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Family history (FH+) of substance use disorder (SUD) is an established risk factor for offspring SUD. The extent to which offspring psychological traits or the family environment, each of which may be relevant to familial transmission of SUD risk, vary by FH+ in socioeconomically disadvantaged populations is less clear. We compared the family/social environmental and psychological characteristics of 73 FH+ and 69 FH- youth ages 12-16, from a study of parental criminal justice system involvement in a primarily low-income, minority urban population. A latent profile analysis (LPA) empirically identified groups of subjects with similar psychological characteristics, which were then compared by FH+. FH+ youths were found to have greater mean household size, greater parental psychological aggression, and a higher mean number of adverse childhood experiences, even without considering parental SUD. FH+ individuals had lower report card grades according to parental report and were more likely to have a history of externalizing disorders than FH- individuals. However, FH+ was not significantly associated with many psychological characteristics or with the class membership from the LPA. In conclusion, among a population of low-income, minority urban youth, FH+ was associated with differences in the family environment and only subtle differences in individual psychological characteristics.

It is difficult to accurately understand the angioarchitecture of cerebral arteriovenous malformations (CAVMs) before surgery using existing imaging methods. This study aimed to evaluate the ability of the stereoscopic virtual reality display system (SVRDS) to display the angioarchitecture of CAVMs by comparing its accuracy with that of the conventional computed tomography workstation (CCTW). Nineteen patients with CAVM confirmed on digital subtraction angiography (DSA) or during surgery were studied. Computed tomography angiography images in the SVRDS and CCTW were retrospectively analyzed by two experienced neuroradiologists using a double-blind method. Angioarchitectural parameters, such as the location and size of the nidus, type and number of the arterial feeders and draining veins, and draining pattern of the vessels, were recorded and compared. The diameter of the nidus ranged from 1.1 to 9 cm. Both CCTW and SVRDS correctly diagnosed the location of the nidus in 19 patients with CAVM. Among the 19 patients, 35 arterial feeders and 25 draining veins were confirmed on DSA and during surgery. With the DSA and intraoperative results as the gold standard bases, the CCTW misjudged one arterial feeder and one draining vein and missed three arterial feeders and two draining veins; meanwhile, the SVRDS missed only two arterial feeders. SVRDS had some advantages in displaying nidus, arterial branches, and draining veins of the CAVM compared with CCTW, as well as SVRDS could more intuitively display the overall angio-architectural spatial picture of CAVM., (© 2023. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

The accuracy of computed tomography angiography (CTA) image interpretation depends on the radiologist. This study aims to develop a new method for automatically detecting intracranial aneurysms from CTA images using deep learning, based on a convolutional neural network (CNN) implemented on the DeepMedic platform. Ninety CTA scans of patients with intracranial aneurysms are collected and divided into two datasets: training (80 subjects) and test (10 subjects) datasets. Subsequently, a deep learning architecture with a three-dimensional (3D) CNN model is implemented on the DeepMedic platform for the automatic segmentation and detection of intracranial aneurysms from the CTA images. The samples in the training dataset are used to train the CNN model, and those in the test dataset are used to assess the performance of the established system. Sensitivity, positive predictive value (PPV), and false positives are evaluated. The overall sensitivity and PPV of this system for detecting intracranial aneurysms from CTA images are 92.3% and 100%, respectively, and the segmentation sensitivity is 92.3%. The performance of the system in the detection of intracranial aneurysms is closely related to their size. The detection sensitivity for small intracranial aneurysms (≤ 3 mm) is 66.7%, whereas the sensitivity of detection for large (> 10 mm) and medium-sized (3-10 mm) intracranial aneurysms is 100%. The deep learning architecture with a 3D CNN model on the DeepMedic platform can reliably segment and detect intracranial aneurysms from CTA images with high sensitivity., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Background: The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression., Methods: The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N-acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively., Results: After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, β- left  = -0.17, β- right  = -0.15, ps = .002), N-acetylaspartate/creatine ratio (β- left = -0.40, β- right = -0.37, ps < .0001), and activation modulated by valence (β- left  = -0.22, β- right  = -0.27, ps < .05) than low-risk individuals. Volume differences were greater at younger ages, and N-acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (β- left  = -0.72, p = .013; β- right  = -0.83, p = .037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 ≤ r ≤ 0.33)., Conclusions: Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Obesity can result from excess intake in response to environmental food cues, and stress can drive greater intake and body weight. We used a novel fMRI task to explore how obesity and stress influenced appetitive responses to relatively minimal food cues (words representing food items, presented similarly to a chalkboard menu). Twenty-nine adults (16F, 13M), 17 of whom had obesity and 12 of whom were lean, completed two fMRI scans, one following a combined social and physiological stressor and the other following a control task. A food word reactivity task assessed subjective food approach (wanting) as well as food avoidant (restraint) responses, along with neural responses, to words denoting high energy-density (ED) foods, low-ED foods, and non-foods. A multi-item ad-libitum meal followed each scan. The obese and lean groups demonstrated differences as well as similarities in activation of appetitive and attention/self-regulation systems in response to food vs. non-food, and to high-ED vs. low-ED food words. Patterns of activation were largely similar across stress and non-stress conditions, with some evidence for differences between conditions within both obese and lean groups. The obese group ate more than the lean group in both conditions. Our results suggest that neural responses to minimal food cues in stressed and non-stressed states may contribute to excess consumption and adiposity., Competing Interests: The authors have declared that no competing interests exist.

The dynamic functional connectivity (dFC) in functional magnetic resonance imaging (fMRI) is beneficial for the analysis and diagnosis of neurological brain diseases. The dFCs between regions of interest (ROIs) are generally delineated by a specific template and clustered into multiple different states. However, these models inevitably fell into the model-driven self-contained system which ignored the diversity at spatial level and the dynamics at time level of the data. In this study, we proposed a spatial and time domain feature extraction approach for Alzheimer's disease (AD) and autism spectrum disorder (ASD)-assisted diagnosis which exploited the dynamic connectivity among independent functional sub networks in brain. Briefly, independent sub networks were obtained by applying spatial independent component analysis (SICA) to the preprocessed fMRI data. Then, a sliding window approach was used to segment the time series of the spatial components. After that, the functional connections within the window were obtained sequentially. Finally, a temporal signal-sensitive long short-term memory (LSTM) network was used for classification. The experimental results on Alzheimer's Disease Neuroimaging Initiative (ADNI) and Autism Brain Imaging Data Exchange (ABIDE) datasets showed that the proposed method effectively predicted the disease at the early stage and outperformed the existing algorithms. The dFCs between the different components of the brain could be used as biomarkers for the diagnosis of diseases such as AD and ASD, providing a reliable basis for the study of brain connectomics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qiao, Wang, Liu, Xu and Wang.)

