Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippo campal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N = 116, 76 female), we found that PTSD symptoms at 2 weeks were associated with decreased hippocampal responses to threat as assessed with fMRI. Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of fear potentiated startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function because of increases in fear-potentiated arousal.SIGNIFICANCE STATEMENT Alterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on nontrauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk

Prior Sexual Trauma Exposure Impacts Posttraumatic Dysfunction and Neural Circuitry Following a Recent Traumatic Event in the AURORA Study

Background: Prior sexual trauma (ST) is associated with greater risk for posttraumatic stress disorder after a subsequent traumatic event; however, the underlying neurobiological mechanisms remain opaque. We investigated longitudinal posttraumatic dysfunction and amygdala functional dynamics following admission to an emergency department for new primarily nonsexual trauma in participants with and without previous ST. Methods: Participants (N = 2178) were recruited following acute trauma exposure (primarily motor vehicle collision). A subset (n = 242) completed magnetic resonance imaging that included a fearful faces task and a resting-state scan 2 weeks after the trauma. We investigated associations between prior ST and several dimensions of posttraumatic symptoms over 6 months. We further assessed amygdala activation and connectivity differences between groups with or without prior ST. Results: Prior ST was associated with greater posttraumatic depression (F1,1120 = 28.35, p = 1.22 × 10−7, ηp2 = 0.06), anxiety (F1,1113 = 17.43, p = 3.21 × 10−5, ηp2 = 0.05), and posttraumatic stress disorder (F1,1027 = 11.34, p = 7.85 × 10−4, ηp2 = 0.04) severity and more maladaptive beliefs about pain (F1,1113 = 8.51, p = .004, ηp2 = 0.02) but was not related to amygdala reactivity to fearful versus neutral faces (all ps \u3e .05). A secondary analysis revealed an interaction between ST and lifetime trauma load on the left amygdala to visual cortex connectivity (peak Z value: −4.41, corrected p \u3c .02). Conclusions: Findings suggest that prior ST is associated with heightened posttraumatic dysfunction following a new trauma exposure but not increased amygdala activity. In addition, ST may interact with lifetime trauma load to alter neural circuitry in visual processing regions following acute trauma exposure. Further research should probe the relationship between trauma type and visual circuitry in the acute aftermath of trauma

Structural covariance of the ventral visual stream predicts posttraumatic intrusion and nightmare symptoms: a multivariate data fusion analysis

Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant\u27s loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms

Neighborhood Disadvantage and Neural Correlates of Threat and Reward Processing in Survivors of Recent Trauma

IMPORTANCE: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry. OBJECTIVE: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data analysis was performed from October 25, 2022, to February 15, 2023. EXPOSURE: Neighborhood disadvantage was measured with the Area Deprivation Index (ADI) for each participant home address. MAIN OUTCOMES AND MEASURES: Participants completed separate threat and reward tasks during functional magnetic resonance imaging. Diffusion-weighted and high-resolution structural images were also collected. Linear models assessed the association of ADI with reactivity, microstructure, and macrostructure of a priori regions of interest after adjusting for income, lifetime trauma, sex at birth, and age. A moderated-mediation model tested whether ADI was associated with neural activity via microstructural changes and if this was modulated by PTSD symptoms. RESULTS: A total of 280 participants (183 females [65.4%]; mean [SD] age, 35.39 [13.29] years) completed the threat task and 244 participants (156 females [63.9%]; mean [SD] age, 35.10 [13.26] years) completed the reward task. Higher ADI (per 1-unit increase) was associated with greater insula (t274 = 3.20; β = 0.20; corrected P = .008) and anterior cingulate cortex (ACC; t274 = 2.56; β = 0.16; corrected P = .04) threat-related activity after considering covariates, but ADI was not associated with reward reactivity. Greater disadvantage was also associated with altered microstructure of the cingulum bundle (t274 = 3.48; β = 0.21; corrected P = .001) and gray matter morphology of the ACC (cortical thickness: t273 = -2.29; β = -0.13; corrected P = .02; surface area: t273 = 2.53; β = 0.13; corrected P = .02). The moderated-mediation model revealed that ADI was associated with ACC threat reactivity via cingulum microstructural changes (index of moderated mediation = -0.02). However, this mediation was only present in individuals with greater PTSD symptom severity (at the mean: β = -0.17; standard error = 0.06, t= -2.28; P = .007; at 1 SD above the mean: β = -0.28; standard error = 0.08; t = -3.35; P \u3c .001). CONCLUSIONS AND RELEVANCE: In this study, neighborhood disadvantage was associated with neurobiology that supports threat processing, revealing associations of neighborhood disadvantage with neural susceptibility for PTSD and suggesting how altered structure-function associations may complicate symptoms. Future work should investigate specific components of neighborhood disadvantage that may be associated with these outcomes

