NonInvasive Brain Stimulation (NIBS) is a potential therapeutic tool with growing interest, but neuronavigation-guided software and tools available for the target determination are mostly either expensive or closed proprietary applications. To address these limitations, we propose GeodesicSlicer, a customizable, free, and open-source NIBS therapy research toolkit. GeodesicSlicer is implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. GeodesicSlicer uses cortical stimulation target from either functional or anatomical images to provide functionality specifically designed for NIBS therapy research. The provided algorithms are tested and they are accessible through a convenient graphical user interface. Modules have been created for NIBS target determination according to the position of the electrodes in the 10–20 system electroencephalogram and calculating correction factors to adjust the repetitive Transcranial Magnetic Stimulation (rTMS) dose for the treatment. Two illustrative examples are processing with the module. This new open-source software has been developed for NIBS therapy: GeodesicSlicer is an alternative for laboratories that do not have access to neuronavigation system. The triangulation-based MRI-guided method presented here provides a reproducible and inexpensive way to position the TMS coil that may be used without the use of a neuronavigation system.

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 opensource 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. (C) 2020 Elsevier B.V. All rights reserved.

For many years, bipedal locomotion has been considered to be one of the main characteristics of the evolution of the Homo genus. However, this locomotor mode is not human specific. In fact, it is c...

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.

Suicidal ideation (SI) has a high risk in adolescents and is now a significant concern due to its problematic outcome. However, few systemic studies of suicidal ideation have been conducted in adolescent patients. Therefore, the current study was aimed to assess the prevalence and its clinical correlate of suicidal ideation among adolescent patients with depression.A total of 1635 adolescent patients (748 males/ 887 females) with depression were recruited in this study. The clinical and demographic data were collected by a self-administered questionnaire. Suicidal ideation was assessed by interview. Children's Depression Inventory (CDI) was used to evaluate depressive symptoms, Adolescent Self-Rating Life Events Check List (ASLEC) was used to assess the stressful life events.The study showed that the prevalence of suicidal ideation in adolescent depression patients was 38.2% (625/1635). Compared to the non-SI patients, SI patients had greater scores on CDI and ASLEC, had inadequate sleeping time, and were more likely to be females. Further logistic regression analysis indicated that suicidal ideation in adolescent patients with depression was significantly associated with females, inadequate sleeping time, the severity of depression, and higher learning pressure.No causal relationship could be drawn due to the cross-sectional design.Our results suggest a high prevalence of suicidal ideation in adolescents with depression. Moreover, the severity of depression, sex, sleep time, and learning pressure are all related to suicidal ideation. Early recognition and treatment of suicidal ideation can effectively prevent the occurrence of suicide among adolescent patients.

Inflammation is associated with both lower and higher activity in brain regions that process rewarding stimuli. How can both low and high sensitivity to rewards be associated with higher inflammation? We propose that one potential mechanism underlying these apparently conflicting findings pertains to how people pursue goals in their environment. This prediction is based on evidence that both an inability to disengage from unattainable goals and low interest in and pursuit of important life goals are associated with poor health outcomes, including inflammation. Accordingly, this study examined the relationship between reward-related brain function and peripheral inflammation among individuals with different levels of ambitious goal-striving tendencies. Eighty-three participants completed an ambitious goal-striving tendency measure, an fMRI Monetary Incentive Delay task assessing orbitofrontal cortex (OFC) and nucleus accumbens (NAc) activation during reward anticipation and outcome, and a venous blood draw to assess the inflammatory biomarkers interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein, from which we computed an inflammation composite score. We observed a reward anticipation by goal-striving interaction on inflammation, such that high OFC and NAc activation to reward anticipation (but not outcome) were associated with more inflammation, among high goal-striving individuals. By contrast, low NAc activation during reward anticipation (but not outcome) was associated with more inflammation, among low goal-striving individuals. The current study provides further evidence that both blunted and elevated reward function can be associated with inflammation. It also highlights the role that goal-striving tendencies may play in moderating the relationship between neural reward anticipation and inflammation.