It has been suggested that intergenerational transmission of risk for substance use disorder (SUD) manifests in the brain anatomy of substance naïve adolescents. While volume and shapes of subcortical structures (SSS) have been shown to be heritable, these structures, especially the pallidum, putamen, nucleus accumbens, and hippocampus, have also been associated with substance use disorders. However, it is not clear if those anatomical differences precede substance use or are the result of that use. Therefore, we examined if volume and SSS of adolescents with a family history (FH+) of SUD differed from adolescents without such a history (FH-). Because risk for SUD is associated with anxiety and impulsivity, we also examined correlations between these psychological characteristics and volume/SSS. Using structural MRI and FSL software, we segmented subcortical structures and obtained indices of SSS and volumes of 64 FH+ and 58 FH- adolescents. We examined group differences in volume and SSS, and the correlations between volume/SSS and trait anxiety and impulsivity. FH+ adolescents had a significant inward deformation in the shape of the right anterior hippocampus compared to FH- adolescents, while the volume of this structure did not differ between groups. Neither shape nor volume of the other subcortical structures differed between groups. In the FH+ adolescents, the left hippocampus shape was positively correlated with both trait anxiety and impulsivity, while in FH- adolescents a negative correlation pattern of SSS was seen in the hippocampus. SSS appears to capture local anatomical features that traditional volumetric analysis does not. The inward shape deformation in the right anterior hippocampus in FH+ adolescents may be related to the known increased risk for behavioral dysregulation leading to SUD in FH+ offspring. Hippocampus shape also exhibits opposite patterns of correlation with anxiety and impulsivity scores across the FH+ and FH- adolescents. These novel findings may reveal neural correlates, not captured by traditional volumetric analysis, of familial transmission of increased vulnerability to SUD., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Obsessive-compulsive disorder (OCD) implicates alterations in cortico-striato-thalamo-cortical and fronto-limbic circuits. Building on prior structural findings, this is the largest study to date examining subcortical surface morphometry in OCD., Methods: Structural magnetic resonance imaging data were collected from 200 participants across development (5-55 years): 28 youth and 75 adults with OCD and 27 psychiatrically healthy youth and 70 adults. General linear models were used to assess group differences and group-by-age interactions on subcortical shape (FSL FIRST)., Results: Compared to healthy participants, those with OCD exhibited surface expansions on the right nucleus accumbens and inward left amygdala deformations, which were associated with greater OCD symptom severity ([Children's] Yale-Brown Obsessive-Compulsive Scale). Group-by-age interactions indicated that accumbens group differences were driven by younger participants and that right pallidum shape was associated inversely with age in healthy participants, but not in participants with OCD. No differences in the shape of other subcortical regions or in volumes (FreeSurfer) were detected in supplementary analyses., Conclusions: This study is the largest to date examining subcortical shape in OCD and the first to do so across the developmental spectrum. NAcc and amygdala shape deformation builds on extant neuroimaging findings and suggests subtle, subregional alterations beyond volumetric findings. Results shed light on morphometric alterations in OCD, informing current pathophysiological models., (© 2022 Wiley Periodicals LLC.)

Previous neuroimaging studies have shown that serotonin-norepinephrine reuptake inhibitor antidepressants alter functional activity in large expanses of brain regions. However, it is not clear how these regions are systemically organized on a connectome level with specific topological properties, which may be crucial to revealing neural mechanisms underlying serotonin-norepinephrine reuptake inhibitor treatment of persistent depressive disorder. To investigate the effect of serotonin-norepinephrine reuptake inhibitor antidepressants on brain functional connectome reconfiguration in persistent depressive disorder and whether this reconfiguration promotes the improvement of clinical symptoms, we combined resting-state functional magnetic resonance imaging (fMRI) scans acquired in two randomized, double-blind, placebo-controlled trial studies of serotonin-norepinephrine reuptake inhibitor antidepressant treatment of patients with persistent depressive disorder. One was a randomized, double-blind, placebo-controlled trial of 10-week duloxetine medication treatment, which included 17 patients in duloxetine group and 17 patients in placebo group (ClinicalTrials.gov Identifier: NCT00360724); the other one was a randomized, double-blind, placebo-controlled trial of 12-week desvenlafaxine medication treatment, which included 16 patients in desvenlafaxine group and 15 patients in placebo group (ClinicalTrials.gov Identifier: NCT01537068). The 24-item Hamilton Depression Rating Scale was used to measure clinical symptoms, and graph theory was employed to examine serotonin-norepinephrine reuptake inhibitor antidepressant treatment effects on the topological properties of whole-brain functional connectome of patients with persistent depressive disorder. We adopted a hierarchical strategy to examine the topological property changes caused by serotonin-norepinephrine reuptake inhibitor antidepressant treatment, calculated their small-worldness, global integration, local segregation and nodal clustering coefficient in turn. Linear regression analysis was used to test associations of treatment, graph properties changes and clinical symptom response. Symptom scores were more significantly reduced after antidepressant than placebo administration ( η 2 = 0.18). There was a treatment-by-time effect that optimized the functional connectome in a small-world manner, with increased global integration and increased nodal clustering coefficient in the bilateral thalamus (left thalamus η 2 = 0.21; right thalamus η 2 = 0.23). The nodal clustering coefficient increment of the right thalamus (ratio = 29.86; 95% confidence interval, -4.007 to -0.207) partially mediated the relationship between treatment and symptom improvement, and symptom improvement partially mediated (ratio = 21.21; 95% confidence interval, 0.0243-0.444) the relationship between treatment and nodal clustering coefficient increments of the right thalamus. Our study may indicate a putative mutually reinforcing association between nodal clustering coefficient increment of the right thalamus and symptom improvement from serotonin-norepinephrine reuptake inhibitor antidepressant treatments with duloxetine or desvenlafaxine., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

A family history (FH+) of substance use disorder (SUD) increases an adolescent's risk for substance use initiation and progression. Greater impulsivity and reward seeking behavior is known to be associated with such risk. At the neurological level, dysfunction of cortico-striatal and cortico-limbic pathways have been proposed as contributors to the increased SUD risk in adolescents with FH+. In addition, disadvantaged environments have been associated with atypical brain connectivity and higher SUD risk. However, it remains unclear if this increased risk is manifested in structural and functional brain abnormalities prior to regular drug use. To examine this, we employed complementary imaging of structural and functional connectivity of 60 FH+ and 55 FH- minority adolescents, all from families with low socio-economic status. We acquired diffusion tensor-imaging (DTI) and resting state fMRI data across the whole brain. Structural connectivity was examined by measuring fractional anisotropy (FA) using DTI, to indicate integrity of the white matter tracts. Functional connectivity within and between resting state networks was assessed by the correlation of blood-oxygen-level-dependent (BOLD) signal between intra and inter-network nodes. Psychological measures of impulsivity and reward seeking were also obtained with standardized measures, the BIS-11 and the BIS/BAS, and their association with FA and functional connectivity was evaluated. We found no differences in white matter integrity between the groups. Compared to FH-, FH + adolescents showed significantly greater functional connectivity between posterior regions of the Default Mode Network (DMN) and the Fronto-Parietal Network (FPN). While psychological measures of reward seeking behavior did not differ between the FH+ and FH- groups, impulsivity, assessed by the BIS-11, was significantly higher for FH+. However, we did not find significant differences between the FH+ and FH- groups when comparing associations of BIS-11 scores and white matter integrity or functional connectivity measures. The stronger inter-network functional connectivity between the DMN and FPN in FH + adolescents suggests that transmitted risk for SUD may be related to large-scale brain dynamics. The lack of structural differences support the importance of early prevention efforts for FH + adolescents, before initiation of drug use, allowing for healthy brain development., Competing Interests: Financial disclosures All authors report no biomedical financial interests and no potential conflicts of interest.

Adolescents with a family history (FH+) of substance use disorder (SUD) are at a greater risk for SUD, suggested to be partly due to the transmission of behavioral impulsivity. We used a delay discounting task to compare impulsivity in decision-making and its associated brain functioning among FH+ and FH - minority adolescents. Participants chose between Smaller Sooner (SS) and Larger Later (LL) rewards. The SS was available immediately (Now trials) or in the future (Not-Now trials), allowing for greater differentiation between impulsive decisions. The FH+ group showed greater impatience by responding SS more frequently than the FH - group, only on the Now trials, and even when the relative reward differences (RRD) increased. Surprisingly, there were no differences in brain activity between the groups. Combined, the groups showed greater reward activity during the Now vs. Not-Now trials in medial prefrontal/anterior cingulate, posterior cingulate, precuneus, and inferior frontal gyrus (i.e., an immediacy effect). As the RRD increased activation in the reward network decreased, including the striatum, possibly reflecting easy decision-making. These results indicate that risk for SUD, seen behaviorally among FH+ adolescents, may not yet be associated with discernable brain changes, suggesting that early intervention has the potential to reduce this risk., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study focused on the ADHD classification through functional connectivity (FC) analysis. Method: An ADHD classification method was proposed with subspace clustering and binary hypothesis testing, wherein partial information of test data was adopted for training. By hypothesizing the binary label (ADHD or control) for the test data, two feature sets of training FC data were generated during the feature selection procedure that employed both training and test data. Then, a multi-affinity subspace clustering approach was performed to obtain the corresponding subspace-projected feature sets. With the energy comparison of projected feature sets, we finally identified ADHD individuals for the test data. Results: Our method outperformed several state-of-the-art methods with the above 90% average identification accuracy. By the discriminative FC contribution analysis, it also proved the reliability of our method. Conclusion: Results demonstrate the remarkable classification performance of our method and reveal some useful brain circuits to identify ADHD.

