Ethnic minority position and migrant status as risk factors for psychotic symptoms in the general population: a meta-analysis.

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.

Incidentaloma Discoveries in the Course of Neuroimaging Research.

ABSTRACTAmong 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.

[Functional Neuroimaging Pilot Study of Borderline Personality Disorder in Adolescents]. / Neuroimagerie fonctionnelle chez l'adolescent avec un trouble de personnalité limite.

Borderline personality disorder (BPD) is being increasingly recognized by clinicians working with adolescents, and the reliability and validity of the diagnosis have been established in the adolescent population. Adolescence is known to be a period of high risk for BPD development as most patients identify the onset of their symptoms to be in the adolescent period. As with other mental health disorders, personality disorder, are thought to result from the interaction between biological and environmental factors. Functional neuroimaging studies are reporting an increasing amount of data on abnormal neuronal functions in BPD adult patients. However, no functional neuroimaging studies have been conducted in adolescents with BPD.Objectives This pilot project aims to evaluate the feasibility of a functional magnetic resonance imaging (fMRI) study coupled with clinical and psychological measures in adolescent girls with a diagnosis of BPD. It also aims to identify neuronal regions of interest (ROI) for the study of BPD in adolescent girls.Method Six female adolescents meeting DSM-IV criteria for BPD and 6 female adolescents without psychiatric disorder were recruited. Both groups were evaluated for BPD symptoms, depressive symptoms, impulsivity, affective lability, and other potential psychiatric comorbidities. We used fMRI to compare patterns of regional brain activation between these two groups as they viewed 20 positive, 20 negative and 20 neutral emotion-inducing pictures, which were presented in random order.Results Participants were recruited over a period of 22 months. The protocol was well tolerated by participants. Mean age of the BPD group and control group was 15.8 ± 0.9 years-old and 15.5 ± 1.2 years-old respectively. Psychiatric comorbidity and use of medication was common among participants in the BPD group. This group showed higher impulsivity and affective lability scores. For the fMRI task, BPD patients demonstrated greater differences in activation than controls, when viewing negative pictures compared with neutral pictures, in limbic regions (amygdala and right hippocampus and parahippocampal areas) as well as in the superior frontal gyrus, right precentral gyrus and cerebellum, while control group showed greater activation in left precentral gyrus and right orbitofrontal area. Viewing positive pictures compared with neutral pictures led to increased activation of the left hippocampus and both parahippocampal regions, as well as middle cingulate cortex, superior temporal gyrus and cerebellum in the BPD group. In the control group, positive-scene viewing led to increased activity in the left superior parietal gyrus and right middle/superior temporal gyrus.Conclusion Limbic regions and areas from the prefrontal and orbitofrontal cortex are potential ROI for the study of the neurophysiology of BPD in female adolescents. The larger studies are needed to better understand the neural features found in these young patients.

NeoRS: A Neonatal Resting State fMRI Data Preprocessing Pipeline.

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.

Altered resting state functional connectivity in youth with congenital heart disease operated during infancy.

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.

fMRI working memory hypo-activations in schizophrenia come with a coupling deficit between arousal and cognition.

Cognition has become a target for therapeutic intervention and favoring arousal could be a way to help patients. Working memory is an arousal dependent cognitive function. This study used functional MRI (fMRI) as a surrogate marker of working memory to evaluate the sensitivity of patients' hypoactive regions to arousal in a subpopulation of rehabilitated patients. Are hypoactive regions sensitive to arousal? Does the deficit result from arousal deficit or improper coupling with cognitive activity? Eighteen patients and matched controls were recruited. Participants performed a working memory task during combined electroencephalographic (EEG) and fMRI measurements. Cortical regions sensitive to arousal were defined as those which were inversely correlated with low EEG frequencies. Overlap between the arousal-sensitive and hypoactive regions was assessed by mutual information. Arousal-cognitive coupling was evaluated by the correlation between the arousal effect and the task effect. In the patient group, most hypoactive voxels were sensitive to arousal and corresponded to the prefronto-parietal network. But patients had no arousal deficit. Although arousal seems to improve cognitive activity in most of the patients' cortical areas, this coupling appears to be specifically disturbed in their hypoactive regions. In conclusion, although increasing arousal may help cognition, it may do so in an unspecific way.

Abnormal medial temporal activity for bound information during working memory maintenance in patients with schizophrenia.

