Resting state functional MRI (rsfMRI) has been shown to be a promising tool to study intrinsic brain functional connectivity and assess its integrity in cerebral development. In neonates, where functional MRI is limited to very few paradigms, rsfMRI was shown to be a relevant tool to explore regional interactions of brain networks. However, to identify the resting state networks, data needs to be carefully processed to reduce artifacts compromising the interpretation of results. Because of the non-collaborative nature of the neonates, the differences in brain size and the reversed contrast compared to adults due to myelination, neonates can't be processed with the existing adult pipelines, as they are not adapted. Therefore, we developed NeoRS, a rsfMRI pipeline for neonates. The pipeline relies on popular neuroimaging tools (FSL, AFNI, and SPM) and is optimized for the neonatal brain. The main processing steps include image registration to an atlas, skull stripping, tissue segmentation, slice timing and head motion correction and regression of confounds which compromise functional data interpretation. To address the specificity of neonatal brain imaging, particular attention was given to registration including neonatal atlas type and parameters, such as brain size variations, and contrast differences compared to adults. Furthermore, head motion was scrutinized, and motion management optimized, as it is a major issue when processing neonatal rsfMRI data. The pipeline includes quality control using visual assessment checkpoints. To assess the effectiveness of NeoRS processing steps we used the neonatal data from the Baby Connectome Project dataset including a total of 10 neonates. NeoRS was designed to work on both multi-band and single-band acquisitions and is applicable on smaller datasets. NeoRS also includes popular functional connectivity analysis features such as seed-to-seed or seed-to-voxel correlations. Language, default mode, dorsal attention, visual, ventral attention, motor and fronto-parietal networks were evaluated. Topology found the different analyzed networks were in agreement with previously published studies in the neonate. NeoRS is coded in Matlab and allows parallel computing to reduce computational times; it is open-source and available on GitHub (https://github.com/venguix/NeoRS). NeoRS allows robust image processing of the neonatal rsfMRI data that can be readily customized to different datasets.

Congenital heart disease (CHD) has been associated with structural brain growth and long-term developmental impairments, including deficits in learning, memory, and executive functions. Altered functional connectivity has been shown to be altered in neonates born with CHD; however, it is unclear if these early life alterations are also present during adulthood. Therefore, this study aimed to compare resting state functional connectivity networks associated with executive function deficits between youth (16 to 24 years old) with complex CHD (mean age = 20.13; SD = 2.35) who underwent open-heart surgery during infancy and age- and sex-matched controls (mean age = 20.41; SD = 2.05). Using the Behavior Rating Inventory of Executive Function-Adult Version questionnaire, we found that participants with CHD presented with poorer performance on the inhibit, initiate, emotional control, working memory, self-monitor, and organization of materials clinical scales than healthy controls. We then compared the resting state networks theoretically corresponding to these impaired functions, namely the default mode, dorsal attention, fronto-parietal, fronto-orbital, and amygdalar networks, between the two groups. Participants with CHD presented with decreased functional connectivity between the fronto-orbital cortex and the hippocampal regions and between the amygdala and the frontal pole. Increased functional connectivity was observed within the default mode network, the dorsal attention network, and the fronto-parietal network. Overall, our results suggest that youth with CHD present with disrupted resting state functional connectivity in widespread networks and regions associated with altered executive functioning.

As the diagnostic power of medical imaging technologies continues to develop, its utilization in healthcare research has proliferated (Sandoval et al. 2018). Consummate with such proliferation has been the aggregation of a large amount of high-quality research medical imaging data across research centres. Henceforth, there is a rising need for an accessible, intuitive, and approachable web interface to organize, visualize, and share the large repertoire of medical imaging data effectively and easily (Sandoval et al. 2018). Since these platforms are complex and aimed at a trained medical or research scientific personnel, efforts to ensure usability are often not the main concern.

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. We analyzed resting-state functional magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We used CNV FC-signatures to identify dimensions contributing to complex idiopathic conditions. CNVs had large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions played a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibited worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms. ### Competing Interest Statement The authors have declared no competing interest.