Background: Major depressive disorder (MDD) is associated with aberrant limbic neural responses to emotional stimuli. We assessed how self-generated emotions modulate trial-by-trial limbic activity and whether this brain-emotion synchrony varies by familial MDD risk (regardless of personal MDD history) and neuroticism., Methods: Participants (n = 74, mean age = 34 years) were later-generation family members of depressed or nondepressed probands as part of a longitudinal cohort study. Using an emotion induction task, we examined participant-specific modulation of anatomically defined limbic neurobiology. Neuroticism, mental health, and familial parenting style were assessed, and MDD assessments were routinely collected throughout the previous longitudinal assessments of the study., Results: Participant-specific emotional arousal modulated amygdala and hippocampal activity. Lasso regression identified attenuated right amygdala arousal modulation as being relatively more associated with neuroticism (even though neuroticism was not associated with arousal ratings). Attenuated amygdala modulation and neuroticism were significantly more likely in offspring of parents with MDD. Parental MDD, but not personal history of MDD, predicted attenuated amygdala modulation., Conclusions: Attenuated right amygdala modulation by emotional arousal was associated with neuroticism, indicating that the amygdala was less synchronous with emotional experiences in individuals higher in neuroticism. This neurophenotype was predicted by participants' parental MDD history but not by their own MDD history; that is, it was observed in unaffected and affected offspring of parents with MDD. These data suggest that weak amygdala-emotion synchrony may be a predisposing risk factor for MDD, rather than a result of the illness, and they suggest pathways by which this risk factor for depression is passed intergenerationally., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Brain gray matter is organized in a manner with interconnected brain regions, resulting in a notable covariance pattern that recapitulates either the functional coactivation or structural connectivity of brain regions, which is believed to underpin psychiatric disorders such as depression. This study aimed to investigate whether and how antidepressants took effect in treating depression and reducing symptoms by altering the gray matter covariance pattern. We combined structural magnetic resonance imaging (MRI) scans acquired in two randomized, double-blind, placebo-controlled trial (RCT) studies of the treatment using serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant medications in patients with persistent depressive disorder (PDD). One was an RCT of 10-week duloxetine medication that consisted of patients who received duloxetine (N = 21) or placebo (N = 21), and the other was an RCT of 12-week desvenlafaxine medication that consisted of 19 and 17 patients respectively who received desvenlafaxine or placebo. We examined treatment effect on gray matter volume (GMV) and topological organization of GMV covariance pattern (i.e., GMV-based network). We found a treatment-by-time effect on GMV in the angular gyrus and cuneus areas, whereas the GMV change rate of the cuneus was inversely correlated with the response rate. We observed a significant increase in the local efficiency of the GMV-based network following medication treatment compared with placebo. Our findings provide preliminary evidence for a GMV-based network-specific reconfiguration caused by antidepressants compared to placebo and the cuneus may be a possible candidate region to predict antidepressant response., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The term perceptual closure refers to the neural processes responsible for "filling-in" missing information in the visual image under highly adverse viewing conditions such as fog or camouflage. Here we used a closure task that required the participants to identify barely recognizable fragmented line-drawings of common objects. Patients with schizophrenia have been shown to perform poorly on this task. Following priming, controls and importantly patients can complete the line-drawings at greater levels of fragmentation behaviorally, suggesting an improvement in their ability to perform the task. Closure phenomena have been shown to involve a distributed network of cortical regions, notably the lateral occipital complex (LOC) of the ventral visual stream, dorsal visual stream (DS), hippocampal formation (HIPP) and the prefrontal cortex (PFC). We have previously demonstrated the failure of closure processes in schizophrenia and shown that the dysregulation in the sensory information transmitted to the prefrontal cortex plays a critical role in this failure. Here, using a multimodal imaging approach in patients, combining event related electrophysiological recordings (ERP) and functional magnetic resonance imaging (fMRI), we characterize the spatiotemporal dynamics of priming in perceptual closure. Using directed functional connectivity measures we demonstrate that priming modifies the network-level interactions between the nodes of closure processing in a manner that is functionally advantageous to patients resulting in the mitigation of their deficit in perceptual closure., (Copyright © 2020 Sehatpour, Bassir Nia, Adair, Wang, DeBaun, Silipo, Martinez and Javitt.)

Objectives: To evaluate bladder cancer by integrating multiple imaging features acquired using multimodal 3.0T magnetic resonance imaging (MRI)., Methods: We prospectively enrolled 163 consecutive patients including 142 men (mean age, 65.2 years) and 21 women (mean age, 65.8 years). We evaluated the efficiency and reliability of the multiple imaging modalities including T2-weighted spectral attenuated inversion recovery (SPAIR) imaging, dynamic contrast-enhanced (DCE) imaging and diffusion-weighted (DW) imaging, and the imaging feature, apparent diffusion coefficient (ADC) in the identification of the T staging and grading. We compared our imaging findings with the results of histological examination using McNemar's test. We reported the results under the significance of p < 0.05. Approval for the study was obtained from the local institutional review board., Results: The sensitivity and specificity using T2 SPAIR plus DW imaging (sensitivity: 85.2%; specificity: 93.2%), DCE plus DW imaging (sensitivity: 92.4%; specificity: 96.8%), and all the three imaging modalities combined, i.e., T2 SPAIR plus DCE plus DW imaging (sensitivity: 92.5%; specificity: 97.4%), were significantly greater than using T2 SPAIR imaging alone (sensitivity: 74.1%; specificity: 72.2%). One hundred six (93.0%) lesions showed a thin, pedicle arch-like shape and thus primarily demonstrated to be in Ta stage; by contrast, a large number of lesions (137 [85.6%]) were sessile and were found to be in T1 stage. The differences in the ADC were significant between low-grade (877.57 ± 24.15) and high-grade (699.54 ± 23.82) lesions (P < .01)., Conclusions: T2 SPAIR and DCE plus DW imaging provided useful information for evaluating T staging and grading in bladder cancer. Those imaging features to distinguish Ta stage from T1 stage were presented., (Copyright © 2020 Yuan, Li, Mu, Zhang, Kong, Cheng, Shu, Zhang and Wang.)

Purpose: Our objectives were to assess the abnormalities of subcortical nuclei by combining volume and shape analyses and potential association with cognitive impairment., Patients and Methods: Twenty-nine patients with severe ACS of the unilateral internal carotid artery and 31 controls were enrolled between January 2017 to August 2018. All participants underwent a comprehensive neuropsychological evaluation, blood lipid biochemical measurements, and structural magnetic resonance imaging (MRI) to measure subcortical volumes and sub-regional shape deformations. Basic statistics, correction for multiple comparisons. Seventeen ACS patients underwent carotid endarterectomy (CEA) within one week after baseline measurements, cognitive assessments and MRI scans were repeated 6 months after CEA., Results: The ACS patients had higher apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio and worse performance in all cognitive domains than controls. Moreover, the ACS patients showed more profound thalamic atrophy assessed by shape and volume analysis, especially in the medial dorsal thalamus. No significant differences were found in other subcortical nuclei after multiple comparisons correction. At baseline, thalamic atrophy correlated with cognitive impairment and ApoB/ApoA1 ratio. Furthermore, mediation analysis at baseline showed that the association of carotid intima-media thickness with executive functioning was mediated by thalamic volume. After CEA, cognitive improvement and increase in the bilateral medial dorsal thalamic volume were observed., Conclusion: Our study identified the distinct atrophy of subcortical nuclei and their association with cognition in patients with ACS. Assessments of the thalamus by volumetric and shape analysis may provide an early marker for cerebral ischemia and reperfusion after CEA., Competing Interests: The authors report no potential conflicts of interest in this work., (© 2020 Zhang et al.)

