Neurobehavioral correlates of impaired emotion recognition in pediatric PTSD.

Despite broad evidence suggesting that adversity-exposed youth experience an impaired ability to recognize emotion in others, the underlying biological mechanisms remains elusive. This study uses a multimethod approach to target the neurological substrates of this phenomenon in a well-phenotyped sample of youth meeting diagnostic criteria for posttraumatic stress disorder (PTSD). Twenty-one PTSD-afflicted youth and 23 typically developing (TD) controls completed clinical interview schedules, an emotion recognition task with eye-tracking, and an implicit emotion processing task during functional magnetic resonance imaging )fMRI). PTSD was associated with decreased accuracy in identification of angry, disgust, and neutral faces as compared to TD youth. Of note, these impairments occurred despite the normal deployment of visual attention in youth with PTSD relative to TD youth. Correlation with a related fMRI task revealed a group by accuracy interaction for amygdala-hippocampus functional connectivity (FC) for angry expressions, where TD youth showed a positive relationship between anger accuracy and amygdala-hippocampus FC; this relationship was reversed in youth with PTSD. These findings are a novel characterization of impaired threat recognition within a well-phenotyped population of severe pediatric PTSD. Further, the differential amygdala-hippocampus FC identified in youth with PTSD may imply aberrant efficiency of emotional contextualization circuits.

Scattering-loss reduction of ridge waveguides by sidewall polishing.

Ridge waveguides provide a large refractive index contrast and thus strong mode confinement, making them highly attractive for building compact photonic integrated circuits. However, ridge waveguides suffer from scattering losses. We demonstrate scattering-loss reduction of ridge waveguides made of lithium-niobate-on-insulator (LNOI) substrates by more than one order of magnitude. This is achieved by gently polishing of the ridge's sidewalls and simultaneous protection of the top surfaces by a metal layer. Whispering-gallery-resonator loss measurements reveal ultra-low losses down to 0.04 dB/cm of the processed waveguides. Our approach pushes ridge waveguides further towards their fundamental absorption-loss limit, enabling highly efficient integrated devices.

Cascaded second-order optical nonlinearities in on-chip micro rings.

We demonstrate cascaded Stimulated Raman Scattering (SRS), Second-Harmonic Generation (SHG), and Sum-Frequency Generation (SFG) in integrated on-chip whispering-gallery resonators (WGRs). These lithium niobate-based WGRs are fabricated using highly-parallel semiconductor manufacturing techniques coupled with specialized polishing as a post-processing step and thus represent a novel means for batch fabrication of this family of non-linear devices. We achieved record high Q-factors for on-chip lithium niobate WGRs reaching up to 3 × 106. Furthermore, we present a flexible but stable coupling scheme, which gives us the opportunity to optimize the coupling regarding the non-linear optical processes we observe.

Ventromedial prefrontal cortex lesions alter neural and physiological correlates of anticipation.

Uncertainty is a ubiquitous feature of our daily lives. Although previous studies have identified a number of neural and peripheral physiological changes associated with uncertainty, there are limited data on the causal mechanisms underlying these responses in humans. In this study, we address this empirical gap through a novel application of fMRI in neurosurgical patients with focal, bilateral ventromedial prefrontal cortex (vmPFC) damage. The fMRI task involved cued anticipation of aversive and neutral picture stimuli; "certain" cues unambiguously indicated the upcoming picture valence, whereas "ambiguous" cues could precede either picture type. Healthy subjects exhibited robust bilateral insula responses to ambiguous cues, and this cue-related insula activity significantly correlated with heart rate variability during the task. By contrast, the vmPFC lesion patients exhibited altered cue-related insula activity and reduced heart rate variability. These findings suggest a role for vmPFC in coordinating neural and physiological responses during anticipation.

Interpersonal traits of psychopathy linked to reduced integrity of the uncinate fasciculus.

