Ashley Ann Huggins

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• Harb, F., Liuzzi, M., Huggins, A., Webb, E., Fitzgerald, J., Krukowski, J., deRoon-Cassini, T., & Larson, C. (2024). Childhood Maltreatment and Amygdala-Mediated Anxiety and Posttraumatic Stress Following Adult Trauma. Biological Psychiatry Global Open Science, 4(4). doi:10.1016/j.bpsgos.2024.100312
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  Background: Childhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. Methods: Two weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. Results: Childhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013–0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. Conclusions: Amygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood.
• Huggins, A., Baird, C., Briggs, M., Laskowitz, S., Hussain, A., Fouda, S., Haswell, C., Sun, D., Salminen, L., Jahanshad, N., Thomopoulos, S., Veltman, D., Frijling, J., Olff, M., van Zuiden, M., Koch, S., Nawjin, L., Wang, L., Zhu, Y., , Li, G., et al. (2024). Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup. Molecular Psychiatry, 29(3). doi:10.1038/s41380-023-02352-0
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  Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.
• Laskowitz, S., Baird, C., Huggins, A., Nadareishvili, N., Bride, J., Wagner, H., Briggs, M., Morey, R., & Turner, R. (2024). Effects of mTBI with loss of consciousness on neurobehavioral symptoms, depression, and insomnia in former collegiate and NFL football athletes. Brain Injury, 38(11). doi:10.1080/02699052.2024.2347552
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  Objective: Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment. Setting: Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes (n = 177) between the ages of 27 and 85 (M = 54.1, SD = 14.7). Design: Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms. Results: Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p =
• Liuzzi, M., Harb, F., Petranu, K., Huggins, A., Webb, E., Fitzgerald, J., Krukowski, J., Miskovich, T., deRoon-Cassini, T., & Larson, C. (2024). The Dichotomy of Threat and Deprivation as Subtypes of Childhood Maltreatment: Differential Functional Connectivity Patterns of Threat and Reward Circuits in an Adult Trauma Sample. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(2). doi:10.1016/j.bpsc.2023.10.001
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  Background: Childhood maltreatment is associated with reduced activation of the nucleus accumbens, a central region in the reward network, and overactivity in the amygdala, a key region in threat processing. However, the long-lasting impact of these associations in the context of later-life stress is not well understood. The current study explored the association between childhood threat and deprivation and functional connectivity of threat and reward regions in an adult trauma sample. Methods: Trauma survivors (N = 169; mean age [SD] = 32.2 [10.3] years; female = 55.6%) were recruited from a level I trauma center. Two weeks after injury, participants completed the Childhood Trauma Questionnaire (measuring experiences of threat and deprivation) and underwent resting-state functional magnetic resonance imaging. Seed-to-voxel analyses evaluated the effect of childhood threat and deprivation on amygdala and nucleus accumbens resting-state connectivity. Results: Higher levels of threat were associated with increased connectivity between the right nucleus accumbens with temporal fusiform gyrus/parahippocampal gyrus and the left amygdala and the precuneus (false discovery rate–corrected p < .05). After controlling for posttraumatic symptoms 2 weeks posttrauma and lifetime trauma exposure, only the nucleus accumbens findings survived. There were no significant relationships between experiences of childhood deprivation and amygdala or nucleus accumbens connectivity. Conclusions: Experiences of threat are associated with increased nucleus accumbens and amygdala connectivity, which may reflect a preparedness to detect salient and visual stimuli. This may also reflect a propensity toward dysregulated reward processing. Overall, these results suggest that childhood threat may be contributing to aberrant neural baseline reward and threat sensitivity later in life in an adult trauma sample.
