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Scholarly Works (8 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2014)

This dissertation is a two-paper investigation of the basic associative and arousal-based processes involved in reinstatement of conditional fear. Clarifying the factors involved in reinstatement of fear--a behavioral phenomenon in which the experience of an aversive event following fear extinction produces a return of fear--provides a better understanding of the factors that contribute to the waxing and waning of untreated fear and the return of fear following exposure treatment. Shedding light on the processes involved in reinstatement of fear will contribute to the development of science-based interventions that offset return of fear following fear extinction and improve long term outcomes from exposure therapies for phobias and anxiety disorders.

Study 1 compared the effects of physical pain versus social pain as a reinstating US on reinstatement of conditioned fear, and compared standard reinstatement (same acquisition and reinstatement US) with cross-US reinstatement (different acquisition and reinstatement US). Results indicated that in standard reinstatement procedures social pain produced differential reinstatement of conditional responding, while physical pain produced non-differential reinstatement (i.e., sensitization) in standard and cross-US reinstatement procedures.

Study 2 aimed to replicate the findings from Study 1, and investigated the role of CS+ belongingness on reinstating of fear. Combining data from both studies, the hypothesis was tested that greater physiological arousal experienced during the reinstatement would predict greater post-reinstatement return of conditional responding. Results replicated Study 1 findings, and found that CS+ belongingness may promote differential return of conditional responding in both standard and cross-US reinstatement. Additionally, findings indicated that higher arousal experienced during reinstatement predicts greater non-differential reinstatement, while concordance between arousal experienced during acquisition and reinstatement does not.

In sum, these studies indicate that both social pain and physical pain can reinstate extinguished fear. Social pain promoted differential return of conditional responding (in standard reinstatement) while physical pain elicited a non-differential increase in responding in both standard and cross-US reinstatement. Unforeseen methodological issues may have muddled the findings regarding cross-US reinstatement with qualitatively distinct USs, while providing tentative evidence that individuals under chronic stress might be at elevated risk of an acute stressor triggering a return of fear generalized beyond the original feared stimulus.

    Cover page: Arousal and Associative Processes in Reinstatement of Fear
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2015)
    The use of quantitative, laboratory-based measures of threat in humans for proof-of-concept studies and target development for novel drug discovery has grown tremendously in the last 2 decades. In particular, in the field of posttraumatic stress disorder (PTSD), human models of fear conditioning have been critical in shaping our theoretical understanding of fear processes and importantly, validating findings from animal models of the neural substrates and signaling pathways required for these complex processes. Here, we will review the use of laboratory-based measures of fear processes in humans including cued and contextual conditioning, generalization, extinction, reconsolidation, and reinstatement to develop novel drug treatments for PTSD. We will primarily focus on recent advances in using behavioral and physiological measures of fear, discussing their sensitivity as biobehavioral markers of PTSD symptoms, their response to known and novel PTSD treatments, and in the case of d-cycloserine, how well these findings have translated to outcomes in clinical trials. We will highlight some gaps in the literature and needs for future research, discuss benefits and limitations of these outcome measures in designing proof-of-concept trials, and offer practical guidelines on design and interpretation when using these fear models for drug discovery.
      Cover page: On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2019)
      Contextual threat learning is often associated with two processes: elemental and configural learning. Few studies have examined configural learning where subjects form a representation of the threat-related context as a gestalt whole from the individual features in the environment. The goal of the current study was to compare and contrast neural circuitry recruited by variation in demands placed on configural threat encoding. Subjects (N = 25) completed a configural threat learning task, where we manipulated the amount of configural encoding required to learn the threat association (low demand: changes to a discrete element of the context; and high demand: rearrangement of elements). US expectancy ratings, skin conductance responses (SCR), and functional magnetic resonance imaging (fMRI) were collected. Subjects successfully learned the configural threat association as measured by US expectancy ratings, SCR, and BOLD activity. Hippocampal and amygdala region of interest analyses indicated differential configural threat learning and predicted SCR measures of learning. Furthermore, whole brain analyses identified four circuits that were impacted by the amount of differential configural encoding required, but none correlated with SCR. These results set the stage for a more detailed understanding of how configural threat learning is instantiated in the brain-an important mechanism associated with PTSD and other fear-related disorders.
        Cover page: Characterizing the neural circuitry associated with configural threat learning
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2016)

