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Patients with schizophrenia (SZ) have a high level of cardiovascular morbidity and some clinical symptoms of illness remain resistant to pharmacological approaches. A large number of studies support the effectiveness of physical activity (PA) in SZ. The aims of this trial is to assess the effects of a remote, web-based adapted PA program (e-APA) compared to a health education program (e-HE) on brain plasticity in SZ and healthy volunteers (HV) and on psychiatric, neurocognitive, circadian and physical variables. The study is an interventional, multicenter, randomized open-label trial. Forty-two SZ will be randomized to either the active group (e-APA, N = 21) or nonactive group (e-HE, N = 21), and 21 HV will be matched to SZ according to age, gender, and level of PA in both e-APA and e-HE groups. Interventions will consist of 32 sessions (2 × 60 min/week, for 16 weeks) via supervised home-based videoconferencing. Cerebral magnetic resonance imaging, psychiatric symptoms, neurocognitive and circadian rhythms assessments as well as physical tests and biological analyses will be assessed at baseline and 16 weeks after the intervention. To our knowledge, this is the first study aiming to evaluate the efficacy of APA delivered by supervised home-based videoconferencing in SZ. Moreover, using multimodal MRI, this study could clarify the pathophysiological mechanisms underlying the efficacy of APA. Finally, this innovative approach might also increase participation in long-term PA since PA-based programs are known to have low adherence and early dropout. Trial registration: ClinicalTrials.gov identifier: NCT03261817. Registered on 16 August 2017.

Neuroimaging studies have revealed brain regions involved in social cognition, which reportedly show functional alterations in schizophrenia. However, the social neural network has not been investigated with regards to language perception and social interactions in daily life. Here we developed and validated an integrative fMRI task to explore the neural basis of social cognition with regards to language perception in schizophrenia. The task comprised listening to film extracts and inferring mental states to characters. We first identified the functional network activated during the task in 28 healthy controls (HC). Next, we evaluated the reproducibility of Blood-Oxygen-Level Dependent (BOLD) variations in 14 HC participants. Finally, we investigated network impairment in 20 patients with schizophrenia (SZ) compared to HC. The HC group exhibited bilateral activation in the superior and middle temporal gyri (including the poles and the temporo-parietal junction). Overall, our novel integrative task induced activation of a functional network with good reproducibility and involved in language conveying social information. Compared to the HC group, the SZ group showed decreased recruitment of the right temporo-parietal junction. These findings may be useful for testing the impact of remediation on the brain, particularly on the network of language conveying social information., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Impairments in language production are common of schizophrenia (SZ) and bipolar disorder (BD). Identifying distinct functional connectivity (FC) patterns in SZ and BD may provide biomarkers for their diagnoses., Methods: Forty-nine participants (15 SZ, 14 BD and 20 healthy controls (HC)) underwent a verbal fluency task consisting of mentally generating verbs in French, alternated with periods of silence. Functional network allowed identifying activation clusters: the medio-frontal cluster (MFC), the left subcortical cluster (LSCC) and the left fronto-lateral cluster (LFLC). FC was calculated between the average blood oxygen level-dependent signal time series in each cluster. Analyses of covariance were performed to test group differences on FC among the three paired-seed regions., Results: SZ presented a significant reduced FC compared to HC within two paired-seed regions between the LFLC and the LSCC and between the MFC and the LSCC while BD were not significantly different from HC. SZ compared to BD exhibited a reduced FC within one paired-seed region between the MFC and the LSCC. There was no group effect between the MFC and the LFLC., Conclusions: A specific medio-prefronto-striato-thalamic functional dysconnectivity may be implicated in the pathophysiology of schizophrenia. This reduced fronto-subcortical FC could be a functional brain biomarker of schizophrenia.

