Hippocampal GABAergic Inhibitory Interneurons.

In the hippocampus GABAergic local circuit inhibitory interneurons represent only ~10-15% of the total neuronal population; however, their remarkable anatomical and physiological diversity allows them to regulate virtually all aspects of cellular and circuit function. Here we provide an overview of the current state of the field of interneuron research, focusing largely on the hippocampus. We discuss recent advances related to the various cell types, including their development and maturation, expression of subtype-specific voltage- and ligand-gated channels, and their roles in network oscillations. We also discuss recent technological advances and approaches that have permitted high-resolution, subtype-specific examination of their roles in numerous neural circuit disorders and the emerging therapeutic strategies to ameliorate such pathophysiological conditions. The ultimate goal of this review is not only to provide a touchstone for the current state of the field, but to help pave the way for future research by highlighting where gaps in our knowledge exist and how a complete appreciation of their roles will aid in future therapeutic strategies.

Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

Real-World Molecular Out-Of-Distribution: Specification and Investigation.

This study presents a rigorous framework for investigating molecular out-of-distribution (MOOD) generalization in drug discovery. The concept of MOOD is first clarified through a problem specification that demonstrates how the covariate shifts encountered during real-world deployment can be characterized by the distribution of sample distances to the training set. We find that these shifts can cause performance to drop by up to 60% and uncertainty calibration by up to 40%. This leads us to propose a splitting protocol that aims to close the gap between the deployment and testing. Then, using this protocol, a thorough investigation is conducted to assess the impact of model design, model selection, and data set characteristics on MOOD performance and uncertainty calibration. We find that appropriate representations and algorithms with built-in uncertainty estimation are crucial to improving performance and uncertainty calibration. This study sets itself apart by its exhaustiveness and opens an exciting avenue to benchmark meaningful algorithmic progress in molecular scoring.

Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation.

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA-PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA-PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem-cortical interplay for consciousness.

Reduced emergent character of neural dynamics in patients with a disrupted connectome.

High-level brain functions are widely believed to emerge from the orchestrated activity of multiple neural systems. However, lacking a formal definition and practical quantification of emergence for experimental data, neuroscientists have been unable to empirically test this long-standing conjecture. Here we investigate this fundamental question by leveraging a recently proposed framework known as "Integrated Information Decomposition," which establishes a principled information-theoretic approach to operationalise and quantify emergence in dynamical systems - including the human brain. By analysing functional MRI data, our results show that the emergent and hierarchical character of neural dynamics is significantly diminished in chronically unresponsive patients suffering from severe brain injury. At a functional level, we demonstrate that emergence capacity is positively correlated with the extent of hierarchical organisation in brain activity. Furthermore, by combining computational approaches from network control theory and whole-brain biophysical modelling, we show that the reduced capacity for emergent and hierarchical dynamics in severely brain-injured patients can be mechanistically explained by disruptions in the patients' structural connectome. Overall, our results suggest that chronic unresponsiveness resulting from severe brain injury may be related to structural impairment of the fundamental neural infrastructures required for brain dynamics to support emergence.

Alterations to parvalbumin-expressing interneuron function and associated network oscillations in the hippocampal - medial prefrontal cortex circuit during natural sleep in AppNL-G-F/NL-G-F mice.

