Magnitude effects for experienced rewards at short delays in the escalating interest task

A first-person shooter video game was adapted for the study of choice between smaller sooner and larger later rewards. Participants chose when to fire a weapon that increased in damage potential over a short interval. When the delay to maximum damage was shorter (5 – 8 s), people showed greater sensitivity to the consequences of their choices than when the delay was longer (17 – 20 s). Participants also evidenced a magnitude effect by waiting proportionally longer when the damage magnitudes were doubled for all rewards. The experiment replicated the standard magnitude effect with this new video game preparation over time scales similar to those typically used in nonhuman animal studies and without complications due to satiation or cost

Outcome probability versus magnitude: When waiting benefits one at the cost of the other

Citation: Young, M. E., Webb, T. L., Rung, J. M., & McCoy, A. W. (2014). Outcome Probability versus Magnitude: When Waiting Benefits One at the Cost of the Other. PLOS ONE, 9(6), e98996. https://doi.org/10.1371/journal.pone.0098996Using a continuous impulsivity and risk platform (CIRP) that was constructed using a video game engine, choice was assessed under conditions in which waiting produced a continuously increasing probability of an outcome with a continuously decreasing magnitude (Experiment 1) or a continuously increasing magnitude of an outcome with a continuously decreasing probability (Experiment 2). Performance in both experiments reflected a greater desire for a higher probability even though the corresponding wait times produced substantive decreases in overall performance. These tendencies are considered to principally reflect hyperbolic discounting of probability, power discounting of magnitude, and the mathematical consequences of different response rates. Behavior in the CIRP is compared and contrasted with that in the Balloon Analogue Risk Task (BART)

Acute White Matter Integrity Post-trauma and Prospective Posttraumatic Stress Disorder Symptoms

Background: Little is known about what distinguishes those who are resilient after trauma from those at risk for developing posttraumatic stress disorder (PTSD). Previous work indicates white matter integrity may be a useful biomarker in predicting PTSD. Research has shown changes in the integrity of three white matter tracts—the cingulum bundle, corpus callosum (CC), and uncinate fasciculus (UNC)—in the aftermath of trauma relate to PTSD symptoms. However, few have examined the predictive utility of white matter integrity in the acute aftermath of trauma to predict prospective PTSD symptom severity in a mixed traumatic injury sample. Method: Thus, the current study investigated acute brain structural integrity in 148 individuals being treated for traumatic injuries in the Emergency Department of a Level 1 trauma center. Participants underwent diffusion-weighted magnetic resonance imaging 2 weeks post-trauma and completed several self-report measures at 2-weeks (T1) and 6 months (T2), including the Clinician Administered PTSD Scale for DSM-V (CAPS-5), post-injury. Results: Consistent with previous work, T1 lesser anterior cingulum fractional anisotropy (FA) was marginally related to greater T2 total PTSD symptoms. No other white matter tracts were related to PTSD symptoms. Conclusions: Results demonstrate that in a traumatically injured sample with predominantly subclinical PTSD symptoms at T2, acute white matter integrity after trauma is not robustly related to the development of chronic PTSD symptoms. These findings suggest the timing of evaluating white matter integrity and PTSD is important as white matter differences may not be apparent in the acute period after injury

Acute posterior cingulum integrity post-trauma prospectively predicts depression but not PTSD symptoms