Introduction Deep learning neural networks are especially potent at dealing with structured data, such as images and volumes. Both modified LiviaNET and HyperDense-Net performed well at a prior competition segmenting 6-month-old infant magnetic resonance images, but neonatal cerebral tissue type identification is challenging given its uniquely inverted tissue contrasts. The current study aims to evaluate the two architectures to segment neonatal brain tissue types at term equivalent age. Methods Both networks were retrained over 24 pairs of neonatal T1 and T2 data from the Developing Human Connectome Project public data set and validated on another eight pairs against ground truth. We then reported the best-performing model from training and its performance by computing the Dice similarity coefficient (DSC) for each tissue type against eight test subjects. Results During the testing phase, among the segmentation approaches tested, the dual-modality HyperDense-Net achieved the best statistically significantly test mean DSC values, obtaining 0.94/0.95/0.92 for the tissue types and took 80 h to train and 10 min to segment, including preprocessing. The single-modality LiviaNET was better at processing T2-weighted images than processing T1-weighted images across all tissue types, achieving mean DSC values of 0.90/0.90/0.88 for gray matter, white matter, and cerebrospinal fluid, respectively, while requiring 30 h to train and 8 min to segment each brain, including preprocessing. Discussion Our evaluation demonstrates that both neural networks can segment neonatal brains, achieving previously reported performance. Both networks will be continuously retrained over an increasingly larger repertoire of neonatal brain data and be made available through the Canadian Neonatal Brain Platform to better serve the neonatal brain imaging research community.

ABSTRACT Among healthy volunteers in psychiatric brain functional magnetic resonance imaging (fMRI) research studies, the prevalence of incidentalomas can be as high as 34%, of which 10% show clinical significance. An incidentaloma is a lesion found by coincidence without clinical symptoms or suspicion. Like lesions and other types of accidental findings, it is found in healthy individuals recruited to take part in psychiatric studies. The prevalence of these accidental findings among specific psychiatric populations remains unknown. However, a precise understanding of cerebral neuroanatomy, neuroradiological expertise, and an appropriate choice of fMRI exploration sequences will increase the sensitivity of identifying these accidental findings and enable researchers to address their clinical relevance and nature. We present recommendations on how to appropriately inform patients or participants of the accidental findings. Additionally, we propose specific suggestions pertaining to the clinical research setting aimed for investigators and psychiatrists. Unlike current articles pertaining to incidentaloma, the current report provides a distinct focus on psychiatric issues and specific recommendations for studies involving psychiatric patients.

With increasing advances in the field of medical brain imaging, the known spectrum of white matter lesions has expanded, and we can now assess the presence of punctate white matter lesions (PWML). These focal small lesions are quite frequently detected in the preterm infant and in full-term infants with congenital heart malformations with, some studies reporting a link between these lesions and adverse long-term outcomes. The etiology of PWML has sparked a lot of questions over the years, some of which still remain unanswered. This narrative review will bring an overview of current knowledge and their significant clinical importance in the newborn brain.

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Brain injury and abnormal maturation in the neonatal period is associated with long-term changes underlying significant cognitive, motor, language and behavioural deficiencies. Our understanding of clear cerebral disruptors of brain development and the extent of their impact are still limited, mostly due to the lack of robust non-invasive biomarkers, difficulties in conducting studies in newborns and the use of small isolated cohorts. To address all these issues, we have created the Canadian Neonatal Brain Platform (CNBP). The aims of CNBP are threefold: 1) To create and manage a national neonatal MRI registry to support prospective multicenter trials; 2) To make accessible to the community standardized sets of tools and protocols for image acquisition and analysis specifically designed for neonatology; 3) To better identify the concerns of parents of preterm infants by building a robust partnership. Aim 1: We modelled our architecture with a semi-decentralized overall structure composed of a site-specific infrastructure for initial localized data aggregation and anonymization, and a central server for post-processing and ensuring long-term scaleability. Aim 2: We conducted experiments to simulate human rater image quality assessment with machine learning. In addition, we performed brain segmentation using various open source neonatal neuroimaging analysis software to qualitatively validate their results against human rater golden standard. Aim 3: We deployed Mieux Agir au Quotidien (http://developpementenfant.ca), a web-based educational and support program for parents of preterm infants that incorporates state-of-the-art teaching modules on developmentally supportive care. Aim 1: Our infrastructure (see Figure 1) was successfully deployed in Compute Canada. We used DICOMTransit to collect, aggregate, anonymize and centralize data from MRI scanners, Canadian Neonatal Network and Canadian Neonatal Follow-up Network. We implemented LORIS (https://dev.cnbp.ca) to build a clinical neonatal imaging registry. Aim 2: Our pipeline reached a 75% sensitivity and 85% positive predictive value to control for quality. Our assessment of the segmentation tools revealed that MANTIS provides the most robust segmentation results. Aim 3: Mieux Agir au Quotidien reached over 700K visits in 2017. We have established a special partnership with parents of preterm infants, which has enabled us to gather first-rate information on parents’ concern and knowledge about the disorders of preterm infants, now available in english. CNBP has successfully progressed towards achieving its aims by establishing an online data processing and integration portal integrated with numerous neonatal specific analysis software while providing social and knowledge transfer to the general public.