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Here, we performed the largest diffusion tensor imaging (DTI) study of incarcerated criminal offenders to date (N = 147) to determine whether psychopathy severity is linked to the microstructural integrity of major white matter tracts in the brain. Consistent with the results of previous studies in smaller samples, we found that psychopathy was associated with reduced fractional anisotropy in the right uncinate fasciculus (UF; the major white matter tract connecting ventral frontal and anterior temporal cortices). We found no such association in the left UF or in adjacent frontal or temporal white matter tracts. Moreover, the right UF finding was specifically related to the interpersonal features of psychopathy (glib superficial charm, grandiose sense of self-worth, pathological lying, manipulativeness), rather than the affective, antisocial, or lifestyle features. These results indicate a neural marker for this key dimension of psychopathic symptomatology.

Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion.

Inherent emotional quality of human speech sounds.

During much of the past century, it was widely believed that phonemes-the human speech sounds that constitute words-have no inherent semantic meaning, and that the relationship between a combination of phonemes (a word) and its referent is simply arbitrary. Although recent work has challenged this picture by revealing psychological associations between certain phonemes and particular semantic contents, the precise mechanisms underlying these associations have not been fully elucidated. Here we provide novel evidence that certain phonemes have an inherent, non-arbitrary emotional quality. Moreover, we show that the perceived emotional valence of certain phoneme combinations depends on a specific acoustic feature-namely, the dynamic shift within the phonemes' first two frequency components. These data suggest a phoneme-relevant acoustic property influencing the communication of emotion in humans, and provide further evidence against previously held assumptions regarding the structure of human language. This finding has potential applications for a variety of social, educational, clinical, and marketing contexts.

Human ventromedial prefrontal cortex lesions enhance the effect of expectations on pain perception.

Pain is strongly modulated by expectations and beliefs. Across species, subregions of ventromedial prefrontal cortex (VMPFC) are implicated in a variety of functions germane to pain, predictions, and learning. Human fMRI studies show that VMPFC activity tracks expectations about pain and mediates expectancy effects on pain-related activity in other brain regions. Prior lesion studies suggest that VMPFC may instead play a more general role in generating affective responses to painful stimuli. To test whether VMPFC is required to generate affective responses to pain or is more specifically involved in expectancy-based pain modulation, we studied responses to heat stimuli in five adults with bilateral surgical lesions of VMPFC and twenty healthy adults without brain damage. All participants underwent a quantitative sensory testing procedure followed by a pain expectancy task in which cues predicting either low or high pain were followed by intermittent medium intensity heat stimuli. Compared to adults without brain damage, individuals with VMPFC lesions reported larger differences in expected pain based on predictive cues and failed to update expectations following the covert introduction of unexpected medium temperature stimuli. Consistent with observed expectancy differences, subjective pain unpleasantness ratings in the VMPFC lesion group were more strongly modulated by cue during thermal stimulation. We found no group differences in overall pain sensitivity, nor in relationships between pain and autonomic arousal, suggesting that VMPFC damage specifically enhances the effect of expectations on pain processing, likely driven by impaired integration of new sensory feedback to update expectations about pain. These results provide essential new data regarding the specific functional contribution of VMPFC to pain modulation.

Prostate angiosarcoma: is there any association with previous radiation therapy?

What's known on the subject? and What does the study add? Angiosarcomas are histological subtype of sarcomas and rarely involve the prostate gland. Only ten cases of prostate angiosarcoma have been reported in the literature to date. Occurrence of post-irradiation prostate angiosarcoma is rare considering the frequency of radiotherapy used for treatment of prostate adenocarcinoma. We provide a brief review of all cases of prostate angiosarcoma and describe the epidemiology, etiology, clinical presentation, histopathology, prognostic factors and current treatment options for prostate angiosarcoma. For the current review a literature search was carried out using Pubmed, EmBase, and Cochrane databases. All cases of prostate angioscaroma reported to date and observational studies evaluating the radiation associated cancer occurrence were reviewed. Despite the rarity, prostate angiosarcomas display remarkable clinical and pathological heterogeneity, and a treatment challenge. We found the association of prostate angiosarcoma with radiation therapy to be weak based upon the results from observational studies and case reports. Although radiation exposure has been suggested etiology of prostate angiosarcomas, assumption of such association is not supported by the current literature.