• Morey, R., Zheng, Y., Bayly, H., Sun, D., Garrett, M., Gasperi, M., Maihofer, A., Baird, C., Grasby, K., Huggins, A., Haswell, C., Thompson, P., Medland, S., Gustavson, D., Panizzon, M., Kremen, W., Nievergelt, C., Ashley-Koch, A., & Logue, M. (2024). Genomic structural equation modeling reveals latent phenotypes in the human cortex with distinct genetic architecture. Translational Psychiatry, 14(1). doi:10.1038/s41398-024-03152-y
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  Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for 34 brain regions recently reported in the ENIGMA cortical GWAS. Genomic SEM uses the empirical genetic covariance estimated from GWAS summary statistics with LD score regression (LDSC) to discover factors underlying genetic covariance, which we are denoting genetically informed brain networks (GIBNs). Genomic SEM can fit a multivariate GWAS from summary statistics for each of the GIBNs, which can subsequently be used for LD score regression (LDSC). We found the best-fitting model of cortical SA identified 6 GIBNs and CT identified 4 GIBNs, although sensitivity analyses indicated that other structures were plausible. The multivariate GWASs of the GIBNs identified 74 genome-wide significant (GWS) loci (p < 5 × 10−8), including many previously implicated in neuroimaging phenotypes, behavioral traits, and psychiatric conditions. LDSC of GIBN GWASs found that SA-derived GIBNs had a positive genetic correlation with bipolar disorder (BPD), and cannabis use disorder, indicating genetic predisposition to a larger SA in the specific GIBN is associated with greater genetic risk of these disorders. A negative genetic correlation was observed between attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD). CT GIBNs displayed a negative genetic correlation with alcohol dependence. Even though we observed model instability in our application of genomic SEM to high-dimensional data, jointly modeling the genetic architecture of complex traits and investigating multivariate genetic links across neuroimaging phenotypes offers new insights into the genetics of cortical structure and relationships to psychopathology.
• Suarez-Jimenez, B., Lazarov, A., Zhu, X., Zilcha-Mano, S., Kim, Y., Marino, C., Rjabtsenkov, P., Bavdekar, S., Pine, D., Bar-Haim, Y., Larson, C., Huggins, A., Tomas, C., Fitzgerald, J., Kennis, M., Varkevisser, T., Geuze, E., El Hage, W., Wang, X., , O'Leary, E., et al. (2024). Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification by the ENIGMA PTSD Consortium. Biological Psychiatry Global Open Science, 4(1). doi:10.1016/j.bpsgos.2023.05.006
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  Background: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. Methods: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n = 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and trauma-exposed (TE)–only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. A random forest classification model was built on a training set using cross-validation, and the averaged cross-validation model performance for classification was evaluated using the area under the curve. The model was tested using a fully independent portion of the data (test dataset), and the test area under the curve was evaluated. Results: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and ITRED-only participants mainly involved default mode network–related pathways. Some unique features, such as connectivity within the frontoparietal network, differentiated TE-only participants from one group (PTSD or ITRED-only) but to a lesser extent from the other group. Conclusions: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.
• Yang, J., Huggins, A., Sun, D., Baird, C., Haswell, C., Frijling, J., Olff, M., van Zuiden, M., Koch, S., Nawijn, L., Veltman, D., Suarez-Jimenez, B., Zhu, X., Neria, Y., Hudson, A., Mueller, S., Baker, J., Lebois, L., Kaufman, M., , Qi, R., et al. (2024). Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods. Neuropsychopharmacology, 49(3). doi:10.1038/s41386-023-01763-5
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  Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.
• Davis, K., Tomas, C., Webb, E., Huggins, A., deRoon-Cassini, T., Larson, C., & Fitzgerald, J. (2023). Neural Processes of Emotional Conflict Detection and Prediction of Posttraumatic Stress Disorder Symptom Clusters in Traumatic Injury Survivors. Psychological Trauma: Theory, Research, Practice, and Policy. doi:10.1037/tra0001586
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  Objective: Given the prevalence and significant burden of posttraumatic stress disorder (PTSD), identifying early predictors of symptom development following trauma is critical. PTSD is a heterogeneous disorder com-prised of distinct symptom clusters—reexperiencing, avoidance, negative mood, and hyperarousal—that con-tribute to the broad range of possible symptom profiles. Affective and attentional regulation processes, such as emotional conflict detection, are impaired in individuals with PTSD; however, the neural mechanisms under-lying these alterations and their predictive utility for the development of PTSD symptoms remain unclear. Method: Traumatic injury survivors (N= 49) without traumatic brain injury were recruited from the emergency department of an urban, Level-1 trauma center. Within 1 month of trauma exposure, participants completed a well-characterized emotional conflict task during a functional magnetic resonance imaging scan. Participants returned 6-month later for a clinical assessment of PTSD symptoms. Using a region-of-interest mask derived from whole-brain voxelwise analyses during emotional conflict detection (vs. no emotional conflict detection) we examined whether differential neural activity predicted 6-month PTSD symptom cluster severity. Results: Greater activation of the right middle frontal gyrus during emotional conflict detection prospectively predicted lower PTSD avoidance symptom severity 6 months later (above and beyond the effects of self-reported baseline PTSD and depressive symptoms, previous traumatic life events, racial discrimination, age, sex, and injury severity). Conclusions: Neural processes of emotion conflict detection measured in the early aftermath of a potentially traumatic event are useful as predictors for the development of PTSD symptoms.
