The role of pain and socioenvironmental factors on posttraumatic stress disorder symptoms in traumatically injured adults: A 1-year prospective study.

Approximately 20% of individuals who experience a traumatic injury will subsequently develop posttraumatic stress disorder (PTSD). Physical pain following traumatic injury has received increasing attention as both a distinct, functionally debilitating disorder and a comorbid symptom related to PTSD. Studies have demonstrated that both clinician-assessed injury severity and patient pain ratings can be important predictors of nonremitting PTSD; however, few have examined pain and PTSD alongside socioenvironmental factors. We postulated that both area- and individual-level socioeconomic circumstances and lifetime trauma history would be uniquely associated with PTSD symptoms and interact with the pain-PTSD association. To test these effects, pain and PTSD symptoms were assessed at four visits across a 1-year period in a sample of 219 traumatically injured participants recruited from a Level 1 trauma center. We used a hierarchal linear modeling approach to evaluate whether (a) patient-reported pain ratings were a better predictor of PTSD than clinician-assessed injury severity scores and (b) socioenvironmental factors, specifically neighborhood socioeconomic disadvantage, individual income, and lifetime trauma history, influenced the pain-PTSD association. Results demonstrated associations between patient-reported pain ratings, but not clinician-assessed injury severity scores, and PTSD symptoms, R2( fvm ) = .65. There was a significant interaction between neighborhood socioeconomic disadvantage and pain such that higher disadvantage decreased the strength of the pain-PTSD association but only among White participants, R2( fvm ) = .69. Future directions include testing this question in a larger, more diverse sample of trauma survivors (e.g., geographically diverse) and examining factors that may alleviate both pain and PTSD symptoms.

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.

Emotion Dysregulation Following Trauma: Shared Neurocircuitry of Traumatic Brain Injury and Trauma-Related Psychiatric Disorders.

The psychological trauma associated with events resulting in traumatic brain injury (TBI) is an important and frequently overlooked factor that may impede brain recovery and worsen mental health following TBI. Indeed, individuals with comorbid posttraumatic stress disorder (PTSD) and TBI have significantly poorer clinical outcomes than individuals with a sole diagnosis. Emotion dysregulation is a common factor leading to poor cognitive and affective outcomes following TBI. Here, we synthesize how acute postinjury molecular processes stemming from either physical or emotional trauma may adversely impact circuitry subserving emotion regulation and ultimately yield long-term system-level functional and structural changes that are common to TBI and PTSD. In the immediate aftermath of traumatic injury, glucocorticoids stimulate excess glutamatergic activity, particularly in prefrontal cortex-subcortical circuitry implicated in emotion regulation. In human neuroimaging work, assessing this same circuitry well after the acute injury, TBI and PTSD show similar impacts on prefrontal and subcortical connectivity and activation. These neural profiles indicate that emotion regulation may be a useful target for treatment and early intervention to prevent the adverse sequelae of TBI. Ultimately, the success of future TBI and PTSD early interventions depends on the fields' ability to address both the physical and emotional impact of physical injury.

Scoring the Life Events Checklist: Comparison of three scoring methods.

OBJECTIVE: Prior trauma history is a reliable and robust risk predictor for PTSD development. Obtaining an accurate measurement of prior trauma history is critical in research of trauma-related outcomes. The Life Events Checklist (LEC) is a widely used self-report measure of trauma history that categorizes events by the proximity to trauma exposure; however, the field has published multiple scoring methods when assessing the LEC. Herein, we propose a novel scoring procedure in which total scores from the LEC are weighted according to the proximity of trauma exposure with "experienced" events weighted most and "learned about" events weighted least. METHOD: The utility of this weighted score was assessed in two traumatically-injured civilian samples and compared against previously published scoring methods, including a nonweighted score including all events experienced, witnessed, and learned about, as well as a score consisting of only experienced events. RESULTS: Results indicated the standard total score was most reliable, followed by the weighted score. The experienced events score was least reliable, but the best predictor of future PTSD symptoms. CONCLUSIONS: One method to balance the predictive strength of experienced events and the excellent reliability of a total LEC score, is to adopt the newly proposed weighted score. Future use of this weighted scoring method can provide a comprehensive estimate of lifetime trauma exposure while still emphasizing the direct proximity of experienced events compared with other degrees of exposure. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.

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.

Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a debilitating disorder, and there is no current accurate prediction of who develops it after trauma. Neurobiologically, individuals with chronic PTSD exhibit aberrant resting-state functional connectivity (rsFC) between the hippocampus and other brain regions (e.g., amygdala, prefrontal cortex, posterior cingulate), and these aberrations correlate with severity of illness. Previous small-scale research (n < 25) has also shown that hippocampal rsFC measured acutely after trauma is predictive of future severity using a region-of-interest-based approach. While this is a promising biomarker, to date, no study has used a data-driven approach to test whole-brain hippocampal FC patterns in forecasting the development of PTSD symptoms. METHODS: A total of 98 adults at risk of PTSD were recruited from the emergency department after traumatic injury and completed resting-state functional magnetic resonance imaging (8 min) within 1 month; 6 months later, they completed the Clinician-Administered PTSD Scale for DSM-5 for assessment of PTSD symptom severity. Whole-brain rsFC values with bilateral hippocampi were extracted (using CONN) and used in a machine learning kernel ridge regression analysis (PRoNTo); a k-folds (k = 10) and 70/30 testing versus training split approach were used for cross-validation (1000 iterations to bootstrap confidence intervals for significance values). RESULTS: Acute hippocampal rsFC significantly predicted Clinician-Administered PTSD Scale for DSM-5 scores at 6 months (r = 0.30, p = .006; mean squared error = 120.58, p = .006; R2 = 0.09, p = .025). In post hoc analyses, hippocampal rsFC remained significant after controlling for demographics, PTSD symptoms at baseline, and depression, anxiety, and stress severity at 6 months (B = 0.59, SE = 0.20, p = .003). CONCLUSIONS: Findings suggest that functional connectivity of the hippocampus across the brain acutely after traumatic injury is associated with prospective PTSD symptom severity.

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.

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.

Structural Connectivity of the Posterior Cingulum Is Related to Reexperiencing Symptoms in Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder with disturbances in hyper-arousal or avoidance behaviors, and intrusive or re-experiencing thoughts. The uncinate fasciculus (UF) and cingulum bundle are white matter pathways implicated in stress and trauma pathophysiology, yet their structural integrity related to PTSD symptom domains is yet to be understood. Forty-four trauma-exposed young adults underwent structural and diffusion-weighted MRI. Stress and trauma exposure indices and severity of PTSD symptoms were collected and used to predict current integrity of the UF and cingulum bundle. Severity of re-experiencing PTSD symptoms was significantly related to increased fractional anisotropy (r=.469 p<.001) and decreased mean diffusivity (r=-.373, p=.013) of the right posterior cingulum bundle. No other findings emerged with respect to stress exposure or of hyper-arousal (p's>0.05) or avoidance (p's>0.2) PTSD symptoms. The posterior cingulum connects medial temporal lobe structures with visual areas in the occipital lobe and has been implicated in visual memory and self-referential thought. Increased structural connectivity along this pathway may therefore explain the emergence of re-experiencing PTSD symptoms. This along with the lack of results with respect to stress exposure suggests structural aberrations in white matter pathways are more strongly linked with the actual experience of stress-related psychological symptoms than just exposure to stress.