Fructan Catabolism by Rumen Microbiota of Cattle and Sheep

Fructans serve as the primary form of storage carbohydrate in cool-season grasses, but little is known about potential differences in ruminal fermentation of fructans between cattle and sheep. An ex vivo study was conducted to evaluate species differences in fructan catabolism. Buffered media containing ground orchardgrass (Dactylis glomerata L.) substrate was inoculated with uncultivated rumen microbiota obtained from cattle and sheep (n = 4 species−1). Fructan profiles were monitored over the incubation period (8 h; 39 °C) using high-performance anion-exchange chromatography coupled to pulsed amperometric detection (HPAEC-PAD). In both species, disappearance of long-chain fructans (degree of polymerization [DP] > 8) was evident by 2 h of incubation (p p p p < 0.01). These results indicate that rumen microbiota of cattle may have a greater capacity for fructan degradation

<i>Ex Vivo</i> Fermentation of Hay and Corn by Rumen Bacteria from Cattle and Sheep

Sheep are often utilized as a model ruminant, despite a lack of functional comparisons of rumen bacterial communities and responses during dietary transitions between sheep and cattle. Therefore, an ex vivo study was conducted to evaluate species differences. Rumen fluid was obtained from hay-fed sheep and cattle (n = 3 species−1). Mixed bacterial cell suspensions in buffered media containing 3% w/v ground hay, corn, or combinations (2:1, 1:2) of substrates were incubated (24 h; 39 °C). Suspension pH, lactate, volatile fatty acids (VFA), and digestibility were assessed, functional guilds enumerated, and amylolytic bacteria isolated. Lactate was fully utilized in all hay incubations, and pH did not differ between species (p > 0.75). In contrast, digestibility, lactate accumulation, and pH decline were greater in bovine suspensions fermenting corn (p Streptococcus bovis was the predominant bacteria regardless of species, but total amylolytic bacteria were 10-fold greater in bovine suspensions (p p p > 0.28). Overall, these results demonstrate differential feed utilization capacities in rumen microbial communities of sheep and cattle as well as potential differences in rumen acidosis susceptibility

Impaired Arousal in Older Adults Is Associated With Prolonged Hospital Stay and Discharge to Skilled Nursing Facility

