Motivational context and neurocomputation of stop expectation moderate early attention responses supporting proactive inhibitory control.

Alterations in attention to cues signaling the need for inhibitory control play a significant role in a wide range of psychopathology. However, the degree to which motivational and attentional factors shape the neurocomputations of proactive inhibitory control remains poorly understood. The present study investigated how variation in monetary incentive valence and stake modulate the neurocomputational signatures of proactive inhibitory control. Adults (N = 46) completed a Stop-Signal Task (SST) with concurrent EEG recording under four conditions associated with stop performance feedback: low and high punishment (following unsuccessful stops) and low and high reward (following successful stops). A Bayesian learning model was used to infer individual's probabilistic expectations of the need to stop on each trial: P(stop). Linear mixed effects models were used to examine whether interactions between motivational valence, stake, and P(stop) parameters predicted P1 and N1 attention-related event-related potentials (ERPs) time-locked to the go-onset stimulus. We found that P1 amplitudes increased at higher levels of P(stop) in punished but not rewarded conditions, although P1 amplitude differences between punished and rewarded blocks were maximal on trials when the need to inhibit was least expected. N1 amplitudes were positively related to P(stop) in the high punishment condition (low N1 amplitude), but negatively related to P(stop) in the high reward condition (high N1 amplitude). Critically, high P(stop)-related N1 amplitude to the go-stimulus predicted behavioral stop success during the high reward block, providing evidence for the role of motivationally relevant context and inhibitory control expectations in modulating the proactive allocation of attentional resources that affect inhibitory control. These findings provide novel insights into the neurocomputational mechanisms underlying proactive inhibitory control under valence-dependent motivational contexts, setting the stage for developing motivation-based interventions that boost inhibitory control.

Resting-state connectivity subtype of comorbid PTSD and alcohol use disorder moderates improvement from integrated prolonged exposure therapy in Veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and are associated with significant functional impairment and inconsistent treatment outcomes. Data-driven subtyping of this clinically heterogeneous patient population and the associated underlying neural mechanisms are highly needed to identify who will benefit from psychotherapy. METHODS: In 53 comorbid PTSD/AUD patients, resting-state functional magnetic resonance imaging was collected prior to undergoing individual psychotherapy. We used a data-driven approach to subgroup patients based on directed connectivity profiles. Connectivity subgroups were compared on clinical measures of PTSD severity and heavy alcohol use collected at pre- and post-treatment. RESULTS: We identified a subgroup of patients associated with improvement in PTSD symptoms from integrated-prolonged exposure therapy. This subgroup was characterized by lower insula to inferior parietal cortex (IPC) connectivity, higher pregenual anterior cingulate cortex (pgACC) to posterior midcingulate cortex connectivity and a unique pgACC to IPC path. We did not observe any connectivity subgroup that uniquely benefited from integrated-coping skills or subgroups associated with change in alcohol consumption. CONCLUSIONS: Data-driven approaches to characterize PTSD/AUD subtypes have the potential to identify brain network profiles that are implicated in the benefit from psychological interventions - setting the stage for future research that targets these brain circuit communication patterns to boost treatment efficacy.

Evaluating wipe sampling parameters to assess method performance and data confidence during remediation of hazardous pesticide misuse chemicals on indoor materials.

Pesticide misuse incidents are reported worldwide each year. The potential exposure to pesticides creates a concern for occupants in affected homes, apartments, and other occupied buildings. Pesticides that are improperly applied within these locations may require remediation prior to reoccupation. Incident response personnel rely heavily on data from sampling results to identify residue levels and determine when site remediation is complete. Surface wipe samples are often collected for this purpose. Therefore, it is important to ensure sampling and analysis procedures are well established for the contaminants of concern, particularly for wipe sampling variables that can affect analysis results. This investigation evaluated the effects of surface wipe media, wipe wetting solvents, pesticide concentrations effects, composite sampling, surface types, and pesticide formulation effects on analysis results for fipronil, permethrin, and deltamethrin. Tested surface types included galvanized steel, vinyl tile, and plywood. Wipe media included pre-packaged, sterile cotton gauze, pre-cleaned cotton twill, and a pre-packaged, pre-wetted wipes. Surface recovery results are reported for commercially available fipronil formulations and compared to technical grade fipronil solutions. Fipronil recoveries were 92-107 % for twill wipes, 81-98 % for cotton gauze wipes, and 79 % for pre-packaged, pre-wetted wipes on a galvanized steel surface. Permethrin recoveries were 83-116 % for twill wipes, 66-94 % for cotton gauze wipes, and 73 % for pre-packaged, pre-wetted wipes on a galvanized steel surface. Deltamethrin recoveries were 67-88 % for twill wipes, 55-71 % for cotton gauze wipes, and 63 % for pre-packaged, pre-wetted wipes on a galvanized steel surface. The data collected in this study can inform surface wipe sampling methods and potentially assist in obtaining more accurate sampling data associated with pesticide misuse incidents involving the target analytes.

