Search

fMRI neurofeedback using autobiographical memory recall to upregulate the amygdala is associated with resting-state functional connectivity (rsFC) changes between the amygdala and the salience and default mode networks (SN and DMN, respectively). We hypothesize the existence of anatomical circuits underlying these rsFC changes. Using a cross-species brain parcellation, we identified in non-human primates locations homologous to the regions of interest (ROIs) from studies showing pre-to-post-neurofeedback changes in rsFC with the left amygdala. We injected bidirectional tracers in the basolateral, lateral, and central amygdala nuclei of adult macaques and used bright- and dark-field microscopy to identify cells and axon terminals in each ROI (SN: anterior cingulate, ventrolateral, and insular cortices; DMN: temporal pole, middle frontal gyrus, angular gyrus, precuneus, posterior cingulate cortex, parahippocampal gyrus, hippocampus, and thalamus). We also performed additional injections in specific ROIs to validate the results following amygdala injections and delineate potential disynaptic pathways. Finally, we used high-resolution diffusion MRI data from four post-mortem macaque brains and one in vivo human brain to translate our findings to the neuroimaging domain. Different amygdala nuclei had significant monosynaptic connections with all the SN and DMN ipsilateral ROIs. Amygdala connections with the DMN contralateral ROIs are disynaptic through the hippocampus and parahippocampal gyrus. Diffusion MRI in both species benefitted from using the ground-truth tracer data to validate its findings, as we identified false-negative ipsilateral and false-positive contralateral connectivity results. This study provides the foundation for future causal investigations of amygdala neurofeedback modulation of the SN and DMN through these anatomic connections., (© 2024. The Author(s).)

Obsessive-compulsive disorder is a psychiatric disorder characterized by intrusive thoughts and repetitive behaviors. There are two prominent features: Harm Avoidance (HA) and Incompleteness (INC). Previous resting-state studies reported abnormally elevated connectivity between prefrontal cortical (PFC) and subcortical regions (thalamus, striatum) in OCD participants. Yet, little is known about the white matter (WM) structural abnormalities in these connections. Using brain parcellation and segmentation, whole brain tractography, and Neurite Orientation Dispersion and Density Imaging (NODDI), we aimed to characterize WM structural abnormalities in OCD vs. healthy controls and determine the extent to which NODDI indices of these connections were associated with subthreshold-threshold HA, INC and overall OCD symptom severity across all participants. Four PFC regions were segmented: ventral medial (vmPFC), ventrolateral (vlPFC), dorsomedial (dmPFC), and dorsolateral (dlPFC). NODDI Neurite Density (NDI) and Orientation Dispersion (ODI) indices of WM structure were extracted from connections between these PFC regions and the thalamus (42 OCD, 44 healthy controls, mean age[SD] = 23.65[4.25]y, 63.9% female) and striatum (38 OCD, 41 healthy controls, mean age[SD] = 23.59[4.27]y, 64.5% female). Multivariate analyses of covariance revealed no between-group differences in these indices. Multivariate regression models revealed that greater NDI in vmPFC-thalamus, greater NDI and ODI in vmPFC-striatum, and greater NDI in dmPFC-thalamus connections were associated with greater INC severity (Q ≤ 0.032). These findings highlight the utility of NODDI in the examination of WM structure in OCD, provide valuable insights into specific WM alterations underlying dimensional INC, and can facilitate the development of customized treatments for OCD individuals with treatment-resistant symptoms., (© 2024. The Author(s).)

The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Comprehensive reconstruction of axonal tracts and small fascicles requires high-resolution technology beyond the ability of current in vivo imaging (e.g. diffusion magnetic resonance imaging). Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) and polarization microscopy can quantify fiber orientation at micrometer resolution but have been limited to two-dimensional in-plane orientation or thin slices, preventing the comprehensive study of connectivity in 3D. In this work we present a novel method to quantify volumetric 3D orientation in full angular space with PS-OCT. We measure the polarization contrasts of the brain sample from two illumination angles of 0 and 15 degrees and apply a computational method that yields the 3D optic axis orientation and true birefringence. We further present 3D fiber orientation maps of entire coronal cerebrum sections and brainstem with 10 μm in-plane resolution, revealing unprecedented details of fiber configurations. We envision that our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain as well as other complex fibrous tissues at microscopic level., Competing Interests: Disclosures B.F. is a medical advisor to DeepHealth, a company whose medical pursuits focus on imaging and measurement technologies. B.F.’s interests were reviewed and are managed by MGH and Partners HealthCare in accordance with their conflict-of-interest policies. Additional Declarations: Competing interest reported. B.F. is a medical advisor to DeepHealth, a company whose medical pursuits focus on imaging and measurement technologies. B.F.’s interests were reviewed and are managed by MGH and Partners HealthCare in accordance with their conflict-of-interest policies.

Axon diameter and myelin thickness are closely related microstructural tissue properties that affect the conduction velocity of action potentials in the nervous system. Imaging them non-invasively with MRI-based methods is thus valuable for studying brain microstructure and function. However, the relationship between MRI-based axon diameter and myelination measures has not been investigated across the brain, mainly due to methodological limitations in estimating axon diameters. In recent years, studies using ultra-high gradient strength diffusion MRI (dMRI) have demonstrated improved estimation of axon diameter across white-matter (WM) tracts in the human brain, making such investigations feasible. In this study, we aim to investigate relationships between tissue microstructure properties with MRI-based methods and compare the imaging findings to histological evidence from the literature. We collected dMRI with ultra-high gradient strength and multi-echo spin-echo MRI on ex vivo macaque and human brain samples on a preclinical scanner. From these data, we estimated axon diameter, intra-axonal signal fraction, myelin water fraction (MWF) and aggregate g-ratio and investigated their correlations. We found that the microstructural imaging parameters exhibited consistent patterns across WM tracts and species. Overall, the findings suggest that MRI-based axon geometry and myelination measures can provide complementary information about fiber morphology, and the relationships between these measures agree with prior histological evidence.

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [ 11 C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [ 18 F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF., Competing Interests: Competing interests statement:The authors declare no competing interest.

Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness in the human brain, but knowledge about the subcortical networks that sustain arousal in humans is incomplete. Here, we aimed to map the connectivity of a proposed subcortical arousal network that sustains wakefulness in the human brain, analogous to the cortical default mode network (DMN) that has been shown to contribute to awareness. We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) of three human brains, obtained at autopsy from neurologically normal individuals, with immunohistochemical staining of subcortical brain sections. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. Deterministic and probabilistic tractography analyses of the ex vivo diffusion MRI data revealed projection, association, and commissural pathways linking dAAN nodes with one another and with DMN nodes. Complementary analyses of in vivo 7-tesla resting-state functional MRI data from the Human Connectome Project identified the dopaminergic ventral tegmental area in the midbrain as a widely connected hub node at the nexus of the subcortical arousal and cortical awareness networks. Our network-based autopsy methods and connectivity data provide a putative neuroanatomic architecture for the integration of arousal and awareness in human consciousness.

Purpose: To investigate whether spatiotemporal magnetic field monitoring can correct pronounced eddy current-induced artifacts incurred by strong diffusion-sensitizing gradients up to 300 mT/m used in high b-value diffusion-weighted (DW) EPI., Methods: A dynamic field camera equipped with 16 1 H NMR field probes was first used to characterize field perturbations caused by residual eddy currents from diffusion gradients waveforms in a 3D multi-shot EPI sequence on a 3T Connectom scanner for different gradient strengths (up to 300 mT/m), diffusion directions, and shots. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-gradient strength, submillimeter resolution whole-brain ex vivo diffusion MRI. A 3D multi-shot image reconstruction framework was developed that incorporated the nonlinear phase evolution measured with the dynamic field camera., Results: Phase perturbations in the readout induced by residual eddy currents from strong diffusion gradients are highly nonlinear in space and time, vary among diffusion directions, and interfere significantly with the image encoding gradients, changing the k-space trajectory. During the readout, phase modulations between odd and even EPI echoes become non-static and diffusion encoding direction-dependent. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting reduction approaches such as navigator- and structured low-rank-based methods or MUSE followed by image-based distortion correction with the FSL tool "eddy.", Conclusion: Strong eddy current artifacts characteristic of high-gradient strength DW-EPI can be well corrected with dynamic field monitoring-based image reconstruction., (© 2023 International Society for Magnetic Resonance in Medicine.)

United States Special Operations Forces (SOF) personnel are frequently exposed to explosive blasts in training and combat. However, the effects of repeated blast exposure on the human brain are incompletely understood. Moreover, there is currently no diagnostic test to detect repeated blast brain injury (rBBI). In this "Human Performance Optimization" article, we discuss how the development and implementation of a reliable diagnostic test for rBBI has the potential to promote SOF brain health, combat readiness, and quality of life., (2023.)

Ferroptosis is a form of cell death that is distinguished from other types of death for its peculiar characteristics of death regulated by iron accumulation, increase in ROS, and lipid peroxidation. In the past few years, experimental evidence has correlated ferroptosis with various pathological processes including neurodegenerative and cardiovascular diseases. Ferroptosis also is involved in several types of cancer because it has been shown to induce tumor cell death. In particular, the pharmacological induction of ferroptosis, contributing to the inhibition of the proliferative process, provides new ideas for the pharmacological treatment of cancer. Emerging evidence suggests that certain mechanisms including the Xc - system, GPx4, and iron chelators play a key role in the regulation of ferroptosis and can be used to block the progression of many diseases. This review summarizes current knowledge on the mechanism of ferroptosis and the latest advances in its multiple regulatory pathways, underlining ferroptosis' involvement in the diseases. Finally, we focused on several types of ferroptosis inducers and inhibitors, evaluating their impact on the cell death principal targets to provide new perspectives in the treatment of the diseases and a potential pharmacological development of new clinical therapies.

Abstract: Emotion dysregulation is considered a core feature of borderline personality disorder (BPD). The role of dissociation in BPD has been discussed from different perspectives. Nevertheless, implications of dissociation for BPD features are not clear. The current study estimated mediation effects of dissociative dimensions on the relationships between several emotion regulation strategies (ERSs) and BPD features among 281 adults recruited from the general population. The online survey administered a comprehensive self-report battery for the assessment of maladaptive and adaptive ERSs together with dissociative dimensions. Borderline personality disorder features were also self-report screened. Results showed significant indirect effects of dissociation on the relationships between ERSs and BPD features. Dissociation was a full mediator of the relationship between deficits with problem-solving skills and BPD criteria. The study confirmed that emotion dysregulation is a core feature of BPD and that the dissociative dimensions should be included as relevant maladaptive mechanisms sustaining BPD emotional difficulties., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The human thalamus is a highly connected brain structure, which is key for the control of numerous functions and is involved in several neurological disorders. Recently, neuroimaging studies have increasingly focused on the volume and connectivity of the specific nuclei comprising this structure, rather than looking at the thalamus as a whole. However, accurate identification of cytoarchitectonically designed histological nuclei on standard in vivo structural MRI is hampered by the lack of image contrast that can be used to distinguish nuclei from each other and from surrounding white matter tracts. While diffusion MRI may offer such contrast, it has lower resolution and lacks some boundaries visible in structural imaging. In this work, we present a Bayesian segmentation algorithm for the thalamus. This algorithm combines prior information from a probabilistic atlas with likelihood models for both structural and diffusion MRI, allowing segmentation of 25 thalamic labels per hemisphere informed by both modalities. We present an improved probabilistic atlas, incorporating thalamic nuclei identified from histology and 45 white matter tracts surrounding the thalamus identified in ultra-high gradient strength diffusion imaging. We present a family of likelihood models for diffusion tensor imaging, ensuring compatibility with the vast majority of neuroimaging datasets that include diffusion MRI data. The use of these diffusion likelihood models greatly improves identification of nuclear groups versus segmentation based solely on structural MRI. Dice comparison of 5 manually identifiable groups of nuclei to ground truth segmentations show improvements of up to 10 percentage points. Additionally, our chosen model shows a high degree of reliability, with median test-retest Dice scores above 0.85 for four out of five nuclei groups, whilst also offering improved detection of differential thalamic involvement in Alzheimer's disease (AUROC 81.98%). The probabilistic atlas and segmentation tool will be made publicly available as part of the neuroimaging package FreeSurfer (https://freesurfer.net/fswiki/ThalamicNucleiDTI)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Departing from existing neurobiological models of dissociation, the current study aims at conducting a quantitative meta-analytic review of neural responses to emotional stimuli among individuals ascribed to the dissociative spectrum (DS). Accordingly, the study explored common and specific brain mechanisms across borderline personality disorder, conversion/somatoform disorders, posttraumatic stress disorder, posttraumatic stress disorder related to repeated interpersonal traumatic experiences, and dissociative disorders., Methods: The meta-analysis included studies that administered emotional stimuli during functional magnetic resonance imaging acquisition among individuals included in the DS. There were two conducted meta-analytic procedures: (i) a Bayesian network meta-analysis for a region-of-interest-based approach; and (ii) robust voxel-based approach., Results: Forty-four independent studies were included for a total of 1384 individuals (DS = 741 patients). The network meta-analysis showed specific patterns of neural activity considering an extended brain network involved in emotion regulation for each condition ascribed to the DS. The voxel-based meta-analysis highlighted an increased activity of dorsal anterior cingulate cortex as a common neurological signature of the DS., Conclusion: The common neural feature of the DS captures an implicit appraisal of emotion-eliciting stimuli as threatening and/or noxious for mental and physical integrity of the individual together with painful subjective experiences associated with physiological emotional reactions. Specific brain responses across the DS suggested the engagement in different mechanisms to address emotional stimuli, including implicit avoidance reactions and attempts to overcontrol of affective states together with a disruption of integrative processes of emotional mind-body features., (© 2023 The Authors Psychiatry and Clinical Neurosciences © 2023 Japanese Society of Psychiatry and Neurology.)

