Neighborhood Socioeconomic Disadvantage and the Neurobiology of Uncertainty in Traumatically Injured Adults.

BACKGROUND: Individuals residing in more socioeconomically disadvantaged neighborhoods experience greater uncertainty through insecurity of basic needs such as food, employment, and housing, compared with more advantaged neighborhoods. Although the neurobiology of uncertainty has been less frequently examined in relation to neighborhood disadvantage, there is evidence that neighborhood disadvantage is associated with widespread neural alterations. METHODS: Recently traumatically injured participants (n = 90) completed a picture anticipation task in the magnetic resonance imaging scanner, in which they viewed images presented in a temporally predictable or unpredictable manner. We investigated how neighborhood disadvantage (via area deprivation index [ADI]) was related to neural activation during anticipation and presentation of negative and neutral images after accounting for individual factors (i.e., age, gender, income, acute posttraumatic stress symptoms). RESULTS: There was a significant interaction during the anticipation period such that higher ADI rankings were related to greater activation of the right anterior cingulate cortex to predictable versus unpredictable neutral stimuli. Although no other robust interactions emerged related to ADI, we note several novel simple effects of ADI during anticipation and presentation periods in the hippocampus and prefrontal, cingulate, and occipital cortices. CONCLUSIONS: Together, these results may represent an adaptive response to predictable and/or negative stimuli, stemming from chronic exposure to socioeconomic-based uncertainties. Although effects were modest, future work should continue to examine pretrauma context on posttrauma outcomes. To better understand trauma outcomes, it is imperative that researchers consider the broader context in which trauma survivors reside.

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.

A 7-Tesla MRI study of the periaqueductal gray: resting state and task activation under threat.

The periaqueductal gray (PAG) is a region of the midbrain implicated in a variety of behaviors including defensive responses to threat. Despite the wealth of knowledge pertaining to the differential functional roles of the PAG columns in nonhuman and human research, the basic functional connectivity of the PAG at rest has not been well characterized. Therefore, the current study utilized 7-Tesla magnetic resonance imaging (MRI) to characterize PAG functional connectivity at rest and task activation under uncertain threat. A sample of 53 neurologically healthy undergraduate participants (Mage = 22.2, s.d.age = 3.62) underwent structural and resting state functional MRI scans. Supporting previous work, voxel-wise analyses showed that the PAG is functionally connected to emotion regulation and fear networks. The comparison of functional connectivity of PAG columns did not reveal any significant differences. Thirty-five participants from the same sample also completed an uncertain threat task with blocks of three conditions-no shock, predictable shock and unpredictable shock. There were no robust activity differences within the PAG columns or the whole PAG across conditions although there was differential activity at the voxel level in the PAG and in other regions theoretically relevant to uncertain threat. Results of this study elucidate PAG connectivity at rest and activation in response to uncertain threat.

Association between spatial working memory and Re-experiencing symptoms in PTSD.

BACKGROUND AND OBJECTIVES: Few studies have evaluated the link between working memory (WM) and post-traumatic stress disorder (PTSD). Further, it is unknown whether this relationship is accounted for by other relevant variables including negative affect, emotional dysregulation, or general non-WM-related cognitive control deficits, which are associated with PTSD. The purpose of this study was to determine the extent to which a computerized WM task could predict PTSD symptomology incrementally beyond the contribution of other relevant variables associated with PTSD. METHODS: Thirty veterans were eligible to complete emotional symptom questionnaires, a heart-rate variability measure, and computerized tasks (i.e., emotional Stroop and automated complex span tasks). A three-stage hierarchical regression was conducted with the PCL-5 total score and symptom clusters (i.e., re-experiencing, avoidance, hyperarousal, and negative cognition/mood) as the dependent variable. RESULTS: Results revealed that only the re-experiencing symptom cluster was significantly predicted by executive, verbal, and visuospatial WM tasks, which explained an additional 29.7% of the variance over and above other relevant variables. Most notably, the visuospatial task was the only WM task that significantly explained PCL-5 re-experiencing symptoms. LIMITATIONS: This study was based on a small sample of veterans with PTSD and causality cannot be determined with this cross-sectional study. CONCLUSIONS: Overall, the results suggest that deficits in visuospatial WM are significantly associated with PTSD re-experiencing symptoms after controlling for other relevant variables. Further research should evaluate whether an intervention to improve visuospatial WM capacity can be implemented to reduce re-experiencing symptoms.

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.

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.

Neural substrates of human fear generalization: A 7T-fMRI investigation.

Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stimuli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater generalization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.