We report on a database, named BIL&GIN, designed for investigating the cognitive, behavioral, genetic, and brain morphological/functional correlates of hemispheric specialization. The database contains records from a sample of 453 adult participants enriched in left-handers (45%, N=205) as compared to the general population. For each subject, socio-demographic data, hand and eye laterality, family handedness, and cognitive abilities in the language, motor, visuo-spatial, and numerical domains have been recorded. T1-MRI and DTI data were also acquired, as well as resting-state functional MRI. Task-evoked functional MRI was performed in a sub-sample of 303 subjects (157 left-handers) using a customized functional battery of 16 cognitive tasks exploring the same three cognitive domains. Performances at the tasks executed in the magnet as well as post-acquisition debriefing were recorded. A saliva sample was obtained from the subjects of this sub-sample from which DNA was extracted. The BIL&GIN contains results of imaging data processing for each subject, namely maps of tissue (GM, WM, CSF) probability, cortical thickness, cortical surface, and diffusion parameters as well as regional values of these phenotypes for regions of both AAL and FreeSurfer parcellations. For the subjects who underwent FMRI, individual SPM contrast maps for each of the 8 runs were also calculated and included in the database, as well as corresponding BOLD variations in ROIs of the AAL and AICHA atlases, and Wilke's hemispheric functional lateralization index. The BIL&GIN data sharing is based on a collaborative model.

La vortioxetine (Brintellix®, 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine), un nouvel antidépresseur (AD) multimodal avec un mécanisme d'action innovant, a obtenu l'autorisation de mise sur le marché de la Food and Drug Administration (FDA) et de la European Medicines Agency (EMA) en 2013. La vortioxetine est présentée comme antidépresseur multimodal puisque c'est non seulement un inhibiteur du transporteur de la sérotonine (SERT), mais aussi un antagoniste des récepteurs sérotoninergiques 5-HT1D, 5-HT3, 5-HT7, un agoniste partiel des récepteurs 5-HT1B et un agoniste des récepteurs 5-HT1A. Son profil pharmacologique particulier lui permet à la fois de moduler les neurotransmissions sérotoninergiques et noradrenergiques centrales, mais aussi les systèmes histaminergiques, cholinergiques, GABAergiques et glutamatergiques. Ainsi, en plus de son activité antidépressive et anxiolytique, la vortioxetine semble apporter un réel bénéfice cognitif dans différents modèles animaux. La synthèse de ces données démontre que, même si des travaux complémentaires restent à réaliser, notamment dans le domaine de la réponse insuffisante à un 1er traitement antidépresseur, la vortioxetine représente d'ores et déjà une nouvelle option thérapeutique pour le traitement des épisodes dépressifs majeurs.Selective Serotonin Reuptake Inhibitors (SSRIs) are extensively used for the treatment of major depressive disorder (MDD). SSRIs are defined as indirect receptor agonists since the activation of postsynaptic receptors is a consequence of an increase in extracellular concentrations of serotonin (5-HT) mediated by the blockade of serotonin transporter. The activation of some serotoninergic receptors (5-HT1A, post-synaptic, 5-HT1B post-synaptic, 5-HT2B, and 5-HT4), but not all (5-HT1A, pre-synaptic, 5-HT1B pre-synaptic, 5-HT2A, 5-HT2C, 5-HT3, and probably 5-HT6), induces anxiolytic/antidepressive – like effects. Targetting specifically some of them could potentially improve the onset of action and/or efficacy and/or prevent MD relapse. Vortioxetine (Brintellix®, 1- [2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a novel multi-target antidepressant drug approved by the Food and Drug Administration (FDA) and by European Medicines Agency. Its properties are markedly different from the extensively prescribed SSRIs. Compared to the SSRIs, vortioxetine is defined as a multimodal antidepressant drug since it is not only a serotonin reuptake inhibitor, but also a 5-HT1D, 5-HT3, 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist and 5-HT1A receptor agonist. This specific pharmacological profile enables vortioxetine to affect not only the serotoninergic and noradrenergic systems, but also the histaminergic, cholinergic, gamma-butyric acid (GABA) ergic and glutamatergic ones. Thus, vortioxetine not only induces antidepressant-like or anxiolytic-like activity but also improves cognitive parameters in several animal models. Indeed, vortioxetine was shown to improve working memory, episodic memory, cognitive flexibility and spatial memory in young adult rodents and also in old animal models. These specific effects of the vortioxetine are of interest considering that cognitive dysfunction is a common comorbidity to MDD. Altogether, even though this molecule still needs to be investigated further, especially in the insufficient-response to antidepressant drugs, vortioxetine is already an innovative therapeutic option for the treatment of major depression.