Background: The zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral modulation, we propose that the ZI is a connectional hub for mediating between top-down and bottom-up control and a possible target for deep brain stimulation for obsessive-compulsive disorder., Methods: We analyzed the trajectory of cortical fibers to the ZI in nonhuman and human primates based on tracer injections in monkeys and high-resolution diffusion magnetic resonance imaging in humans. The organization of cortical and subcortical connections within the ZI were identified in the nonhuman primate studies., Results: Monkey anatomical data and human diffusion magnetic resonance imaging data showed a similar trajectory of fibers/streamlines to the ZI. Prefrontal cortex/anterior cingulate cortex terminals all converged within the rostral ZI, with dorsal and lateral areas being most prominent. Motor areas terminated caudally. Dense subcortical reciprocal connections included the thalamus, medial hypothalamus, substantia nigra/ventral tegmental area, reticular formation, and pedunculopontine nucleus and a dense nonreciprocal projection to the lateral habenula. Additional connections included the amygdala, dorsal raphe nucleus, and periaqueductal gray., Conclusions: Dense connections with dorsal and lateral prefrontal cortex/anterior cingulate cortex cognitive control areas and the lateral habenula and the substantia nigra/ventral tegmental area, coupled with inputs from the amygdala, hypothalamus, and brainstem, suggest that the rostral ZI is a subcortical hub positioned to modulate between top-down and bottom-up control. A deep brain stimulation electrode placed in the rostral ZI would not only involve connections common to other deep brain stimulation sites but also capture several critically distinctive connections., (Copyright © 2023. Published by Elsevier Inc.)

Recent studies on natural antioxidant compounds have highlighted their potentiality against various pathological conditions. The present review aims to selectively evaluate the benefits of catechins and their polymeric structure on metabolic syndrome, a common disorder characterized by a cluster of three main risk factors: obesity, hypertension, and hyperglycemia. Patients with metabolic syndrome suffer chronic low inflammation state and oxidative stress both conditions effectively countered by flavanols and their polymers. The mechanism behind the activity of these molecules has been highlighted and correlated with the characteristic features present on their basic flavonoidic skelethon, as well as the efficient doses needed to perform their activity in both in vitro and in vivo studies. The amount of evidence provided in this review offers a starting point for flavanol dietary supplementation as a potential strategy to counteract several metabolic targets associated with metabolic syndrome and suggests a key role of albumin as flavanol-delivery system to the different target of action inside the organism.

New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes following TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. Here, we propose a pipeline that combines automated tractography reconstructions of 40 white matter tracts with multivariate analysis of along-tract diffusion metrics to assess the presence of TAI in individual patients with acute severe TBI. We used the Mahalanobis distance to identify abnormal white matter tracts in each of 18 patients with acute severe TBI as compared to 33 healthy subjects. In all patients for which a FreeSurfer anatomical segmentation could be obtained (17 of 18 patients), including 13 with focal lesions, the automated pipeline successfully reconstructed a mean of 37.5 ± 2.1 white matter tracts without the need for manual intervention. A mean of 2.5 ± 2.1 tracts resulted in partial or failed reconstructions and needed to be reinitialized upon visual inspection. The pipeline detected at least one abnormal tract in all patients (mean: 9.1 ± 7.9) and accurately discriminated between patients and controls (AUC: 0.91). The number and neuroanatomic location of abnormal tracts varied across patients and levels of consciousness. The premotor, temporal, and parietal sections of the corpus callosum were the most commonly damaged tracts (in 10, 9, and 8 patients, respectively), consistent with prior histopathological studies of TAI. TAI measures were not associated with concurrent behavioral measures of consciousness. In summary, we provide proof-of-principle evidence that an automated tractography pipeline has translational potential to detect and quantify TAI in individual patients with acute severe TBI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been fully elucidated. We present a protocol for an observational pilot study, Long-Term Effects of Repeated Blast Exposure in U.S. SOF Personnel (ReBlast). In this exploratory study, 30 active-duty SOF personnel with RBE will participate in a comprehensive evaluation of: 1) brain network structure and function using Connectome magnetic resonance imaging (MRI) and 7 Tesla MRI; 2) neuroinflammation and tau deposition using positron emission tomography; 3) blood proteomics and metabolomics; 4) behavioral and physical symptoms using self-report measures; and 5) cognition using a battery of conventional and digitized assessments designed to detect subtle deficits in otherwise high-performing individuals. We will identify clinical, neuroimaging, and blood-based phenotypes that are associated with level of RBE, as measured by the Generalized Blast Exposure Value. Candidate biomarkers of RBE-related brain injury will inform the design of a subsequent study that will test a diagnostic assessment battery for detecting RBE-related brain injury. Ultimately, we anticipate that the ReBlast study will facilitate the development of interventions to optimize the brain health, quality of life, and battle readiness of U.S. SOF personnel.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background : The contradictory nature of behavioral addictions has sustained a nondefinitive debate regarding their construct validity. Objective(s): The current study aims at exploring mechanisms underlying two distinct classes of behaviors-behavioral addictions characterized by core alterations in reward processing systems (ARPS) and behaviors with a main function of maladaptive coping. Methods: This case-control study included 99 treatment-seeking individuals with a primary diagnosis of alcohol use disorder (male: N  = 68; female: N  = 31) and 74 healthy control (HC) subjects (male: N  = 38; female: N  = 36). The severity of maladaptive behaviors was measured through the Shorter PROMIS Questionnaire (SPQ). Latent mechanisms were assessed by the Disinhibition Domain of the Personality Inventory for DSM-5 (PID-5-DI) and the Acceptance and Action Questionnaire-II (AAQ-II). Results : The clinical group showed higher severity of behavioral addictions than HC. This difference was not replicated for the other class of maladaptive behaviors, except for compulsive buying. Ordinal regression analysis showed that the clinical group significantly predicted SPQ scores reflecting ARPS, SPQ shopping and starving subscales. This was not replicated for the overall SPQ score capturing maladaptive coping and binge eating behaviors. Controlling for PID-5-DI and AAQ-II scores, which were significantly associated to SPQ subscales, effects of the aforementioned clinical group were not significant. Conclusions: The study highlighted distinct and common mechanisms underlying different classes of maladaptive behaviors. Results supported future neuroscience research for clarifying the role of ARPS in compulsive sex and buying in order to consider them as addictive disorders.