This exploratory study investigated the functional connectivity (FC) in the language network in schizophrenia patients (SZ) with auditory verbal hallucinations (AVHs), and the therapeutic efficacy of rTMS on it. Eleven SZ with AVHs and 10 healthy controls (HC) underwent two fMRI sessions using a speech listening paradigm. SZ received 20Hz rTMS following the first fMRI session. Compared to HC, SZ showed a reduced FC in the language network. While AVHs improved after 12days, no changes in FC were observed. This suggests the efficacy of high-frequency rTMS on AVH without any impact for rTMS on FC within the language network., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to compare the functional and gray matter asymmetries in patients with schizophrenia (SZ), patients with bipolar disorders (BD), and healthy controls (HCs) to test whether decreased leftward functional hemispheric lateralization and gray matter volume asymmetry could mark the boundary between schizophrenia and bipolar disorder., Methods: A total of 31 right-handed SZ and 20 right-handed BD underwent a session of functional MRI with a speech listening paradigm. Participants were matched with HCs for gender, age, and education. Functional laterality indices (FLI) and gray matter volume asymmetry indices (GVAI) were computed from the individual functional language network. Correlations between the FLI and GVAI indices were also examined., Results: SZ exhibited significantly decreased leftward functional hemispheric lateralization whereas BD did not. The GVAIs did not differ significantly between SZ and HCs or between BD and HCs. There were positive correlations between GVAIs and FLIs in all groups., Conclusions: Loss of laterality for language comprehension with retention of gray matter volume asymmetry indicates that gray matter loss alone will not account for the pathophysiology of schizophrenia. Impaired leftward functional hemispheric lateralization for language but not gray matter volume asymmetry can be considered a biomarker of SZ., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Schizophrenia is a mental disorder characterized by functional abnormalities in the language network. Anatomical white matter (WM) abnormalities (volume and integrity) have also been reported for this pathology. Nevertheless, few studies have investigated anatomo-functional relationships in schizophrenia, and none has focused on the language comprehension network in relation to various diffusion parameters. We hypothesized that the WM abnormalities that are reflected by several diffusion parameters underlie functional deficits in the language network., Methods: Eighteen DSM-IV patients with schizophrenia and 18 healthy controls without any significant differences in sex, age, or level of education were included. First, functional brain activation within the language network was estimated. Then, using diffusion tensor imaging, fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) values were extracted within WM regions adjacent to this network and their anatomo-functional relationships were investigated., Results: Compared with healthy participants, both functional and diffusion deficits were observed in patients with schizophrenia. Primarily, an altered diffusion-functional relationship was observed in patients in the left middle temporal region: functional activations were positively correlated with FA, but were negatively correlated with RD., Conclusions: Our findings indicate a close relationship between diffusion and functional deficits in patients with schizophrenia, suggesting that WM integrity disturbance might be one cause of functional alterations in the language network in patients with schizophrenia. Thus, the present multimodal study improves our understanding of the pathophysiology of schizophrenia., (© 2013 Elsevier B.V. All rights reserved.)