Pre-deployment threat learning predicts increased risk for post-deployment insomnia: Evidence from the Marine Resiliency Study.

Insomnia is a common and impairing consequence of military deployment, but little is known about pre-deployment risk factors for post-deployment insomnia. Abnormal threat learning tendencies are commonly observed in individuals with insomnia and maladaptive responses to stress have been implicated in the development of insomnia, suggesting that threat learning could be an important risk factor for post-deployment insomnia. Here, we examined pre-deployment threat learning as a predictor of post-deployment insomnia and the potential mechanisms underlying this effect. Male servicemembers (N = 814) completed measures of insomnia, psychiatric symptoms, and a threat learning task before and after military deployment. Threat learning indices that differentiated participants with versus withoutinsomnia at post-deployment were tested as pre-deployment predictors of post-deployment insomnia. Post-deployment insomnia was linked to elevations on several threat learning indices at post-deployment, but only higher threat conditioning, as indexed by higher threat expectancy ratings to the danger cue, emerged as a pre-deployment predictor of post-deployment insomnia. This effect was independent of combat exposure levels and partially mediated by greater post-deployment nightmares. The tendency to acquire stronger expectations of aversive events following encounters with danger cues may increase risk for post-deployment insomnia, in part due to the development of more severe nightmares.

Deriving psychiatric symptom-based biomarkers from multivariate relationships between psychophysiological and biochemical measures.

Identification of biomarkers for psychiatric disorders remains very challenging due to substantial symptom heterogeneity and diagnostic comorbidity, limiting the ability to map symptoms to underlying neurobiology. Dimensional symptom clusters, such as anhedonia, hyperarousal, etc., are complex and arise due to interactions of a multitude of complex biological relationships. The primary aim of the current investigation was to use multi-set canonical correlation analysis (mCCA) to derive biomarkers (biochemical, physiological) linked to dimensional symptoms across the anxiety and depressive spectrum. Active-duty service members (N = 2,592) completed standardized depression, anxiety and posttraumatic stress questionnaires and several psychophysiological and biochemical assays. Using this approach, we identified two phenotype associations between distinct physiological and biological phenotypes. One was characterized by symptoms of dysphoric arousal (anhedonia, anxiety, hypervigilance) which was associated with low blood pressure and startle reactivity. This finding is in line with previous studies suggesting blunted physiological reactivity is associated with subpopulations endorsing anxiety with comorbid depressive features. A second phenotype of anxious fatigue (high anxiety and reexperiencing/avoidance symptoms coupled with fatigue) was associated with elevated blood levels of norepinephrine and the inflammatory marker C-reactive protein in conjunction with high blood pressure. This second phenotype may describe populations in which inflammation and high sympathetic outflow might contribute to anxious fatigue. Overall, these findings support the growing consensus that distinct neuropsychiatric symptom patterns are associated with differential physiological and blood-based biological profiles and highlight the potential of mCCA to reveal important psychiatric symptom biomarkers from several psychophysiological and biochemical measures.

Anhedonia in Posttraumatic Stress Disorder: Prevalence, Phenotypes, and Neural Circuitry.