Tremendous efforts have been made in the last decade to advance cutting-edge MRI technology in pursuit of mapping structural connectivity in the living human brain with unprecedented sensitivity and speed. The first Connectom 3T MRI scanner equipped with a 300 mT/m whole-body gradient system was installed at the Massachusetts General Hospital in 2011 and was specifically constructed as part of the Human Connectome Project. Since that time, numerous technological advances have been made to enable the broader use of the Connectom high gradient system for diffusion tractography and tissue microstructure studies and leverage its unique advantages and sensitivity to resolving macroscopic and microscopic structural information in neural tissue for clinical and neuroscientific studies. The goal of this review article is to summarize the technical developments that have emerged in the last decade to support and promote large-scale and scientific studies of the human brain using the Connectom scanner. We provide a brief historical perspective on the development of Connectom gradient technology and the efforts that led to the installation of three other Connectom 3T MRI scanners worldwide - one in the United Kingdom in Cardiff, Wales, another in continental Europe in Leipzig, Germany, and the latest in Asia in Shanghai, China. We summarize the key developments in gradient hardware and image acquisition technology that have formed the backbone of Connectom-related research efforts, including the rich array of high-sensitivity receiver coils, pulse sequences, image artifact correction strategies and data preprocessing methods needed to optimize the quality of high-gradient strength diffusion MRI data for subsequent analyses. Finally, we review the scientific impact of the Connectom MRI scanner, including advances in diffusion tractography, tissue microstructural imaging, ex vivo validation, and clinical investigations that have been enabled by Connectom technology. We conclude with brief insights into the unique value of strong gradients for diffusion MRI and where the field is headed in the coming years., (Copyright © 2022. Published by Elsevier Inc.)

hMT + /V5 is a region in the middle occipitotemporal cortex that responds preferentially to visual motion in sighted people. In cases of early visual deprivation, hMT + /V5 enhances its response to moving sounds. Whether hMT + /V5 contains information about motion directions and whether the functional enhancement observed in the blind is motion specific, or also involves sound source location, remains unsolved. Moreover, the impact of this cross-modal reorganization of hMT + /V5 on the regions typically supporting auditory motion processing, like the human planum temporale (hPT), remains equivocal. We used a combined functional and diffusion-weighted MRI approach and individual in-ear recordings to study the impact of early blindness on the brain networks supporting spatial hearing in male and female humans. Whole-brain univariate analysis revealed that the anterior portion of hMT + /V5 responded to moving sounds in sighted and blind people, while the posterior portion was selective to moving sounds only in blind participants. Multivariate decoding analysis revealed that the presence of motion direction and sound position information was higher in hMT + /V5 and lower in hPT in the blind group. While both groups showed axis-of-motion organization in hMT + /V5 and hPT, this organization was reduced in the hPT of blind people. Diffusion-weighted MRI revealed that the strength of hMT + /V5-hPT connectivity did not differ between groups, whereas the microstructure of the connections was altered by blindness. Our results suggest that the axis-of-motion organization of hMT + /V5 does not depend on visual experience, but that congenital blindness alters the response properties of occipitotemporal networks supporting spatial hearing in the sighted. SIGNIFICANCE STATEMENT Spatial hearing helps living organisms navigate their environment. This is certainly even more true in people born blind. How does blindness affect the brain network supporting auditory motion and sound source location? Our results show that the presence of motion direction and sound position information was higher in hMT + /V5 and lower in human planum temporale in blind relative to sighted people; and that this functional reorganization is accompanied by microstructural (but not macrostructural) alterations in their connections. These findings suggest that blindness alters cross-modal responses between connected areas that share the same computational goals., (Copyright © 2022 the authors.)

Objective: The current quantitative review aims at comprehensively clarifying the role of rumination in borderline personality disorder (BPD) considering its relevance for several clinical models of the disorder., Method: This meta-analysis included 29 independent studies assessing different forms of rumination-general tendency to engage in ruminative thinking patterns and four types of emotion-based rumination among both nonclinical subjects reporting BPD features and patients with BPD. Furthermore, the study tested whether rumination could be considered a widespread emotion-based cognitive vulnerability in BPD., Results: Meta-analytic procedures were based on 46 r coefficients that showed large pooled effect sizes for all forms of rumination. With the exception of interpersonal rumination, the remaining forms of rumination were equally involved in BPD features., Conclusions: Rumination should be considered a widespread emotion-based cognitive vulnerability in BPD. Future studies should provide longitudinal and contextual-based evaluations of rumination among treatment-seeking individuals with BPD., (© 2021 Wiley Periodicals LLC.)

