left MGN to the bilateral calcarine gyrus, bilateral cuneus gyrus, bilateral lingual gyrus. The Auditory Hallucination Rating Scale (AHRS) was significantly positively correlated with the dFC values of cluster 1 (bilateral calcarine gyrus, cuneus gyrus, lingual gyrus, superior occipital gyrus, precuneus gyrus, and posterior cingulate gyrus) using left AAC seed, cluster 2 (right middle temporal gyrus and right middle occipital gyrus) using left AAC seed, cluster 1 (bilateral calcarine gyrus, cuneus gyrus, lingual gyrus, superior occipital gyrus, precuneus gyrus and posterior cingulate gyrus) using right AAC seed and cluster 2 (posterior cingulate gyrus) using right HES seed in the AVH group. In both AVH and NAVH groups, a significantly negative correlation is also found between the dFC values of cluster 2 (posterior cingulate gyrus) using the right HES seed and the PANSS negative sub-scores. Conclusions: The present findings demonstrate that schizophrenia patients with AVH showed multiple abnormal dFC regions using auditory related cortex and nucleus as seeds, particularly involving the occipital lobe, default mode network (DMN), and middle temporal lobe, implying that the different dFC patterns of auditory related areas could provide a neurological mechanism of AVH in schizophrenia.

Aberrant Cerebello-Thalamo-Cortical Functional and Effective Connectivity in First-Episode Schizophrenia With Auditory Verbal Hallucinations.

The thalamus is known to be impaired in schizophrenia patients with auditory verbal hallucinations (AVHs). Abnormal filtering function of the thalamus has been found in schizophrenia patients with AVHs. However, a whole-structure approach has commonly been adopted when investigating thalamic dysconnectivity in patients with AVHs, and it remains unclear which thalamic nucleus is the critical structure underlying AVHs. Here, we investigated voxel-wise resting-state functional connectivity (rsFC) of the thalamic nucleus in drug-naïve patients with first-episode schizophrenia (FES) with AVHs. In addition, dynamic causal modeling was applied to compute effective connectivity and estimate causal relationships that could explain aberrant rsFC. Compared with the FES patients without AVH (NAVH) and normal controls, patients with AVHs had weaker rsFC of the bilateral medial pulvinar (PuM) nucleus-cerebellum. Moreover, compared with the normal control group, the AVH and NAVH groups had significantly stronger rsFC of the bilateral PuM nucleus-cerebral cortex, as well as weaker rsFC of the right medial geniculate nucleus-cerebral cortex. Compared with the NAVH and normal control groups, dynamic causal modeling revealed significantly stronger effective connectivity from the left PuM nucleus to the right inferior frontal gyrus in the AVH group. These findings indicate that the critical structure in the thalamus underlying AVHs is the PuM nucleus, and provide direct evidence that the cerebello-thalamo-cortical circuit is associated with AVHs.

Altered Coupling of Cerebral Blood Flow and Functional Connectivity Strength in First-Episode Schizophrenia Patients With Auditory Verbal Hallucinations.

Objective: Auditory verbal hallucinations (AVHs) are a major symptom of schizophrenia and are connected with impairments in auditory and speech-related networks. In schizophrenia with AVHs, alterations in resting-state cerebral blood flow (CBF) and functional connectivity have been described. However, the neurovascular coupling alterations specific to first-episode drug-naïve schizophrenia (FES) patients with AVHs remain unknown. Methods: Resting-state functional MRI and arterial spin labeling (ASL) was performed on 46 first-episode drug-naïve schizophrenia (FES) patients with AVHs (AVH), 39 FES drug-naïve schizophrenia patients without AVHs (NAVH), and 48 healthy controls (HC). Then we compared the correlation between the CBF and functional connection strength (FCS) of the entire gray matter between the three groups, as well as the CBF/FCS ratio of each voxel. Correlation analyses were performed on significant results between schizophrenia patients and clinical measures scale. Results: The CBF/FCS ratio was reduced in the cognitive and emotional brain regions in both the AVH and NAVH groups, primarily in the crus I/II, vermis VI/VII, and cerebellum VI. In the AVH group compared with the HC group, the CBF/FCS ratio was higher in auditory perception and language-processing areas, primarily the left superior and middle temporal gyrus (STG/MTG). The CBF/FCS ratio in the left STG and left MTG positively correlates with the score of the Auditory Hallucination Rating Scale in AVH patients. Conclusion: These findings point to the difference in neurovascular coupling failure between AVH and NAVH patients. The dysfunction of the forward model based on the predictive and computing role of the cerebellum may increase the excitability in the auditory cortex, which may help to understand the neuropathological mechanism of AVHs.