Neighborhood disadvantage is associated with stable deficits in neurocognitive functioning in traumatically-injured adults.

BACKGROUND: In trauma-exposed adults, the relationship between an individual's socioeconomic position (SEP) and post-traumatic stress disorder (PTSD) has been well demonstrated. One potential mechanism by which the stress associated with lower SEPs may impact trauma outcomes is through changes in neurocognition. In both healthy and clinical samples, area-level factors also appear to be independently related to neurocognition. Far less is known about how neighborhood socioeconomic disadvantage, may impact cognition in traumatically-injured adults. The current study employed hierarchical linear modeling to longitudinally investigate whether neighborhood disadvantage was associated with neurocognitive functioning in five domains: processing speed, sustained attention, controlled attention, cognitive flexibility, and response inhibition. METHODS: One-hundred and ninety-five socioeconomically diverse traumatically-injured subjects (mean age = 32.8, 52.8% female) were recruited from an Emergency Department. Two-weeks, three-months, and six-months post-trauma, participants completed self-report measures and a computerized test battery to evaluate neurocognition. An Area Deprivation Index (ADI) score, a measure of a neighborhood's socioeconomic disadvantage, was derived from each participants' home address. RESULTS: Greater neighborhood disadvantage was significantly related to lower scores in all domains. Results of hierarchical linear models revealed neighborhood disadvantage was significantly associated with processing speed, controlled attention, cognitive flexibility, and response inhibition across time, even after adjusting for individual annual household income, baseline PTSD symptoms, and previous adverse life experiences. This relationship was stable for all domains except sustained attention, which varied across time. CONCLUSION: These findings indicate neighborhood disadvantage contributes uniquely to neurocognitive functioning and, for the majority of domains, these contributions are stable across time. The relationship between area-level variables and cognitive function may underlie individual vulnerability to developing psychiatric disorders. Future work should continue to examine the interaction between socioenvironmental stressors and PTSD symptoms longitudinally.

High-Resolution Resting-State Functional Connectivity of the Extended Amygdala.

The extended amygdala has been implicated as a critical region in the neurocircuitry underlying anxiety. The circuitry of the extended amygdala, including the central (CeA) and basolateral (BLA) nuclei of the amygdala and the bed nucleus of the stria terminalis (BNST), has been well defined in nonhuman animals; however, much less is known about the roles and interactions of these structures in humans given their small size. Therefore, this study used high-resolution 7-Tesla magnetic resonance imaging to define, compare, and contrast functional connectivity (FC) of these structures in 57 neurologically healthy young adults. In addition, FC was investigated in relation to self-reported measures of anxiety and intolerance of uncertainty, a key feature of anxiety. Results of the FC analysis of each of the nuclei largely replicated previous work. Conjunction analyses showed that nuclei of the extended amygdala shared FC with hippocampal, cingulate, medial prefrontal, and subgenual cortices. Comparison of seed-to-voxel time series correlation maps demonstrated that compared with the BNST, the CeA and BLA were more strongly coupled with parahippocampal, temporal, fusiform, and occipital gyri. Relative to the CeA and BLA, the BNST was more strongly coupled with the anterior caudate and anterior cingulate cortex. Finally, trait anxiety and intolerance of uncertainty were not robustly related to FC of the extended amygdala at rest. Results of this study extend previous work to provide more clarity of the nuances of extended amygdala resting FC and its relationship with anxiety.

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.

A pilot randomized trial of a dual n-back emotional working memory training program for veterans with elevated PTSD symptoms.

Anxiety is characterized by excessive attention to threatening information, leading to impaired working memory (WM) performance and elevated anxious thoughts. Preliminary research indicates that individuals with PTSD show particular difficulty with WM in emotional contexts (Schweizer et al., 2011). Although several studies show that computerized training can improve WM capacity for anxious individuals (Owens et al., 2013; Schweizer et al., 2011; 2013), there has been very little research on WM training for PTSD or with Veterans (Saunders et al., 2015). In a pilot randomized trial, we assigned Veterans with elevated PTSD symptoms to an online emotional WM training, either adaptive (n-back; n = 11) or a less potent training (1-back; n = 10). Overall, both groups showed significant decreases in PTSD symptoms. The n-back group showed a trend of outperforming the 1-back group in improving reexperiencing symptoms (which are likely to be associated with impaired WM functioning). This population anecdotally found the intervention quite challenging, which may be why even the less potent 1-back was still helpful. These preliminary findings justify the effort for developing new WM-focused PTSD intervention for complex, vulnerable populations, particularly as online training can improve accessibility.