• Fitzgerald, J., & Huggins, A. (2023). Editorial: Perspectives on PTSD and its treatment. Frontiers in Behavioral Neuroscience, 17. doi:10.3389/fnbeh.2023.1327251
• Webb, E., Timmer-Murillo, S., Huggins, A., Tomas, C., deRoon-Cassini, T., & Larson, C. (2023). Attributional negativity bias and acute stress disorder symptoms mediate the association between trauma history and future posttraumatic stress disorder. Journal of Traumatic Stress, 36(4). doi:10.1002/jts.22942
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  Individuals who have experienced more trauma throughout their life have a heightened risk of developing posttraumatic stress disorder (PTSD) following injury. Although trauma history cannot be retroactively modified, identifying the mechanism(s) by which preinjury life events influence future PTSD symptoms may help clinicians mitigate the detrimental effects of past adversity. The current study proposed attributional negativity bias, the tendency to perceive stimuli/events as negative, as a potential intermediary in PTSD development. We hypothesized an association between trauma history and PTSD symptom severity following a new index trauma via heightened negativity bias and acute stress disorder (ASD) symptoms. Recent trauma survivors (N =189, 55.5% women, 58.7% African American/Black) completed assessments of ASD, negativity bias, and lifetime trauma 2-weeks postinjury; PTSD symptoms were assessed 6 months later. A parallel mediation model was tested with bootstrapping (10,000 resamples). Both negativity bias, Path b1: β = −.24, t(187) = −2.88, p =.004, and ASD symptoms, Path b2: β =.30, t(187) = 3.71, p
• Zhu, X., Kim, Y., Ravid, O., He, X., Suarez-Jimenez, B., Zilcha-Mano, S., Lazarov, A., Lee, S., Abdallah, C., Angstadt, M., Averill, C., Baird, C., Baugh, L., Blackford, J., Bomyea, J., Bruce, S., Bryant, R., Cao, Z., Choi, K., , Cisler, J., et al. (2023). Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium. NeuroImage, 283. doi:10.1016/j.neuroimage.2023.120412
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  Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for D-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.
• Fitzgerald, J., Webb, E., Weis, C., Huggins, A., Bennett, K., Miskovich, T., Krukowski, J., deRoon-Cassini, T., & Larson, C. (2022). Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 7(2). doi:10.1016/j.bpsc.2021.08.007
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  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.
• Tomas, C., Webb, E., Bennett, K., Huggins, A., Fitzgerald, J., Miskovich, T., Krukowki, J., deRoon-Cassini, T., & Larson, C. (2022). Neighborhood Socioeconomic Disadvantage and the Neurobiology of Uncertainty in Traumatically Injured Adults. Biological Psychiatry Global Open Science, 2(3). doi:10.1016/j.bpsgos.2022.02.006
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  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.
• Webb, E., Bird, C., Deroon-Cassini, T., Weis, C., Huggins, A., Fitzgerald, J., Miskovich, T., Bennett, K., Krukowski, J., Torres, L., & Larson, C. (2022). Racial Discrimination and Resting-State Functional Connectivity of Salience Network Nodes in Trauma-Exposed Black Adults in the United States. JAMA Network Open. doi:10.1001/jamanetworkopen.2021.44759
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  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.
• Weis, C., Bennett, K., Huggins, A., Parisi, E., Gorka, S., & Larson, C. (2022). A 7-Tesla MRI study of the periaqueductal gray: Resting state and task activation under threat. Social Cognitive and Affective Neuroscience, 17(2). doi:10.1093/scan/nsab085
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  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.