Introduction The question of a continuum or a dichotomy between schizophrenia and bipolar disorders is not clearly elucidated. Objectives The objective of the present study was to identify specific functional connectivity (FC) patterns in schizophrenia and bipolar disorders. Aims Therefore, the aim was to explore FC within the language production network in response to a verbal fluency task in patients with schizophrenia, patients with bipolar disorders and healthy participants. We hypothesized that prefronto-subcortical FC patterns within the language production network differ between the three groups. Methods Forty nine participants, comprising 15 patients with schizophrenia, 14 patients with bipolar disorders (DSM-IV) and 20 healthy controls were included in the study. FC was calculated using functional magnetic resonance imaging during a verbal fluency task between the activated pair-seed regions. Results Firstly, patients with schizophrenia presented a significantly reduced FC compared to controls within two pair-seed regions (medio-frontal cluster – left subcortical cluster and left fronto-lateral cluster – left subcortical cluster) while bipolar patients were not significantly different from healthy participants. Secondly, patients with schizophrenia compared to patients with bipolar disorders exhibited reduced FC within one pair-seed region (medio-frontal cluster – left subcortical cluster). Conclusions Our results support the hypothesis of a specific medio-prefronto-striato-thalamic functional dysconnectivity implicated in the pathophysiology of schizophrenia. This fronto-subcortical dysconnectivity in schizophrenia could underlie language production symptoms observed in this pathology and could be a functional brain marker of schizophrenia.

Purpose: Conventional MRI based on contrast enhancement is often not sufficient in differentiating grade II from grade III and grade III from grade IV diffuse gliomas. We assessed advanced MRI, MR spectroscopy and [F-18]-fluoro-L-thymidine ([F-18]-FLT) PET as tools to overcome these limitations.Methods: In this prospective study, thirty-nine patients with diffuse gliomas of grades II, III or IV underwent conventional MRI, perfusion, diffusion, proton MR spectroscopy (H-1-MRS) and [F-18]-FLT-PET imaging before surgery. Relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC), Cho/Cr, NAA/Cr, Cho/NAA and FLT-SUV were compared between grades.Results: Cho/Cr showed significant differences between grade II and grade III gliomas (p = 0.03). To discriminate grade II from grade IV and grade III from grade IV gliomas, the most relevant parameter was the maximum value of [F-18]-FLT uptake FLTmax (respectively, p < 0.001 and p < 0.0001). The parameter showing the best correlation with the grade was the mean value of [F-18]-FLT uptake FLTmean (R-2 = 0.36, p < 0.0001) and FLTmax (R-2 = 0.5, p < 0.0001).Conclusion: Whereas advanced MRI parameters give indications for the grading of gliomas, the addition of [F-18]-FLT-PET could be of interest for the accurate preoperative classification of diffuse gliomas, particularly for identification of doubtful grade III and IV gliomas. (C) 2015 The Authors. Published by Elsevier Inc.

IntroductionLe trouble bipolaire (TB) et la schizophrénie (SZ) sont deux entités distinctes mais qui partagent certaines similarités [1]. Il apparaît donc nécessaire de mettre en évidence des biomarqueurs spécifiques de l’une ou l’autre de ces pathologies. Il a été démontré dans ces deux troubles l’existence d’anomalies du corps calleux (CC) [2] ainsi que des anomalies fonctionnelles liées au langage [3]. Cependant, le lien entre la volumétrie du CC et la latéralisation fonctionnelle pour le langage reste à préciser chez ces deux populations. Nous émettons l’hypothèse que ces deux pathologies présenteraient des anomalies cérébrales différentes.Matériels et méthodesVingt patients TB, 20 patients SZ et 40 témoins volontaires sains (TVS) ont été inclus. Un index de latéralisation fonctionnelle (ILF) a été extrait chez chaque participant au sein du réseau de la compréhension du langage. Les données de volumétrie ont été calculées dans la totalité du CC et dans ses différentes sous-régions. Les relations anatomo-fonctionnelles entre ces variables ont été testées.RésultatsLes patients SZ présentaient une réduction de l’ILF gauche pour le langage comparativement aux TVS, non retrouvée chez les patients TB. Une réduction du volume du CC a été mise en évidence chez les TB comparativement aux SZ et aux TVS. De plus, les patients TB présentaient une réduction du volume callosal associée à une diminution de l’ILF gauche pour le langage.ConclusionNotre étude a révélé l’existence d’une réduction de la volumétrie callosale chez les patients TB, laquelle pourrait être considérée comme un biomarqueur spécifique de cette pathologie. Il semblerait que ces anomalies puissent être à l’origine d’une diminution de la latéralisation fonctionnelle gauche pour le langage. Ainsi, ces résultats nous permettent de conclure que les patients TB auraient une altération du CC plus marquée que les patients SZ, suggérant que le TB et la SZ présentent des mécanismes physiopathologiques distincts.