Abnormal interhemispheric and intrahemispheric functional connectivity dynamics in drug-naïve first-episode schizophrenia patients with auditory verbal hallucinations.

Numerous studies indicate altered static local and long-range functional connectivity of multiple brain regions in schizophrenia patients with auditory verbal hallucinations (AVHs). However, the temporal dynamics of interhemispheric and intrahemispheric functional connectivity patterns remain unknown in schizophrenia patients with AVHs. We analyzed resting-state functional magnetic resonance imaging data for drug-naïve first-episode schizophrenia patients, 50 with AVHs and 50 without AVH (NAVH), and 50 age- and sex-matched healthy controls. Whole-brain functional connectivity was decomposed into ipsilateral and contralateral parts, and sliding-window analysis was used to calculate voxel-wise interhemispheric and intrahemispheric dynamic functional connectivity density (dFCD). Finally, the correlation analysis was performed between abnormal dFCD variance and clinical measures in the AVH and NAVH groups. Compared with the NAVH group and healthy controls, the AVH group showed weaker interhemispheric dFCD variability in the left middle temporal gyrus (p < .01; p < .001), as well as stronger interhemispheric dFCD variability in the right thalamus (p < .001; p < .001) and right inferior temporal gyrus (p < .01; p < .001) and stronger intrahemispheric dFCD variability in the left inferior frontal gyrus (p < .001; p < .01). Moreover, abnormal contralateral dFCD variability of the left middle temporal gyrus correlated with the severity of AVHs in the AVH group (r = -.319, p = .024). The findings demonstrate that abnormal temporal variability of interhemispheric and intrahemispheric dFCD in schizophrenia patients with AVHs mainly focus on the temporal and frontal cortices and thalamus that are pivotal components of auditory and language pathways.

Common abnormal connectivity in first-episode and chronic schizophrenia in pre- and post-central regions: Implications for neuromodulation targeting.

Schizophrenia is a neurodevelopmental disorder manifesting differing impairments at early onset and chronic disease stages. Brain imaging research suggests a core pathological region in patients with first-episode schizophrenia is Broca's area. With disease progression, alterations in thalamic connectivity becomes more prevalent. Understanding the common circuitry underlying pathology in these two groups might highlight a critical common network and novel targets for treatment. In this study, 937 subject samples were collected including patients with first-episode schizophrenia and those with chronic schizophrenia. We used hypothesis-based voxel-level functional connectivity analyses to calculate functional connectivity using the left Broca's area and thalamus as regions of interest in those with first-episode and chronic schizophrenia, respectively. We show for the first time that in both patients with first-episode and chronic schizophrenia the greatest functional connectivity disruption ended in the pre- and postcentral regions. At the early-onset stage, the core brain region is abnormally connected to pre- and postcentral areas responsible for mouth movement, while in the chronic stage, it expanded to a wider range of sensorimotor areas. Our findings suggest that expanding the focus on the low-order sensory-motor systems beyond high-order cognitive impairments in schizophrenia may show potential for neuromodulation treatment, given the relative accessibility of these cortical regions and their functional and structural connections to the core region at different stages of illness.

Clinical and imaging features of carcinosarcoma of the uterus and cervix.

AIM: The purpose of our study was to analyze the clinical and imaging features of uterine carcinosarcoma (UCS) and cervical carcinosarcoma (CCS), and to explore the diagnostic and staging accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) examinations. METHODS: 41 patients including 37 with UCS and 4 with CCS from July 2011 to September 2020 were enrolled in the study. Of the 37 UCS cases, 7 had CT images, 27 had MRI images, and 3 had both CT and MRI images. The Clinical data, CT or MRI imaging findings were analyzed. Diagnosis and staging accuracy of CT and MRI images were also analyzed. RESULTS: Carcinosarcoma usually occurs in postmenopausal women (40/41), with the typical clinical symptom being vaginal bleeding (33/41). The CA125 degree was significantly different between the two invasion depth groups (p = 0.011). Most uterine carcinosarcomas showed unclear boundaries, uneven density, low or equal signal on T1WI, high or mixed signal on T2WI, uneven high signal on diffusion-weighted image (DWI), and mild enhancement. The diagnostic accuracies of CT and MRI for carcinosarcoma were 0% and 3.33%, respectively. The diagnostic accuracy for malignant tumors on CT and MRI was 50% and 83.33%, respectively. CONCLUSIONS: Carcinosarcoma lesions presented with huge mass filling in the cavity, and some presented with small polypoid lesions or endometrial thickening. Evaluation of lymph node metastasis is a significant challenge for imaging staging.