Diffuse Auroral Electron and Ion Precipitation Effects on RCM-E Comparisons With Satellite Data During the 17 March 2013 Storm.

Effects of scattering of electrons from whistler chorus waves and of ions due to field line curvature on diffuse precipitating particle fluxes and ionospheric conductance during the large 17 March 2013 storm are examined using the self-consistent Rice Convection Model Equilibrium (RCM-E) model. Electrons are found to dominate the diffuse precipitating particle integrated energy flux, with large fluxes from ~21:00 magnetic local time (MLT) eastward to ~11:00 MLT during the storm main phase. Simulated proton and oxygen ion precipitation due to field line curvature scattering is sporadic and localized, occurring where model magnetic field lines are significantly stretched on the night side at equatorial geocentric radial distances r 0 ≳8 R E and/or at r 0 ~5.5 to 6.5 R E from dusk to midnight where the partial ring current field has perturbed the magnetic field. The precipitating protons likewise contribute sporadically to the storm time Hall and Pedersen conductance in localized regions whereas the precipitating electrons are the dominate storm time contributor to enhanced Hall and Pedersen conductance at auroral magnetic latitudes on the night and morning side. The RCM-E model can reproduce general features of the Van Allen Probe/MagEIS observed trapped electron differential flux spectrograms over energies of ~37 to 150 keV. The simulations with a parameterized electron loss model also reproduce reasonably well the storm time Defense Meteorological Satellite Program integrated electron energy flux at 850 km at satellite crossings from predawn to midmorning. However, model-data agreement is not as good from dusk to premidnight where there are large uncertainties in the electron loss model.

Psychopathic traits are associated with reduced fixations to the eye region of fearful faces.

Impairments in processing fearful faces have been documented in both children and adults with psychopathic traits, suggesting a potential mechanism by which psychopathic individuals develop callous and manipulative interpersonal and affective traits. Recently, research has demonstrated that psychopathic traits are associated with reduced fixations to the eye regions of faces in samples of children and community-dwelling adults, however this relationship has not yet been established in an offender sample with high levels of psychopathy. In the current study, we employed eye-tracking with paradigms involving the identification and passive viewing of facial expressions of emotion, respectively, in a sample of adult male criminal offenders (n = 108) to elucidate the relationship between visual processing of fearful facial expressions and interpersonal and affective psychopathic traits. We found that the interpersonal-affective traits of psychopathy were significantly related to fewer fixations to the eyes of fear faces during the emotion recognition task. This association was driven particularly by the interpersonal psychopathic traits (e.g., egocentricity, deceitfulness), whereas fear recognition accuracy was inversely related to the affective psychopathic traits (e.g., callousness, lack of empathy). These findings highlight potential mechanisms for the subset of the interpersonal-affective traits exhibited by psychopathic individuals. (PsycINFO Database Record

Psychopathic traits linked to alterations in neural activity during personality judgments of self and others.

Psychopathic individuals are notorious for their grandiose sense of self-worth and disregard for the welfare of others. One potential psychological mechanism underlying these traits is the relative consideration of "self" versus "others". Here we used task-based functional magnetic resonance imaging (fMRI) to identify neural responses during personality trait judgments about oneself and a familiar other in a sample of adult male incarcerated offenders (n = 57). Neural activity was regressed on two clusters of psychopathic traits: Factor 1 (e.g., egocentricity and lack of empathy) and Factor 2 (e.g., impulsivity and irresponsibility). Contrary to our hypotheses, Factor 1 scores were not significantly related to neural activity during self- or other-judgments. However, Factor 2 traits were associated with diminished activation to self-judgments, in relation to other-judgments, in bilateral posterior cingulate cortex and right temporoparietal junction. These findings highlight cortical regions associated with a dimension of social-affective cognition that may underlie psychopathic individuals' impulsive traits.