Background: It is widely reported that patients with schizophrenia exhibit decreased hemispheric lateralization. However, no study has evaluated relationships between the hemispheric anatomical and functional asymmetry in language areas. The present study aimed to determine whether decreased leftward hemispheric lateralization could be related to asymmetry of the grey matter volume in patients with schizophrenia. This investigation was the first to use a functional index of laterality to analyze the global functional network specifically involved in the language task., Methods: Twenty-seven right-handed patients with schizophrenia and 54 right-handed control subjects underwent a session of a functional magnetic resonance imaging (fMRI) with a speech listening paradigm. Functional laterality indices (FLI) were calculated (Wilke, M. and Lidzba, K., 2007. LI-tool: a new toolbox to assess lateralization in functional MR-data. J Neurosci Methods. 163, 128-136). The indices of asymmetry in the volume of grey matter (GVAIs) were computed from the functional language network., Results: Patients with schizophrenia exhibited significantly decreased leftward hemispheric lateralization. There was a positive correlation between GVAIs and FLIs in healthy subjects, while no such correlation was seen in patients with schizophrenia., Discussion: This study reports for the first time a significant relationship between the anatomical and functional asymmetry in healthy subjects, but not in patients with schizophrenia. While decreased leftward functional lateralization for language was observed in patients with schizophrenia compared to the control group, this functional abnormality was not related to asymmetry in the volume of grey matter., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Neuroimaging data support the idea that schizophrenia is a brain disorder with altered brain structure and function. New resting-state functional connectivity techniques allow us to highlight synchronization of large-scale networks, such as the default-mode network (DMN) and salience network (SN). A large body of work suggests that disruption of these networks could give rise to specific schizophrenia symptoms. We examined the intra-network connectivity strength and gray matter content (GMC) of DMN and SN in 26 schizophrenia patients using resting-state functional magnetic resonance imaging and voxel-based morphometry. Resting-state data were analyzed with independent component analysis and dual-regression techniques. We reported reduced functional connectivity within both DMN and SN in patients with schizophrenia. Concerning the DMN, patients showed weaker connectivity in a cluster located in the right paracingulate cortex. Moreover, patients showed decreased GMC in this cluster. With regard to the SN, patients showed reduced connectivity in the left and right striatum. Decreased connectivity in the paracingulate cortex was correlated with difficulties in abstract thinking. The connectivity decrease in the left striatum was correlated with delusion and depression scores. Correlation between the connectivity of DMN frontal regions and difficulties in abstract thinking emphasizes the link between negative symptoms and the likely alteration of the frontal medial cortex in schizophrenia. Correlation between the connectivity of SN striatal regions and delusions supports the aberrant salience hypothesis. This work provides new insights into dysfunctional brain organization in schizophrenia and its contribution to specific schizophrenia symptoms., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A prerequisite to longitudinal fMRI studies in schizophrenia is the knowledge on fMRI signal reliability in schizophrenia patients. We assessed the reproducibility of activations elicited by two fMRI sessions, which were 21 months apart, of a story listening paradigm in 10 schizophrenia patients and 10 healthy subjects. In both groups, we observed a high degree of spatial overlap of activation maps as well as a good reproducibility of signal variations assessed on a voxel-wise basis in temporal areas underlying early stages of language processing. Task performance, assessed through a comprehension questionnaire, had no impact on the activation reproducibility., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Among new-generation antipsychotics, quetiapine was found to be associated with a partial 'normalization' of reduced functional activation in prefrontal and temporal areas and studies conducted by our group found a clinical improvement in negative symptoms in addition to restoration of frontal activation in schizophrenia patients with blunted affect after treatment with quetiapine. Here we investigated the parallelism between improved clinical symptoms and grey mater density (GMD) changes in the frontal region after quetiapine treatment in 15 schizophrenia patients. We hypothesize that improvement in clinical symptoms will be associated with change in GMD in prefrontal regions of interest. By using voxel-based morphometry, paired t-test random-effect analysis showed a significant increase in GMD bilaterally in the inferior frontal cortex/orbitofrontal gyrus and anterior cingulate cortex after 5.5 months of treatment with quetiapine. This GMD increase was associated with a significant improvement in negative symptoms. When GMD was correlated with psychiatric assessment scores, there was a negative correlation between GMD in the anterior cingulate cortex and the Rating Scale for Emotional Blunting score (r=-665, P=0.008) and between the orbitofrontal gyrus and the total Positive and Negative Syndrome Scale negative score (r=-764, P=0.001). Results suggest that increased GMD in some frontal regions are associated with an improvement of negative symptoms. Although not unique to quetiapine, it would be reasonable to attribute the GMD changes in the study to treatment.

Background: Cross-sectional functional imaging studies have shown a reduced leftward language lateralization in schizophrenic patients. An unanswered question is whether this reduced leftward lateralization is stable over time or is modified over the course of the illness., Methods: Ten right-handed (RH) patients (DSM-IV) and 10 RH controls were matched one-to-one for sex, age, and level of education. The subjects underwent two separate fMRI sessions while engaged in a story listening task, 21 months apart. After each session, story comprehension (task performance) was assessed through a 12-item questionnaire. The stability of the decreased asymmetry indices in the semantic region of interest (LANG) was investigated with an ANOVA to compare groups and sessions. In order to test the evolution of functional asymmetry indices at an individual level, a linear correlation between both fMRI session asymmetry indices was calculated in all subjects. Correlations between asymmetry indices and the severity of psychotic symptoms or task performances were computed., Results: The asymmetry indices of the LANG were significantly reduced in patients as compared to controls and strongly correlated between sessions. Values of asymmetry indices were unrelated to either psychotic symptoms or task performances., Conclusions: This reduced leftward lateralization for language did not vary over time and was not influenced by the psychosis severity or the task performances. This result reinforces the hypothesis that schizophrenia is characterized by a particular organization of language.