Background: Little is known about what distinguishes those who are resilient after trauma from those at risk for developing posttraumatic stress disorder (PTSD). Previous work indicates white matter integrity may be a useful biomarker in predicting PTSD. Research has shown changes in the integrity of three white matter tracts—the cingulum bundle, corpus callosum (CC), and uncinate fasciculus (UNC)—in the aftermath of trauma relate to PTSD symptoms. However, few have examined the predictive utility of white matter integrity in the acute aftermath of trauma to predict prospective PTSD symptom severity in a mixed traumatic injury sample. Method: Thus, the current study investigated acute brain structural integrity in 148 individuals being treated for traumatic injuries in the Emergency Department of a Level 1 trauma center. Participants underwent diffusion-weighted magnetic resonance imaging 2 weeks post-trauma and completed several self-report measures at 2-weeks (T1) and 6 months (T2), including the Clinician Administered PTSD Scale for DSM-V (CAPS-5), post-injury. Results: Consistent with previous work, T1 lesser anterior cingulum fractional anisotropy (FA) was marginally related to greater T2 total PTSD symptoms. No other white matter tracts were related to PTSD symptoms. Conclusions: Results demonstrate that in a traumatically injured sample with predominantly subclinical PTSD symptoms at T2, acute white matter integrity after trauma is not robustly related to the development of chronic PTSD symptoms. These findings suggest the timing of evaluating white matter integrity and PTSD is important as white matter differences may not be apparent in the acute period after injury

Racial Discrimination and Resting-State Functional Connectivity of Salience Network Nodes in Trauma-Exposed Black Adults in the United States

Importance For Black US residents, experiences of racial discrimination are still pervasive and frequent. Recent empirical work has amplified the lived experiences and narratives of Black people and further documented the detrimental effects of racial discrimination on both mental and physical health; however, there is still a need for further research to uncover the mechanisms connecting experiences of racial discrimination with adverse health outcomes. Objective To examine neurobiological mechanisms that may offer novel insight into the association of racial discrimination with adverse health outcomes. Design, Setting, and Participants This cross-sectional study included 102 Black adults who had recently experienced a traumatic injury. In the acute aftermath of the trauma, participants underwent a resting-state functional magnetic resonance imaging scan. Individuals were recruited from the emergency department at a Midwestern level 1 trauma center in the United States between March 2016 and July 2020. Data were analyzed from February to May 2021. Exposures Self-reported lifetime exposure to racial discrimination, lifetime trauma exposure, annual household income, and current posttraumatic stress disorder (PTSD) symptoms were evaluated. Main Outcomes and Measures Seed-to-voxel analyses were conducted to examine the association of racial discrimination with connectivity of salience network nodes (ie, amygdala and anterior insula). Results A total of 102 individuals were included, with a mean (SD) age of 33 (10) years and 58 (57%) women. After adjusting for acute PTSD symptoms, annual household income, and lifetime trauma exposure, greater connectivity between the amygdala and thalamus was associated with greater exposure to discrimination (t(97) = 6.05; false discovery rate (FDR)–corrected P = .03). Similarly, racial discrimination was associated with greater connectivity between the insula and precuneus (t(97) = 4.32; FDR-corrected P = .02). Conclusions and Relevance These results add to the mounting literature that racial discrimination is associated with neural correlates of vigilance and hyperarousal. The study findings extend this theory by showing that this association is apparent even when accounting for socioeconomic position, lifetime trauma, and symptoms of psychological distress related to an acute trauma

Neural Impact of Neighborhood Socioeconomic Disadvantage in Traumatically Injured Adults

Nearly 14 percent of Americans live in a socioeconomically disadvantaged neighborhood. Lower individual socioeconomic position (iSEP) has been linked to increased exposure to trauma and stress, as well as to alterations in brain structure and function; however, the neural effects of neighborhood SEP (nSEP) factors, such as neighborhood disadvantage, are unclear. Using a multi-modal approach with participants who recently experienced a traumatic injury (N = 185), we investigated the impact of neighborhood disadvantage, acute post-traumatic stress symptoms, and iSEP on brain structure and functional connectivity at rest. After controlling for iSEP, demographic variables, and acute PTSD symptoms, nSEP was associated with decreased volume and alterations of resting-state functional connectivity in structures implicated in affective processing, including the insula, ventromedial prefrontal cortex, amygdala, and hippocampus. Even in individuals who have recently experienced a traumatic injury, and after accounting for iSEP, the impact of living in a disadvantaged neighborhood is apparent, particularly in brain regions critical for experiencing and regulating emotion. These results should inform future research investigating how various levels of socioeconomic circumstances may impact recovery after a traumatic injury as well as policies and community-developed interventions aimed at reducing the impact of socioeconomic stressors

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage

Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family