Alterations of binding in long-term memory in schizophrenia are well established and occur as a result of aberrant activity in the medial temporal lobe (MTL). In working memory (WM), such a deficit is less clear and the pathophysiological bases remain unstudied. Seventeen patients with schizophrenia and 17 matched healthy controls performed a WM binding task while undergoing functional magnetic resonance imaging. Binding was assessed by contrasting two conditions comprising an equal amount of verbal and spatial information (i.e., three letters and three spatial locations), but differing in the absence or presence of a link between them. In healthy controls, MTL activation was observed for encoding and maintenance of bound information but not for its retrieval. Between-group comparisons revealed that patients with schizophrenia showed MTL hypoactivation during the maintenance phase only. In addition, BOLD signals correlated with behavioral performance in controls but not in patients with schizophrenia. Our results confirm the major role that the MTL plays in the pathophysiology of schizophrenia. Short-term and long-term relational memory deficits in schizophrenia may share common cognitive and functional pathological bases. Our results provide additional information about the episodic buffer that represents an integrative interface between WM and long-term memory.

The right parahippocampal gyrus contributes to the formation and maintenance of bound information in working memory.

Working memory is devoted to the temporary storage and on-line manipulation of information. Recently, an integrative system termed the episodic buffer has been proposed to integrate and hold information being entered or retrieved from episodic memory. Although the brain system supporting such an integrative buffer is still in debate, the medial temporal lobe appears to be a promising candidate for the maintenance of bound information. In the current work, binding was assessed by comparing two conditions in which participants had to retain three letters and three spatial locations presented either bound or separate. At the behavioral level, lower performance was found for bound information than for separate information. When contrasting the two conditions, activation in the right parahippocampal gyrus was greater for the encoding and maintenance of bound information. No activation was observed in the medial temporal lobe during the retrieval of bound information. Together, our results suggest that the parahippocampal gyrus may underlie the integrative and maintenance functions of the episodic buffer.

Using Deep Convolutional Neural Networks for Neonatal Brain Image Segmentation.

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.

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia.

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.

Examining the effects of two factors on working memory maintenance of bound information in schizophrenia.

Integrating information in space and time is a central feature of episodic memory. Although disturbance of the binding processes in episodic memory is well established in patients with schizophrenia, data on working memory (WM) remain discrepant. In a change detection procedure, two target displays of pairs of letters located in cells of grid were successively presented. Participants attempted to detect changes in binding information (i.e., recombination of studied features) or feature information (i.e., a novel letter and/or a novel spatial location). Recombinations consisted of features belonging to the same display (intradisplay) or different displays (interdisplays). Results showed that patients demonstrated overall lower performance, with no specific deficit for recognizing bound information or feature information. In addition, patients did not demonstrate deficits for interdisplay recombinations or intradisplay recombinations. Patients' ability to remember temporal occurrence of stimuli was not affected. Together, these results suggest that in patients with schizophrenia, binding processes in WM are not specifically disturbed.

Selective pair recognition memory impairment with no response bias in schizophrenia.

Memory is one of the cognitive functions most affected in schizophrenia, but the severity of deficits varies from one task to another. In particular, greater impairments have been reported for pair recognition than item recognition. However, decision biases and how they could affect memory dysfunction in schizophrenia have received scant attention. In this study, 26 people with schizophrenia and 28 healthy controls were administrated an association item recognition task. During encoding, participants studied pairs of visual objects, and they had to memorise objects and their pairing. In a subsequent retrieval task, participants performed an item recognition test (old/new items) and a pair recognition test (intact/rearranged pairs). Results showed that both groups were better at recognizing items than pairs, with lower performance for pair recognition, but not for item recognition, in people with schizophrenia. Analyses of response biases revealed that patients had a conservative response bias for items but not for pairs. The study also provides evidence that associative impairment may not result from decisional bias but rather from impairments in mnesic processes.

The brain's kryptonite: Overview of punctate white matter lesions in neonates.

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.

Assessment of single and bound features in a working memory task in schizophrenia.

If disturbance of binding in long term memory is well established in schizophrenia, data concerning working memory maintenance are less clear. Feature binding in working memory was investigated in 19 patients with schizophrenia and 19 healthy controls. Binding was assessed by comparing two conditions in which participants had to retain four letters and four spatial locations. These features were presented either bound or separate. Results showed that both groups had better performances for bound than separate features, despite the fact that patients performed significantly worse than controls. When maintenance for isolated features was assessed, patients were severely disturbed for spatial locations but not for letters. Such a result suggests that reduced working memory performance in patients with schizophrenia for bound features is probably a consequence of a spatial deficit rather than a specific deficit of the binding process. Thus, not all form of binding are disturbed in schizophrenia.

Examining the neural correlates of active and passive forms of verbal-spatial binding in working memory.

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.

Effects of repeated transcranial direct current stimulation on smoking, craving and brain reactivity to smoking cues.

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.

A neuroimaging study of emotion-cognition interaction in schizophrenia: the effect of ziprasidone treatment.

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.

The puzzling question of inhibitory control in Tourette syndrome: A meta-analysis.

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.

Abnormal prefrontal and parietal activity linked to deficient active binding in working memory 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.

Tone-matching ability in patients with schizophrenia: A systematic review and meta-analysis.

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, I2=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.