Anhedonia, the reduction of pleasure and reward-seeking behavior, is a transdiagnostic construct associated with a range of important health outcomes. As with other psychiatric disorders, anhedonia is a relatively common, though understudied, feature of posttraumatic stress disorder (PTSD) that is not adequately targeted by existing treatments. The purpose of this review is to describe the current state of the literature on anhedonia in PTSD and highlight areas for future research based on gaps in the existing evidence base. First, we review evidence for anhedonia symptoms as a distinct PTSD symptom factor and its associations with psychiatric comorbidity, disease trajectory, and quality of life outcomes, as well as describe theories that seek to explain the occurrence of anhedonia among individuals with PTSD. Second, we review evidence for behavioral and neural alterations in reward processing and circuitry, a marker of anhedonia, among individuals with PTSD and in animal models relevant to this disorder. Finally, we discuss key gaps in our understanding of anhedonia in PTSD and suggest areas for future research. Specifically, the timing of anhedonia symptom development and underlying circuit dysfunction in the trauma response trajectory, as well as potential differential associations of facets of anhedonia on clinical outcomes, remain unclear. Additionally, further research is needed to determine potential moderators of anhedonia, as well as the efficacy and effectiveness of psychotherapeutic, psychopharmacological, and device-based interventions targeting anhedonia among individuals with PTSD. A more thorough understanding of these topics will ultimately improve prevention and intervention efforts for PTSD.

Dissociable impact of childhood trauma and deployment trauma on affective modulation of startle.

Trauma disorders are often associated with alterations in aversive anticipation and disruptions in emotion/fear circuits. Heightened or blunted anticipatory responding to negative cues in adulthood may be due to differential trauma exposure during development, and previous trauma exposure in childhood may also modify effects of subsequent trauma in adulthood. The aim of the current investigation was to examine the contributions of childhood trauma on affective modulation of startle before and after trauma exposure in adulthood (a combat deployment). Adult male participants from the Marine Resilience Study with (n = 1145) and without (n = 1312) a history of reported childhood trauma completed an affective modulation of startle task to assess aversive anticipation. Affective startle response was operationalized by electromyography (EMG) recording of the orbicularis oculi muscle in response to acoustic stimuli when anticipating positive and negative affective images. Startle responses to affective images were also assessed. Testing occurred over three time-points; before going on a 7 month combat deployment and 3 and 6 months after returning from deployment. Startle response when anticipating negative images was greater compared to pleasant images across all three test periods. Across all 3 time points, childhood trauma was consistently associated with significantly blunted startle when anticipating negative images, suggesting reliable effects of childhood trauma on aversive anticipation. Conversely, deployment trauma was associated with increased startle reactivity post-deployment compared to pre-deployment, which was independent of childhood trauma and image valence. These results support the hypothesis that trauma exposure during development vs. adulthood may have dissociable effects on aversive anticipation and arousal mechanisms. Further study in women and across more refined age groups is needed to test generalizability and identify potential developmental windows for these differential effects.

Neutral and threatening distracter word stimuli are unnecessarily stored in working memory but do not differ in their degree of working memory storage.

Evidence suggests that threatening stimuli induce attentional biases compared to neutral stimuli, leading to subsequent storage in working memory. The current study examined how threatening versus neutral word distracters influence attention, and how this affects the unnecessary storage of these task-irrelevant stimuli in working memory. We measured the N2pc and contralateral delay activity (CDA), two event-related potentials (ERPs) that index attentional selection and the number of items maintained in WM, respectively, as participants completed a lateralized change detection task using word stimuli. Our results replicated work demonstrating a CDA effect for word stimuli, and found that distracter words are unnecessarily stored in working memory. However, we observed non-significant differences in attentional bias and working memory storage between distracter word conditions, and individual variation in anxiety was not associated with these processes. Bayes Factor analyses supported these null effects, suggesting that differences between neutral and threatening distracter words are unlikely.

Pyrethroid exposure among children residing in green versus non-green multi-family, low-income housing.

BACKGROUND: There is growing concern about children's chronic low-level pesticide exposure and its impact on health. Green building practices (e.g., reducing leakage of the thermal and pressure barrier that surrounds the structure, integrated pest management, improved ventilation) have the potential to reduce pesticide exposure. However, the potential impact of living in green housing on children's pesticide exposure is unknown. OBJECTIVE: To address this question, a longitudinal study of pyrethroid metabolites (3-phenoxybenzoic acid [3-PBA], 4-fluoro-3-phenoxybenzoic acid [4-F-3-PBA], trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid [trans-DCCA]) in first morning void urine, collected from 68 children from New Orleans, Louisiana residing in green and non-green housing was conducted. METHODS: Children were followed for 1 year with three repeated measures of pesticide exposure. Generalized estimating equations examined associations between housing type (green vs. non-green) and urinary pyrethroid metabolite concentrations adjusting for demographic and household factors over the year. RESULTS: Ninety-five percent of samples had detectable concentrations of 3-PBA (limit of detection [LOD]: 0.1 µg/L); 8% of 4-F-3-PBA (LOD: 0.1 µg/L), and 12% of trans-DCCA (LOD: 0.6 µg/L). In adjusted models, green housing was not associated with statistically significant differences in children's 3-PBA urinary concentrations compared to non-green housing.