The natural tendency of the mind to wander (i.e., mind wandering), is often connected to negative thoughts and emotional states. On the other hand, mindfulness (i.e., the ability to focus one's attention on the present moment in a non-judgmental way) has acquired a growing interest in recent years given its beneficial role in improving awareness and self-regulation. Starting from previous evidence, this study aims to clarify the psychological, physiological, and affective impact of a mindfulness exercise on mind wandering. Twenty-eight non-expert female meditators were recruited for this study. Heart rate variability (HRV), state mindfulness, mind wandering manifestations, and affective states, were recorded during a baseline condition, a mindfulness breathing observation exercise, and a final rest condition. Subjects reported significant decreases in mind wandering comparing baseline and mindfulness. Changes in mind wandering were mirrored by changes in HRV, with higher HRV during the breathing observation exercise. Significant associations were found between scores of mindfulness, mind wandering, and affective states measured during the task. Our findings confirmed the role of mindfulness in reducing mind wandering and increasing HRV. Results are discussed considering mindfulness associations with self-regulation and well-being., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The link between attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) has been largely demonstrated. Some scholars have hypothesized that self-regulation mechanisms might play a key role in explaining this association. Objective(s): The current study tested the hypothesis that retrospective childhood ADHD symptoms might lead to more severe SUDs and this association should be mediated by current self-ratings of behavioral disinhibition, inattention, and emotional dysregulation among 204 treatment-seeking adults (male: 67.3%; female: 32.7%) with a primary diagnosis of alcohol use disorder and other SUDs. Methods: The mediational model was estimated through self-report measures of childhood ADHD symptoms (independent variable; WURS), current self-regulation mechanisms (mediators)-behavioral disinhibition (BIS-11 motor subscale), difficulties with attention regulation (MAAS) and emotion regulation (DERS)-and severity of SUDs (dependent variable; SPQ alcohol, illicit and prescribed drugs). Results: The analysis showed that alterations in the self-regulation system fully mediated the association between the severity of childhood ADHD symptoms and SUDs in adulthood. Behavioral disinhibition and difficulties in attention regulation were the most representative alterations in self-regulation processes that explained this association. Conclusions: These findings suggest it is useful to implement several therapeutic approaches (e.g. behavioral, mindfulness-based, and pharmacological) to increase the self-regulation abilities of children and adolescents with ADHD in order to reduce the probability of SUD onset in adulthood. However, future longitudinal neuroimaging and neuropsychological studies are needed to further support the role of self-regulation mechanisms in explaining the prospective association between childhood ADHD symptoms and SUDs in adulthood.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

While many useful microstructural indices, as well as orientation distribution functions, can be obtained from multi-shell dMRI data, there is growing interest in exploring the richer set of microstructural features that can be extracted from the full ensemble average propagator (EAP). The EAP can be readily computed from diffusion spectrum imaging (DSI) data, at the cost of a very lengthy acquisition. Compressed sensing (CS) has been used to make DSI more practical by reducing its acquisition time. CS applied to DSI (CS-DSI) attempts to reconstruct the EAP from significantly undersampled q-space data. We present a post mortem validation study where we evaluate the ability of CS-DSI to approximate not only fully sampled DSI but also multi-shell acquisitions with high fidelity. Human brain samples are imaged with high-resolution DSI at 9.4T and with polarization-sensitive optical coherence tomography (PSOCT). The latter provides direct measurements of axonal orientations at microscopic resolutions, allowing us to evaluate the mesoscopic orientation estimates obtained from diffusion MRI, in terms of their angular error and the presence of spurious peaks. We test two fast, dictionary-based, L2-regularized algorithms for CS-DSI reconstruction. We find that, for a CS acceleration factor of R=3, i.e., an acquisition with 171 gradient directions, one of these methods is able to achieve both low angular error and low number of spurious peaks. With a scan length similar to that of high angular resolution multi-shell acquisition schemes, this CS-DSI approach is able to approximate both fully sampled DSI and multi-shell data with high accuracy. Thus it is suitable for orientation reconstruction and microstructural modeling techniques that require either grid- or shell-based acquisitions. We find that the signal-to-noise ratio (SNR) of the training data used to construct the dictionary can have an impact on the accuracy of CS-DSI, but that there is substantial robustness to loss of SNR in the test data. Finally, we show that, as the CS acceleration factor increases beyond R=3, the accuracy of these reconstruction methods degrade, either in terms of the angular error, or in terms of the number of spurious peaks. Our results provide useful benchmarks for the future development of even more efficient q-space acceleration techniques., Competing Interests: Declaration of Competing Interest BF has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. BF's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies., (Copyright © 2021. Published by Elsevier Inc.)

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Clinical and neurobiological models posited that dissociative mechanisms might affect processes involved in emotional generation and regulation. However, there is a lack of a comprehensive theoretical framework that systematically includes dissociation within emotional functioning., Methods: The current study aims at conducting a meta-analytic review on the relationship between dissociation and emotion regulation in order to empirically estimate to what extent dissociation is related to emotion regulation processes. The meta-analysis was based on r coefficient as effect size measure, using a random-effect approach., Results: The meta-analysis included 57 independent studies for a total of 11596 individuals. Findings showed an overall moderate relationship between dissociation and emotion regulation (r w  = .32; p < .05). The association between dissociation and emotion regulation was the same among clinical samples than non-clinical ones. Furthermore, dissociation showed moderate to large relationships with maladaptive domains of emotion regulation, namely disengagement (r w  = 0.34; p < .01) (i.e., behavioral avoidance, experiential avoidance, thought and emotional suppression) and aversive cognitive perseveration (r w  = 0.38; p < .001) (i.e., rumination, worry and nonacceptance). The analysis did not find significant relationship between dissociation and adaptive domain of emotional regulation (i.e., problem solving, mindfulness)., Conclusion: Dissociation in the context of emotion regulation might be viewed as a basic neuro-mental mechanism that automatically contribute to the over-modulation of emotional states through avoidance reactions from internal and external reality. Future longitudinal studies are needed to clarify the causal relationships between dissociation and emotion regulation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In vivo diffusion-weighted magnetic resonance imaging is limited in signal-to-noise-ratio (SNR) and acquisition time, which constrains spatial resolution to the macroscale regime. Ex vivo imaging, which allows for arbitrarily long scan times, is critical for exploring human brain structure in the mesoscale regime without loss of SNR. Standard head array coils designed for patients are sub-optimal for imaging ex vivo whole brain specimens. The goal of this work was to design and construct a 48-channel ex vivo whole brain array coil for high-resolution and high b-value diffusion-weighted imaging on a 3T Connectome scanner. The coil was validated with bench measurements and characterized by imaging metrics on an agar brain phantom and an ex vivo human brain sample. The two-segment coil former was constructed for a close fit to a whole human brain, with small receive elements distributed over the entire brain. Imaging tests including SNR and G-factor maps were compared to a 64-channel head coil designed for in vivo use. There was a 2.9-fold increase in SNR in the peripheral cortex and a 1.3-fold gain in the center when compared to the 64-channel head coil. The 48-channel ex vivo whole brain coil also decreases noise amplification in highly parallel imaging, allowing acceleration factors of approximately one unit higher for a given noise amplification level. The acquired diffusion-weighted images in a whole ex vivo brain specimen demonstrate the applicability and advantage of the developed coil for high-resolution and high b-value diffusion-weighted ex vivo brain MRI studies., (Copyright © 2021. Published by Elsevier Inc.)