Resolving heterogeneity in schizophrenia through a novel systems approach to brain structure: individualized structural covariance network analysis.

Reliable mapping of system-level individual differences is a critical first step toward precision medicine for complex disorders such as schizophrenia. Disrupted structural covariance indicates a system-level brain maturational disruption in schizophrenia. However, most studies examine structural covariance at the group level. This prevents subject-level inferences. Here, we introduce a Network Template Perturbation approach to construct individual differential structural covariance network (IDSCN) using regional gray-matter volume. IDSCN quantifies how structural covariance between two nodes in a patient deviates from the normative covariance in healthy subjects. We analyzed T1 images from 1287 subjects, including 107 first-episode (drug-naive) patients and 71 controls in the discovery datasets and established robustness in 213 first-episode (drug-naive), 294 chronic, 99 clinical high-risk patients, and 494 controls from the replication datasets. Patients with schizophrenia were highly variable in their altered structural covariance edges; the number of altered edges was related to severity of hallucinations. Despite this variability, a subset of covariance edges, including the left hippocampus-bilateral putamen/globus pallidus edges, clustered patients into two distinct subgroups with opposing changes in covariance compared to controls, and significant differences in their anxiety and depression scores. These subgroup differences were stable across all seven datasets with meaningful genetic associations and functional annotation for the affected edges. We conclude that the underlying physiology of affective symptoms in schizophrenia involves the hippocampus and putamen/pallidum, predates disease onset, and is sufficiently consistent to resolve morphological heterogeneity throughout the illness course. The two schizophrenia subgroups identified thus have implications for the nosology and clinical treatment.

Brain iron assessment in patients with First-episode schizophrenia using quantitative susceptibility mapping.

PURPOSE: Decreased serum ferritin level was recently found in schizophrenia. Whether the brain iron concentration in schizophrenia exists abnormality is of research significance. Quantitative susceptibility mapping (QSM) was used in this study to assess brain iron changes in the grey matter nuclei of patients with first-episode schizophrenia. METHODS: The local ethics committee approved the study, and all subjects gave written informed consent. Thirty patients with first-episode schizophrenia and 30 age and gender-matched healthy controls were included in this study. QSM and effective transverse relaxation rate (R2*) maps were reconstructed from a three-dimensional multi-echo gradient-echo sequence. The inter-group differences of regional QSM values, R2* values and volumes were calculated in the grey matter nuclei, including bilateral caudate nucleus, putamen, globus pallidus, substantia nigra, red nucleus, and thalamus. The diagnostic performance of QSM and R2* was evaluated using receiver operating characteristic curve. The correlations between regional iron variations and clinical PANSS (Positive and Negative Syndrome Scale) scores were assessed using partial correlation analysis. RESULTS: Compared to healthy controls, patients with first-episode schizophrenia had significantly decreased QSM values (less paramagnetic) in the bilateral substantia nigra, left red nucleus and left thalamus (p < 0.05, FDR correction). QSM proved more sensitive than R2* regarding inter-group differences. The highest diagnostic performance for first-episode schizophrenia was observed in QSM value of the left substantia nigra (area under the curve, AUC = 0.718, p = 0.004). Regional volumes of bilateral putamen and bilateral substantia nigra were increased (p < 0.05, FDR correction) in first-episode schizophrenia. However, both QSM and R2* values did not show significant correlations with PANSS scores (p > 0.05). CONCLUSION: This study reveals decreased iron concentration in grey matter nuclei of patients with first-episode schizophrenia. QSM provides superior sensitivity over R2* in the evaluation of schizophrenia-related brain iron changes. It demonstrated that QSM may be a potential biomarker for further understanding the pathophysiological mechanism of first-episode schizophrenia.

Combined Diagnosis of Whole-Lesion Histogram Analysis of T1- and T2-Weighted Imaging for Differentiating Adrenal Adenoma and Pheochromocytoma: A Support Vector Machine-Based Study.