Background: Poor cognitive function is associated with negative consequences across settings of care, but research instruments are arduous for routine clinical implementation. This study examined the association between impaired arousal, as measured using an ultra-brief screen, and risk of 2 adverse clinical outcomes: hospital length of stay and discharge to a skilled nursing facility (SNF). Design, Setting, and Participants: A secondary data analysis was conducted using 2 separate groups of medical ward patients: a Veterans Affairs medical center in the northeast (N = 1487, between 2010 and 2012) 60 years and older and a large tertiary care, university-based medical center (N = 669, between 2007 and 2013) 65 years and older in the southeastern United States. Measurements: The impact of impaired arousal, defined by the Richmond Agitation Sedation Scale as anything other than awake and alert, was determined using Cox Proportional Hazard Regression for time to hospital discharge and logistic regression for discharge to a SNF. Hazard ratios (HRs) and odds ratios (OR) with their 95% confidence intervals (CI) are reported, respectively. Both models were adjusted age, sex, and dementia. Results: The 2156 total patients included in these groups had a mean age of 76 years, of whom 16.4% in group 1 and 28.5% in group 2 had impaired arousal. In the first group, patients with normal arousal spent an average of 5.9 days (standard deviation 6.2) in the hospital, while those with impaired arousal spent 8.5 days (9.2). On any given day, patients with impaired arousal had 27% lower chance of being discharged (adjusted HR 0.73 (95% CI 0.63-0.84). In the second group, individuals with normal arousal spent 3.8 (4.1) days in the hospital compared with 4.7 (4.6) for those with impaired arousal; indicating a 21% lower chance of being discharged [adjusted HR 0.79 (95% CI 0.66-0.95). With regard to risk of discharge to SNF, those with impaired arousal in group 1 had a 65% higher risk than those without impaired arousal [adjusted OR 1.65 (95% CI 1.21-2.25)], and those in group 2 had a nonsignificant 27% higher risk [adjusted OR 1.27 (0.80-2.03)]. Because of the quality improvement nature, this analysis did not control for comorbidities, which is a significant limitation. Conclusions: In this study of over 2000 older hospitalized patients, the simple observation of an abnormal arousal level may be an independent predictor of a longer hospital stay and discharge to SNF

Impaired Arousal in Older Adults Is Associated With Prolonged Hospital Stay and Discharge to Skilled Nursing Facility

BACKGROUND: Poor cognitive function is associated with negative consequences across settings of care, but research instruments are arduous for routine clinical implementation. This study examined the association between impaired arousal, as measured using an ultra-brief screen, and risk of two adverse clinical outcomes: hospital length of stay and discharge to a skilled nursing facility (SNF). DESIGN, SETTING, & PARTICIPANTS: A secondary data analysis was conducted using two separate groups of medical ward patients: a VA medical center in the northeast (N=1,487, between 2010 and 2012) 60 years and older and a large tertiary care, university-based medical center (N=669, between 2007 and 2013) 65 years and older in the southeastern United States. MEASUREMENTS: The impact of impaired arousal, defined by the Richmond Agitation Sedation Scale (RASS) as anything other than “awake and alert,” was determined using Cox Proportional Hazard Regression for time to hospital discharge and logistic regression for discharge to a SNF. Hazard ratios (HR) and odds ratios (OR) with their 95% confidence intervals (CI) are reported, respectively. Both models were adjusted age, sex, and dementia. RESULTS: The 2,156 total patients included in these groups had a mean age of 76 years, of whom 16.4% in group one and 28.5% in group two had impaired arousal. In the first group, patients with normal arousal spent an average of 5.9 days (SD 6.2) in the hospital, while those with impaired arousal spent 8.5 days (9.2). On any given day, patients with impaired arousal had 27% lower chance of being discharged (adjusted hazard ratio 0.73 (95%CI: 0.63 – 0.84). In the second group, individuals with normal arousal spent 3.8 (4.1) days in the hospital compared to 4.7 (4.6) for those with impaired arousal; indicating a 21% lower chance of being discharged [adjusted HR 0.79 (95%CI: 0.66 – 0.95). With regard to risk of discharge to SNF, those with impaired arousal in group 1 had a 65% higher risk than those without impaired arousal [adjusted OR 1.65 (95%CI: 1.21 – 2.25)], and those in group 2 had a non-significant 27% higher risk [adjusted OR 1.27 (0.80 – 2.03)]. Due to the quality improvement nature, this analysis did not control for comorbidities, which is a significant limitation. CONCLUSIONS: In this study of over 2,000 older hospitalized patients, the simple observation of an abnormal arousal level may be an independent predictor of a longer hospital stay and discharge to SNF