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OBJECTIVE. To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. METHODS: Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription-polymerase chain reaction, normalized to 18S ribosomal RNA. RESULTS: In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. CONCLUSION: The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon. [ABSTRACT FROM AUTHOR]

The bioinformational theory of emotional imagery is a model of the hypothetical mental representations activated when people imagine emotionally engaging events, and was initially proposed to guide research and practice in the use of imaginal exposure as a treatment for fear and anxiety (Lang, 1979). In this 50 year overview, we discuss the development of bioinformational theory and its impact on the study of psychophysiology and psychopathology, most importantly assessing its viability and predictions in light of more recent brain-based studies of neural functional activation. Bioinformational theory proposes that narrative imagery, typically cued by language scripts, activates an associative memory network in the brain that includes stimulus (e.g., agents, contexts), semantic (e.g., facts and beliefs) and, most critically for emotion, response information (e.g., autonomic and somatic) that represents relevant real-world coping actions and reactions. Psychophysiological studies in healthy and clinical samples reliably find measurable response output during aversive and appetitive narrative imagery. Neuroimaging studies confirm that emotional imagery is associated with significant activation in motor regions of the brain, as well as in regions implicated in episodic and semantic memory retrieval, supporting the bioinformational view that narrative imagery prompts mental simulation of events that critically includes the actions and reactions engaged in emotional contexts., 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 Elsevier B.V. All rights reserved.)

Thickness of the medial orbitofrontal cortex (mOFC) was assessed as it varied with reported symptoms of anxiety and depression in a large sample of anxiety patients. A principal component analysis identified a primary factor of transdiagnostic dimensional distress that predicted 24% of the mOFC variance. Severity of distress symptomology was associated with thinning of the mOFC in both hemispheres for both men and women, regardless of the primary DSM diagnosis. Taken together, the data indicate that mOFC thickness might be useful as an objective measure of disorder severity as well as to assess pharmacological or psychological treatment outcome., 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 Elsevier B.V. All rights reserved.)

Reduced hippocampal and/or amygdala volumes have been reported in patients with a variety of different anxiety diagnoses, suggesting that structural alterations may vary transdiagnostically across the internalizing disorders. The current study measured hippocampal and amygdala volumes in anxiety and mood disorder patients assessing differences that vary dimensionally with transdiagnostic factors of distress, anxious arousal, and trauma, based on a principal components analysis of questionnaires relating to symptomology. High-resolution structural images were collected in a sample of 165 patients, and volumes extracted from the hippocampal formation (including CA1, CA2/3, CA4/DG, subiculum, and molecular layer) and the amygdala. Transdiagnostically, increasing distress was associated with reduced hippocampal CA1 volume, increasing anxious arousal was associated with reduced hippocampal CA4/DG volume, and increasing trauma severity was associated with reduced amygdala volume in women. Taken together, the data indicate that subcortical brain volumes decrease as the severity of transdiagnostic psychopathological symptomology increases., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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.

Understanding the neural correlates of repetitive retrieval of emotional events is critical in addressing pathological emotional processing, as repeated processing is central for a number of different therapeutic interventions. In the current study, single-trial functional brain activity was assessed in key regions implicated in episodic retrieval, including the medial prefrontal cortex (mPFC), anterior hippocampus, posterior hippocampus, and the posteromedial parietal cortex (i.e., posterior cingulate cortex and the precuneus) following repeated retrieval of pleasant and unpleasant autobiographical events. Replicating previous studies, repetition prompted reduced blood-oxygen-level-dependent (BOLD) amplitude in the anterior hippocampus and the mPFC, but not in the posterior hippocampus, due to no functional activity during mental imagery, or in the posteromedial parietal cortex, due to enhanced activation that was sustained across repetitions. Neural activation during pleasant and unpleasant autobiographical retrieval did not differ as a function of repetition, indicating similar processing effects regardless of motivational relevance. Taken together, the hedonic valence of retrieved memories does not affect functional activity associated with repeated retrieval of episodic events, in which the pattern of BOLD amplitude change suggests a dissociation between the hippocampal-prefrontal circuit, which shows repetition suppression, and the posteromedial parietal cortex, which shows sustained activation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A variety of psychological and physical phenomena elicit variations in the diameter of pupil of the eye. Changes in pupil size are mediated by the relative activation of the sphincter pupillae muscle (decrease pupil diameter) and the dilator pupillae muscle (increase pupil diameter), innervated by the parasympathetic and sympathetic branches, respectively, of the autonomic nervous system. The current guidelines are intended to inform and guide psychophysiological research involving pupil measurement by (1) summarizing important aspects concerning the physiology of the pupil, (2) providing methodological and data-analytic guidelines and recommendations, and (3) briefly reviewing psychological phenomena that modulate pupillary reactivity. Because of the increased ease and tractability of pupil measurement, the goal of these guidelines is to promote accurate recording, analysis, and reporting of pupillary data in psychophysiological research., (© 2022 Society for Psychophysiological Research.)

