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.

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 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.