We designed an fMRI study to pinpoint the neural correlates of active and passive binding in working memory. Participants were instructed to memorize three words and three spatial locations. In the passive binding condition, words and spatial locations were directly presented as bound. Conversely, in the active binding condition, words and spatial locations were presented as separated, and participants were directed to intentionally create associations between them. Our results showed that participants performed better on passive binding relative to active binding. FMRI analysis revealed that both binding conditions induced greater activity within the hippocampus. Additionally, our analyses divulged regions specifically engaged in passive and active binding. Altogether, these data allow us to propose the hippocampus as a central candidate for working memory binding. When needed, a frontal-parietal network can contribute to the rearrangement of information. These findings may inform theories of working memory binding.

Recent studies have shown that transcranial direct current stimulation (tDCS) may reduce craving and smoking. However, little is known regarding brain correlates of these behavioral changes. We aimed to evaluate whether 10 sessions of tDCS modulate cigarette consumption, craving and brain reactivity to smoking cues in subjects with tobacco use disorder (TUD). In a double blind parallel-arms study, 29 subjects with TUD who wished to quit smoking were randomly assigned to receive 10 sessions of either active or sham tDCS applied with the anode over the right dorsolateral prefrontal cortex (DLPFC) and a large cathode over the left occipital region. As compared to sham, active tDCS significantly reduced smoking craving and increased brain reactivity to smoking-cues within the right posterior cingulate, as measured with a functional magnetic resonance imaging event-related paradigm. However, we failed to find a significant difference between active and sham groups regarding the self-reported number of cigarettes smoked and the exhaled carbon monoxide during one month. These findings suggested that 10 sessions of tDCS over the right DLPFC may reduce craving by modulating activity within the resisting-to-smoke network but might not be significantly more effective than sham to decrease cigarette consumption.

Psychotic symptoms (PS) are experienced by a substantial proportion of the general population. When not reaching a threshold of clinical relevance, these symptoms are defined as psychotic experiences (PEs) and may exist on a continuum with psychotic disorders. Unfavorable socio-environmental conditions, such as ethnic minority position (EMP) and migrant status (MS), may increase the risk of developing PS and PEs. We conducted an electronic systematic review and a meta-analysis assessing the role of EMP and MS for the development and persistence of PS in the general population. Sub-group analyses were performed investigating the influence of ethnic groups, host countries, age, types of PS, and scales. Twenty-four studies met our inclusion criteria. EMP was a relevant risk factor for reporting PS [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.22-1.70) and PEs (OR 1.36, 95% CI 1.16-1.60). The greatest risk was observed in people from the Maghreb and the Middle East ethnic groups in Europe (OR 3.30, 95% CI 2.09-5.21), in Hispanic in the USA (OR 1.98, 95% CI 1.43-2.73), and in the Black populations (OR 1.85, 95% CI 1.39-2.47). We found a significant association between MS and delusional symptoms (OR 1.47, 95% CI 1.33-1.62). We found no association between EMP and persistence of PEs.EMP was associated with increased risk of reporting PS and PEs, and the risk was higher in ethnic groups facing deprivation and discrimination. We found an association between MS and delusional symptoms. These results raise questions about the precise role of socio-environmental factors along the psychosis continuum.