The default mode network (DMN) is activated when constructing and imagining narrative events, with functional brain activity in the medial-prefrontal cortex hypothesized to be modulated during emotional processing by adding value (or pleasure) to the episodic representation. However, since enhanced reactivity during emotional, compared to neutral, content is a more frequent finding in both the brain and body in physiological, neural, and behavioral measures, the current study directly assesses the effects of pleasure and emotion during narrative imagery in the DMN by using a within-subject design to first identify the DMN during resting state and then assess activation during pleasant, neutral, or unpleasant imagery. Replicating previous findings, enhanced functional activity in the medial prefrontal cortex was found when imagining pleasant, compared to unpleasant, events. On the other hand, emotion-related activation was found when imagining either pleasant or unpleasant, compared to neutral, events in other nodes of the DMN including the posterior cingulate cortex (PCC), angular gyrus, anterior hippocampus, lateral temporal cortex, temporal pole, dorsomedial prefrontal cortex (dmPFC), and ventrolateral prefrontal cortex (vlPFC). Pervasive emotional modulation in the DMN is consistent with the view that a primary function of event retrieval and construction is to remember, recreate, and imagine motivationally relevant events important for planning adaptive behavior., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Reduced reactivity to pleasurable stimulation is a defining symptom of post-traumatic stress disorder (PTSD), but trauma exposure also increases the severity of many anxiety and mood disorders, including depression, social anxiety, and panic disorder, suggesting that reward system dysfunction might be pervasive in the internalizing disorders. The ventromedial prefrontal cortex (vmPFC) and ventral striatum are core components of the reward circuit and the current study assesses functional activity and connectivity in this circuit during emotional picture viewing in anxiety and mood disorder patients., Method: Functional brain activity (fMRI) and functional connectivity in the fronto-striatal circuit were measured in a large sample of patients diagnosed with anxiety and mood disorders (n=155) during affective scene viewing as it varied with trauma exposure and temperament., Results: In women, but not men, blunted fronto-striatal connectivity was associated with increased posttraumatic anhedonic symptoms, whereas the amplitude of functional activity was not related to trauma exposure. In both men and women, reduced fronto-striatal connectivity was associated with decreases in temperamental positive affect. When predicting fronto-striatal connectivity, temperament and posttraumatic symptomology accounted for independent proportions of variance., Limitations: In this civilian sample of anxiety disorder patients, men reported very little trauma-related symptomology., Conclusions: Because dysfunctional reward processing due to trauma and temperament is pervasive across the internalizing disorder spectrum, assessing the integrity of the fronto-striatal reward circuit could provide important information in diagnostic and treatment protocols., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: The DSM-5 explicitly states that the neural system model of specific phobia is centered on the amygdala. However, this hypothesis is predominantly supported by human studies on animal phobia, whereas visual cuing of other specific phobias, such as dental fear, do not consistently show amygdala activation. Considering that fear of anticipated pain is one of the best predictors of dental phobia, the current study investigated neural and autonomic activity of pain anticipation in individuals varying in the degree of fear of dental pain., Method: Functional brain activity (fMRI) was measured in women (n = 31) selected to vary in the degree of self-reported fear of dental pain when under the threat of shock, in which one color signaled the possibility of receiving a painful electric shock and another color signaled safety., Results: Enhanced functional activity during threat, compared to safety, was found in regions including anterior insula and anterior/mid cingulate cortex. Importantly, threat reactivity in the anterior insula increased as reported fear of pain increased and further predicted skin conductance changes during pain anticipation., Limitations: The sample was comprised of women., Conclusions: Individual differences in fear of pain vary with activation in the anterior insula, rather than with the amygdala, indicating that fear is not uniquely associated with amygdala activation. Whereas coping techniques such as emotion regulation have been found to vary with activation in a frontal-amygdala circuit when confronted with visual cues, precision psychiatry may need to target specific brain circuits to diagnose and treat different types of specific phobia., (Copyright © 2020. Published by Elsevier B.V.)

Unpleasant, compared to neutral, scenes reliably prompt enhanced functional brain activity in the amygdala and inferotemporal cortex. Considering data from psychophysiological studies in which defensive reactivity is further enhanced when viewing unpleasant scenes under threat of shock (compared to safety), the current study investigates functional activation in the amygdala-inferotemporal circuit when unpleasant (or neutral) scenes are viewed under threat of shock or safety. In this paradigm, a cue signaling threat or safety was presented in conjunction with either an unpleasant or neutral picture. Replicating previous studies, unpleasant, compared to neutral, scenes reliably enhanced activation in the amygdala and inferotemporal cortex. Functional activity in these regions, however, did not differ whether scenes were presented in a context threatening shock exposure, compared to safety, which instead activated regions of the anterior insula and cingulate cortex. Taken together, the data support a view in which neural regions activated in different defensive situations act independently., 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 © 2020 Elsevier B.V. All rights reserved.)

Pupil diameter is dynamically modulated by a number of factors, including emotion, motor activity, and attention. Here, pupil modulation was examined as it varies with locus of control during aversive processing. Participants could control aversive exposure either by escape (terminating the event) or avoidance (blocking the event entirely), or they had no control. Highly anxious (n = 19), moderately anxious (n = 23), and less anxious (n = 23) participants saw cues that signaled whether a fast button press would terminate, prevent, or not affect subsequent presentation of an aversive picture. Pupil diameter was measured throughout the cuing interval. Pupil diameter was larger when preparing to escape or avoid compared to anticipating uncontrollable exposure. All participants, regardless of reported anxiety, showed increased pupil diameter in coping, relative to uncontrollable, contexts. Results support hypotheses that pupil diameter reflects action preparation and that differences in trait anxiety do not modulate this aspect of coping behavior in healthy subjects., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Meta-analytic and experimental studies investigating the neural basis of emotion often compare functional activation in different emotional induction contexts, assessing evidence for a "core affect" or "salience" network. Meta-analyses necessarily aggregate effects across diverse paradigms and different samples, which ignore potential neural differences specific to the method of affect induction. Data from repeated measures designs are few, reporting contradictory results with a small N. In the current study, functional brain activity is assessed in a large (N = 61) group of healthy participants during two common emotion inductions-scene perception and narrative imagery-to evaluate cross-paradigm consistency. Results indicate that limbic and paralimbic regions, together with visual and parietal cortex, are reliably engaged during emotional scene perception. For emotional imagery, in contrast, enhanced functional activity is found in several cerebellar regions, hippocampus, caudate, and dorsomedial prefrontal cortex, consistent with the conception that imagery is an action disposition. Taken together, the data suggest that a common emotion network is not engaged across paradigms, but that the specific neural regions activated during emotional processing can vary significantly with the context of the emotional induction., (© 2020 Society for Psychophysiological Research.)