In the early stages of Alzheimer's disease (AD), the accumulation of the peptide amyloid-ß (Aß) damages synapses and disrupts neuronal activity, leading to the disruption of neuronal oscillations associated with cognition. This is thought to be largely due to impairments in CNS synaptic inhibition, particularly via parvalbumin (PV)-expressing interneurons that are essential for generating several key oscillations. Research in this field has largely been conducted in mouse models that over-express humanised, mutated forms of AD-associated genes that produce exaggerated pathology. This has prompted the development and use of knock-in mouse lines that express these genes at an endogenous level, such as the AppNL-G-F/NL-G-F mouse model used in the present study. These mice appear to model the early stages of Aß-induced network impairments, yet an in-depth characterisation of these impairments in currently lacking. Therefore, using 16 month-old AppNL-G-F/NL-G-F mice, we analysed neuronal oscillations found in the hippocampus and medial prefrontal cortex (mPFC) during awake behaviour, rapid eye movement (REM) and non-REM (NREM) sleep to assess the extent of network dysfunction. No alterations to gamma oscillations were found to occur in the hippocampus or mPFC during either awake behaviour, REM or NREM sleep. However, during NREM sleep an increase in the power of mPFC spindles and decrease in the power of hippocampal sharp-wave ripples was identified. The latter was accompanied by an increase in the synchronisation of PV-expressing interneuron activity, as measured using two-photon Ca2+ imaging, as well as a decrease in PV-expressing interneuron density. Furthermore, although changes were detected in local network function of mPFC and hippocampus, long-range communication between these regions appeared intact. Altogether, our results suggest that these NREM sleep-specific impairments represent the early stages of circuit breakdown in response to amyloidopathy.

Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017.

BACKGROUND: Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action. METHODS: Using data from patients hospitalized in a cohort of 890 U.S. hospitals during the period 2012-2017, we generated national case counts for both hospital-onset and community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant acinetobacter species, and MDR Pseudomonas aeruginosa. RESULTS: The hospital cohort in the study accounted for 41.6 million hospitalizations (>20% of U.S. hospitalizations annually). The overall rate of clinical cultures was 292 cultures per 1000 patient-days and was stable throughout the time period. In 2017, these pathogens caused an estimated 622,390 infections (95% confidence interval [CI], 579,125 to 665,655) among hospitalized patients. Of these infections, 517,818 (83%) had their onset in the community, and 104,572 (17%) had their onset in the hospital. MRSA and ESBL infections accounted for the majority of the infections (52% and 32%, respectively). Between 2012 and 2017, the incidence decreased for MRSA infection (from 114.18 to 93.68 cases per 10,000 hospitalizations), VRE infection (from 24.15 to 15.76 per 10,000), carbapenem-resistant acinetobacter species infection (from 3.33 to 2.47 per 10,000), and MDR P. aeruginosa infection (from 13.10 to 9.43 per 10,000), with decreases ranging from -20.5% to -39.2%. The incidence of carbapenem-resistant Enterobacteriaceae infection did not change significantly (from 3.36 to 3.79 cases per 10,000 hospitalizations). The incidence of ESBL infection increased by 53.3% (from 37.55 to 57.12 cases per 10,000 hospitalizations), a change driven by an increase in community-onset cases. CONCLUSIONS: Health care-associated antimicrobial resistance places a substantial burden on patients in the United States. Further work is needed to identify improved interventions for both the inpatient and outpatient settings. (Funded by the Centers for Disease Control and Prevention.).

Emotion recognition profiles in clusters of youth based on levels of callous-unemotional traits and reactive and proactive aggression.

Youth with disruptive behavior showing high callous-unemotional (CU) traits and proactive aggression are often assumed to exhibit distinct impairments in emotion recognition from those showing mainly reactive aggression. Yet, reactive and proactive aggression and CU traits may co-occur to varying degrees across individuals. We aimed to investigate emotion recognition in more homogeneous clusters based on these three dimensions. In a sample of 243 youth (149 with disruptive behavior problems and 94 controls) aged 8-18 years, we used model-based clustering on self-report measures of CU traits and reactive and proactive aggression and compared the resulting clusters on emotion recognition (accuracy and response bias) and working memory. In addition to a Low and Low-Moderate symptom cluster, we identified two high CU clusters. The CU-Reactive cluster showed high reactive and low-to-medium proactive aggression; the CU-Mixed cluster showed high reactive and proactive aggression. Both CU clusters showed impaired fear recognition and working memory, whereas the CU-Reactive cluster also showed impaired recognition of disgust and sadness, partly explained by poor working memory, as well as a response bias for anger and happiness. Our results confirm the importance of CU traits as a core dimension along which youth with disruptive behavior may be characterized, yet challenge the view that high CU traits are closely linked to high proactive aggression per se. Notably, distinct neurocognitive processes may play a role in youth with high CU traits and reactive aggression with lower versus higher proactive aggression.