Working Memory Performance for Differentially Conditioned Stimuli.

Previous work suggests that threat-related stimuli are stored to a greater degree in working memory compared to neutral stimuli. However, most of this research has focused on stimuli with physically salient threat attributes (e.g., angry faces), failing to account for how a "neutral" stimulus that has acquired threat-related associations through differential aversive conditioning influences working memory. The current study examined how differentially conditioned safe (i.e., CS-) and threat (i.e., CS+) stimuli are stored in working memory relative to a novel, non-associated (i.e., N) stimuli. Participants (n = 69) completed a differential fear conditioning task followed by a change detection task consisting of three conditions (CS+, CS-, N) across two loads (small, large). Results revealed individuals successfully learned to distinguishing CS+ from CS- conditions during the differential aversive conditioning task. Our working memory outcomes indicated successful load manipulation effects, but no statistically significant differences in accuracy, response time (RT), or Pashler's K measures of working memory capacity between CS+, CS-, or N conditions. However, we observed significantly reduced RT difference scores for the CS+ compared to CS- condition, indicating greater RT differences between the CS+ and N condition vs. the CS- and N condition. These findings suggest that differentially conditioned stimuli have little impact on behavioral outcomes of working memory compared to novel stimuli that had not been associated with previous safe of aversive outcomes, at least in healthy populations.

Preparations for a Controversial Speaker and Anticipated Volatility in a College Town.

In summer of 2017 in Charlottesville, Virginia, white nationalists clashed with counterprotestors, ultimately leading to the death of three people and leaving 34 more injured. Soon after, the same group was granted permission to speak on the campus of the University of Florida in Gainesville, Florida. Despite our college town having limited resources and personnel, the comprehensive and extensive preparation preceding the event ensured a peaceful resolution for such a large and potentially volatile situation. The preparatory steps required joint efforts from local and state partners in law enforcement, emergency medical services, and emergency departments. We describe here the situation we faced, the pre-event preparations, the response in the field and in our emergency department, and the outcomes from an emergency and tactical medicine perspective. We hope our successful experience will impart knowledge for similar events.

Remediating Indoor Pesticide Contamination from Improper Pest Control Treatments: Persistence and Decontamination Studies.

The improper and excessive use of pesticides in indoor environments can result in adverse human health effects, sometimes necessitating decontamination of residential or commercial buildings. A lack of information on effective approaches to remediate pesticide residues prompted the decontamination and persistence studies described in this study. Decontamination studies evaluated the effectiveness of liquid-based surface decontaminants against pesticides on indoor surfaces. Building materials were contaminated with 25-2,400 µg/100cm2 of the pesticides malathion, carbaryl, fipronil, deltamethrin, and permethrin. Decontaminants included both off-the-shelf and specialized solutions representing various chemistries. Pesticides included in this study were found to be highly persistent in a dark indoor environment with surface concentrations virtually unchanged after 140 days. Indoor light conditions degraded some of the pesticides, but estimated half-lives exceeded the study period. Decontamination efficacy results indicated that the application of household bleach or a hydrogen peroxide-based decontaminant offered the highest efficacy, reducing malathion, fipronil, and deltamethrin by >94-99% on some surfaces. Bleach effectively degraded permethrin (>94%), but not carbaryl (<70%) while the hydrogen peroxide containing products degraded carbaryl (>71-99%) but not permethrin (<54%). These results will inform responders, the general public and public health officials on potential decontamination solutions to remediate indoor surfaces.

Aversive distractors modulate affective working memory in frontoparietal regions.