We investigated if dietary exposure to persistent organic pollutants (POPs) affect mandibular asymmetry and periodontal disease in paired male-siblings of Arctic foxes (Vulpes lagopus). During ontogeny, one group of siblings was exposed to the complexed POP mixture in naturally contaminated minke whale (Balaenoptere acutorostarta) blubber (n = 10), while another group was given wet feed based on pig (Sus scrofa) fat as a control (n = 11). The ∑POP concentrations were 802 ng/g ww in the whale-based feed compared to 24 ng/g ww in the control diet. We conducted a two-dimensional geometric morphometric (GM) analysis of mandibular shape and asymmetry in the foxes and compared the two groups. The analyses showed that directional asymmetry was higher than fluctuating asymmetry in both groups and that mandibular shape differed significantly between the exposed and control group based on discriminant function analysis (T 2  = 58.52, p = 0.04, 1000 permutations). We also found a non-significantly higher incidence of periodontal disease (two-way ANOVA: p = 0.43) and greater severity of sub-canine alveolar bone deterioration similar to periodontitis (two-way ANOVA: p = 0.3) in the POP-exposed group. Based on these results, it is possible that dietary exposure to a complexed POP mixture lead to changes in jaw morphology in Arctic foxes. This study suggests that extrinsic factors, such as dietary exposure to POPs, may affect mandibular shape and health in a way that could be harmful to wild Arctic populations. Therefore, further studies using GM analysis as an alternative to traditional morphometric methods should be conducted for wild Arctic fox populations exposed to environmental contaminants., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Stimulus repetition elicits either enhancement or suppression in neural activity, and a recent fMRI meta-analysis of repetition effects for visual stimuli (Kim, 2017) reported cross-stimulus repetition enhancement in medial and lateral parietal cortex, as well as regions of prefrontal, temporal, and posterior cingulate cortex. Repetition enhancement was assessed here for repeated and novel scenes presented in the context of either an explicit episodic recognition task or an implicit judgment task, in order to study the role of spontaneous retrieval of episodic memories. Regardless of whether episodic memory was explicitly probed or not, repetition enhancement was found in medial posterior parietal (precuneus/cuneus), lateral parietal cortex (angular gyrus), as well as in medial prefrontal cortex (frontopolar), which did not differ by task. Enhancement effects in the posterior cingulate cortex were significantly larger during explicit compared to implicit task, primarily due to a lack of functional activity for new scenes. Taken together, the data are consistent with an interpretation that medial and (ventral) lateral parietal cortex are associated with spontaneous episodic retrieval, whereas posterior cingulate cortical regions may reflect task or decision processes., (© 2018 Society for Psychophysiological Research.)

Background: The National Institute of Mental Health Research Domain Criteria initiative encourages a search for dimensional biological measures of psychopathology unconstrained by current diagnostic categories. Consistent with this aim, the presented research studies a large sample of anxiety and mood disorder patients, assessing differences in principal diagnoses and comorbidity patterns, clinicians' ratings, and questionnaire measures of negative affect and life dysfunction as they relate to a potential brain marker of pathology: the amplitude of the event-related potential (ERP) elicited by a startle-evoking stimulus., Methods: Patients seeking evaluation or treatment for anxiety and mood disorders (N = 208) participated in two tasks at the University of Florida (Gainesville, FL): 1) imagining emotional and neutral events and 2) viewing emotional and neutral pictures while acoustic startle probes were presented and the ERP was recorded. For a comparison patient group (N = 120), startle probes were administered and ERPs recorded at the University of Greifswald (Greifswald, Germany) while performing the same imagery task., Results: Reduced positive amplitude of a centroparietal startle-evoked ERP (156-352 ms after onset) significantly predicted higher questionnaire scores of anxiety/depression, reports of increased life dysfunction, greater comorbidity, and clinician ratings of heightened severity and poorer prognosis. The effect was general across principal diagnoses, found for both the Florida and German samples, and consistent in pattern despite differences in the tasks administered., Conclusions: The startle-evoked ERP reliably predicts severity and breadth of psychopathology, independent of task context. It is a potential significant contributor to a needed array of biological measures that might improve classification of anxiety and mood disorders., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Pupil diameter is enhanced in a variety of emotional contexts, including viewing pictures, listening to sounds, and during threat of shock. In this study, we investigated pupil diameter changes during emotional imagery. Participants imagined scenes describing pleasant, unpleasant, or neutral events while pupil diameter was continuously recorded. Second by second changes in pupil diameter were analyzed to determine whether, and when, modulation of the pupil as a function of hedonic content is found. Results indicated a significant effect of hedonic content beginning shortly after script onset, with enhanced pupil diameter when imagining emotional (pleasant or unpleasant), compared to neutral, scenes. Pupil diameter during imagery covaried with rated emotional arousal, consistent with an interpretation that changes in pupil diameter during emotional imagery reflect sympathetic nervous system activity. Because emotional imagery is a key element in clinical assessment and treatment, pupil diameter could prove a useful index of emotional engagement in a variety of clinically pertinent contexts., (© 2017 Society for Psychophysiological Research.)

Visuocortical activity and pupil diameter both increase in tasks involving memory, attention, and physiological arousal. Thus, the question arises whether pupil dilation prompts a subsequent increase in visuocortical activity. In this study, we investigated the extent to which changes in visuocortical activity relate to changes in pupil diameter. The amplitude of the sustained visuocortical response to a flickering stimulus (i.e., steady-state visually evoked potential [ssVEP] power) was examined in 39 participants while pupil diameter was measured. To generalize across stimulus conditions, Gabor stimuli varied in brightness and ssVEP driving frequency. As expected, brighter stimuli prompted pupil constriction and larger ssVEP power. To determine whether momentary fluctuations in pupil size contribute to the ssVEP amplitude under conditions of constant luminance and frequency, the single-trial means from each measure were correlated and the shape of the pupil-diameter waveform related to the ssVEP amplitude time course, both within and between participants. Under constant conditions, changes in pupil diameter were not related to changes in ssVEP amplitude, at any luminance level or driving frequency. Findings suggest that pupil dilation does not systematically prompt subsequent changes in visuocortical activity, and thus is not a sufficient cause of visuocortical modulation in cognitive or affective tasks.