Background: Exposure therapy is the treatment of choice for anxiety disorders but requires people to confront feared situations and can be distressing. We tested the hypothesis that exposure without conscious awareness would reduce fear in participants with specific phobia by harnessing the neural circuitry supporting the automatic extinction of fear., Methods: In this single-centre, randomised controlled experiment, we recruited women aged 18-29 years from an ethnically diverse, community-based population in northeastern USA, between Sept 1, 2013, and Aug 1, 2016. Eligible participants classified as having phobia met the DSM-5 criteria for specific phobia but not for any other disorder, had scores in the top 10% of respondents to the Fear of Spiders Questionnaire, and exhibited impairing avoidance of a live tarantula. Eligible controls met no criteria for any disorder, were in the bottom 30% of questionnaire respondents, and displayed no avoidance of the tarantula. The randomisation schedule was generated with the open source Research Randomizer Tool. A research assistant randomly assigned participants to the active intervention of very brief exposure (VBE)-the repeated presentation of masked phobic stimuli (ie, spiders)-or the control intervention which used masked flowers (VBF). VBE and VBF were given code numbers to prevent staff from knowing which intervention they were administering. During a 10 min functional MRI (fMRI) task, each participant was exposed to 16 blocks of ten masked target stimuli (spiders or flowers), alternating with 16 blocks of ten masked neutral stimuli. A few minutes after fMRI, participants with spider phobia approached the tarantula again so we could measure changes in phobic behaviour. The primary outcome was real-time changes in brain activity measured by fMRI. All analyses were done by intention to treat., Results: We recruited 82 women, of whom 42 had spider phobia and 40 were controls. VBE generated stronger neural activity in participants with spider phobia than in controls, particularly in regions supporting emotion, emotion regulation, and attention systems, such as the inferior frontal cortex (Cohen's d 0·95, 95% CI 0·93-0·98, Bayesian posterior probability 99·5%) and the caudate nucleus (1·16, 1·14-1·18, 100·0%). In participants with phobia, VBE also generated stronger activity in these regions than did VBF (eg, dorsal anterior cingulate cortex Cohen's d 0·80, 95% CI 0·78-0·80, Bayesian posterior probability 98·5%; caudate nucleus 1·0, 0·98-1·02, 99·5%). VBE reduced avoidance of the live tarantula in participants with phobia. Regions supporting fear extinction (including ventral medial prefrontal cortex) and emotional salience processing mediated this effect. No adverse events occurred., Interpretation: VBE reduced fear non-consciously in participants with spider phobia by recruiting brain regions supporting automatic fear extinction, emotion regulation, and top-down attentional processing. Future studies should explore the use of VBE in other fear-based disorders., Funding: National Institutes of Mental Health and Brain & Behavior Research Foundation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Premature ejaculation (PE) is the most common male sexual dysfunction. The brain disturbances that cause this disorder remain poorly understood. This study aimed to investigate how the morphology of cortical and subcortical brain structures differed in PE, how these morphologic differences were associated with severity measures of PE, such as intravaginal ejaculatory latency time (IELT), and how these cortical and subcortical structures were causally connected through mediation analysis. Anatomical MRI scans were acquired from 39 male participants, 23 with PE (28.78 ± 4.32 years), and 16 without PE (27.88 ± 3.65 years). We used a subcortical analysis package within FSL to perform subcortical shape segmentation and statistical analysis. The PE group was compared with the normal control (NC) group in the shapes of 15 subcortical structures with general linear models [ p < 0.05, family-wise error (FWE)-corrected]. We analyzed the cortical complexity revealed by the gyrification index using the Computational Anatomy Toolbox (CAT12). Vertex-wise shape analyses revealed outward shape deformations (expansions) in the left hippocampus and bilateral thalamus. Gyrification index analyses revealed that the right orbital frontal cortex and the right nucleus accumbens had greater complexity in PE patients. The shape deformations were positively correlated with the IELTs in the NC group, while this relationship was interrupted in the PE group. PE is associated with outward deformations of the subcortical surfaces and more complexity of the cortical structures. These morphological differences may be the basis of the brain functional alterations underlying PE., (Copyright © 2020 Lu, Yuan, Jin, Yang, Zhang, Li, Zhang, Wang, Wu, Chen, Qing, Dai, Zhang and Wang.)

Objective: The purpose of this study was to examine the neural substrates and mechanisms that generate memory deficits, seizures and neuropsychiatric abnormalities in encephalitis with LGI1 antibodies using a data-driven, multimodal magnetic resonance imaging (MRI) approach. Methods: Functional MRI data were acquired from 14 anti-LGI1 encephalitis patients and 14 age and gender matched normal controls. Independent component analysis with hierarchical partner matching (HPM-ICA) was used to assess the whole-brain intrinsic functional connectivity. Granger causality (GC) was applied to investigate the effective connectivity among the brain regions that identified by HPM-ICA. Diffusion tensor imaging (DTI) was utilized to investigate white matter microstructural changes of the patients. Results: Participants with LGI1 antibodies encephalitis presented reduced functional connectivity in the brain areas associated with memory, cognition and motion circuits, while increased functional connectivity in putamen and caudate in comparison to the normal controls. Moreover, the effective connectivity in patients was decreased from the frontal cortex to supplementary motor area. Finally, patients had significant reductions in fractional anisotropy (FA) for the corpus callosum, internal capsule, corona radiata and superior longitudinal fasciculus, accompanied by increases in mean diffusivity (MD) for these regions as compared to controls. Conclusion: Our findings suggest that the neural disorder and behavioral deficits of anti-LGI1 encephalitis may be associated with extensive changes in brain connectivity and microstructure. These pathological alterations affect the basal ganglia and limbic system besides the temporal and frontal lobe., (Copyright © 2020 Qiao, Zhao, Wang, Li, Wang, Cao and Wang.)

Background: Interstitial lung disease requires frequent re-examination, which directly causes excessive cumulative radiation exposure. To date, AI has not been applied to CT for enhancing clinical care; thus, we hypothesize AI may empower CT with intelligence to realize automatic and accurate pulmonary scanning, thus dramatically decrease medical radiation exposure without compromising patient care., Methods: Facial boundary detection was realized by recognizing adjacent jaw position through training and testing a region proposal network (RPN) on 76,882 human faces using a preinstalled 2-dimensional camera; the lung-fields was then segmented by V-Net on another training set with 314 subjects and calculated the moving distance of the scanning couch based on a pre-generated calibration table. A multi-cohort study, including 1,186 patients was used for validation and radiation dose quantification under three clinical scenarios., Findings: A U-HAPPY (United imaging Human Automatic Planbox for PulmonarY) scanning CT was designed. Error distance of RPN was 4·46±0·02 pixels with a success rate of 98·7% in training set and 2·23±0·10 pixels with 100% success rate in testing set. Average Dice's coefficient was 0·99 in training set and 0·96 in testing set. A calibration table with 1,344,000 matches was generated to support the linkage between camera and scanner. This real-time automation makes an accurate plan-box to cover exact location and area needed to scan, thus reducing amounts of radiation exposures significantly (all, P<0·001)., Interpretation: U-HAPPY CT designed for pulmonary imaging acquisition standardization is promising for reducing patient risk and optimizing public health expenditures., Funding: The National Natural Science Foundation of China., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