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

Birth of the blues: emotional sound processing in infants exposed to prenatal maternal depression.

BACKGROUND: Offspring exposed to prenatal maternal depression (PMD) are vulnerable to depression across their lifespan. The underlying cause(s) for this elevated intergenerational risk is most likely complex. However, depression is underpinned by a dysfunctional frontal-limbic network, associated with core information processing biases (e.g. attending more to sad stimuli). Aberrations in this network might mediate transmission of this vulnerability in infants exposed to PMD. In this study, we aimed to explore the association between foetal exposure to PMD and frontal-limbic network function in infancy, hypothesising that, in response to emotional sounds, infants exposed to PMD would exhibit atypical activity in these regions, relative to those not exposed to PMD. METHOD: We employed a novel functional magnetic resonance imaging sequence to compare brain function, whilst listening to emotional sounds, in 78 full-term infants (3-6 months of age) born to mothers with and without a diagnosis of PMD. RESULTS: After exclusion of 19 datasets due to infants waking up, or moving excessively, we report between-group brain activity differences, between 29 infants exposed to PMD and 29 infants not exposed to PMD, occurring in temporal, striatal, amygdala/parahippocampal and frontal regions (p < 0.005). The offspring exposed to PMD exhibited a relative increase in activation to sad sounds and reduced (or unchanged) activation to happy sounds in frontal-limbic clusters. CONCLUSIONS: Findings of a differential response to positive and negative valanced sounds by 3-6 months of age may have significant implications for our understanding of neural mechanisms that underpin the increased risk for later-life depression in this population.

The effects of callous-unemotional traits and aggression subtypes on amygdala activity in response to negative faces.

BACKGROUND: Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing. METHODS: We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8-18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task. RESULTS: Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression. CONCLUSIONS: Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

Mitigation translocation as a management tool.

Mitigation translocation is a subgroup of conservation translocation, categorized by a crisis-responsive time frame and the immediate goal of relocating individuals threatened with death. However, the relative successes of conservation translocations with longer time frames and broader metapopulation- and ecosystem-level considerations have been used to justify the continued implementation of mitigation translocations without adequate post hoc monitoring to confirm their effectiveness as a conservation tool. Mitigation translocations now outnumber other conservation translocations, and understanding the effectiveness of mitigation translocations is critical given limited global conservation funding especially if the mitigation translocations undermine biodiversity conservation by failing to save individuals. We assessed the effectiveness of mitigation translocations by conducting a quantitative review of the global literature. A total of 59 mitigation translocations were reviewed for their adherence to the adaptive scientific approach expected of other conservation translocations and for the testing of management options to continue improving techniques for the future. We found that mitigation translocations have not achieved their potential as an effective applied science. Most translocations focused predominantly on population establishment- and persistence-level questions, as is often seen in translocations more broadly, and less on metapopulation and ecosystem outcomes. Questions regarding the long-term impacts to the recipient ecosystem (12% of articles) and the carrying capacity of translocation sites (24% of articles) were addressed least often, despite these factors being more likely to influence ultimate success. Less than half (47%) of studies included comparison of different management techniques to facilitate practitioners selecting the most effective management actions for the future. To align mitigation translocations with the relative success of other conservation translocations, it is critical that future mitigation translocations conform to an established experimental approach to improve their effectiveness. Effective mitigation translocations will require significantly greater investment of time, expertise, and resources in the future.