Although avoidance and escape behaviors each contribute to maintaining anxiety disorders, only avoidance completely eliminates exposure to the aversive context. Current research compared anticipatory defensive engagement when aversion could either be completely avoided or escaped after initial exposure; in addition, this research examined the impact of trait anxiety on coping-related defensive engagement. Cues signaled that upcoming rapid action would avoid (block), escape (terminate), or not affect subsequent aversive exposure; the acoustic startle reflex was measured during each anticipatory interval to index defensive engagement, and blink magnitudes were compared across low-, moderate-, and high-anxious individuals. For all participants, startle was potentiated when aversive exposure was uncontrollable and attenuated when aversion was avoidable. On escape trials, on the other hand, startle potentiation increased with rising participant anxiety. Results suggest 1) defensive engagement is generally reduced in avoidance contexts relative to contexts in which exposure is certain, and; 2) trait anxiety increases defensive engagement specifically when aversive exposure can be controlled but remains certain., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

During threat of shock, the startle reflex is potentiated, suggesting modulation by defensive mobilization. To determine whether startle potentiation is specific to aversive anticipation, startle reflexes were measured in the context of either aversive or appetitive anticipation in a between-subject study. Participants wore a device on the wrist that could deliver electrical shock (n = 49), or vibrotactile stimulation indicating monetary reward (n = 48). Cues signaling "threat" or "safe" periods were presented alone, or accompanied by presentation of affective and neutral pictures on half of the trials. Results indicated that the startle reflex was significantly potentiated when anticipating either shock or reward, compared to safe periods, both when no picture was presented, as well as during picture viewing. The difference between threat and safety in both reflex magnitude and skin conductance changes was larger for those anticipating shock, suggesting that the aversive context was more motivationally engaging. The pattern of reflex modulation as a function of picture valence varied under threat and safety, but was identical in the shock and reward groups, consistent with a hypothesis that anticipation of either aversive or appetitive events prompts heightened perceptual vigilance, potentiating the acoustic startle reflex., (© 2017 Society for Psychophysiological Research.)

A series of studies investigated the effects of hedonic content, brightness, and contrast on pupil diameter during free viewing of natural scenes, assessing the amplitude of the initial light reflex and subsequent sustained pupil diameter change. Hedonic picture content varied from highly arousing scenes of erotica and violence to scenes depicting nature, babies, loss, contamination, food, and more. Despite equivalent overall picture brightness and contrast, pupil diameter still varied as a function of the local brightness of central vision at fixation. Statistical (Experiment 1) and methodological (Experiment 2, 3) solutions produced complementary data indicating that scenes of erotica and violence reliably attenuate the amplitude of the initial light reflex and prompt enhanced late diameter pupil changes, compared to other scene contents. A principal components analysis supported the hypothesis that a single sympathetically mediated process enhances pupil dilation during picture viewing, modulating both initial constriction and late diameter changes. Rather than being a subtle index of "liking," pupil diameter is primarily sensitive to events that reliably elicit measurable sympathetic nervous system activity., (© 2017 Society for Psychophysiological Research.)

This research examined human defensive reactivity when exposure to an aversive event could be escaped but not entirely avoided. Prolonged visual cues indicated whether exposure to an upcoming aversive (i.e., disgusting) picture could be terminated after onset (escaped) or not, or that a neutral go signal would appear. Acoustically elicited startle reflexes were measured during each cue interval, as were cardiac and skin conductance activity. Early in the cuing interval, startle reflexes were potentiated during both escape and inescapable exposure trials, compared to the simple motor context. Later in the interval, reflexes remained potentiated for both escapable and inescapable trials, with potentiation further enhanced when aversive exposure could not be escaped compared to when exposure could be escaped. Heart rate deceleration in the cuing interval indicated increased vigilance when preparing any (escape or neutral) action, whereas skin conductance responding indicated enhanced sympathetic action mobilization particularly in an escape context. These data suggest that startle reflexes engaged in an escape context reflect both motor-related response inhibition and aversive potentiation, and they indicate that defensive motivation is engaged whenever aversive exposure is guaranteed, regardless of whether it can be escaped or not., (© 2017 Society for Psychophysiological Research.)

fMRI studies of reward find increased neural activity in ventral striatum and medial prefrontal cortex (mPFC), whereas other regions, including the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and anterior insula, are activated when anticipating aversive exposure. Although these data suggest differential activation during anticipation of pleasant or of unpleasant exposure, they also arise in the context of different paradigms (e.g., preparation for reward vs. threat of shock) and participants. To determine overlapping and unique regions active during emotional anticipation, we compared neural activity during anticipation of pleasant or unpleasant exposure in the same participants. Cues signalled the upcoming presentation of erotic/romantic, violent, or everyday pictures while BOLD activity during the 9-s anticipatory period was measured using fMRI. Ventral striatum and a ventral mPFC subregion were activated when anticipating pleasant, but not unpleasant or neutral, pictures, whereas activation in other regions was enhanced when anticipating appetitive or aversive scenes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The climate in which scientific research is conducted changes over time, and in recent years there has been a shift from a positive view of programmatic science to a more negative evaluation that its contribution to scientific progress is only incremental. In this special issue focusing on the tools of a programmatic approach-replication, reliability and reproducibility-I reflect on changes in scientific practice over my research career, considering some factors contributing to changes in emphasis and highlighting potential pitfalls, particularly in terms of the impact on scientific progress and future scientists. In concluding, I suggest that, as members of the scientific community, we can influence current scientific practices in our day-to-day roles as authors, reviewers, investigators, editors, employers, and educators., (© 2016 Society for Psychophysiological Research.)

