Selectively Interfering With Intrusive but Not Voluntary Memories of a Trauma Film: Accounting for the Role of Associative Memory.

Intrusive memories of a traumatic event can be reduced by a subsequent interference procedure, seemingly sparing voluntary memory for that event. This selective-interference effect has potential therapeutic benefits (e.g., for emotional disorders) and legal importance (e.g., for witness testimony). However, the measurements of intrusive memory and voluntary memory typically differ in the role of associations between a cue and the emotional memory "hotspots." To test this, we asked participants to watch a traumatic film followed by either an interference procedure (reminder plus Tetris) or control procedure (reminder only). Measurement of intrusions (using a laboratory task) and voluntary memory (recognition for film stills) were crossed with the presence or absence of associative cues. The reminder-plus-Tetris group exhibited fewer intrusions despite comparable recognition memory, replicating the results of prior studies. Note that this selective interference did not appear to depend on associative cues. This involuntary versus voluntary memory dissociation for emotional material further supports separate-trace memory theories and has applied advantages.

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).

Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates.

The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor-binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.

Taxing working memory to modulate mental imagery of the 9/11 terrorist attacks following media exposure during childhood: a pilot study in young adult UK residents.

BACKGROUND AND OBJECTIVES: Media trauma in civilians is linked to intrusive imagery-based memory symptoms. We investigated whether mental imagery of the 9/11 terrorist attacks following media exposure is dampened by taxing working memory (WM). METHODS: Forty-five young adult UK residents, who were exposed to the 9/11 terrorist attacks as children via the media, identified a personally-relevant mental image of the attacks. They were then randomly allocated to: (1) recall + Tetris, (2) recall + eye movements (EMs), or (3) recall-only. Ratings on imagery vividness and emotionality were provided at three time points: pre-, post-manipulations, and at 24-hr follow-up. RESULTS: Repeated measures ANOVAs revealed that recall + Tetris and recall + EMs (relative to recall-only) significantly reduced imagery vividness and emotionality from pre- to post-manipulations, but not to follow-up. LIMITATIONS: A passive control group is needed to fully rule out the role of natural memory decay; the follow-up was exploratory and took place outside the laboratory with reduced experimental control. CONCLUSIONS: Aversive memory imagery from media trauma in civilians can be dampened by taxing WM, at least temporarily, which could be therapeutically useful. The use of such cognitive techniques may also hold relevance for public health approaches to address the impact of collective trauma.

Emotional Mental Imagery Abnormalities in Monozygotic Twins With, at High-Risk of, and Without Affective Disorders: Present in Affected Twins in Remission but Absent in High-Risk Twins.

Background: Mental imagery abnormalities feature across affective disorders including bipolar disorder (BD) and unipolar depression (UD). Maladaptive emotional imagery has been proposed as a maintenance factor for affective symptomatology and a target for mechanism-driven psychological treatment developments. Where imagery abnormalities feature beyond acute affective episodes, further opportunities for innovation arise beyond treatments, such as for tertiary/relapse prevention (e.g., in remitted individuals) or primary prevention (e.g., in non-affected but at-risk individuals). The aim of our study was to investigate for the first time the presence of possible mental imagery abnormalities in affected individuals in remission and at-risk individuals for affective disorders using a familial risk design. Methods: A population-based cohort of monozygotic twins was recruited through linkage between the Danish national registries (N=204). Participants were grouped as: affected (remitted BD/UD; n = 115); high-risk (co-twin with history of BD/UD; n = 49), or low-risk (no co-twin history of BD/UD; n = 40). Twins completed mental imagery measures spanning key subjective domains (spontaneous imagery use and emotional imagery) and cognitive domains (imagery inspection and imagery manipulation). Results: Affected twins in remission reported enhanced emotional mental imagery compared to both low- and high-risk twins. This was characterized by greater impact of i) intrusive prospective imagery (Impact of Future Events Scale) and ii) deliberately-generated prospective imagery of negative scenarios (Prospective Imagery Task). There were no significant differences in these key measures between affected BD and UD twins in remission. Additionally, low- and high-risk twins did not significantly differ on these emotional imagery measures. There were also no significant differences between the three groups on non-emotional measures including spontaneous imagery use and cognitive stages of imagery. Conclusions: Abnormalities in emotional prospective imagery are present in monozygotic twins with affective disorders in remission-despite preserved cognitive stages of imagery-but absent in unaffected high-risk twins, and thus do not appear to index familial risk (i.e., unlikely to qualify as "endophenotypes"). Elevated emotional prospective imagery represents a promising treatment/prevention target in affective disorders.