Background: Dialectical Behavior Therapy Skills Training (DBT-ST) as stand-alone treatment has demonstrated promising outcomes for the treatment of alcohol use disorder (AUD) and concurrent substance use disorders (SUDs). However, no studies have so far empirically investigated factors that might predict efficacy of this therapeutic model., Methods: 275 treatment-seeking individuals with AUD and other SUDs were consecutively admitted to a 3-month DBT-ST program (in- + outpatient; outpatient settings). The machine learning routine applied (i.e. penalized regression combined with a nested cross-validation procedure) was conducted in order to estimate predictive values of a wide panel of clinical variables in a single statistical framework on drop-out and substance-use behaviors, dealing with related multicollinearity, and eliminating redundant variables., Results: The cross-validated elastic net model significantly predicted the drop-out. The bootstrap analysis revealed that subjects who showed substance-use behaviors during the intervention and who were treated with the mixed setting (i.e., in- and outpatient) program, together with higher ASI alcohol scores were associated with an higher probability of drop-out. On the contrary, older subjects, higher levels of education, together with higher scores of DERS awareness subscale were negatively associated to drop-out. Similarly, lifetime co-diagnoses of anxiety, bipolar, and gambling disorders, together with bulimia nervosa negatively predicted the drop-out. The machine learning model did not identify predictive variables of substance-use behaviors during the treatment., Conclusions: The DBT-ST program could be considered a valid therapeutic approach especially when AUD and other SUDs co-occur with other psychiatric conditions and, it is carried out as a full outpatient intervention., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In humans, the occipital middle-temporal region (hMT + /V5) specializes in the processing of visual motion, while the planum temporale (hPT) specializes in auditory motion processing. It has been hypothesized that these regions might communicate directly to achieve fast and optimal exchange of multisensory motion information. Here we investigated, for the first time in humans (male and female), the presence of direct white matter connections between visual and auditory motion-selective regions using a combined fMRI and diffusion MRI approach. We found evidence supporting the potential existence of direct white matter connections between individually and functionally defined hMT + /V5 and hPT. We show that projections between hMT + /V5 and hPT do not overlap with large white matter bundles, such as the inferior longitudinal fasciculus and the inferior frontal occipital fasciculus. Moreover, we did not find evidence suggesting the presence of projections between the fusiform face area and hPT, supporting the functional specificity of hMT + /V5-hPT connections. Finally, the potential presence of hMT + /V5-hPT connections was corroborated in a large sample of participants ( n = 114) from the human connectome project. Together, this study provides a first indication for potential direct occipitotemporal projections between hMT + /V5 and hPT, which may support the exchange of motion information between functionally specialized auditory and visual regions. SIGNIFICANCE STATEMENT Perceiving and integrating moving signal across the senses is arguably one of the most important perceptual skills for the survival of living organisms. In order to create a unified representation of movement, the brain must therefore integrate motion information from separate senses. Our study provides support for the potential existence of direct connections between motion-selective regions in the occipital/visual (hMT + /V5) and temporal/auditory (hPT) cortices in humans. This connection could represent the structural scaffolding for the rapid and optimal exchange and integration of multisensory motion information. These findings suggest the existence of computationally specific pathways that allow information flow between areas that share a similar computational goal., (Copyright © 2021 the authors.)

This perspective paper aims at discussing theoretical principles that could explain how emotion regulation and physical diseases mutually influence each other in the context of borderline personality disorder (BPD). Furthermore, this paper discusses the clinical implications of the functional relationships between emotion regulation, BPD and medical conditions considering dialectical behavior therapy (DBT) as a well-validated therapeutic intervention, which encompasses these issues. The inflexible use of maladaptive emotion regulation strategies (e.g., suppression, experiential avoidance, and rumination) might directly increase the probability of developing physical diseases through a physiological pathway, or indirectly through a behavioral pathway. Some metabolic and chronic medical conditions could significantly impact emotional functioning through biological alterations involved in emotion regulation. Several empirical studies have shown high co-occurrence rates between BPD and several chronic physical diseases, especially ones linked to emotion-based maladaptive behaviors. DBT addresses physical diseases reported by individuals with BPD reducing problematic behaviors functionally associated to emotion dysregulation and identifying physical health as a goal for Building a Life Worth Living ., 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 © 2021 Cavicchioli, Barone, Fiore, Marchini, Pazzano, Ramella, Riccardi, Sanza and Maffei.)

Background: Neuropsychological abnormalities have been proposed to contribute to the development and maintenance of Borderline Personality Disorder (BPD). Previous meta-analyses and reviews confirmed deficits in a broad range of cognitive domains, including attention, cognitive flexibility, memory, executive functions, planning, information processing, and visuospatial abilities, often suggested to underlie brain abnormalities. However, no study directly explored the structural neural correlates of these deficits in BPD, also accounting for the possible confounding effect of pharmacological treatments, often used as adjunctive symptom-targeted therapy in clinical setting., Methods: In this study we compared the performance of 24 BPD patients to 24 healthy controls obtained at the neuropsychological battery "Brief Assessment and Cognition in Schizophrenia", exploring the relationship between the cognitive impairments and current symptomatology, brain grey matter volumes and cortical thickness, controlling for medications load., Results: Data revealed deficits in verbal memory and fluency, working memory, attention and speed of information processing and psychomotor speed and coordination when medication load was not in the model. Correcting for this variable, only the impairment in psychomotor abilities remained significant. A multiple regression confirmed the effect of this neuropsychological domain on the severity of BPD symptomatology (Borderline Evaluation of Severity Over Time). In BPD, the performance at psychomotor speed and coordination was also directly associated to cortical thickness in postcentral gyrus., Limitations: Relatively small sample size, especially for neuroimaging., Conclusions: Our study highlighted an influence of BPD neuropsychological impairments on symptomatology, and cortical thickness, prompting the potential clinical utility of a cognitive remediation program in BPD., (Copyright © 2020. Published by Elsevier B.V.)