La Translocación para Mitigación como una Herramienta de Gestión Resumen La translocación para mitigación es un subgrupo de la translocación para la conservación, caracterizada por un marco de tiempo que responda a la crisis y la meta inmediata de reubicar a individuos amenazados de muerte. Sin embargo, el éxito relativo de las traslocaciones para conservación con marcos de tiempo mayores y consideraciones a nivel metapoblación y ecosistema más amplias han sido utilizadas para justificar la implementación de translocaciones para mitigación sin monitoreo post hoc adecuado para confirmar su efectividad como herramienta de conservación. Las translocaciones para mitigación ahora son más numerosas que otras translocaciones, por lo que es fundamental entender la efectividad de las translocaciones para mitigación debido a las limitaciones en el financiamiento para la conservación global - especialmente si las translocaciones para mitigación socavan la conservación de la biodiversidad al fallar en salvar individuos. Evaluamos la efectividad de translocaciones para mitigación mediante una revisión cuantitativa de la literatura global. Revisamos un total de 59 translocaciones para mitigación para analizar su adhesión al método científico adaptativo esperado de otras translocaciones de conservación y para probar las opciones de gestión para mejorar las técnicas en el futuro. Encontramos que las mitigaciones para translocación no han alcanzado su potencial como una ciencia aplicada efectiva. La mayoría de las translocaciones se centraron predominantemente en preguntas relacionadas con el establecimiento y nivel de persistencia de la población, como se observa en translocaciones más generales, y menos en resultados a nivel metapoblación y ecosistema. Aspectos relacionados con los impactos a largo plazo sobre el ecosistema recipiente (12% de los artículos) y la capacidad de carga de los sitios de translocación (24% de los artículos) fueron poco abordados, no obstante que es más probable que estos factores influyan en el éxito final. Menos de la mitad (47%) de los estudios incluyó la comparación de métodos de gestión diferentes para facilitar que los practicantes selecciones las acciones de gestión más efectivas para el futuro. Para alinear las translocaciones para mitigación con el éxito relativo de otras translocaciones para conservación, es crítico que las futuras translocaciones para mitigación se apeguen a un método experimental establecido para incrementar su efectividad. Para ser efectivas, las translocaciones para mitigación requerirán una inversión de tiempo, conocimientos técnicos y recursos significativamente mayores.

Life Cycle Greenhouse Gas Emissions of the USPS Next-Generation Delivery Vehicle Fleet.

The United States Postal Service (USPS) plans to purchase 165,000 next-generation delivery vehicles (NGDVs) between 2023 and 2032. The USPS submitted an environmental impact statement (EIS) for two NGDV procurement scenarios: (1) 90% internal combustion engine vehicles (ICEVs) and 10% battery electric vehicles (BEVs) ("ICEV scenario") and (2) 100% BEVs ("BEV scenario"). To correct several significant deficiencies in the EIS, we conduct a cradle-to-grave life cycle greenhouse gas (GHG) assessment of these two scenarios. Our analysis improves upon the USPS's EIS by including vehicle production and end-of-life emissions, future grid decarbonization, and more accurate vehicle operating emissions. In our base case, we find that the ICEV and BEV scenarios would result in 15% greater and 8% fewer GHG emissions, respectively, than the USPS estimate. Favorable vehicle and grid development would result in 63% lower BEV scenario emissions than the USPS estimate. Consequently, we calculate a cumulative lifetime emission reduction of 57-82% (14.7-21.4 Mt CO2e) from procuring 100% BEVs instead of 10% BEVs, compared to the USPS's estimate of 10.3 Mt. Given the long NGDV lifetimes, committing to the ICEV scenario squanders an ideal use case for BEVs, jeopardizes meeting our climate goals, and forgoes potential climate and environmental justice co-benefits.

Examining the Boundary Sharpness Coefficient as an Index of Cortical Microstructure in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration. Here, we propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient). Using a vertex-based meta-analysis and a large multicenter structural magnetic resonance imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male), and 721 controls (283 female; 438 male), we observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities. Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus. Increases were observed in different brain regions in males and females, with larger effect sizes in females. BSC correlated with ADOS-2 Calibrated Severity Score in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared with cortical thickness. These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.

The factor structure of the Edinburgh Postnatal Depression Scale among perinatal high-risk and community samples in London.