• Huggins, A., Weis, C., Parisi, E., Bennett, K., Miskovic, V., & Larson, C. (2021). Neural substrates of human fear generalization: A 7T-fMRI investigation. NeuroImage, 239. doi:10.1016/j.neuroimage.2021.118308
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  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.
• Ritchay, M., Huggins, A., Wallace, A., Larson, C., & Lisdahl, K. (2021). Resting state functional connectivity in the default mode network: Relationships between cannabis use, gender, and cognition in adolescents and young adults. NeuroImage: Clinical, 30. doi:10.1016/j.nicl.2021.102664
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  Introduction: Cannabis is the most commonly used illicit substance in the United States, and nearly 1 in 4 young adults are current cannabis users. Chronic cannabis use is associated with changes in resting state functional connectivity (RSFC) in the default mode network (DMN) in adolescents and young adults; results are somewhat inconsistent across studies, potentially due to methodological differences. The aims of the present study were to examine potential differences in DMN RSFC between cannabis users and controls, and to examine, as an exploratory analysis, if gender moderated any findings. We further examined whether differences in RSFC related to differences in performance on selected neuropsychological measures. Materials and methods: Seventy-seven 16–26-year-old participants underwent an MRI scan (including resting state scan), neuropsychological battery, toxicology screening, and drug use interview. Differences in DMN connectivity were examined between groups (cannabis vs. control) and with an exploratory group by gender interaction, using a left posterior cingulate cortex (PCC) seed-based analysis conducted in AFNI. Results: Cannabis users demonstrated weaker connectivity than controls between the left PCC and various DMN nodes, and the right Rolandic operculum/Heschl's gyrus. Cannabis users demonstrated stronger connectivity between the left PCC and the cerebellum and left supramarginal gyrus. The group by gender interaction was not significantly associated with connectivity differences. Stronger left PCC—cerebellum connectivity was associated with poorer performance on cognitive measures in cannabis users. In controls, intra-DMN connectivity was positively correlated with performance on a speeded selective/sustained attention measure. Discussion: Consistent with our hypotheses and other studies, cannabis users demonstrated weaker connectivity between the left PCC and DMN nodes. Chronic THC exposure may alter GABA and glutamate concentrations, which may alter brain communication. Future studies should be conducted with a larger sample size and examine gender differences and the mechanism by which these differences may arise.
• Webb, E., Weis, C., Huggins, A., Fitzgerald, J., Bennett, K., Bird, C., Parisi, E., Kallenbach, M., Miskovich, T., Krukowski, J., deRoon-Cassini, T., & Larson, C. (2021). Neural impact of neighborhood socioeconomic disadvantage in traumatically injured adults. Neurobiology of Stress, 15. doi:10.1016/j.ynstr.2021.100385
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  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.
• Webb, E., Weis, C., Huggins, A., Parisi, E., Bennett, K., Miskovich, T., Krukowski, J., deRoon-Cassini, T., & Larson, C. (2021). Neighborhood disadvantage is associated with stable deficits in neurocognitive functioning in traumatically-injured adults. Health and Place, 67. doi:10.1016/j.healthplace.2020.102493
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  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.
• Weis, C., Huggins, A., Miskovich, T., Fitzgerald, J., Bennett, K., Krukowski, J., Webb, E., deRoon-Cassini, T., & Larson, C. (2021). Acute White Matter Integrity Post-trauma and Prospective Posttraumatic Stress Disorder Symptoms. Frontiers in Human Neuroscience, 15. doi:10.3389/fnhum.2021.742198
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  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.
• Weis, C., Webb, E., Huggins, A., Kallenbach, M., Miskovich, T., Fitzgerald, J., Bennett, K., Krukowski, J., deRoon-Cassini, T., & Larson, C. (2021). Stability of hippocampal subfield volumes after trauma and relationship to development of PTSD symptoms. NeuroImage, 236. doi:10.1016/j.neuroimage.2021.118076
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  Background: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus’ functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0. Methods: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. Results: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl – T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. Conclusion: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).