        Background

        Heightened startle response is a symptom of PTSD, but evidence for exaggerated startle in PTSD is inconsistent. This prospective study aimed to clarify whether altered startle reactivity represents a trait risk-factor for developing PTSD or a marker of current PTSD symptoms.

        Methods

        Marines and Navy Corpsmen were assessed before (n = 2,571) and after (n = 1,632) deployments to Iraq or Afghanistan with the Clinician-Administered PTSD Scale (CAPS). A predeployment startle-threshold task was completed with startle probes presented over 80-114 dB[A] levels. Latent class mixture modeling identified three growth classes of startle performance: "high," "low," and "moderate" threshold classes. Zero-inflated negative binomial regression was used to assess relationships between predeployment startle threshold and pre- and postdeployment psychiatric symptoms.

        Results

        At predeployment, the low-threshold class had higher PTSD symptom scores. Relative to the moderate-threshold class, low-threshold class membership was associated with decreased likelihood of being symptom-free at predeployment, based on CAPS, with particular associations with numbing and hyperarousal subscales, whereas high-threshold class membership was associated with more severe predeployment PTSD symptoms, in particular avoidance. Associations between low-threshold membership and CAPS symptoms were independent from measures of trauma burden, whereas associations between high-threshold membership and CAPS were not. Predeployment startle threshold did not predict postdeployment symptoms.

        Conclusions

        This study found that both low startle threshold (heightened reactivity) and high startle threshold (blunted reactivity) were associated with greater current PTSD symptomatology, suggesting that startle reactivity is associated with current PTSD rather than a risk marker for developing PTSD.
          Cover page: HIGH AND LOW THRESHOLD FOR STARTLE REACTIVITY ASSOCIATED WITH PTSD SYMPTOMS BUT NOT PTSD RISK: EVIDENCE FROM A PROSPECTIVE STUDY OF ACTIVE DUTY MARINES
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2018)
          Contextual threat learning reflects two often competing processes: configural and elemental learning. Configural threat learning is a hippocampal-dependent process of forming a conjunctive representation of a context through binding of several multi-modal elements. In contrast, elemental threat-learning is governed by the amygdala and involves forming associative relationships between individual features within the context. Contextual learning tasks in humans however, rarely probe if a learned fear response is truly due to configural learning vs. simple elemental associations. The aim of the current study was to probe both constructs separately to enable a more refined interpretation of configural vs. elemental threat learning performance and mediating circuits. Subjects (n = 25) performed both a novel feature-identical contextual threat conditioning task and a discrete cue threat acquisition task while undergoing functional magnetic resonance imaging. Results demonstrated increased hippocampus activity for the threat configuration compared to the safe configuration. This pattern was not observed in the amygdala. In contrast, elemental threat learning was associated with increased amygdala, but not hippocampus activity. Whole-brain analyses revealed that both configural and elemental threat acquisition share neural circuitry related to fear expression. These results provide support for the importance of the hippocampus specifically in configural threat acquisition and fear expression.
            Cover page: Neural measures associated with configural threat acquisition
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2017)

            Background

            It is unknown how traumatic brain injury (TBI) increases risk for posttraumatic stress disorder (PTSD). One potential mechanism is via alteration of fear-learning processes that could affect responses to trauma memories and cues. We utilized a prospective, longitudinal design to determine if TBI is associated with altered fear learning and extinction, and if fear processing mediates effects of TBI on PTSD symptom change.