As one of the most common neurobehavioral diseases in school-age children, Attention Deficit Hyperactivity Disorder (ADHD) has been increasingly studied in recent years. But it is still a challenge problem to accurately identify ADHD patients from healthy persons. To address this issue, we propose a dual subspace classification algorithm by using individual resting-state Functional Connectivity (FC). In detail, two subspaces respectively containing ADHD and healthy control features, called as dual subspaces, are learned with several subspace measures, wherein a modified graph embedding measure is employed to enhance the intra-class relationship of these features. Therefore, given a subject (used as test data) with its FCs, the basic classification principle is to compare its projected component energy of FCs on each subspace and then predict the ADHD or control label according to the subspace with larger energy. However, this principle in practice works with low efficiency, since the dual subspaces are unstably obtained from ADHD databases of small size. Thereby, we present an ADHD classification framework by a binary hypothesis testing of test data. Here, the FCs of test data with its ADHD or control label hypothesis are employed in the discriminative FC selection of training data to promote the stability of dual subspaces. For each hypothesis, the dual subspaces are learned from the selected FCs of training data. The total projected energy of these FCs is also calculated on the subspaces. Sequentially, the energy comparison is carried out under the binary hypotheses. The ADHD or control label is finally predicted for test data with the hypothesis of larger total energy. In the experiments on ADHD-200 dataset, our method achieves a significant classification performance compared with several state-of-the-art machine learning and deep learning methods, where our accuracy is about 90 % for most of ADHD databases in the leave-one-out cross-validation test., Competing Interests: Declaration of Competing Interest We confirm that there are no known conflicts of interest associated with this publication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Chronic pain is highly prevalent among patients with mood, anxiety, personality, and somatic symptom disorders; and patients with chronic pain often suffer from persistent interpersonal distress. However, the neural mechanisms underlying this phenomenon and its possible role in the etiology of chronic pain are not yet understood. Based on our Developmental Theory of Centralized/Somatoform Pain, and prior research suggesting the existence of a shared neural system subserving interpersonal emotions and pain, we aimed to identify the neural basis for modulation of pain by feelings of interpersonal rejection and the role of the early interpersonal environment in development of this shared neural system., Methods: During fMRI scanning, 22 healthy participants received moderately painful thermal stimuli in 3 interpersonal contexts: Acceptance, Rejection, and Reacceptance (modified Cyberball paradigm). Early interpersonal environment was assessed using the Parental Bonding Instrument., Results: Interpersonal context modulated activity in pain neural systems during rejection and during accepting interactions with previously rejecting others. Moreover, the subjective perception of rejection, even when rejection was not occurring, correlated positively with reported pain severity and neural activity in the insula. The magnitude of neural modulation in pain circuits by feelings of rejection was associated with the quality of early interpersonal experience with caregivers., Conclusions: Results suggest that interpersonal emotions play an important role in the development and functioning of the pain system, supporting our Developmental Theory of predisposition to chronic centralized pain. These findings have direct implications for clinical practice, including the importance of treating interpersonal distress to alleviate pain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Bulimia nervosa (BN) is associated with functional abnormalities in frontostriatal and frontolimbic circuits. Although structural alterations in the frontal portions of these circuits have been observed, this is the first study of subcortical surface morphometry and the largest study of subcortical volume in BN., Methods: Anatomical magnetic resonance scans were acquired from 62 female participants with full and subthreshold BN (mean age ± SD, 18.7 ± 4.0 years) and 65 group-matched healthy control participants (mean age ± SD, 19.3 ± 5.7 years). General linear models were used to compare groups and assess the significance of group-by-age interactions on the shape and total volume of 15 subcortical structures (p < .05, familywise error corrected). Associations with illness severity and duration were assessed in the BN group., Results: Subcortical volumes did not differ across groups, but vertexwise analyses revealed inward shape deformations on the anterior surface of the pallidum in BN relative to control participants that were associated with binge-eating frequency and illness duration. Inward deformations on the ventrolateral thalamus and dorsal amygdala were more pronounced with advancing age in the BN group, and inward deformations on the caudate, putamen, and amygdala were associated with self-induced vomiting frequency., Conclusions: Our findings point to localized deformations on the surface of subcortical structures in areas that comprise both reward and cognitive control circuits. These deformations were more pronounced among older BN participants and among those with the most severe symptoms. Such precise localization of alterations in subcortical morphometry may ultimately aid in efforts to identify markers of risk and BN persistence., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Patient expectancy of therapeutic improvement is a primary mediator of placebo effects in antidepressant clinical trials, but its mechanisms are poorly understood. This study employed a novel antidepressant trial design, with integrated functional magnetic resonance imaging (fMRI), to manipulate patient outcome expectancy and examine its neural mediators., Method: Twenty-three depressed outpatients, in a randomized controlled trial were assigned to either Open (high outcome expectancy) or Placebo-controlled (low outcome expectancy) treatment with citalopram for eight weeks. fMRI scans were acquired before and after the expectancy manipulation (before medication treatment), while participants performed a masked emotional face task. Focusing on an amygdala region-of-interest (ROI), we tested a model where reduction in amygdala activation mediated outcome expectancy effects on the slope of change in depressive symptoms., Results: Following the manipulation, significant differences between conditions were found in neural activation changes in the amygdala, as well as in superior temporal gyrus, insula, and thalamus. Findings support the proposed mediation model according to which activation in the left amygdala ROI decreased significantly in the Open as opposed to the Placebo-controlled group following randomization (p = 0.009) for sad vs. neutral face contrast. The reduced left amygdala activation, in turn, was a significant predictor of decreased depressive symptoms during the trial (p = 0.007), and the mediation model was significant., Conclusions: Results from this study, the first designed to identify the neural mechanisms of expectancy augmentation in an antidepressant randomized control trial, suggest that therapeutic modulation of amygdala activity may be an important pathway by which patient outcome expectancy influences depressive symptoms. CLINICALTRIALS., Gov Identifier: NCT01919216; Trial name: Placebo Effects in the Treatment of Depression: Cognitive and Neural Mechanisms, URL: https://clinicaltrials.gov/ct2/show/NCT01919216., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Machine learning and pattern recognition have been widely investigated in order to look for the biomarkers of Alzheimer's disease (AD). However, most existing methods extract features by seed-based correlation, which not only requires prior information but also ignores the relationship between resting state functional magnetic resonance imaging (rs-fMRI) voxels. In this study, we proposed a deep learning classification framework with multivariate data-driven based feature extraction for automatic diagnosis of AD. Specifically, a three-level hierarchical partner matching independent components analysis (3LHPM-ICA) approach was proposed first in order to address the issues in spatial individual ICA, including the uncertainty of the numbers of components, the randomness of initial values, and the correspondence of ICs of multiple subjects, resulting in stable and reliable ICs which were applied as the intrinsic brain functional connectivity (FC) features. Second, Granger causality (GC) was utilized to infer directional interaction between the ICs that were identified by the 3LHPM-ICA method and extract the effective connectivity features. Finally, a deep learning classification framework was developed to distinguish AD from controls by fusing the functional and effective connectivities. A resting state fMRI dataset containing 34 AD patients and 34 normal controls (NCs) was applied to the multivariate deep learning platform, leading to a classification accuracy of 95.59%, with a sensitivity of 97.06% and a specificity of 94.12% with leave-one-out cross validation (LOOCV). The experimental results demonstrated that the measures of neural connectivities of ICA and GC followed by deep learning classification represented the most powerful methods of distinguishing AD clinical data from NCs, and these aberrant brain connectivities might serve as robust brain biomarkers for AD. This approach also allows for expansion of the methodology to classify other psychiatric disorders.

Background: Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls., Methods: We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age., Results: We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness., Limitations: These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms., Conclusion: Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Purpose: To investigate the effect of ozone oxidative preconditioning (OzoneOP) on inflammation and oxidative stress injury in rat model of renal transplantation., Methods: Thirty six male Sprague Dawley (SD) rats were randomly divided into three groups. Sham group: rats were treated with opening and closing abdomen. Kidney transplantation group (KT group): SD rat received the donor's left kidney derived from another SD rat. Ozone oxidative preconditioning and kidney transplantation (OOP+KT group): donor SD rats received OzoneOP treatments by transrectal insufflations before kidney transplantation. After transplantation, parameters of renal function of recipients were determined. Morphology and pathological changes of renal allograft were examined. Expression of NF-κBp65, HMGB-1 were also determined by Western-blot., Results: Compared to KT group, the morphology and pathological damages of renal allograft were less serious in OOP+KT group. Meanwhile, levels of SOD and GSH-Px of renal allograft in OOP+KT group were higher than those in KT group respectively. Western-blot showed that the expressions of NF-κBp65 and HMGB-1 in OOP+KT group were obviously less than those in KT group., Conclusion: Ozone oxidative preconditioning could attenuate the inflammatory reaction and oxidative stress injury in renal allograft, which might be related with the enhancement of anti-oxidative system and suppression of inflammatory reaction.

Verbal-spatial discrepancies are common in healthy individuals and in those with neurodevelopmental disorders associated with cognitive control deficits including: Autism Spectrum Disorder, Non-Verbal Learning Disability, Fragile X, 22q11 deletion, and Turner Syndrome. Previous data from healthy individuals suggest that the magnitude of the difference between verbal IQ (VIQ) and performance IQ (PIQ) scores (the VIQ>PIQ discrepancy) is associated with reduced thickness in frontal and parietal cortices (inferior frontal, anterior cingulate, inferior parietal lobule, and supramarginal gyrus) that support cognitive control. Unknown is whether the VIQ>PIQ discrepancy is associated with functional deficits in these areas in healthy or ill children and adolescents. We assessed the effects of the VIQ>PIQ discrepancy on fMRI BOLD response during the resolution of cognitive conflict in 55 healthy children and adolescents during performance of a Simon Spatial Incompatibility task. As the magnitude of the VIQ>PIQ discrepancy increased, activation of fronto-striatal, limbic, and temporal regions decreased during conflict resolution (p < .05, corrected). In exploratory analyses, the VIQ>PIQ discrepancy was associated with reduced functional connectivity from right inferior frontal gyrus to right thalamus and increased functional connectivity to right supramarginal gyrus (ps < .03, uncorrected). The VIQ>PIQ discrepancy may be an important aspect of an individual's cognitive profile and likely contributes to, or is associated with, deficient cognitive control processes characteristic of many childhood disorders., (© 2017 John Wiley & Sons Ltd.)