Background and Objectives: Current studies on emotional dysregulation in BPD suggest that it might be manifested by altered appraisal and biased attentional mechanisms, rather than by hyperreactivity. The aim of this study was to acquire more evidence on this topic by testing the hypothesis that BPD patients are characterized by a negative evaluation bias and reduced visual exploration in response to socio-emotional content. Moreover, the association between the previous conceptualizations and typical dysfunctional processes in BPD were evaluated., Methods: Fifty-four socio-emotional pictures were administered to 20 female BPD patients and 20 healthy controls (HCs) divided into three blocks characterized by different stimulus durations (500 ms, 3s, 18s). Self-reported and eye-tracking data were collected during the experiment., Results: BPD patients showed lower valence ratings and reduced visual exploration of socio-emotional pictures compared to HCs. Visual exploration in BPD was affected by exposure time with reduced exploration in response to prolonged stimuli presentation. Dysfunctional features and pre-task negative affectivity level in BPD were correlated with self-reported evaluations and eye-tracking data., Limitations: Possible effects of gender on emotional responsivity could not be addressed given the female composition of our sample. Moreover, the role of psychiatric symptoms and medications should be addressed in future research., Conclusions: This study presented evidence on dysfunctional mechanisms sustaining emotional dysregulation in BPD. This construct seemed supported by a well-established negative bias towards emotional stimuli together with a reduced processing of social information as manifestations of emotional hypersensitivity., (Copyright © 2020. Published by Elsevier Ltd.)

In order to assess the relationships between DSM-5 Alternative Model of Personality Disorder (AMPD) maladaptive personality traits and self-reports of aggression, 508 Italian adult participants who met at least one DSM-IV Axis II/ DSM-5 Section II personality disorder (PD) diagnosis were administered the Personality Inventory for DSM-5 (PID-5) and the Aggression Questionnaire (AQ). Analysis results showed that multiple regression results, PID-5 Hostility, Callousness, and Risk Taking trait scale scores explained a large amount of variance in AQ Physical Aggression (PA) scores. Moreover, PID-5 Hostility, Callousness, and Risk Taking explained more than 20% of the variance in the AQ Physical Aggression scale scores that was left unexplained by selected continuously scored DSM-IV Axis II/ DSM-5 Section II PDs, whereas SCID-II Paranoid, Narcissistic, Borderline, and Antisocial PDs added only 4% of variance to the amount of variance in AQ Physical Aggression scores that was already explained by the PID-5 trait scale scores.

The outcome of kidney transplant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. Here we describe the clinical characteristics, disease outcome, and risk factors for acute respiratory distress syndrome (ARDS) and death of a cohort of 53 kidney transplant patients with coronavirus disease 2019 (COVID-19). Eight of 53 have been handled as outpatients because of mild disease, on average with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin; no patients required admission, developed ARDS, or died. Because of severe symptoms, 45/53 required admission: this cohort has been managed with immunosuppression withdrawal, methylprednisolone 16 mg/d, hydroxychloroquine, and antiviral drugs. Dexamethasone and tocilizumab were considered in case of ARDS. About 33% of the patients developed acute kidney injury, 60% ARDS, and 33% died. In this group, thrombocytopenia was associated to ARDS whereas lymphopenia at the baseline, higher D-dimer, and lack of C-reactive protein reduction were associated with risk of death. In the overall population, dyspnea was associated with the risk of ARDS and age older than 60 years and dyspnea were associated with the risk of death with only a trend toward an increased risk of death for patients on tacrolimus. In conclusion, SARS-CoV-2 infection may have a variable outcome in renal transplant patients, with higher risk of ARDS and death in the ones requiring admission., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting., Methods: We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment., Results: The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians., Conclusions: Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.