• Huggins, A., Harvey, A., Miskovich, T., Lee, H., & Larson, C. (2020). Resting-state functional connectivity of supplementary motor area associated with skin-picking symptom severity. Journal of Obsessive-Compulsive and Related Disorders, 26. doi:10.1016/j.jocrd.2020.100551
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  Pathological skin picking (excoriation) is a relatively common disorder. Although it has been hypothesized to share a similar pathophysiological basis as other obsessive-compulsive (OC) spectrum disorders, to date, little work has specifically examined the precise neurobiological mechanisms involved in excoriation. Disruption in functional circuits involving the right inferior frontal gyrus (rIFG) and supplementary motor area (SMA) may be particularly relevant to skin-picking pathology as these regions have been implicated in other OC-spectrum disorders for their roles in response inhibition and voluntary motor action, respectively. To this end, the present study examined the associations between skin-picking symptom severity and resting-state functional connectivity of the rIFG and bilateral SMA. Participants endorsing elevated symptoms of excoriation completed a self-report measure of symptom severity and resting-state functional magnetic resonance imaging scan. Results indicated that symptom severity was associated with weaker connectivity between the SMA and clusters within the orbitofrontal cortex and angular gyrus. Contrary to hypotheses, there were no effects of symptom severity on functional connectivity of the rIFG. Overall, these findings suggest that skin-picking symptom severity may be associated with disruption in higher-order motor networks contributing to deficits in top-down regulation of motor behavior.
• Webb, E., Huggins, A., Belleau, E., Taubitz, L., Hanson, J., deRoon-Cassini, T., & Larson, C. (2020). Acute Posttrauma Resting-State Functional Connectivity of Periaqueductal Gray Prospectively Predicts Posttraumatic Stress Disorder Symptoms. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 5(9). doi:10.1016/j.bpsc.2020.03.004
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  Background: Posttraumatic stress disorder (PTSD) is characterized by hyperarousal, avoidance, and intrusive/re-experiencing symptoms. The periaqueductal gray (PAG), which generates behavioral responses to physical and psychological stressors, is also implicated in threat processing. Distinct regions of the PAG elicit opposing responses to threatening or stressful stimuli; the ventrolateral PAG evokes passive coping strategies (e.g., analgesia), whereas the dorsolateral PAG (dlPAG) promotes active responses (e.g., fight or flight). We investigated whether altered PAG resting-state functional connectivity (RSFC) prospectively predicted PTSD symptoms. Methods: A total of 48 trauma-exposed individuals underwent an RSFC scan 2 weeks posttraumatic injury. Self-report measures, including the visual analog scale for pain and the Impact of Event Scale, were collected at 2 weeks and 6 months posttrauma. We analyzed whether acute bilateral PAG RSFC was a marker of risk for total 6-month symptom severity and specific symptom clusters. In an exploratory analysis, we investigated whether dlPAG RSFC predicted PTSD symptoms. Results: After adjusting for physical pain ratings, greater acute posttrauma PAG–frontal pole and PAG–posterior cingulate cortex connectivity was positively associated with 6-month total PTSD symptoms. Weaker dlPAG–superior/inferior parietal lobule connectivity predicted both higher hyperarousal and higher intrusive symptoms, while weaker dlPAG–supramarginal gyrus RSFC was associated with only hyperarousal symptoms. Conclusions: Altered connectivity of the PAG 2 weeks posttrauma prospectively predicted PTSD symptoms. These findings suggest that aberrant PAG function may serve as a marker of risk for chronic PTSD symptoms, possibly by driving specific symptom clusters, and more broadly that connectivity of specific brain regions may underlie specific symptom profiles.