Context: Patients with schizophrenia display abnormalities in pitch discrimination of non-verbal tones as revealed by the Tone-Matching Task (TMT). It may lead to deficits in higher-order cognitive functions and clinical symptoms.Objectives: We conducted a systematic review and meta-analysis pooling data about TMT score differences between patients with schizophrenia and healthy controls, to evaluate the deficit's effect size, and to develop reliable knowledge about pitch processing impairment and its pejorative impact.Method: Relevant publications were identified by a systematic search of PubMed and EMBASE databases. Then, we excluded non-relevant studies for the meta-analysis. Effect size for percent of correct responses to the TMT was expressed as standardized mean difference (SMD).Results: Eighteen of 167 identified studies met eligibility criteria for review, of which 10 were included in the meta-analysis. Our meta-analysis showed that the effect size for the percent of correct response to the TMT between patients (N=371) and controls (N=342) was large: SMD=1.17 [95% CI: 0.926-1.418] (z-value=9.338 and p-value = 0.001). Meta-analysis showed moderate heterogeneity between studies (Q(9)=17.22, p=0.04, I-2=47.74%). The relationship between tone-matching impairment and clinical symptoms of schizophrenia remains heterogeneous across studies. Some authors observed significant correlations between tone-matching performance and a number of higher-order cognitive abilities.Conclusion: This review and meta-analysis highlights a large significant disturbance in tone-matching ability in patients as compared with controls. The study of basic auditory processing opens promising perspectives for pathophysiological modelling of the disorder and therapeutic issues. (C) 2016 Elsevier B. V. All rights reserved.

Tourette syndrome (TS) is a neuropsychiatric disorder involving motor and phonic tics. Inhibitory control is a key issue in TS, and many disruptive or impulsive behaviors might arise from inhibitory deficits. However, conflicting findings regarding TS patients’ inhibitory performance in neuropsychological tasks have been reported throughout the literature. Therefore, this meta-analysis aimed to evaluate inhibitory control through neuropsychological tasks, and to analyze the factors modulating inhibitory deficits. To this end, a literature search was performed through MEDLINE and PsycINFO, to retrieve studies including neuropsychological tasks that assessed inhibitory control in TS patients. Of the 4020 studies identified, 61 were included in the meta-analysis, for a total of 1717 TS patients. Our analyses revealed a small to medium effect in favor of inhibitory deficits in TS patients. This effect was larger in TS + ADHD patients, but pure TS patients also showed some inhibitory deficits. Therefore, deficits in inhibitory control seem to be an inherent component of TS, and are exacerbated when ADHD is concomitant.

Functional and structural brain changes associated with the cognitive processing of emotional visual stimuli were assessed in schizophrenic patients after 16 weeks of antipsychotic treatment with ziprasidone. Forty-five adults aged 18 to 40 were recruited: 15 schizophrenia patients (DSM-IV criteria) treated with ziprasidone (mean daily dose = 120 mg), 15 patients treated with other antipsychotics, and 15 healthy controls who did not receive any medication. Functional and structural neuroimaging data were acquired at baseline and 16 weeks after treatment initiation. In each session, participants selected stimuli, taken from standardized sets, based on their emotional valence. After ziprasidone treatment, several prefrontal regions, typically involved in cognitive control (anterior cingulate and ventrolateral prefrontal cortices), were significantly activated in patients in response to positive versus negative stimuli. This effect was greater whenever they had to select negative compared to positive stimuli, indicating an asymmetric effect of cognitive treatment of emotionally laden information. No such changes were observed for patients under other antipsychotics. In addition, there was an increase in the brain volume commonly recruited by healthy controls and patients under ziprasidone, in response to cognitive processing of emotional information. The structural analysis showed no significant changes in the density of gray and white matter in ziprasidone-treated patients compared to patients receiving other antipsychotic treatments. Our results suggest that functional changes in brain activity after ziprasidone medication precede structural and clinical manifestations, as markers that the treatment is efficient in restoring the functionality of prefrontal circuits involved in processing emotionally laden information in schizophrenia.