Sequence requirements for Lon-dependent degradation of the Escherichia coli transcription activator SoxS: identification of the SoxS residues critical to proteolysis and specific inhibition of in vitro degradation by a peptide comprised of the N-terminal 21 amino acid residues.

When Escherichia coli encounter redox-cycling compounds that endogenously generate superoxide, the cell's defense response is initiated by the de novo synthesis of SoxS, which then activates transcription of the genes of the SoxRS regulon. Recently, we showed that after the oxidative stress is relieved, the SoxRS system resets by an active process wherein SoxS synthesis ceases and the intrinsically unstable SoxS protein is rapidly degraded, primarily by Lon protease. Here, we use deletion mutants and a library of alanine-stretch mutants of the entire protein to identify the SoxS features responsible for Lon-dependent proteolysis in vivo. We found that the 17 amino acid residues at the SoxS N terminus play the primary role in protease recognition and that the addition of the N-terminal 21 residues of SoxS to the otherwise stable green fluorescent protein is sufficient to signal the chimera for Lon-dependent degradation. With a minimal in vitro degradation system, we confirm the intrinsic instability of SoxS and the sequence requirements for Lon-dependent degradation. Lastly, we demonstrate that the addition of a peptide comprised of the 21 N-terminal amino acid residues of SoxS is able to inhibit specifically the in vitro proteolysis of SoxS.

Reversal learning deficits in criminal offenders: Effects of psychopathy, substance use, and childhood maltreatment history.

Deficits in reinforcement learning are presumed to underlie the impulsive and incorrigible behavior exhibited by psychopathic criminals. However, previous studies documenting reversal learning impairments in psychopathic individuals have not investigated this relationship across a continuous range of psychopathy severity, nor have they examined how reversal learning impairments relate to different psychopathic traits, such as the interpersonal-affective and lifestyle-antisocial dimensions. Furthermore, previous studies have not considered the role that childhood maltreatment and substance use may have in this specific cognitive deficit. Using a standard reversal learning task in a sample of N = 114 incarcerated male offenders, we demonstrate a significant relationship between psychopathy severity and reversal learning errors. Furthermore, we show a significant interaction between psychopathy and childhood maltreatment, but not substance use, such that individuals high in psychopathy with an extensive history of maltreatment committed the greatest number of reversal learning errors. These findings extend the current understanding of reversal learning performance among psychopathic individuals, and highlight the importance of considering childhood maltreatment when studying psychopathy.

Prefrontal-Amygdala Dysregulation to Threat in Pediatric Posttraumatic Stress Disorder.

Functional abnormalities in fear circuitry are likely to underlie the pathophysiology of pediatric posttraumatic stress disorder (PTSD), but the few studies to date have yielded conflicting findings. Furthermore, network level functional connectivity and age-related disruptions in fear circuitry have not been thoroughly explored. In a cross-sectional design, 24 healthy and 24 medication-free youth with severe PTSD completed an event-related emotion-processing task during functional MRI. Youth viewed threat and neutral images, half of which were paired with a neutral male face. Group- and age-related differences in brain activation were examined in the medial prefrontal cortex (mPFC), amygdala, and hippocampus. Amygdala functional connectivity was examined using a seed-based approach. PTSD youth showed hyperactivation of the dorsal anterior cingulate cortex (dACC) to threat images. In the dorsomedial PFC (dmPFC), age positively predicted activation in healthy youth but negatively predicted activation in PTSD youth. In the amygdala functional connectivity analysis, PTSD youth showed decreased amygdala-mPFC connectivity to threat images. Furthermore, age positively predicted amygdala-vmPFC connectivity in healthy youth, but negatively predicted connectivity in PTSD youth. Finally, dmPFC activation and amygdala-mPFC connectivity were inversely related to PTSD severity. Pediatric PTSD involves abnormal functional activation and connectivity in fear circuitry. Specifically, dACC hyperactivation is consistent with abnormal promotion of fear responses, whereas reduced amygdala-mPFC connectivity suggests impaired regulation of amygdala responses to threat. Importantly, age-dependent decreases in dmPFC activation and amygdala-vmPFC connectivity may indicate abnormal developmental processes in key emotion pathways in pediatric PTSD.