Intrusive memories of trauma: A target for research bridging cognitive science and its clinical application.

Intrusive memories of a traumatic event can be distressing and disruptive, and comprise a core clinical feature of post-traumatic stress disorder (PTSD). Intrusive memories involve mental imagery-based impressions that intrude into mind involuntarily, and are emotional. Here we consider how recent advances in cognitive science have fueled our understanding of the development and possible treatment of intrusive memories of trauma. We conducted a systematic literature search in PubMed, selecting articles published from 2008 to 2018 that used the terms "trauma" AND ("intrusive memories" OR "involuntary memories") in their abstract or title. First, we discuss studies that investigated internal (neural, hormonal, psychophysiological, and cognitive) processes that contribute to intrusive memory development. Second, we discuss studies that targeted these processes using behavioural/pharmacological interventions to reduce intrusive memories. Third, we consider possible clinical implications of this work and highlight some emerging research avenues for treatment and prevention, supplemented by new data to examine some unanswered questions. In conclusion, we raise the possibility that intrusive memories comprise an alternative, possibly more focused, target in translational research endeavours, rather than only targeting overall symptoms of disorders such as PTSD. If so, relatively simple approaches could help to address the need for easy-to-deliver, widely-scalable trauma interventions.

Intrusive Memories of Trauma in the Laboratory: Methodological Developments and Future Directions.

PURPOSE OF THE REVIEW: Intrusive memories are those that spring to mind unbidden, e.g. sensory recollections of stressful/traumatic events. We review recent methods to monitor intrusions of a stressor (a trauma film) within the laboratory. RECENT FINDINGS: Recent studies suggest three main methodologies after viewing a trauma film by which to monitor intrusions in the laboratory: during post-film rest periods, after exposure to trigger cues, and while performing an ongoing task. These approaches allow factors to be tested (e.g. psychological or pharmacological) that may influence the frequency of occurrence of intrusions. SUMMARY: We raise methodological considerations to guide trauma film studies using intrusion monitoring in the laboratory to complement monitoring approaches in daily life (e.g. diaries). Intrusion monitoring in the laboratory also confers greater experimental control and may open novel research avenues, to advance intervention development to mitigate problematic intrusive memory symptoms.

Selective Association Between Tetris Game Play and Visuospatial Working Memory: A Preliminary Investigation.

Recent experimental and clinical research has suggested that Tetris game play can disrupt maladaptive forms of mental imagery because Tetris competes for limited cognitive resources within visuospatial working memory (WM) that contribute to imagery. Whether or not Tetris performance is selectively associated with visuospatial WM remains to be tested. In this study, young adults (N = 46) completed six standardized measures indexing verbal and non-verbal reasoning, verbal and visuospatial short-term memory, and verbal and visuospatial WM. They also played Tetris. Consistent with the hypothesis that visuospatial WM resources support Tetris game play, there was a significant moderate positive relationship between Tetris scores and visuospatial WM performance but no association with other cognitive ability measures. Findings suggest that Tetris game play involves both storage and processing resources within visuospatial WM. These preliminary results can inform interventions involving computer games to disrupt the development of maladaptive visual imagery, for example, intrusive memories of trauma. © 2017 The Authors. Applied Cognitive Psychology Published by John Wiley & Sons Ltd.

An investigation of mental imagery in bipolar disorder: Exploring "the mind's eye".