Timely and accurate detection of perinatal mental health problems is essential for the wellbeing of both mother and child. Growing evidence has suggested that the Edinburgh Postnatal Depression Scale (EPDS) is not a unidimensional measure of perinatal depression, but can be used to screen for anxiety disorders. We aimed to assess the factor structure of the EPDS in 3 different groups of women: n = 266 pregnant women at high-risk of depression ("Perinatal Stress Study"), n = 471 pregnant women from a community sample, and n = 637 early postnatal women from a community sample ("developing Human Connectome Project"). Exploratory factor analysis (40% of each sample) and confirmatory factor analysis (60% of each sample) were performed. The relationship between EPDS scores and history of mental health concerns was investigated. Results suggested that a 3-factor model (depression, anxiety, and anhedonia) is the most appropriate across groups. The anxiety subscale (EPDS-3A) emerged consistently and was related to maternal history of anxiety disorders in the prenatal sample (W = 6861, p < 0.001). EPDS total score was related to history of mental health problems in both the prenatal (W = 12,185, p < 0.001) and postnatal samples (W = 30,044, p < 0.001). In both high-risk and community samples in the perinatal period, the EPDS appears to consist of depression, anxiety, and anhedonia subscales. A better understanding of the multifactorial structure of the EPDS can inform diagnosis and management of women in the prenatal and postnatal period. Further research is required to validate the EPDS-3A as a screening tool for anxiety.

Subgrouping children and adolescents with disruptive behaviors: symptom profiles and the role of callous-unemotional traits.

Disruptive behavior during childhood and adolescence is heterogeneous and associated with several psychiatric disorders. The identification of more homogeneous subgroups might help identify different underlying pathways and tailor treatment strategies. Children and adolescents (aged 8-18) with disruptive behaviors (N = 121) and healthy controls (N = 100) were included in a European multi-center cognition and brain imaging study. They were assessed via a battery of standardized semi-structured interviews and questionnaires. K-means cluster-model analysis was carried out to identify subgroups within the group with disruptive behaviors, based on clinical symptom profiles, callous-unemotional (CU) traits, and proactive and reactive aggression. The resulting subgroups were then compared to healthy controls with regard to these clinical variables. Three distinct subgroups were found within the group with disruptive behaviors. The High CU Traits subgroup presented elevated scores for CU traits, proactive aggression and conduct disorder (CD) symptoms, as well as a higher proportion of comorbidities (CD + oppositional defiant disorder + attention deficit hyperactivity disorder (ADHD). The ADHD and Affective Dysregulation subgroup showed elevated scores for internalizing and ADHD symptoms, as well as a higher proportion of females. The Low Severity subgroup had relatively low levels of psychopathology and aggressive behavior compared to the other two subgroups. The High CU Traits subgroup displayed more antisocial behaviors than the Low Severity subgroup, but did not differ when compared to the ADHD and Affective Dysregulation subgroup. All three subgroups differed significantly from the healthy controls in all the variables analyzed. The present study extends previous findings on subgrouping children and adolescents with disruptive behaviors using a multidimensional approach and describes levels of anxiety, affective problems, ADHD, proactive aggression and CU traits as key factors that differentiate conclusively between subgroups.

A study on episodic memory reconsolidation that tells us more about consolidation.

Awake quiescence immediately after encoding is conducive to episodic memory consolidation. Retrieval can render episodic memories labile again, but reconsolidation can modify and restrengthen them. It remained unknown whether awake quiescence after retrieval supports episodic memory reconsolidation. We sought to examine this question via an object-location memory paradigm. We failed to probe the effect of quiescence on reconsolidation, but we did observe an unforeseen "delayed" effect of quiescence on consolidation. Our findings reveal that the beneficial effect of quiescence on episodic memory consolidation is not restricted to immediately following encoding but can be achieved at a delayed stage and even following a period of task engagement.

Examining volumetric gradients based on the frustum surface ratio in the brain in autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is accompanied by neurodevelopmental differences in regional cortical volume (CV), and a potential layer-specific pathology. Conventional measures of CV, however, do not indicate how volume is distributed across cortical layers. In a sample of 92 typically developing (TD) controls and 92 adult individuals with ASD (aged 18-52 years), we examined volumetric gradients by quantifying the degree to which CV is weighted from the pial to the white surface of the brain. Overall, the spatial distribution of Frustum Surface Ratio (FSR) followed the gyral and sulcal pattern of the cortex and approximated a bimodal Gaussian distribution caused by a linear mixture of vertices on gyri and sulci. Measures of FSR were highly correlated with vertex-wise estimates of mean curvature, sulcal depth, and pial surface area, although none of these features explained more than 76% variability in FSR on their own. Moreover, in ASD, we observed a pattern of predominant increases in the degree of FSR relative to TD controls, with an atypical neurodevelopmental trajectory. Our findings suggest a more outward-weighted gradient of CV in ASD, which may indicate a larger contribution of supragranular layers to regional differences in CV.