Background: Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls., Methods: We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age., Results: We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness., Limitations: These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms., Conclusion: Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Neural disruptions during emotion regulation are common of generalized anxiety disorder (GAD). Identifying distinct functional and effective connectivity patterns in GAD may provide biomarkers for their diagnoses. This study aims to investigate the differences of features of brain network connectivity between GAD patients and healthy controls (HC), and to assess whether those differences can serve as biomarkers to distinguish GAD from controls. Independent component analysis (ICA) with hierarchical partner matching (HPM-ICA) was conducted on resting-state functional magnetic resonance imaging data collected from 20 GAD patients with medicine-free and 20 matched HC, identifying nine highly reproducible and significantly different functional brain connectivity patterns across diagnostic groups. We then utilized Granger causality (GC) to study the effective connectivity between the regions that identified by HPM-ICA. The linear discriminant analysis was finally used to distinguish GAD from controls with these measures of neural connectivity. The GAD patients showed stronger functional connectivity in amygdala, insula, putamen, thalamus, and posterior cingulate cortex, but weaker in frontal and temporal cortex compared with controls. Besides, the effective connectivity in GAD was decreased from the cortex to amygdala and basal ganglia. Applying the ICA and GC features to the classifier led to a classification accuracy of 87.5%, with a sensitivity of 90.0% and a specificity of 85.0%. These findings suggest that the presence of emotion dysregulation circuits may contribute to the pathophysiology of GAD, and these aberrant brain features may serve as robust brain biomarkers for GAD.

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo . Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro . Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro . In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats.

Background: Rates of adolescent obesity and overweight are high. The offspring of overweight parents are at increased risk of becoming obese later in life. Investigating neural correlates of familial obesity risk and current overweight status in adolescence could help identify biomarkers that predict future obesity and that may serve as novel targets for obesity interventions., Objective: Our primary aim was to use functional MRI to compare neural responses to words denoting high or low energy density (ED) foods and non-foods, in currently lean adolescents at higher compared with lower familial risk for obesity, and in overweight compared with lean adolescents. Secondary aims were to assess group differences in subjective appetite when viewing food and non-food words, and in objective ad libitum intake of high-ED foods in a laboratory setting., Design: We recruited 36 adolescents (14-19y), of whom 10 were (obese/overweight "overweight"), 16 lean with obese/overweight mothers (lean high-risk, "lean-HR"), and 10 lean with lean mothers (lean low-risk, "lean-LR"). All underwent fMRI scanning while they viewed words representing high-ED foods, low-ED foods, or non-foods, and provided appetitive ratings in response to each word stimulus. They then consumed a multi-item ad libitum buffet meal., Results: Food compared with non-food words activated a distributed emotion/reward system including insula and pregenual anterior cingulate cortex (ACC). Participants who were at increasing risk for obesity exhibited progressively weaker activation of an attentional/regulatory system including dorsolateral prefrontal cortex (PFC), dorsal ACC, and basal ganglia nuclei (activation was greatest in lean-LR, intermediate in lean-HR, and weakest in the overweight group). These group differences were most apparent for neural responses to high-compared with low-ED foods. Lean-HR (compared with lean-LR and overweight) adolescents reported greater desire for high-ED foods. Meal intake was greatest for the overweight, then lean-HR, then lean-LR groups., Conclusions: Adolescents at higher obesity risk exhibited reduced neural responses to high-ED food cues in a neural system that subserves attention and self-regulation. They also reported heightened appetitive responses to high-ED cues. Interventions that promote the capacity for self-regulation could prevent youth who have a familial predisposition for obesity from translating risk into reality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to identify differences in functional and effective brain connectivity between persons who stutter (PWS) and typically developing (TD) fluent speakers, and to assess whether those differences can serve as biomarkers to distinguish PWS from TD controls. We acquired resting-state functional magnetic resonance imaging data in 44 PWS and 50 TD controls. We then used Independent Component Analysis (ICA) together with Hierarchical Partner Matching (HPM) to identify networks of robust, functionally connected brain regions that were highly reproducible across participants, and we assessed whether connectivity differed significantly across diagnostic groups. We then used Granger Causality (GC) to study the causal interactions (effective connectivity) between the regions that ICA and HPM identified. Finally, we used a kernel support vector machine to assess how well these measures of functional connectivity and granger causality discriminate PWS from TD controls. Functional connectivity was stronger in PWS compared with TD controls in the supplementary motor area (SMA) and primary motor cortices, but weaker in inferior frontal cortex (IFG, Broca's area), caudate, putamen, and thalamus. Additionally, causal influences were significantly weaker in PWS from the IFG to SMA, and from the basal ganglia to IFG through the thalamus, compared to TD controls. ICA and GC indices together yielded an accuracy of 92.7% in classifying PWS from TD controls. Our findings suggest the presence of dysfunctional circuits that support speech planning and timing cues for the initiation and execution of motor sequences in PWS. Our high accuracy of classification further suggests that these aberrant brain features may serve as robust biomarkers for PWS.