Unlabelled: Sinistrality, characterized by an excess of non-right-handedness, has been reported in schizophrenic patients, but the findings are controversial., Aim: As sinistrality could be linked to a failure of hemisphere specialization in schizophrenia that would translate into language disorders, sinistrality was found out in disorganized and positive schizophrenic patients characterized by language disorders., Methods: Seventy-three schizophrenic patients (DSM IV) and 81 controls were evaluated with the Edinburgh Handedness Inventory (EHI). Patients were evaluated and classified into five subtypes (deficit, positive, disorganized, mixed and residual) with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome., Results: Disorganized patients had a significantly more severe sinistrality in comparison to the deficit, residual and mixed subtypes and controls. A negative correlation was found between the disorganization and the EHI scores (r = - 0.34; P < 0.01). A significantly more severe sinistrality was also observed in the positive subtype in comparison to controls, but there was no correlation between hallucinatory and EHI scores (r = 0.06)., Conclusion: The findings provided further evidence that the defects in the normal process of lateralization observed in schizophrenia affects primarily disorganized patients.

Numerous studies have shown alterations of some structures and/or cerebral functions in patients with schizophrenia. However, the nature of the neurobiological process which could be at the origin of schizophrenic symptoms is still unknown. Magnetic resonance spectroscopy (MRS) is a unique technique which allows us to estimate the concentrations of endogenous substances which contain natural paramagnetic nuclei such as phosphorus (31P) and hydrogen (proton or 1H). The non invasive character of this technique, the absence of side effects, and the possibility of repetitive evaluations allowing for longitudinal studies, make possible MRS studies on the in vivo cerebral metabolism in schizophrenia. The prefrontal cortex, the hippocampus and the basal ganglia have all been implicated in the pathophysiology of schizophrenia. Therefore these brain regions have been frequently studied using MRS. Both proton and phosphorus spectroscopy have been used to study schizophrenia. Compounds that are detectable by 1H-MRS include N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (ml). A deficit in NAA has been consistently shown in both the frontal and temporal lobes suggesting neuronal loss in these areas. Compounds detectable by 31P-MRS include phosphomonoesters (PMEs) and phosphodiesters (PDEs), which largely represent metabolites generated by lipid turnover. 31P-MRS can also detect certain energy-containing phosphorus metabolites such as phosphocreatine (PCr) and nucleotide triphosphates. Decreased levels of PMEs and increased levels of PDEs have been consistently described in the prefrontal lobes suggesting an alteration of phospholipid metabolism. The purpose of this review is to summarize the research on schizophrenia using MRS, to show the utility of this technique in understanding schizophrenia.

Background: Most repetitive transcranial magnetic stimulation (rTMS) studies aiming to reduce auditory verbal hallucinations (AVH) in schizophrenia target the left temporo-parietal junction (TPJ), but the efficacy of this approach remains controversial. The observed differences in efficacy could be attributed to inaccurate target localization. Here, to precisely quantify anatomical bias induced by localization method, we developed a free open-source software (GeodesicSlicer) that computes shortest curved path (i.e. geodesic) between rTMS targets. Here we compare a personalized target with accurate anatomical criteria with a standardized target based on the 10-20 EEG system (the middle between T3 and P3 electrodes: T3P3).Methods: We compare in 69 patients with schizophrenia the geodesic distances of two approaches for rTMS target localization within the left TPJ. In addition, we characterize the personalized target according to the 10-20 EEG system.Results: A differential of 3 cm in term of geodesic distance between rTMS localization approaches was observed. Moreover, this personalized target to treat AVH is located at 25% in the T3-P3 axis.Conclusions: This software for rTMS localization comparison demonstrates the difference between standardized and personalized rTMS target. This difference has the potential to explain a part of the dissonant clinical results found in previous rTMS studies. [ABSTRACT FROM AUTHOR]