• Huggins, A., Weinberg, A., Gorka, S., & Shankman, S. (2019). Blunted neural response to gains versus losses associated with both risk-prone and risk-averse behavior in a clinically diverse sample. Psychophysiology, 56(6). doi:10.1111/psyp.13342
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  Reduced responsiveness to reward has been associated with both risk-prone and risk-averse behavior, common features of externalizing and internalizing psychopathology, respectively. Thus, evidence has suggested a potential quadratic relationship (i.e., inverted U) between reward sensitivity and risk-taking propensity. Blunted response to reward compared to loss may therefore demonstrate transdiagnostic utility as it relates to different patterns of maladaptive risk behavior. The current study sought to disentangle the relationship between risk and reward in a clinically diverse sample. In a sample of 210 adults (aged 18–30), the RewP (an ERP indexing differentiation between rewards and losses) was measured during a monetary guessing game, and risk-taking propensity was measured with a behavioral task (i.e., BART) that simulates real-world risk taking. Participants also completed clinical assessments to assess for lifetime psychopathology. Results indicated that there was no linear association between the RewP and risk-taking propensity; however, there was a significant quadratic relationship. Thus, a reduced sensitivity to reward receipt was associated with both risk-prone and risk-averse behavior. There was also a significant quadratic relationship between the RewP and money won during the BART, indicating that being too risk prone or risk averse is disadvantageous and leads to missed reward. Overall, these findings suggested that blunted neural differentiation between gains and losses may contribute to deficits in effectively weighing reward and loss and result in maladaptive risk-taking behavior. These findings support continued examination of reward dysfunction dimensionally in order to better characterize behavioral profiles implicated in clinical phenotypes.
• Weis, C., Huggins, A., Bennett, K., Parisi, E., & Larson, C. (2019). High-Resolution Resting-State Functional Connectivity of the Extended Amygdala. Brain Connectivity, 9(8). doi:10.1089/brain.2019.0688
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  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.
• Huggins, A., Belleau, E., Miskovich, T., Pedersen, W., & Larson, C. (2018). Moderating effects of harm avoidance on resting-state functional connectivity of the anterior insula. Frontiers in Human Neuroscience, 12. doi:10.3389/fnhum.2018.00447
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  As an index of behavioral inhibition and an individual’s propensity to avoid, rather than seek, potentially dangerous situations, harm avoidance has been linked to internalizing psychopathology. Altered connectivity within intrinsic functional neural networks (i.e., default mode [DMN], central executive [CEN] and salience networks [SN]) has been related to internalizing psychopathology; however, less is known about the effects of harm avoidance on functional connectivity within and between these networks. Importantly, harm avoidance may be distinguishable from trait anxiety and have clinical relevance as a risk factor for internalizing psychopathology. A sample of young adults (n = 99) completed a resting state functional magnetic resonance imaging (fMRI) scan and self-report measures of harm avoidance and trait anxiety. Whole brain seed-to-voxel and seed-to-network connectivity analyses were conducted using anterior insula seeds to examine associations between harm avoidance/trait anxiety and connectivity. After adjusting for sex and age, there was a significant negative effect of harm avoidance on connectivity between the anterior insula and clusters in the precuneus/posterior cingulate cortex (PCC) left superior/middle frontal gyrus, dorsal anterior cingulate cortex (dACC) and bilateral inferior parietal lobule (IPL)/angular gyrus. Seed-to-network analyses indicated a negative effect of harm avoidance on connectivity between the right anterior insula and anterior and posterior DMN. There were no effects of trait anxiety on functional connectivity of the anterior insula. Overall, the results indicate that individual differences in harm avoidance relate to disruptions in internetwork connectivity that may contribute to deficits in appropriately modulating attentional focus.
• Lieberman, L., Stevens, E., Funkhouser, C., Weinberg, A., Sarapas, C., Huggins, A., & Shankman, S. (2017). How many blinks are necessary for a reliable startle response? A test using the NPU-threat task. International Journal of Psychophysiology, 114. doi:10.1016/j.ijpsycho.2017.01.012
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  Emotion-modulated startle is a frequently used method in affective science. Although there is a growing literature on the reliability of this measure, it is presently unclear how many startle responses are necessary to obtain a reliable signal. The present study therefore evaluated the reliability of startle responding as a function of number of startle responses (NoS) during a widely used threat-of-shock paradigm, the NPU-threat task, in a clinical (N = 205) and non-clinical (N = 92) sample. In the clinical sample, internal consistency was also examined independently for healthy controls vs. those with panic disorder and/or major depression and retest reliability was assessed as a function of NoS. Although results varied somewhat by diagnosis and for retest reliability, the overall pattern of results suggested that six startle responses per condition were necessary to obtain acceptable reliability in clinical and non-clinical samples during this threat-of-shock paradigm in the present study.