Research on automatic processes in fear has emphasized the provocation of fear responses rather than their attenuation. We have previously shown that the repeated presentation of feared images without conscious awareness via backward masking reduces avoidance of a live tarantula in spider-phobic participants. Herein we investigated the neural basis for these adaptive effects of masked exposure. 21 spider-phobic and 21 control participants, identified by a psychiatric interview, fear questionnaire, and approaching a live tarantula, viewed stimuli in each of three conditions: (1) very brief exposure (VBE) to masked images of spiders, severely limited awareness; (2) clearly visible exposure (CVE) to spiders, full awareness; and (3) masked images of flowers (control), severely limited awareness. Only VBE to masked spiders generated neural activity more strongly in phobic than in control participants, within subcortical fear, attention, higher-order language, and vision systems. Moreover, VBE activated regions that support fear processing in phobic participants without causing them to experience fear consciously. Counter-intuitively, CVE to the same spiders generated stronger neural activity in control rather than phobic participants within these and other systems. CVE deactivated regions supporting fear regulation and caused phobic participants to experience fear. CVE-induced activations also correlated with measures of explicit fear ratings, whereas VBE-induced activations correlated with measures of implicit fear (color-naming interference of spider words). These multiple dissociations between the effects of VBE and CVE to spiders suggest that limiting awareness of exposure to phobic stimuli through visual masking paradoxically facilitates their processing, while simultaneously minimizing the experience of fear. Hum Brain Mapp 38:2466-2481, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objective: To study resting cerebral blood flow in children and adults with developmental stuttering., Methods: We acquired pulsed arterial spin labeling magnetic resonance imaging data in 26 participants with stuttering and 36 healthy, fluent controls. While covarying for age, sex, and IQ, we compared perfusion values voxel-wise across diagnostic groups and assessed correlations of perfusion with stuttering severity within the stuttering group and with measures of motor speed in both groups., Results: We detected lower regional Cerebral Blood Flow (rCBF) at rest in the stuttering group compared with healthy controls in Broca's area bilaterally and the superior frontal gyrus. rCBF values in Broca's area bilaterally correlated inversely with the severity of stuttering and extended posteriorly into other portions of the language loop. We also found increased rCBF in cerebellar nuclei and parietal cortex in the stuttering group compared with healthy controls. Findings were unchanged in child-only analyses and when excluding participants with comorbid illnesses or those taking medication., Conclusions: rCBF is reduced in Broca's region in persons who stutter. More severe stuttering is associated with even greater reductions in rCBF to Broca's region, additive to the underlying putative trait reduction in rCBF relative to control values. Moreover, a greater abnormality in rCBF in the posterior language loop is associated with more severe symptoms, suggesting that a common pathophysiology throughout the language loop likely contributes to stuttering severity. Hum Brain Mapp 38:1865-1874, 2017. © 2017 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Major depressive disorder (MDD) is approximately twice as common in females than males. Furthermore, female patients with MDD tend to manifest comorbid anxiety. Few studies have explored the potential anatomical and functional brain changes associated with MDD in females. Therefore, the purpose of the present study was to investigate the anatomical and functional changes underlying MDD in females, especially within the context of comorbid anxiety., Methods: In this study, we recruited antidepressant-free females with MDD (N = 35) and healthy female controls (HC; N = 23). The severity of depression and anxiety were evaluated by the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Structural and resting-state functional images were acquired on a Siemens 3.0 Tesla scanner. We compared the structural volumetric differences between patients and HC with voxel-based morphometry (VBM) analyses. Seed-based voxel-wise correlative analyses were used to identify abnormal functional connectivity. Regions with structural deficits showed a significant correlation between gray matter (GM) volume and clinical variables that were selected as seeds. Furthermore, voxel-wise functional connectivity analyses were applied to identify the abnormal connectivity relevant to seed in the MDD group., Results: Decreased GM volume in patients was observed in the insula, putamen, amygdala, lingual gyrus, and cerebellum. The right amygdala was selected as a seed to perform connectivity analyses, since its GM volume exhibited a significant correlation with the clinical anxiety scores. We detected regions with disrupted connectivity relevant to seed primarily within the cortico-striatal-pallidal-thalamic circuit., Conclusions: Amygdaloid atrophy, as well as decreased functional connectivity between the amygdala and the cortico-striatal-pallidal-thalamic circuit, appears to play a role in female MDD, especially in relation to comorbid anxiety., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Our flexible and adaptive interactions with the environment are guided by our individual representation of the physical world, estimated through sensation and evaluation of available information against prior knowledge. When linking sensory evidence with higher-level expectations for action, the central nervous system (CNS) in typically developing (TD) individuals relies in part on distributed and interacting cortical regions to communicate neuronal signals flexibly across the brain. Increasing evidence suggests that the balance between levels of signal and noise during information processing may be disrupted in individuals with Autism Spectrum Disorders (ASD)., Methods: Participants with and without ASD performed a visuospatial interference task while undergoing functional Magnetic Resonance Imaging (fMRI). We empirically estimated parameters characterizing participants' latencies and their subtle fluctuations (noise accumulation) over the 16-min scan. We modeled hemodynamic activation and used seed-based analyses of neural coupling to study dysfunction in interference-specific connectivity in a subset of ASD participants who were nonparametrically matched to TD participants on age, male-to-female ratio, and magnitude of movement during the scan., Results: Stochastic patterns of response fluctuations reveal significantly higher noise-to-signal levels and a more random and noisy structure in ASD versus TD participants, and in particular ASD adults who have the greatest clinical autistic deficits. While individuals with ASD show an overall weaker modulation of interference-specific functional connectivity relative to TD individuals, in particular between the seeds of Anterior Cingulate Cortex (ACC) and Inferior Parietal Sulcus (IPS) and the rest of the brain, we found that in ASD, higher uncertainty during the task is linked to increased interference-specific coupling between bilateral anterior insula and prefrontal cortex., Conclusions: Subtle and informative differences in the structure of experiencing information exist between ASD and TD individuals. Our findings reveal in ASD an atypical capacity to apply previously perceived information in a manner optimal for adaptive functioning, plausibly revealing suboptimal message-passing across the CNS.

Individuals at high risk for depression have increased default mode network (DMN) connectivity, as well as reduced inverse connectivity between the DMN and the central executive network (CEN) [8]. Other studies have indicated that the belief in the importance of religion/spirituality (R/S) is protective against depression in high risk individuals [5]. Given these findings, we hypothesized that R/S importance would moderate DMN connectivity, potentially reducing DMN connectivity or increasing DMN-CEN inverse connectivity in individuals at high risk for depression. Using resting-state functional connectivity MRI (rs-fcMRI) in a sample of 104 individuals (aged 11-60) at high and low risk for familial depression, we previously reported increased DMN connectivity and reduced DMN-CEN inverse connectivity in high risk individuals. Here, we found that this effect was moderated by self-report measures of R/S importance. Greater R/S importance in the high risk group was associated with decreased DMN connectivity. These results may represent a protective neural adaptation in the DMN of individuals at high risk for depression, and may have implications for other meditation-based therapies for depression., (Published by Elsevier Ireland Ltd.)

Objective: To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder., Method: We compared functional magnetic resonance imaging blood oxygen level-dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning., Results: Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in the fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage the right inferior frontal gyrus during maze navigation, activated the right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated the left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes., Conclusion: Adolescents with BN displayed abnormal functioning of the anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information-An fMRI Study of Self-Regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/; NCT00345943., Competing Interests: Drs. Cyr, Wang, Tau, Friedl, Marsh, Mr. Zhao, Ms. Stefan, and Ms. Terranova report no biomedical financial interests or potential conflicts of interest., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to determine the effects of ozone therapy on restoring impaired Nrf2 activation to ameliorate chronic tubulointerstitial injury in rats with adenine-induced CKD., Materials and Methods: Sprague-Dawley rats were fed with 0.75% adenine-containing diet to induce CKD and chronic tubulointerstitial injury. Ozone therapy was administered by rectal insufflation. After 4 weeks, serum and kidney samples were collected and analyzed. Renal function and systemic electrolyte level were detected. Pathological changes in kidney were assessed by hematoxylin-eosin staining and Masson trichrome staining. Nrf2 activation was detected by immunohistochemistry and Western blot analyses. The levels of SOD, CAT, GSH, PCO, and MDA were detected in the kidney. Immunohistochemistry, Western blot, and real-time PCR analyses were performed to evaluate the activation of the nuclear factor kappa B (NF-κB) P65 pathway and inflammation infiltration in the tubulointerstitium of the rats., Results: Ozone therapy improved severe renal insufficiency and tubulointerstitial morphology injury as well as restored Nrf2 activation and inhibited the NF-κB pathway in rats with adenine-induced CKD. Ozone therapy also up-regulated anti-oxidation enzymes (SOD, CAT, and GSH) and down-regulated oxidation products (PCO and MDA), as well as inflammatory cytokines (IL-1β, IL-6, TNF-α, and ICAM-1) in the kidney., Conclusion: These findings indicated that ozone therapy could attenuate tubulointerstitial injury in rats with adenine-induced CKD by mediating Nrf2 and NF-κB.

Pleomorphic adenoma gene like-2 (PLAGL2) is a member of the PLAG gene family. Previous studies have revealed that overexpression of PLAGL2 is associated with many human cancers. However, it has been reported that PLAGL2 also plays as a tumor suppressor. The precise role of PLAGL2 in prostate cancer (PCa) is still unknown. The aim of this study was to investigate the expression and prognostic value of PLAGL2 in PCa. Data from microarray datasets demonstrated that the DNA copy number and mRNA level of PLAGL2 were significantly increased in PCa compared with normal prostate. qRT-PCR and western blot analysis from paired PCa samples and prostate cell lines confirmed upregulated mRNA and protein expression levels in PCa. Immunohistochemistry analysis showed that staining of PLAGL2 in PCa tissues was significantly higher than that in benign prostatic hyperplasia (BPH) tissues. In addition, the high expression of PLAGL2 was only involved in preoperative PSA, but was not related to age, Gleason score, seminal vesicle invasion, surgical margin status, clinical stage and positive lymph node metastasis. Moreover, our results showed that PLAGL2 was an independent prognostic factor for biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients, and overexpressed PLAGL2 was related to early development of BCR and poor OS. In conclusion, our findings suggest that PLAGL2 is overexpressed in PCa. The increased expression of PLAGL2 correlates to PCa progression following radical prostatectomy and may serve as a novel poor prognostic marker for PCa.