Emotion recognition deficits associated with ventromedial prefrontal cortex lesions are improved by gaze manipulation.

Facial emotion recognition is a critical aspect of human communication. Since abnormalities in facial emotion recognition are associated with social and affective impairment in a variety of psychiatric and neurological conditions, identifying the neural substrates and psychological processes underlying facial emotion recognition will help advance basic and translational research on social-affective function. Ventromedial prefrontal cortex (vmPFC) has recently been implicated in deploying visual attention to the eyes of emotional faces, although there is mixed evidence regarding the importance of this brain region for recognition accuracy. In the present study of neurological patients with vmPFC damage, we used an emotion recognition task with morphed facial expressions of varying intensities to determine (1) whether vmPFC is essential for emotion recognition accuracy, and (2) whether instructed attention to the eyes of faces would be sufficient to improve any accuracy deficits. We found that vmPFC lesion patients are impaired, relative to neurologically healthy adults, at recognizing moderate intensity expressions of anger and that recognition accuracy can be improved by providing instructions of where to fixate. These results suggest that vmPFC may be important for the recognition of facial emotion through a role in guiding visual attention to emotionally salient regions of faces.

Genetic evidence for pre-recruitment as the mechanism of transcription activation by SoxS of Escherichia coli: the dominance of DNA binding mutations of SoxS.

SoxS, the direct transcriptional activator of the Escherichia coli superoxide (SoxRS) regulon, displays several unusual characteristics which suggest that it is unlikely to activate transcription by the ususal recruitment mechanism. Thus, agents that generate superoxide endogenously and thereby provoke the defense response elicit the de novo synthesis of SoxS, and with the SoxS binding site being highly degenerate, the number of SoxS binding sites per cell far exceeds the number of SoxS molecules per cell. To account for these distinctive features of the SoxRS system, we proposed "pre-recruitment" as the mechanism by which SoxS activates transcription of the regulon's genes. In pre-recruitment, newly synthesized SoxS molecules form binary complexes with RNA polymerase in solution. These complexes provide the information content to allow the 2500 molecules of SoxS per cell to scan the 65,000 SoxS binding sites per cell for the 200 binding sites per cell that reside within SoxS-dependent promoters. As a test of whether SoxS activates transcription by recruitment or pre-recruitment, we determined the dominance relationships of SoxS mutations conferring defective DNA binding. We found that soxS DNA binding mutations are dominant to the wild-type allele, a result consistent with the pre-recruitment hypothesis, but opposite to that expected for an activator that functions by recruitment. Moreover, whereas positive control mutations of activators functioning by recruitment are usually dominant, a soxS positive control mutation was not. Lastly, with the SoxRS system as an example, we discuss the physiological requirement for stringent regulation of transcriptional activators that function by pre-recruitment.

Novel protein--protein interaction between Escherichia coli SoxS and the DNA binding determinant of the RNA polymerase alpha subunit: SoxS functions as a co-sigma factor and redeploys RNA polymerase from UP-element-containing promoters to SoxS-dependent promoters during oxidative stress.