            Methods

            Eight hundred fifty two active-duty Marines and Navy Corpsmen were assessed before and after deployment. Assessments included TBI history, PTSD symptoms, combat trauma and deployment stress, and a fear-potentiated startle task of fear acquisition and extinction. Startle response and self-reported expectancy and anxiety served as measures of fear conditioning, and PTSD symptoms were measured with the Clinician-Administered PTSD Scale.

            Results

            Individuals endorsing "multiple hit" exposure (both deployment TBI and a prior TBI) showed the strongest fear acquisition and highest fear expression compared to groups without multiple hits. Extinction did not differ across groups. Endorsing a deployment TBI was associated with higher anxiety to the fear cue compared to those without deployment TBI. The association of deployment TBI with increased postdeployment PTSD symptoms was mediated by postdeployment fear expression when recent prior-TBI exposure was included as a moderator. TBI associations with increased response to threat cues and PTSD symptoms remained when controlling for deployment trauma and postdeployment PTSD diagnosis.

            Conclusions

            Deployment TBI, and multiple-hit TBI in particular, are associated with increases in conditioned fear learning and expression that may contribute to risk for developing PTSD symptoms.
              Cover page: Fear learning alterations after traumatic brain injury and their role in development of posttraumatic stress symptoms
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2014)

              Objective

              In the current study, we compared measures of treatment outcome and engagement for Latino and non-Latino White patients receiving a cognitive behavioral therapy (CBT) program delivered in primary care.

              Method

              Participants were 18-65 years old and recruited from 17 clinics at 4 different sites to participate in a randomized controlled trial for anxiety disorders, which compared the Coordinated Anxiety Learning and Management (CALM) intervention (consisting of CBT, medication, or both) with usual care. Of those participants who were randomized to the intervention arm and selected CBT (either alone or in combination with medication), 85 were Latino and 251 were non-Latino White; the majority of the Latino participants received the CBT intervention in English (n = 77). Blinded assessments of clinical improvement and functioning were administered at baseline and at 6, 12, and 18 months after baseline. Measures of engagement, including attendance, homework adherence, understanding of CBT principles, and commitment to treatment, were assessed weekly during the CBT intervention.

              Results

              Findings from propensity-weighted linear and logistic regression models revealed no statistically significant differences between Latinos and non-Latino Whites on symptom measures of clinical improvement and functioning at almost all time points. There were significant differences on 2 of 7 engagement outcomes, namely, number of sessions attended and patients' understanding of CBT principles.

              Conclusions

              These findings suggest that CBT can be an effective treatment approach for Latinos who are primarily English speaking and likely more acculturated, although continued attention should be directed toward engaging Latinos in such interventions.
                Cover page: Treatment Engagement and Response to CBT Among Latinos With Anxiety Disorders in Primary Care
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2017)
                The Marine Resiliency Study-II examined changes in symptomatology across a deployment cycle to Afghanistan. U.S. Servicemembers (N = 1041) received clinical testing at two time points either bracketing a deployment (855) or not (186). Factor analyses were used to generate summary and change scores from Time 1 to Time 2. A between-subject design was used to examine changes across the deployment cycle with deployment (low-trauma, high-trauma, and non-deployed) and social support (low vs. high) as the grouping variables. Insomnia increased post-deployment regardless of deployment trauma (std. effect for high-trauma and low-trauma = 0.39 and 0.26, respectively). Only the high-trauma group showed increased PTSD symptoms and non-perspective-taking (std. effect = 0.40 and 0.30, respectively), while low-trauma showed decreased anxiety symptoms after deployment (std. effect = -0.17). These associations also depend on social support, with std. effects ranging from -0.22 to 0.51. When the groups were compared, the high-trauma deployed group showed significantly worse PTSD and non-perspective-taking than all other groups. Similar to studies in other military divisions, increased clinical symptoms were associated with high deployment stress in active duty Servicemembers, and social support shows promise as a moderator of said association.
                  Cover page: Effects of military service and deployment on clinical symptomatology: The role of trauma exposure and social support
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