A set of studies are reviewed that investigate the effects of repetition during scene perception on event-related potentials, elucidating perceptual, memory and emotional processes. Repetition suppression was consistently found for the amplitude of early frontal N2 and posterior P2 components, which was greatly enhanced for massed, compared to distributed, repetition. Both repetition suppression and enhancement of the amplitude of a centro-parietal positive potential (LPP) were found in specific contexts. Suppression was reliably found following a massive number of repetitions of few items, whereas enhancement is found when repetitions are spaced; enhancement was apparent both during simple free viewing as well as on an explicit recognition test. Regardless of repetition, an enhanced LPP was always found for emotional, compared to neutral, scenes. Taken together, the data suggest that different effects of massed and distributed repetitions on specific ERP components index perceptual priming, habituation, and spontaneous episodic retrieval., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hedonic bias during free viewing of novel emotional and neutral scenes was investigated in older adults and college students. A neurophysiological index of emotional picture processing-the amplitude of the centroparietal late positive potential (LPP)-was recorded from the scalp using a dense sensor array while participants (29 older adults; 21 college students) viewed emotionally engaging or mundane natural scenes that varied in specific content. Both students and older adults showed LPP enhancement when viewing affective, compared to neutral, scenes, and there was no difference in LPP amplitude between older individuals and college students when viewing neutral everyday scenes. However, compared to the college students, older individuals showed attenuated LPP amplitude when viewing emotional scenes, regardless of hedonic valence or specific content. Age related differences could be mediated by a reduction in reactive emotional arousal with age, possible mediated by repeated life exposure to emotional stimuli., Competing Interests: The authors have declared that no competing interests exist.

Evidence is presented supporting a dimension of defensive reactivity that varies across the anxiety disorder spectrum and is defined by physiological responses during threat-imagery challenges that covary with objective measures of psychopathology. Previous imagery studies of anxiety disorders are reviewed, highlighting that, regardless of contemporary diagnostic convention, reliable psychophysiological patterns emerge for patients diagnosed with circumscribed fear compared to those diagnosed with pervasive anxious-misery disorders. Based on the heuristic outlined by the Research Domain Criteria (RDoC) initiative, an exploratory transdiagnostic analysis is presented, based on a sample of 425 treatment-seeking patients from across the spectrum of DSM-IV anxiety diagnoses. Using a composite index of startle reflex and heart rate reactivity during idiographic fear imagery for each patient, a defensive dimension was defined by ranking patients from most defensively reactive to least reactive and then creating five groups of equivalent size (quintile; N = 85). Subsequent analyses showed significant parallel trends of diminishing reactivity in both electrodermal and facial electromyographic reactions across this defensive dimension. Negative affectivity, defined by questionnaire and extent of functional interference, however, showed consistent, inverse trends with defensive reactivity-as reports of distress increased, defensive reactivity was increasingly attenuated. Notably, representatives of each principal diagnosis appeared in each quintile, underscoring the reality of pronounced within-diagnosis heterogeneity in defensive reactivity. In concluding, we describe our new RDoC research project, focusing on the assessment of brain circuit function as it determines hypo/hyperreactivity to challenge-somatic and autonomic-and may relate to patients' stress history and genetic inheritance., (© 2016 Society for Psychophysiological Research.)

The current study investigated whether motivational dysfunction in Parkinson's patients is related to a deficit in preparing for motivated behavior. Based on previous studies, it was hypothesized that PD patients would show reduced preparation for action specifically when faced with threat (of loss) and that reduced action preparation would relate to self-report of apathy symptoms. The study measured an electrocortical correlate of preparation for action (CNV amplitude) in PD patients and healthy controls, as well as defensive and appetitive activation during emotional perception (LPP amplitude). The sample included 18 non-demented PD patients (tested on dopaminergic medications) and 15 healthy controls who responded as quickly as possible to cues signaling threat of loss or reward, in which the speed of the response determined the outcome. Results indicated that, whereas PD patients showed similar enhanced action preparation with the addition of incentives to controls, PD patients showed generally reduced action preparation, evidenced by reduced CNV amplitude overall. Results suggest that PD patients may have behavioral issues due to globally impaired action preparation but that this deficit is not emotion-specific, and movement preparation may be aided by incentive in PD patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Previous research indicates that predictive cues can dampen subsequent defensive reactions. The present study investigated whether effects of cuing are specific to aversive stimuli, using modulation of the blink startle reflex as a measure of emotional reactivity. Participants viewed pictures depicting violence, romance/erotica, or mundane content. On half of all trials, a cue (color) predicted the content of the upcoming picture; on the remaining trials, scenes were presented without a cue. Acoustic startle probes were presented during picture viewing on trials with predictive cues and trials without a cue. Replicating previous studies, blink reflexes elicited when viewing violent pictures that had not been preceded by a cue were potentiated compared to uncued mundane scenes, and reflexes were attenuated when viewing scenes of erotica/romance that had not been cued. On the other hand, reflex potentiation when viewing scenes of violence (relative to mundane scenes) was eliminated when these pictures were preceded by a predictive cue, whereas scenes of romance prompted reliable reflex attenuation regardless of whether pictures were cued or not. Taken together, the data suggest that cuing elicits an anticipatory coping process that is specific to aversive stimuli., (© 2015 Society for Psychophysiological Research.)