SoxS is the transcription activator of the SoxRS regulon. Despite being synthesized de novo in response to oxidative stress and despite the large disparity between the number of SoxS binding sites and the number of SoxS molecules per cell, SoxS-dependent promoters are rapidly activated after the onset of the stress. With the usual recruitment/post-recruitment mechanisms being unsuitable for activating gene expression under these conditions, we previously proposed that SoxS functions by "pre-recruitment". In pre-recruitment, SoxS forms SoxS-RNA polymerase binary complexes, which use the DNA binding properties of SoxS and sigma(70) to distinguish SoxS-dependent promoters from housekeeping promoters and from the large number of sequence-equivalent but functionally irrelevant SoxS binding sites. With previous work in Escherichia coli having indicated that the most likely target on RNA polymerase for interaction with SoxS is the C-terminal domain of alpha, we investigated the interaction directly with the yeast two-hybrid system. We found that SoxS interacts with the alphaCTD and that SoxS positive control mutations disrupt the interaction. Moreover, single alanine substitutions of the alphaCTD that reduce or enhance SoxS activation in E.coli reduce or enhance the interaction between SoxS and the alphaCTD in yeast. Significantly, the critical amino acid residues lie in and around the DNA binding determinant of the alphaCTD, the first example of an activator contacting this determinant. These interactions were confirmed with an affinity immobilization assay. Lastly, we found that SoxS induction interferes with utilization of the UP element of an rRNA promoter. Thus, by functioning as a co-sigma factor that interacts with the DNA binding determinant of the alphaCTD, SoxS diverts RNA polymerase from UP-containing promoters to SoxS-activatable promoters.

A comprehensive alanine scanning mutagenesis of the Escherichia coli transcriptional activator SoxS: identifying amino acids important for DNA binding and transcription activation.

SoxS is the direct transcriptional activator of the superoxide regulon. SoxS recognizes a highly degenerate "soxbox" DNA sequence, and activates transcription from class I and class II promoters. SoxS is the smallest member of the AraC/XylS family of transcription regulators whose hallmark is dual helix-turn-helix (HTH) DNA-binding motifs. Evidence suggests that the N-terminal HTH motif of SoxS interacts with a highly conserved region of the soxbox termed recognition element 1 (RE1), while the C-terminal HTH motif interacts with the less conserved recognition element 2 (RE2). In the work described here, we prepared a complete library of 101 SoxS mutants containing single alanine substitutions of SoxS, and we characterized the mutant proteins in vivo and in vitro. With SoxS being closely related to MarA, we analyzed the effects of the SoxS mutations in the context of the MarA-mar crystal structure and with respect to the NMR study of MarA-DNA complexes in solution. From the properties of the alanine substitutions, we conclude the following. (1) Surface-exposed residues of helix 3 and helix 6, the recognition helices of the dual HTH motifs, are important to DNA binding and transcription activation; however, substitutions of residues predicted from the MarA-mar crystal structure to make contact with the sugar-phosphate backbone are more detrimental to DNA binding than mutations predicted to make base-specific contacts. (2) Substitution of several residues within the recognition helix predicted to make base-specific contacts with RE2 have relatively little effect on DNA-binding, suggesting the possibility of alternative protein-DNA interactions than those inferred from the MarA-mar crystal structure. (3) DNA binding and transcription activation were reduced by substitution of conserved amino acid residues comprising the hydrophobic core, presumably because they disrupt the structural integrity of SoxS. (4) Mutant K30A appears to be a positive control mutant defective in a protein-protein interaction with RNA polymerase that is required for transcription activation at all SoxS-dependent promoters because it binds and bends DNA normally but fails to activate transcription from both classes of promoters. Alanine substitutions of surface-exposed residues H3, K5, D9, S31, and V45 confer a similar phenotype. Since these residues are near K30 on the surface of the protein, the surface formed by the six residues may be used to make protein-protein interactions with RNA polymerase that are required for transcription activation at both class I and class II SoxS-dependent promoters. (5) Mutants F74A, D75A, M78A, D79A and Q85A appear to define a surface required for protein-protein interaction with RNA polymerase specifically at class II promoters because these positive control mutants bind and bend DNA normally but are defective in activation of class II promoters but not class I promoters. These SoxS mutants that bind and bend DNA normally but are defective in transcription activation represent the first positive control mutants with putative defects in protein-protein interactions with RNA polymerase among the SoxS/MarA/Rob subset of the AraC/XylS family of transcription regulators.