The SARS-CoV-2 epidemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience of four dialysis centers of the Brescia Renal COVID Task Force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis, whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70), and dyspnea at presentation were associated with the risk of developing ARDS, whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: It is still unclear whether craving should be considered a key risk factor for substance-use behaviors (SUB) among treatment-seeking individuals with alcohol (AUD) and other drugs use disorders. Therefore, this study aims at clarifying this topic using a meta-analytic approach., Methods: Cohen's d was computed as effect size (ES) measure. Heterogeneity of ESs was computed using the Q statistic and I 2 index. The analyses also evaluated the impact assessment length on ESs. Furthermore, proximal effects of craving on SUB were compared to distal ones. The diagnoses of specific substance use disorders (SUDs), together with assessment instruments and research design were considered as additional moderators., Results: Thirty-six independent studies were included for a total of 4868 treatment-seeking individuals with SUDs. Patients who used substances showed slightly higher levels of craving than abstinent ones. The heterogeneity of results was large and significant. The length of period of assessment was positively related to ESs. The analyses highlighted no differences between pooled ESs of proximal and distal impacts of craving on SUB. The diagnoses of SUDs were significant moderators. Considering AUD, assessment instruments and research design were additional moderators., Conclusions: Craving is a modest time-dependent proximal and distal risk factor for SUB among individuals with SUDs. Both the frequency of craving episodes and a heightened reactivity to craving cues are largely associated to SUB among individuals with AUD. Future studies should evaluate the mediating and moderating roles of self-regulatory mechanisms on the relationship between craving and SUB., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors report no relevant financial conflicts., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The outcome of SARS-CoV2 infection in patients who have received a kidney allograft and are being treated with immunosuppression is unclear. We describe 20 kidney transplant recipients (median age 59 years [inter quartile range 51-64 years], median age of transplant 13 years [9-20 years], baseline eGFR 36.5 [23-47.5]) with SARS-CoV2 induced pneumonia. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney function. At baseline, all patients presented fever but only one complained of difficulty in breathing. Half of patients showed chest radiographic evidence of bilateral infiltrates while the other half showed unilateral changes or no infiltrates. During a median follow-up of seven days, 87% experienced a radiological progression and among those 73% required escalation of oxygen therapy. Six patients developed acute kidney injury with one requiring hemodialysis. Six of 12 patients were treated with tocilizumab, a humanized monoclonal antibody to the IL-6 receptor. Overall, five kidney transplant recipients died after a median period of 15 days [15-19] from symptom onset. These preliminary findings describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with SARS-Cov2 pneumonia. Thus, in this limited cohort of long-term kidney transplant patients, SARS-CoV-2 induced pneumonia is characterized by high risk of progression and significant mortality., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Individuals with alcohol use disorder (AUD) and other substance use disorders (SUDs) frequently show co-occurrent behavioral addictions (BAs) (i.e., gambling and compulsive sex) and other inflexible behaviors (IBs) (i.e., compulsive buying and dysfunctional eating behaviors). The covariation of these conditions might be explained by a role of emotion dysregulation (ED) and executive dysfunctions. This study aims at investigating whether ED and self-regulation of attention (SRA) could be common processes that underpin BAs and other IBs among individuals with AUD. The study hypothesized that SRA should represent a key protective factor for the relationships between ED and BAs/IBs. The research included 319 treatment-seeking individuals with a primary diagnosis of AUD. Five independent multiple parallel mediational models were tested. Self-report instruments were administered in order to assess ED, BAs and other IBs, which represented independent and dependent variables respectively. SRA was self-report assessed and, it was considered the key mediator variable. The analyses highlighted significant total effects of ED on the severity of BAs and IBs. SRA fully mediated the relationships between ED and BAs/IBs, with exception of gambling. ED and SRA should be considered common dimensions that explain the covariation of BAs and IBs among individuals with AUD. SRA represents an adaptive form of emotion regulation that sustains the engagement in goal-oriented behaviors. Future neuroimaging and longitudinal studies are recommended in order to demonstrate the role of ED and SRA on development, maintenance and treatment of BAs and IBs among individuals with SUDs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Backgrounds: Dialectical behavior therapy skills training (DBT-ST) is an effective treatment for alcohol use disorder (AUD). AUD frequently co-occurs with other addictive behaviors., Objective: s: These secondary analyses of prior studies on the effectiveness of a 3-month DBT-ST program for AUD investigated pre- post-treatment changes in the severity of concurrent addictive behaviors. The study hypothesized that emotion regulation and experiential avoidance should be the key therapeutic mechanisms involved in the treatment of addictive behaviors., Methods: The research included 186 individuals (110 males; 76 females) with a primary diagnosis of AUD. Mediational models were performed considering shorter PROMIS questionnaire subscales (i.e., gambling, sex, shopping, food binging, and starvation) as dependent variables. The difficulties in emotion regulation scale and acceptance and action questionnaire-II total scores were independent and mediator variables, respectively., Results: Clinical variables significantly improved during the treatment, independent of baseline levels. Changes in emotion regulation showed significant total effects on improvements in addictive behaviors. Significant indirect effects of changes in experiential avoidance were detected considering compulsive buying and dysfunctional eating behaviors., Conclusion: The DBT-ST was a feasible treatment for several addictive behaviors frequently reported by individuals with AUD. The improvements in emotion regulation and experiential avoidance were relevant therapeutic mechanisms involved in the treatment of these conditions. Future controlled trials and follow-up studies are recommended to support the efficacy of DBT-ST as a stand-alone intervention for the treatment of different classes of addictive behaviors.

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called "virtual dissection." Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC-ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real-life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and "virtual dissection" across various laboratories and hospitals. Intra-rater agreement (Dice score) was approximately 0.77, while inter-rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

We are in the midst of a health emergency that is totally new for us all and that requires a concerted effort, especially when it comes to safeguarding patients on hemodialysis, and kidney transplant recipients. Brescia is currently a very active cluster of infections (2918 cases on the 17/03/2020), second only to Bergamo. The way our structure is organised has allowed us to treat nephropathic patients directly within the Nephrology Unit, following of course a great deal of reshuffling; at the moment, we are treating 21 transplanted patients and 17 on hemodialysis. This has led us to adopt a systematic approach to handling this emergency, not only in managing inpatients, but also in researching the new disease. Our approach is mirrored in the guidelines attached to this article, originally intended for internal use only but potentially very useful to our colleagues, as they face the same exact problems. We have also started collecting data on our positive patients with the aim of understanding better the functioning of this disease and how best to manage it. If anyone is interested, we ask you to please get in touch with us, so we can coordinate our efforts., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease (COVID-19), is a major pandemic challenging health care systems around the world. The optimal management of patients infected with COVID-19 is still unclear, although the consensus is moving toward the need of a biphasic approach. During the first phase of the disease (from onset of the symptoms up to 7-10 days) viral-induced effects are prominent, with the opportunity to institute antiviral therapy. In the second inflammatory phase of the disease, immunosuppressive strategies (for example with glucocorticoids or anticytokine drugs) may be considered. This latter stage is characterized by the development of progressive lung involvement with increasing oxygen requirements and occasionally signs of the hemophagocytic syndrome. The management of the disease in patients with kidney disease is even more challenging, especially in those who are immunosuppressed or with severe comorbidities. Here we present the therapeutic approach used in Brescia (Italy) for managing patients infected with COVID-19 who underwent kidney transplantation and are receiving hemodialysis. Furthermore, we provide some clinical and physiopathological background, as well as preliminary outcome data of our cohort, to better clarify the pathogenesis of the disease and clinical management., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Emotional hyperreactivity (Linehan, 1993) is the most investigated construct in borderline personality disorder (BPD). However, experimental studies revealed mixed results on the topic. Our main objective is to comprehensively summarize the results on emotional reactivity in BPD compared to healthy controls (HCs), using a meta-analytic approach, considering different emotional response systems (physiology, behavior, self-report). We included 31 experimental studies (1,675 subjects). We observed null to small effect sizes for several physiological and behavioral outcomes. Conversely, BPD subjects revealed a moderate to large difference in valence attributed to emotional stimuli and a small difference in self-reported arousal. Significant differences in pooled effect sizes were found between self-report and physiological outcomes. Several sources of heterogeneity were explored. In general, the hyperreactivity hypothesis was not supported. Additional dysfunctional processes should be taken into consideration to understand BPD emotional responsiveness.