PURPOSE: This study aimed to determine whether a combined diagnosis of whole-lesion histogram analysis of T1- and T2-weighted imaging based on support vector machine (SVM) can distinguish pheochromocytoma from adrenal adenoma. METHODS: A pathology database was retrospectively appraised over a period of 7 years and we obtained 40 histopathologically proven adrenal adenomas and 20 pheochromocytomas with magnetic resonance images. The T1-weighted imaging (T1WI, including both in phase and opposed phase) and T2-weighted imaging (T2WI) images of each patients were analyzed using Mazda software. Nine parameters were selected as indicators of comparison: variance, skewness, kurtosis, mean, 1st percentile, 10th percentile, 50th percentile, 90th percentile, and 99th percentile. The parameters with differential-diagnosis significance were used to establish the combined diagnostic model of SVM. RESULTS: Among the 9 parameters extracted using histogram analysis, the 1st percentile, 10th percentile, and 50th percentile of T1WI (in phase) and the skewness of T2WI and almost all parameters of T1WI (opposed phase), except variance and 99th percentile, showed statistical significance between groups. Among the above parameters, the area under the curve (AUC) of 10th percentile of T1WI (opposed phase) was the largest with the value of 0.909 (100.0% sensitivity and 80.0% specificity). After the analysis of combined diagnosis was performed, the AUC of SVM model in testing set showed the value of 0.917 (85.0% accuracy). CONCLUSIONS: Whole-lesion histogram analysis of T1WI and T2WI may help differentiate adrenal adenomas from pheochromocytomas. Furthermore, the combined diagnosis of T1WI and T2WI histogram based on SVM was more effective than most of individual histogram parameters.

Abnormal dynamics of functional connectivity in first-episode and treatment-naive patients with obsessive-compulsive disorder.

AIM: The aim of this study was to assess the whole-brain dynamic functional connectivity of first-episode and treatment-naive patients with obsessive-compulsive disorder (OCD) and to investigate the clinical correlations of abnormal changes in dynamic functional connectivity. METHODS: Twenty-nine patients in our hospital diagnosed with first-episode OCD and 29 healthy controls matched for age, sex, and education were included in our study. Resting-state functional magnetic resonance imaging scans were performed on a 3.0-Tesla magnetic resonance scanner in our hospital. Three temporal metrics of connectivity state expression were calculated: (i) fraction of time; (ii) mean dwell time; and (iii) number of transitions. The Yale-Brown Obsessive-Compulsive Scale was used to assess the severity of OCD symptoms. RESULTS: In the comparison of dynamic functional connectivity indicators, we found that there were significant differences in the number of transitions among the four functional connectivity states but no significant differences in the fraction of time or the mean dwell time. The total Yale-Brown Obsessive-Compulsive Scale score was positively correlated with the number of transitions. In the validation analysis, when the size of the sliding window changed, there was still a significant difference in the number of transitions between OCD patients and healthy controls. CONCLUSION: The functional networks of OCD patients have lost the correct dynamic rhythm, which may be considered as a potential marker for OCD and for new directions for its intervention.

Test-retest multisite reproducibility of neurovascular 4D flow MRI.

BACKGROUND: 4D flow MRI shows great potential in neurovascular disorders such as stenosis, atherosclerotic disease, aneurysms, and vascular malformations. Its widespread application in the neurovascular system requires evidence of good test-retest multicenter reproducibility. PURPOSE: To assess the multicenter reproducibility, test-retest reliability and interobserver dependence of 4D flow MRI in measurements of cerebral blood flow/velocity in main intracranial vessels. STUDY TYPE: Prospective study. SUBJECTS: Ten healthy subjects underwent 4D flow scans at three different centers. All subjects were scanned twice at 2 different days at each center. FIELD STRENGTH/SEQUENCE: 3.0 T; 4D flow sequence. ASSESSMENT: Multicenter reproducibility, test-retest reliability and interobserver agreement for measurements of the blood flow and peak velocity from five regions of interest were assessed (bilateral internal carotid arteries, bilateral medial cerebral arteries, and sagittal sinus). STATISTICAL TEST: A Shapiro-Wilks test was conducted to assess normality of measurements in each scan. Coefficient of variances (CVs) was computed to evaluate intra- and intersite variances of all measurements. The multicenter reproducibility was assessed by two-way mixed intraclass correlation coefficient (ICC). A Bland-Altman plot and Pearson correlation were used to evaluate test-retest reliability. ICC was calculated to assess interobserver agreements. RESULTS: All P-values for Shapiro-Wilks tests were greater than 0.05, which indicated the normality of all measurements. Both intra- and intersite CVs were lower than 12%. There was good test-retest reliability for both blood flow and peak velocity of all ROIs (r = 0.75-0.94). In addition, high multicenter reproducibility was detected (ICC = 0.77-0.96, all P < 0.001). The results of these measurements also showed great interobserver agreement (all ICC > 0.9 and all P < 0.001). DATA CONCLUSION: High multicenter reproducibility and test-retest reliability was shown for 4D flow in the measurements of blood flow and peak velocity of intracranial vessels. In addition, these measurements showed great interobserver agreement. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1543-1552.