Tubulointerstitium inflammation is a common pathway aggravating chronic kidney disease (CKD) progression and the mechanism is partly associated with excessive activation of toll-like receptor 4 (TLR4) in tubulointerstitium. Ozone therapy is demonstrated to alleviate inflammation in some experiments. The aim of this study is to examine whether ozone therapy could ameliorate chronic tubulointerstitium inflammation by suppressing TLR4 in adenine-induced CKD rats. Sprague-Dawley rats were fed with 0.75% adenine-containing diet to induce CKD and tubulointerstitium inflammation injury. Ozone therapy (1.1 mg/kg) was simultaneously administrated by rectal insufflations (i.r.). After 4 weeks, serum and kidney samples were collected for detection. Renal function and systemic electrolyte were detected. Renal pathological changes were assessed by hematoxylin-eosin (H&E) staining and Masson trichrome (MT) staining. Immunohistochemistry, Western blot and Real-time PCR were applied to evaluate tubulointerstitium inflammation as well as the expression of TLR4 and phosphorylated nuclear factor kappa B P65 (p-NF-κB P65) in rats. The results showed ozone therapy improved serious renal insufficiency, systemic electrolyte disorder and tubulointerstitium morphology damages in adenine-induced CKD rats. In addition, ozone therapy suppressed excessive activation of TLR4 and p-NF-κB P65 in the tubulointerstitium of adenine-induced CKD rats, accompanied by the reduction of inflammation-related cytokines including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The protein expression of TLR4 was positively correlated with the protein expression levels of MCP-1 (r = 0.7863, p < 0.01) and TNF-α (r = 0.7547, p < 0.01) in CKD rats. These findings indicated ozone therapy could attenuate tubulointerstitium inflammation injury in adenine-induced CKD rats and the mechanism might associate with the mediation of TLR4.

Research into the pathophysiology of major depressive disorder (MDD) has focused largely on individuals already affected by MDD. Studies have thus been limited in their ability to disentangle effects that arise as a result of MDD from precursors of the disorder. By studying individuals at high familial risk for MDD, we aimed to identify potential biomarkers indexing risk for developing MDD, a critical step toward advancing prevention and early intervention. Using resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 111 individuals, aged 11-60 years, at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Based on rs-fcMRI, individuals at high vs low familial risk for depression showed increased DMN connectivity, as well as decreased DMN-CEN-negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMN-CEN-negative connectivity. Path analyses indicated that decreased DMN-CEN-negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Our findings suggest that DMN and DMN-CEN connectivity differ in those at high vs low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD.

A failure of adaptive inference-misinterpreting available sensory information for appropriate perception and action-is at the heart of clinical manifestations of schizophrenia, implicating key subcortical structures in the brain including the hippocampus. We used high-resolution, three-dimensional (3D) fractal geometry analysis to study subtle and potentially biologically relevant structural alterations (in the geometry of protrusions, gyri and indentations, sulci) in subcortical gray matter (GM) in patients with schizophrenia relative to healthy individuals. In particular, we focus on utilizing Fractal Dimension (FD), a compact shape descriptor that can be computed using inputs with irregular (i.e., not necessarily smooth) surfaces in order to quantify complexity (of geometrical properties and configurations of structures across spatial scales) of subcortical GM in this disorder. Probabilistic (entropy-based) information FD was computed based on the box-counting approach for each of the seven subcortical structures, bilaterally, as well as the brainstem from high-resolution magnetic resonance (MR) images in chronic patients with schizophrenia (n = 19) and age-matched healthy controls (n = 19) (age ranges: patients, 22.7-54.3 and healthy controls, 24.9-51.6 years old). We found a significant reduction of FD in the left hippocampus (median: 2.1460, range: 2.07-2.18 vs. median: 2.1730, range: 2.15-2.23, p<0.001; Cohen's effect size, U3 = 0.8158 (95% Confidence Intervals, CIs: 0.6316, 1.0)), the right hippocampus (median: 2.1430, range: 2.05-2.19 vs. median: 2.1760, range: 2.12-2.21, p = 0.004; U3 = 0.8421 (CIs: 0.5263, 1)), as well as left thalamus (median: 2.4230, range: 2.40-2.44, p = 0.005; U3 = 0.7895 (CIs: 0.5789, 0.9473)) in schizophrenia patients, relative to healthy individuals. Our findings provide in-vivo quantitative evidence for reduced surface complexity of hippocampus, with reduced FD indicating a less complex, less regular GM surface detected in schizophrenia.

Connectivity between brain networks may adapt flexibly to cognitive demand, a process that could underlie adaptive behaviors and cognitive deficits, such as those observed in neuropsychiatric conditions like schizophrenia. Dopamine signaling is critical for working memory but its influence on internetwork connectivity is relatively unknown. We addressed these questions in healthy humans using functional magnetic resonance imaging (during ann-back working-memory task) and positron emission tomography using the radiotracer [(11)C]FLB457 before and after amphetamine to measure the capacity for dopamine release in extrastriatal brain regions. Brain networks were defined by spatial independent component analysis (ICA) and working-memory-load-dependent connectivity between task-relevant pairs of networks was determined via a modified psychophysiological interaction analysis. For most pairs of task-relevant networks, connectivity significantly changed as a function of working-memory load. Moreover, load-dependent changes in connectivity between left and right frontoparietal networks (Δ connectivity lFPN-rFPN) predicted interindividual differences in task performance more accurately than other fMRI and PET imaging measures. Δ Connectivity lFPN-rFPN was not related to cortical dopamine release capacity. A second study in unmedicated patients with schizophrenia showed no abnormalities in load-dependent connectivity but showed a weaker relationship between Δ connectivity lFPN-rFPN and working memory performance in patients compared with matched healthy individuals. Poor working memory performance in patients was, in contrast, related to deficient cortical dopamine release. Our findings indicate that interactions between brain networks dynamically adapt to fluctuating environmental demands. These dynamic adaptations underlie successful working memory performance in healthy individuals and are not well predicted by amphetamine-induced dopamine release capacity., Significance Statement: It is unclear how communication between brain networks responds to changing environmental demands during complex cognitive processes. Also, unknown in regard to these network dynamics is the role of neuromodulators, such as dopamine, and whether their dysregulation could underlie cognitive deficits in neuropsychiatric illness. We found that connectivity between brain networks changes with working-memory load and greater increases predict better working memory performance; however, it was not related to capacity for dopamine release in the cortex. Patients with schizophrenia did show dynamic internetwork connectivity; however, this was more weakly associated with successful performance in patients compared with healthy individuals. Our findings indicate that dynamic interactions between brain networks may support the type of flexible adaptations essential to goal-directed behavior., (Copyright © 2016 the authors 0270-6474/16/364378-12$15.00/0.)

Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control has a role in conferring vulnerability for the development of psychotic illness is still unknown. The aim of this study was to investigate the neural systems supporting cognitive control in individuals deemed to be potentially prodromal for psychotic illness. We recruited 56 participants at clinical high-risk (CHR) for psychosis based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 49 healthy controls. Twelve of the CHR participants eventually developed psychosis. We compared functional magnetic resonance imaging (fMRI) BOLD signal during the performance of the Simon task. We tested for differences between CHR individuals and controls in conflict-related functional activity. In the CHR group when compared with controls, we detected smaller conflict-related activations in several cortical areas, including the Dorsolateral Prefrontal Cortex (DLPFC). Furthermore, conflict-related activations in the DLPFC of those CHR individuals who ultimately developed psychosis (CHR converters) were smaller than in non-converters (CHR non-converters). Higher levels of conflict-related activation were associated with better social and role outcome. Risk for psychosis was associated at the neural level with reduced conflict-related brain activity. This neural phenotype appears correlated within the DLPFC with the development of psychosis and with functional outcome.

The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in individuals with and without an illness history of an internalizing disorder. We compared functional magnetic resonance imaging blood-oxygenation-level-dependent responses in both males (n=63) and females (n=80) with and without this illness history during performance of the Simon task. Females deactivated superior frontal gyrus, inferior parietal lobe, and posterior cingulate cortex to a greater extent than males. Females with a prior history of internalizing disorder also deactivated these regions more compared to males with that history, and they additionally demonstrated greater activation of right inferior frontal gyrus. These group differences were represented in a significant sex-by-illness interaction in these regions. These deactivated regions compose a task-negative or default mode network, whereas the inferior frontal gyrus usually activates when performing an attention-demanding task and is a key component of a task-positive network. Our findings suggest that a prior history of internalizing disorders disproportionately influences functioning of the default mode network and is associated with an accompanying activation of the task-positive network in females during the resolution of cognitive interference., (Copyright © 2016. Published by Elsevier Ireland Ltd.)