Choice viewing behavior when looking at affective scenes was assessed to examine differences due to hedonic content and gender by monitoring eye movements in a selective looking paradigm. On each trial, participants viewed a pair of pictures that included a neutral picture together with an affective scene depicting either contamination, mutilation, threat, food, nude males, or nude females. The duration of time that gaze was directed to each picture in the pair was determined from eye fixations. Results indicated that viewing choices varied with both hedonic content and gender. Initially, gaze duration for both men and women was heightened when viewing all affective contents, but was subsequently followed by significant avoidance of scenes depicting contamination or nude males. Gender differences were most pronounced when viewing pictures of nude females, with men continuing to devote longer gaze time to pictures of nude females throughout viewing, whereas women avoided scenes of nude people, whether male or female, later in the viewing interval. For women, reported disgust of sexual activity was also inversely related to gaze duration for nude scenes. Taken together, selective looking as indexed by eye movements reveals differential perceptual intake as a function of specific content, gender, and individual differences., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Recent studies have suggested that pupil diameter, like the "old-new" ERP, may be a measure of memory. Because the amplitude of the old-new ERP is enhanced for items encoded in the context of repetitions that are distributed (spaced), compared to massed (contiguous), we investigated whether pupil diameter is similarly sensitive to repetition. Emotional and neutral pictures of natural scenes were viewed once or repeated with massed (contiguous) or distributed (spaced) repetition during incidental free viewing and then tested on an explicit recognition test. Although an old-new difference in pupil diameter was found during successful recognition, pupil diameter was not enhanced for distributed, compared to massed, repetitions during either recognition or initial free viewing. Moreover, whereas a significant old-new difference was found for erotic scenes that had been seen only once during encoding, this difference was absent when erotic scenes were repeated. Taken together, the data suggest that pupil diameter is not a straightforward index of prior occurrence for natural scenes., (© 2015 Society for Psychophysiological Research.)

Neural measures of repetition can result in either repetition suppression or enhancement effects, with enhancement sometimes interpreted as indicating episodic retrieval, rather than stimulus habituation. Here, we manipulated whether repetitions were massed (consecutive) or distributed (intermixed) and measured event-related potentials and oscillatory activity, investigating the question of whether there is evidence of "spontaneous" episodic retrieval for distributed, but not massed, repetition. Results showed that distributed repetition uniquely prompted a significant centroparietal old-new effect as well as enhanced theta, compared to either novel presentations or massed repetitions, consistent with a hypothesis of spontaneous retrieval. Massed repetition, on the other hand, prompted repetition suppression and reduction of the N2/P2. Taken together, the data suggest that distributed repetition may facilitate later memory performance because it spontaneously retrieves prior representations., (© 2015 Society for Psychophysiological Research.)

Repetitions that are distributed (spaced) across time prompt enhancement of a memory-related event-related potential, compared to when repetitions are massed (contiguous). Here, we used fMRI to investigate neural enhancement and suppression effects during free viewing of natural scenes that were either novel or repeated four times with massed or distributed repetitions. Distributed repetition was uniquely associated with a repetition enhancement effect in a bilateral posterior parietal cluster that included the precuneus and posterior cingulate and which has previously been implicated in episodic memory retrieval. Unique to massed repetition, conversely, was enhancement in a right dorsolateral prefrontal cluster that has been implicated in short-term maintenance. Repetition suppression effects for both types of spacing were widespread in regions activated during novel picture processing. Taken together, the data are consistent with a hypothesis that distributed repetition prompts spontaneous retrieval of prior occurrences, whereas massed repetition prompts short-term maintenance of the episodic representation, due to contiguous presentation. These processing differences may mediate the classic spacing effect in learning and memory., (© 2014 Wiley Periodicals, Inc.)

Cues that signal the possibility of receiving an electric shock reliably induce defensive activation. To determine whether cues can also easily reverse defensive reactions, a threat reversal paradigm was developed in which a cue signaling threat of shock reversed its meaning across the course of the study. This allowed us to contrast defensive reactions to threat cues that became safe cues, with responses to cues that continued to signal threat or safety. Results showed that, when participants were instructed that a previously threatening cue now signaled safety, there was an immediate and complete attenuation of defensive reactions compared to threat cues that maintained their meaning. These findings highlight the role that language can play both in instantiating and attenuating defensive reactions, with implications for understanding emotion regulation, social communication, and clinical phenomena., (© 2014 Society for Psychophysiological Research.)

Emotionally arousing scenes readily capture visual attention, prompting amplified neural activity in sensory regions of the brain. The physical stimulus features and related information channels in the human visual system that contribute to this modulation, however, are not known. Here, we manipulated low-level physical parameters of complex scenes varying in hedonic valence and emotional arousal in order to target the relative contributions of luminance based versus chromatic visual channels to emotional perception. Stimulus-evoked brain electrical activity was measured during picture viewing and used to quantify neural responses sensitive to lower-tier visual cortical involvement (steady-state visual evoked potentials) as well as the late positive potential, reflecting a more distributed cortical event. Results showed that the enhancement for emotional content was stimulus-selective when examining the steady-state segments of the evoked visual potentials. Response amplification was present only for low spatial frequency, grayscale stimuli, and not for high spatial frequency, red/green stimuli. In contrast, the late positive potential was modulated by emotion regardless of the scene's physical properties. Our findings are discussed in relation to neurophysiologically plausible constraints operating at distinct stages of the cortical processing stream., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The extent and time course of competition between a specific fear cue and task-related stimuli in early human visual cortex was investigated using electrophysiology. Steady-state visual evoked potentials (ssVEPs) were evoked using random-dot kinematograms that consisted of rapidly flickering (8.57 Hz) dots moving randomly, superimposed upon emotional or neutral distractor pictures. Participants were asked to detect intervals of coherently moving dots, ignoring the distractor pictures that varied in hedonic content. Women reporting high or low levels of snake fear were recruited from a large sample of healthy college students, and snake pictures served as fear-relevant distractors. The time-varying amplitude of the ssVEP evoked by the motion detection task showed significant reduction when viewing emotionally arousing, compared to neutral, distractors, replicating previous studies. For high-fear participants, snake distractors elicited a sustained attenuation of task evoked ssVEP amplitude, greater than the attenuation prompted by other unpleasant arousing content. These findings support a hypothesis that fear cues prompt sustained hypervigilance rather than perceptual avoidance., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The startle reflex is potentiated when anticipating emotional, compared to neutral, pictures. This study investigated the time course of reflex modulation during anticipation and the impact of informative cuing on picture perception. Colors were used to signal the thematic content of emotional and neutral scenes; blink response modulation was measured by presenting acoustic startle probes 3, 2, or 1 s before picture onset or 2 s after picture onset. During anticipation of neutral scenes, blink magnitude showed increasing attenuation as picture onset approached, consistent with a modality-directed vigilance account. Conversely, when anticipating emotional scenes, reflex magnitude did not change over time, and blinks elicited closest to picture onset were potentiated compared to neutral. During perception, the expected reflex potentiation for unpleasant pictures was not found, suggesting that cuing may dampen defensive activation., (Copyright © 2014 Society for Psychophysiological Research.)