Rumination and worry are prominent symptoms of many psychiatric disorders. These symptoms compete for the same working memory (WM) storage space as those required for task-goals, leaving few cognitive resources available for successful goal-directed behavior. Once lodged in WM, negative information reduces cognitive control and further biases cognition toward affective stimuli. However, few studies have examined the neural mechanisms associated with maintaining affectively negative information in WM and the filtering of aversive distractors. Here, subjects completed an affective verbal WM task while distractor-cues that predicted aversive or positive stimuli were presented during the delay period while undergoing functional MRI (fMRI). Results revealed that during aversive distractors, there was a decrease in both dlPFC and PPC activity, but only when maintaining negative affective information in WM. Furthermore, dlPFC and PPC activity predicted behavioral performance. This pattern was not observed when maintaining positive words in WM or when positive distractors were presented. These findings demonstrate that the affective valence of the items stored in WM modulates "top-down" control networks necessary for the execution of cognitive control related to affective distractor interreference. Furthermore, these results provide a neurocognitive framework for understanding how rumination and worry produce negative downstream failures in cognitive control and emotion regulation. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Reward-related distracters and working memory filtering.

Reward-related stimuli capture attention, even when they are task irrelevant. A consequence of attentional prioritization of reward-related stimuli is that they may also have preferential access to working memory like other forms of emotional information. However, whether reward-related distracters leak into working memory remains unknown. Here, using a well-validated change detection task of visual working memory capacity and filtering, we conducted two studies to directly assess the impact of reward-related distracters on working memory. In both studies, the distracters consisted of colored bars or circles that were previously associated with monetary reward. In Experiment 1, results indicated that previously rewarded distracters did not impact behavioral measures of working memory filtering efficiency compared to neutral distracters. In Experiment 2, using ERPs, we measured the contralateral delay activity (CDA), a psychophysiological index of the number of items retained in working memory, to further assess filtering efficiency. We observed that the CDA for high reward distracters was similar to low reward and neutral distracters. However, in early trials, behavioral measures revealed that previously rewarded stimuli negatively impacted working memory capacity, an effect not observed with neutral distracters. This effect, though, was not found for the CDA in early trials. In summary, our findings across two studies suggest that attentional capture by task-irrelevant reward may have minimal impact on visual working memory-findings that have important implications for delineating the boundaries of reward-cognition interactions.

Characterizing the neural circuitry associated with configural threat learning.

Contextual threat learning is often associated with two processes: elemental and configural learning. Few studies have examined configural learning where subjects form a representation of the threat-related context as a gestalt whole from the individual features in the environment. The goal of the current study was to compare and contrast neural circuitry recruited by variation in demands placed on configural threat encoding. Subjects (N = 25) completed a configural threat learning task, where we manipulated the amount of configural encoding required to learn the threat association (low demand: changes to a discrete element of the context; and high demand: rearrangement of elements). US expectancy ratings, skin conductance responses (SCR), and functional magnetic resonance imaging (fMRI) were collected. Subjects successfully learned the configural threat association as measured by US expectancy ratings, SCR, and BOLD activity. Hippocampal and amygdala region of interest analyses indicated differential configural threat learning and predicted SCR measures of learning. Furthermore, whole brain analyses identified four circuits that were impacted by the amount of differential configural encoding required, but none correlated with SCR. These results set the stage for a more detailed understanding of how configural threat learning is instantiated in the brain-an important mechanism associated with PTSD and other fear-related disorders.

Multimodal canonical correlation reveals converging neural circuitry across trauma-related disorders of affect and cognition.

Trauma-related disorders of affect and cognition (TRACs) are associated with a high degree of diagnostic comorbidity, which may suggest that these disorders share a set of underlying neural mechanisms. TRACs are characterized by aberrations in functional and structural circuits subserving verbal memory and affective anticipation. Yet, it remains unknown how the neural circuitry underlying these multiple mechanisms contribute to TRACs. Here, in a sample of 47 combat Veterans, we measured affective anticipation using functional magnetic resonance imaging (fMRI), verbal memory with fluorodeoxyglucose positron emission tomography (FDG-PET), and grey matter volume with structural magnetic resonance imaging (sMRI). Using a voxel-based multimodal canonical correlation analysis (mCCA), the set of neural measures were statistically integrated, or fused, with a set of TRAC symptom measures including mild traumatic brain injury (mTBI), posttraumatic stress, and depression severity. The first canonical correlation pair revealed neural convergence in clusters encompassing the middle frontal gyrus and supplemental motor area, regions implicated in top-down cognitive control and affect regulation. These results highlight the potential of leveraging multivariate neuroimaging analysis for linking neurobiological mechanisms associated with TRACs, paving the way for transdiagnostic biomarkers and targets for treatment.