Working memory deficits have been widely reported in schizophrenia, and may result from inefficient binding processes. These processes, and their neural correlates, remain understudied in schizophrenia. Thus, we designed an FMRI study aimed at investigating the neural correlates of both passive and active binding in working memory in schizophrenia. Nineteen patients with schizophrenia and 23 matched controls were recruited to perform a working memory binding task, in which they were instructed to memorize three letters and three spatial locations. In the passive binding condition, letters and spatial locations were directly presented as bound. Conversely, in the active binding condition, words and spatial locations were presented as separated, and participants were instructed to intentionally create associations between them. Patients exhibited a similar performance to the controls for the passive binding condition, but a significantly lower performance for the active binding. FMRI analyses revealed that this active binding deficit was related to aberrant activity in the posterior parietal cortex and the ventrolateral prefrontal cortex. This study provides initial evidence of a specific deficit for actively binding information in schizophrenia, which is linked to dysfunctions in the neural networks underlying attention, manipulation of information, and encoding strategies. Together, our results suggest that all these dysfunctions may be targets for neuromodulation interventions known to improve cognitive deficits in schizophrenia.

De nombreuses études en neuroimagerie fonctionnelle (IRMf) menées chez les adultes présentant un trouble de personnalité limite (TPL) convergent pour identifier un patron d’activation neuronale, notamment fronto-limbique, différent de celui activé chez les adultes sans TPL lors des tâches de visualisation d’images émotionnelles. À ce jour, aucune étude en IRMf n’a été réalisée chez les adolescents avec TPL. Ce projet pilote vise à évaluer la faisabilité d’un protocole d’IRMf chez des adolescentes avec TPL et à identifier les régions neuronales d’intérêt pour les études de neuroimagerie chez cette population. Le projet porte sur six adolescentes euthymiques présentant un diagnostic de TPL (âge moyen : 15,8 ± 0,9 ans) et six adolescentes témoins sans diagnostic psychiatrique (âge moyen : 15,5 ± 1,2 ans). Après l’évaluation diagnostique incluant le Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime et le Diagnostic Interview for Borderline – Revised version, les participantes ont complété une tâche d’IRMf au cours de laquelle elles devaient regarder 20 images à valence affective positive, 20 images à valence affective négative et 20 images neutres. L’étude de faisabilité montre que les participantes ont été recrutées en 22 mois et que le protocole était bien toléré par celles-ci. Les résultats montrent que le visionnement des scènes positives et négatives a entraîné une plus grande activation de plusieurs aires limbiques ainsi que frontales, temporales et du cervelet chez le groupe TPL. Les aires limbiques et préfrontales semblent être des régions d’intérêt dans l’étude du fonctionnement neuronal chez les adolescentes avec TPL.

Self-disturbances in schizophrenia have been regarded as a fundamental vulnerability marker for this disease, and have begun to be studied from the standpoint of an abnormal "sense of agency (SoA)" in cognitive neuroscience. To clarify the nature of aberrant SoA in schizophrenia, it needs to be investigated in various clinical subtypes and stages. The residual type of chronic schizophrenia with predominant negative symptoms (NS) has never been investigated for SoA. Accordingly, we investigated SoA by an original agency attribution task in NS-predominant schizophrenia, and evaluated the dynamic interplay between the predictive and postdictive components of SoA in the optimal cue integration framework. We studied 20 patients with NS-predominant schizophrenia, and compared with 30 patients with paranoid-type schizophrenia and 35 normal volunteers. NS-predominant schizophrenia showed markedly diminished SoA compared to normal controls and paranoid-type schizophrenia, indicating a completely opposite direction in agency attribution compared with excessive SoA demonstrated in paranoid-type schizophrenia. Reduced SoA was detected in experimental studies of schizophrenia for the first time. According to the optimal cue integration framework, these results indicate that there was no increase in compensatory contributions of the postdictive processes despite the existence of inadequate predictions, contrary to the exaggerated postdictive component in paranoid-type schizophrenia.