WITHDRAWN: Solve it Like Sherlock: Misplaced Electrodes.

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Observations on the use of the aVR-V6 relationship to recognize limb lead error.

Electrocardiograms are subject to technical errors that confound interpretation, and although some are readily apparent, others are overlooked by experienced physicians. Thus, failure to recognize a recording error can lead to faulty clinical actions. By exploiting the reciprocal relationship of leads aVR and V6, this article provides a simple and useful way to quickly and confidently determine whether a tracing was properly recorded.

Mycotic femoral aneurysm.

After several weeks of fever and chills, a 31-year-old logger developed pain in his right thigh. Upon examination a tender, pulsating upper thigh mass was found with a long loud bruit arising from it. Severe aortic insufficiency was present; however, blood cultures were negative. An angiogram, captured blood with contrast spewing from the profunda femoral artery to fill a 5 x 10 cm sac. A false aneurysm was diagnosed and resected; numerous gram positive cocci were present in cut sections, but cultures from the cavity grew the gram negative bacteria Salmonella and Alcaligenes. After one month of intravenous ampicillin the aortic valve was replaced after being destroyed by endocarditis. Ampicillin was continued and recovery was uneventful. Mycotic aneurysms are commonly caused by Salmonella (10%), which was second only to Staphylococcus (30%). The femoral artery accounts for 38% of all mycotic aneurysms. They typically present with a pulsatile mass (52%), bruit (50%), and fever (48%). This diagnosis can be supported by leukocytosis (64-71%), positive blood cultures (50-85%), and a history of arterial trauma (51%) (injection drug use, intravascular procedure, or trauma) or endocarditis (10%).

Spontaneous migration of an inferior vena cava filter resulting in cardiac tamponade and percutaneous filter retrieval.

Thromboembolic disease accounts for thousands of hospitalizations every year in the US. Its primary management consists of anticoagulation. However, in certain instances this may be contraindicated or not sufficient. Mechanic occlusion of the inferior vena cava (IVC) becomes then a viable alternative. In this case a 35-year-old man presented with a saddle pulmonary embolus but was unable to be anticoagulated due to intestinal bleed. A removable IVC filter was then placed. The filter spontaneously migrated into the right atrium causing severe tricuspid regurgitation, perforation of the atrial wall, and cardiac tamponade. The device was successfully retrieved percutaneously and the patient discharged from the hospital in stable condition. This case illustrates the potentially lethal complications associated with the use of IVC filters, as well as the possibility to percutaneously recover them from within the right atrium.

Adenosine infusion increases plasma levels of VEGF in humans.

BACKGROUND: Many in vitro studies have shown that adenosine (Ado) can induce vascular endothelial growth factor (VEGF) mRNA and protein expression and stimulate endothelial proliferation. In the present study, we seek to determine whether Ado can increase circulating levels of VEGF protein in the intact human. METHODS: Five outpatients 49.3 +/- 6.7 years of age and weighing 88.2 +/- 8.5 kg were selected. They were given a 6 min intravenous infusion of Ado (0.14 mg kg-1 min-1) in conjunction with sestamibi myocardial perfusion scans. Mean blood pressure (MBP, calculated from systolic and diastolic values) and heart rate (HR) were determined before Ado infusion and every 2 min for the next 10 min. Plasma VEGF concentrations (ELISA) were determined immediately before Ado infusion and 1 h, 2 h, and 8 h after the infusion. RESULTS: Plasma VEGF concentration averaged 20.3 +/- 2.0 pg ml-1 prior to Ado infusion, and increased to 62.7 +/- 18.1 pg ml-1 at 1 h post- infusion (p < 0.01). VEGF plasma concentration returned to basal levels 2 h after infusion (23.3 +/- 3.4 pg ml-1). MBP averaged 116 +/- 7 mmHg and heart rate averaged 70 +/- 7 prior to Ado infusion. MBP decreased by a maximum of approximately 22% and HR increased by a maximum of approximately 17% during the infusion. CONCLUSION: We conclude from these preliminary findings that intravenous infusion of adenosine can increase plasma levels of VEGF in humans.

Einthoven's triangle: lead errors and an algorithm for solution.

The three bipolar leads (I, II, and III) of the 12-lead electrocardiogram are subject to technical errors that not only confound interpretation but may lead to faulty clinical actions. While some errors are readily recognized, even experienced electrocardiographers overlook others. This paper reviews the nature of limb lead errors and offers what we think is a generally useful method to deduce the observed, but erroneous, lead configurations.