• Lieberman, L., Gorka, S., Huggins, A., Katz, A., Sarapas, C., & Shankman, S. (2016). Agreement between self- and informant-reported ratings of personality traits: The moderating effects of major depressive and/or panic disorder. Journal of Nervous and Mental Disease, 204(4). doi:10.1097/nmd.0000000000000448
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  Several personality traits are risk factors for psychopathology. As symptoms of psychopathology may influence self-rated personality, informant reports of personality are also sometimes collected. However, little is known about self-informant agreement in individuals with anxiety and/or depression. We investigated whether self-informant agreement on positive and negative affectivity (PA and NA) and anxiety sensitivity differs for individuals with major depressive disorder (MDD) and/or panic disorder (PD; total n = 117). Informant- and self-reported PA was correlated among those with MDD, but not among those without MDD. Informant- and self-reported anxiety sensitivity was correlated among those with PD, but not among those without PD. Informant- and self-reported NAwas correlated irrespective of diagnosis. Results indicate that the agreement of self- and informant-reported personality may vary as a function of depression and/or anxiety disorders.
• Lieberman, L., Liu, H., Huggins, A., Katz, A., Zvolensky, M., & Shankman, S. (2016). Comparing the validity of informant and self-reports of personality using laboratory indices of emotional responding as criterion variables. Psychophysiology, 53(9). doi:10.1111/psyp.12680
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  Personality traits relate to risk for psychopathology and can inform predictions about treatment outcome. In an effort to obtain a comprehensive index of personality, informant reports of personality are sometimes obtained in addition to self-reports of personality. However, there is limited research comparing the validity of self- and informant reports of personality, particularly among those with internalizing psychopathology. This is important given that informants may provide an additional (and perhaps different) perspective on individuals' personality. The present study therefore compared how both reports of positive affectivity (PA) and negative affectivity (NA) relate to psychophysiological and subjective measures of emotional responding to positive and negative stimuli. Given that our sample (n = 117) included individuals with no history of psychopathology, as well as individuals with major depressive disorder (MDD) and/or panic disorder (PD), we were also able to explore whether these internalizing diagnoses moderated the association between personality reports and measures of emotional responding. Informant-reported PA predicted physiological responses to positive stimuli (but not negative). Informant-reported NA predicted physiological responses to negative stimuli (but not positive). Self-reported personality did not predict physiological responding, but did predict subjectively measured emotional responding (NA for negative responding, PA for positive responding). Diagnoses of internalizing psychopathology (PD or MDD) did not moderate these associations. Results suggest self- and informant reports of personality may each provide valid indices of an individual's emotional response tendencies, but predict different aspects of those tendencies.
• Gorka, S., Huggins, A., Fitzgerald, D., Nelson, B., Phan, K., & Shankman, S. (2014). Neural response to reward anticipation in those with depression with and without panic disorder. Journal of Affective Disorders, 164. doi:10.1016/j.jad.2014.04.019
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  Background One of the hallmark features of major depressive disorder (MDD) is reduced reward anticipation. There have been mixed findings in the literature as to whether reward anticipation deficits in MDD are related to diminished mesolimbic activation and/or enhanced dorsal anterior cingulate activation (dACC). One of the reasons for these mixed findings is that these studies have typically not addressed the role of comorbid anxiety, a class of disorders which frequently co-occur with depression and have a common neurobiology. Methods The aim of the current study was to examine group differences in neural responses to reward anticipation in 40 adults with either: (1) current MDD with no lifetime diagnosis of an anxiety disorder (MDD-only), (2) current MDD with comorbid panic disorder (MDD-PD), or (3) no lifetime diagnosis of psychopathology. All participants completed a passive slot machine task during a functional magnetic resonance imaging (fMRI) scan. Results Analyses indicated that there were no group differences in activation of mesolimbic reward regions; however, the MDD-only group exhibited greater dACC activation during the anticipation of rewards compared with the healthy controls and the comorbid MDD-PD group (who did not differ from each other). Limitations The sample size was small which limits generalizability. Conclusions These findings provide preliminary support for the role of hyperactive dACC functioning in reduced reward anticipation in MDD. They also indicate that comorbid anxiety may alter the association between MDD and neural responding to reward anticipation. © 2014 Elsevier B.V.