An initial reflexive constriction of the pupil to stimulation-the light reflex-is primarily modulated by brightness, but is attenuated when participants are under threat of shock (i.e., fear-inhibited light reflex). The present study assessed whether the light reflex is similarly attenuated when viewing emotional pictures. Pupil diameter was recorded while participants viewed erotic, violent, and neutral scenes that were matched in brightness; scrambled versions identical in brightness were also presented as an additional control. Compared to viewing neutral scenes, the light reflex was reliably modulated by hedonic content, with significant attenuation both when viewing unpleasant as well as pleasant pictures. No differences in the light reflex were found among scrambled versions. Thus, emotional modulation of the initial light reflex is not confined to a context of fear and is not indicative of brightness differences when viewing pictures of natural scenes., (Copyright © 2014 Society for Psychophysiological Research.)

On a recognition test, stimuli originally encoded in the context of shock threat show an enhanced late parietal positivity during later recognition compared to stimuli encoded during safety, particularly for emotionally arousing stimuli. The present study investigated whether this ERP old/new effect is further influenced when a threat context is reinstated during the recognition test. ERPs were measured in a yes-no recognition test for words rated high or low in emotional arousal that were encoded and recognized in the context of cues that signaled threat of shock or safety. Correct recognition of words encoded under threat, irrespective of reinstatement, was associated with an enhanced old-new ERP difference (500-700ms; centro-parietal), and this difference was only reliable for emotionally arousing words. Taken together, the data suggest that information processed in a stressful context are associated with better recollection on later recognition, an effect that was not modulated by reinstating the stressful context at retrieval., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology-across and within diagnoses-extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.

Repetition has long been known to facilitate memory performance, but its effects on event-related potentials (ERPs), measured as an index of recognition memory, are less well characterized. In Experiment 1, effects of both massed and distributed repetition on old-new ERPs were assessed during an immediate recognition test that followed incidental encoding of natural scenes that also varied in emotionality. Distributed repetition at encoding enhanced both memory performance and the amplitude of an old-new ERP difference over centro-parietal sensors. To assess whether these repetition effects reflect encoding or retrieval differences, the recognition task was replaced with passive viewing of old and new pictures in Experiment 2. In the absence of an explicit recognition task, ERPs were completely unaffected by repetition at encoding, and only emotional pictures prompted a modestly enhanced old-new difference. Taken together, the data suggest that repetition facilitates retrieval processes and that, in the absence of an explicit recognition task, differences in old-new ERPs are only apparent for affective cues.

During rapid serial visual presentation (RSVP), the perceptual system is confronted with a rapidly changing array of sensory information demanding resolution. At rapid rates of presentation, previous studies have found an early (e.g., 150-280 ms) negativity over occipital sensors that is enhanced when emotional, as compared with neutral, pictures are viewed, suggesting facilitated perception. In the present study, we explored how picture composition and the presence of people in the image affect perceptual processing of pictures of natural scenes. Using RSVP, pictures that differed in perceptual composition (figure-ground or scenes), content (presence of people or not), and emotional content (emotionally arousing or neutral) were presented in a continuous stream for 330 ms each with no intertrial interval. In both subject and picture analyses, all three variables affected the amplitude of occipital negativity, with the greatest enhancement for figure-ground compositions (as compared with scenes), irrespective of content and emotional arousal, supporting an interpretation that ease of perceptual processing is associated with enhanced occipital negativity. Viewing emotional pictures prompted enhanced negativity only for pictures that depicted people, suggesting that specific features of emotionally arousing images are associated with facilitated perceptual processing, rather than all emotional content.

When event-related potentials (ERP) are measured during a recognition task, items that have previously been presented typically elicit a larger late (400-800 ms) positive potential than new items. Recent data, however, suggest that emotional, but not neutral, pictures show ERP evidence of spontaneous retrieval when presented in a free-viewing task (Ferrari, Bradley, Codispoti, Karlsson, & Lang, 2012). In two experiments, we further investigated the brain dynamics of implicit and explicit retrieval. In Experiment 1, brain potentials were measured during a semantic categorization task, which did not explicitly probe episodic memory, but which, like a recognition task, required an active decision and a button press, and were compared to those elicited during recognition and free viewing. Explicit recognition prompted a late enhanced positivity for previously presented, compared with new, pictures regardless of hedonic content. In contrast, only emotional pictures showed an old-new difference when the task did not explicitly probe episodic memory, either when making an active categorization decision regarding picture content, or when simply viewing pictures. In Experiment 2, however, neutral pictures did prompt a significant old-new ERP difference during subsequent free viewing when emotionally arousing pictures were not included in the encoding set. These data suggest that spontaneous retrieval is heightened for salient cues, perhaps reflecting heightened attention and elaborative processing at encoding.