OBJECTIVES: Mental imagery abnormalities occur across psychopathologies and are hypothesized to drive emotional difficulties in bipolar disorder (BD). A comprehensive assessment of mental imagery in BD is lacking. We aimed to test whether (i) mental imagery abnormalities (abnormalities in cognitive stages and subjective domains) occur in BD relative to non-clinical controls; and (ii) to determine the specificity of any abnormalities in BD relative to depression and anxiety disorders. METHODS: Participants included 54 subjects in the BD group (depressed/euthymic; n=27 in each subgroup), subjects with unipolar depression (n=26), subjects with anxiety disorders (n=25), and non-clinical controls (n=27) matched for age, gender, ethnicity, education, and premorbid IQ. Experimental tasks assessed cognitive (non-emotional) measures of mental imagery (cognitive stages). Questionnaires, experimental tasks, and a phenomenological interview assessed subjective domains including spontaneous imagery use, interpretation bias, and emotional mental imagery. RESULTS: (i) Compared to non-clinical controls, the BD combined group reported a greater impact of intrusive prospective imagery in daily life, more vivid and "real" negative images (prospective imagery task), and higher self-involvement (picture-word task). The BD combined group showed no clear abnormalities in cognitive stages of mental imagery. (ii) When depressed individuals with BD were compared to the depressed or anxious clinical control groups, no significant differences remained-across all groups, imagery differences were associated with affective lability and anxiety. CONCLUSIONS: Compared to non-clinical controls, BD is characterized by abnormalities in aspects of emotional mental imagery within the context of otherwise normal cognitive aspects. When matched for depression and anxiety, these abnormalities are not specific to BD-rather, imagery may reflect a transdiagnostic marker of emotional psychopathology.

The trauma film paradigm as an experimental psychopathology model of psychological trauma: intrusive memories and beyond.

A better understanding of psychological trauma is fundamental to clinical psychology. Following traumatic event(s), a clinically significant number of people develop symptoms, including those of Acute Stress Disorder and/or Post Traumatic Stress Disorder. The trauma film paradigm offers an experimental psychopathology model to study both exposure and reactions to psychological trauma, including the hallmark symptom of intrusive memories. We reviewed 74 articles that have used this paradigm since the earliest review (Holmes & Bourne, 2008) until July 2014. Highlighting the different stages of trauma processing, i.e. pre-, peri- and post-trauma, the studies are divided according to manipulations before, during and after film viewing, for experimental as well as correlational designs. While the majority of studies focussed on the frequency of intrusive memories, other reactions to trauma were also modelled. We discuss the strengths and weaknesses of the trauma film paradigm as an experimental psychopathology model of trauma, consider ethical issues, and suggest future directions. By understanding the basic mechanisms underlying trauma symptom development, we can begin to translate findings from the laboratory to the clinic, test innovative science-driven interventions, and in the future reduce the debilitating effects of psychopathology following stressful and/or traumatic events.

Bowel and bladder-control anxiety: a preliminary description of a viscerally-centred phobic syndrome.

BACKGROUND: People with anxiety disorders occasionally report fears about losing control of basic bodily functions in public. These anxieties often occur in the absence of physical disorder and have previously been recognized as "obsessive" anxieties reflecting a preoccupation with loss of bowel/bladder control. Motivated by our observations of the non-trivial occurrence of such anxieties in our clinical practice we sought to fill a gap in the current understanding of "bowel/bladder-control anxieties". METHOD: Eligible participants completed an internet survey. RESULTS: Bowel/bladder-control anxieties (n = 140) tended to emerge in the mid to late 20s and were associated with high levels of avoidance and functional impairment. There was a high prevalence of panic attacks (78%); these were especially prevalent among those with bowel-control anxiety. Of those with panic attacks, 62% indicated that their main concern was being incontinent during a panic attack. Significantly, a proportion of respondents (~16%) reported actually being incontinent during a panic attack. Seventy percent of participants reported intrusive imagery related to loss of bowel/bladder control. Intrusion-related distress was correlated with agoraphobic avoidance and general role impairment. Some differences were noted between those with predominantly bowel-, predominantly bladder- and those with both bowel and bladder-control anxieties. CONCLUSION: This preliminary characterization indicates that even in a non-treatment seeking community sample, bowel/bladder-control anxieties are associated with high levels of distress and impairment. Further careful characterization of these anxieties will clarify their phenomenology and help us develop or modify treatment protocols in a way that takes account of any special characteristics of such viscerally-centred phobic syndromes.