Atypical measures of diffusion at the gray-white matter boundary in autism spectrum disorder in adulthood.

Autism spectrum disorder (ASD) is a highly complex neurodevelopmental condition that is accompanied by neuroanatomical differences on the macroscopic and microscopic level. Findings from histological, genetic, and more recently in vivo neuroimaging studies converge in suggesting that neuroanatomical abnormalities, specifically around the gray-white matter (GWM) boundary, represent a crucial feature of ASD. However, no research has yet characterized the GWM boundary in ASD based on measures of diffusion. Here, we registered diffusion tensor imaging data to the structural T1-weighted images of 92 adults with ASD and 92 matched neurotypical controls in order to examine between-group differences and group-by-sex interactions in fractional anisotropy and mean diffusivity sampled at the GWM boundary, and at different sampling depths within the superficial white and into the gray matter. As hypothesized, we observed atypical diffusion at and around the GWM boundary in ASD, with between-group differences and group-by-sex interactions depending on tissue class and sampling depth. Furthermore, we identified that altered diffusion at the GWM boundary partially (i.e., ~50%) overlapped with atypical gray-white matter tissue contrast in ASD. Our study thus replicates and extends previous work highlighting the GWM boundary as a crucial target of neuropathology in ASD, and guides future work elucidating etiological mechanisms.

Magnitude and heterogeneity of brain structural abnormalities in 22q11.2 deletion syndrome: a meta-analysis.

The 22q11.2 deletion syndrome (22q11.2DS) is a neurodevelopmental disorder associated with a number of volumetric brain abnormalities. The syndrome is also associated with an increased risk for neuropsychiatric disorders including schizophrenia and autism spectrum disorder. An earlier meta-analysis showed reduced grey and white matter volumes in individuals with 22q11.2DS. Since this analysis was conducted, the number of studies has increased markedly, permitting more precise estimates of effects and more regions to be examined. Although 22q11.2DS is clinically heterogeneous, it is not known to what extent this heterogeneity is mirrored in neuroanatomy. The aim of this study was thus to investigate differences in mean brain volume and structural variability within regions, between 22q11.2DS and typically developing controls. We examined studies that reported measures of brain volume using MRI in PubMed, Web of Science, Scopus and PsycINFO from inception to 1 May 2019. Data were extracted from studies in order to calculate effect sizes representing case-control difference in mean volume, and in the variability of volume (as measured using the log variability ratio (lnVR) and coefficient of variation ratio (CVR)). We found significant overall decreases in mean volume in 22q11.2DS compared with control for: total brain (g = -0.96; p < 0.001); total grey matter (g = -0.81, p < 0.001); and total white matter (g = -0.81; p < 0.001). There was also a significant overall reduction of mean volume in 22q11.2DS subjects compared with controls in frontal lobe (g = -0.47; p < 0.001), temporal lobe (g = -0.84; p < 0.001), parietal lobe (g = -0.73; p = 0.053), cerebellum (g = -1.25; p < 0.001) and hippocampus (g = -0.90; p < 0.001). Significantly increased variability in 22q11.2DS individuals compared with controls was found only for the hippocampus (VR, 1.14; p = 0.036; CVR, 1.30; p < 0.001), and lateral ventricles (VR, 1.56; p = 0.004). The results support the notion that structural abnormalities in 22q11.2DS and schizophrenia are convergent, and also to some degree with findings in autism spectrum disorder. Finally, the increased variability seen in the hippocampus in 22q11.2DS may underlie some of the heterogeneity observed in the neuropsychiatric phenotype.