Our view is that fundamental appetitive and defensive motivation systems evolved to mediate a complex array of adaptive behaviors that support the organism's drive to survive-defending against threat and securing resources. Activation of these motive systems engages processes that facilitate attention allocation, information intake, sympathetic arousal, and, depending on context, will prompt tactical actions that can be directed either toward or away from the strategic goal, whether defensively or appetitively determined. Research from our laboratory that measures autonomic, central, and somatic reactions when processing emotional scenes is described which indicates that motivationally relevant cues, whether appetitive or defensive, capture attention preferentially, prompt enhanced perceptual processing and information gathering, and occasion metabolic arousal that mobilizes the organism for coping actions.

Parkinson's disease is associated with emotional changes including depression, apathy, and anxiety. The current study investigated emotional processing in non-demented individuals with Parkinson disease (PD) using an electrophysiological measure, the centro-parietal late positive potential (LPP). Non-demented patients with Parkinson's disease (n=17) and healthy control participants (n=16) viewed pleasant, neutral, and unpleasant pictures while EEG was recorded from a 64-channel geodesic net. The Parkinson patients did not differ from controls in terms of early electrophysiological components that index perceptual processing (occipital P100, N150, P250). Parkinson patients, however, showed reduced LPP amplitude specifically when viewing unpleasant, compared to pleasant, pictures as well as when compared to controls, consistent with previous studies suggesting a specific difference in aversive processing between PD patients and healthy controls. Importantly, LPP amplitude during unpleasant picture viewing was most attenuated for patients reporting high apathy. The data suggest that apathy in PD may be related to a deficit in defensive activation, and may be indexed cortically using event-related potentials., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The anticipation of highly aversive events is associated with measurable defensive activation, and both animal and human research suggests that stress-inducing contexts can facilitate memory. Here, we investigated whether encoding stimuli in the context of anticipating an aversive shock affects recognition memory. Event-related potentials (ERPs) were measured during a recognition test for words that were encoded in a font color that signaled threat or safety. At encoding, cues signaling threat of shock, compared to safety, prompted enhanced P2 and P3 components. Correct recognition of words encoded in the context of threat, compared to safety, was associated with an enhanced old-new ERP difference (500-700 msec; centro-parietal), and this difference was most reliable for emotional words. Moreover, larger old-new ERP differences when recognizing emotional words encoded in a threatening context were associated with better recognition, compared to words encoded in safety. Taken together, the data indicate enhanced memory for stimuli encoded in a context in which an aversive event is merely anticipated, which could assist in understanding effects of anxiety and stress on memory processes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Viewing emotional pictures is associated with heightened perception and attention, indexed by a relative increase in visual cortical activity. Visual cortical modulation by emotion is hypothesized to reflect re-entrant connectivity originating in higher-order cortical and/or limbic structures. The present study used dense-array electroencephalography and individual brain anatomy to investigate functional coupling between the visual cortex and other cortical areas during affective picture viewing. Participants viewed pleasant, neutral, and unpleasant pictures that flickered at a rate of 10 Hz to evoke steady-state visual evoked potentials (ssVEPs) in the EEG. The spectral power of ssVEPs was quantified using Fourier transform, and cortical sources were estimated using beamformer spatial filters based on individual structural magnetic resonance images. In addition to lower-tier visual cortex, a network of occipito-temporal and parietal (bilateral precuneus, inferior parietal lobules) structures showed enhanced ssVEP power when participants viewed emotional (either pleasant or unpleasant), compared to neutral pictures. Functional coupling during emotional processing was enhanced between the bilateral occipital poles and a network of temporal (left middle/inferior temporal gyrus), parietal (bilateral parietal lobules), and frontal (left middle/inferior frontal gyrus) structures. These results converge with findings from hemodynamic analyses of emotional picture viewing and suggest that viewing emotionally engaging stimuli is associated with the formation of functional links between visual cortex and the cortical regions underlying attention modulation and preparation for action., (Copyright © 2011 Wiley Periodicals, Inc.)

Human emotions are considered here to be founded on motivational circuits in the brain that evolved to protect (defensive) and sustain (appetitive) the life of individuals and species. These circuits are phylogenetically old, shared among mammals, and involve the activation of both subcortical and cortical structures that mediate attention, perception, and action. Circuit activation begins with a feature-match between a cue and an existing representation in memory that has motivational significance. Subsequent processes include rapid cue-directed orienting, information gathering, and action selection - What is it? Where is it? What to do? In our studies of emotional perception, we have found that measures that index orienting to emotional cues generally show enhanced circuit activation and response facilitation, relative to orienting indicators occasioned by affectively neutral cues, whether presented concurrently or independently. Here, we discuss these findings, considering both physiological reflex and brain measures as they are modulated during orienting and emotional perception.

Respiratory sensory gating is evidenced by decreased amplitudes of the respiratory-related evoked potentials (RREP) N1 peak for the second (S2) compared to the first occlusion (S1) when two paired occlusions are presented with a 500-millisecond (ms) inter-stimulus-interval during one inspiration. Because anxiety is prevalent in respiratory diseases and associated with altered respiratory perception, we tested whether anxiety can modulate individuals' respiratory neural gating mechanism. By using high-density EEG, RREPs were measured in a paired inspiratory occlusion paradigm in 11 low and 10 higher anxious individuals with normal lung function. The N1 peak gating S2/S1 ratio and the N1 S2 amplitudes were greater in higher compared to low anxious individuals (p's<0.05). In addition, higher anxiety levels were correlated with greater S2/S1 ratios (r=0.54, p<0.05) and S2 amplitudes (r=-0.49, p<0.05). The results demonstrate that anxiety is associated with reduced respiratory sensory gating which might underlie altered respiratory symptom perception in anxious individuals., (Copyright © 2012 Elsevier B.V. All rights reserved.)