Platelet status in cancer cachexia progression in ApcMin/+ mice.

Cachexia, a complex wasting syndrome, significantly affects the quality of life and treatment options for cancer patients. Studies have reported a strong correlation between high platelet count and decreased survival in cachectic individuals. Therefore, this study aimed to investigate the immunopathogenesis of cancer cachexia using the ApcMin/+ mouse model of spontaneous colorectal cancer. The research focused on identifying cellular elements in the blood at different stages of cancer cachexia, assessing inflammatory markers and fibrogenic factors in the skeletal muscle, and studying the behavioral and metabolic phenotype of ApcMin/+ mice at the pre-cachectic and severely cachectic stages. Platelet measurements were also obtained from other animal models of cancer cachexia - Lewis Lung Carcinoma and Colon 26 adenocarcinoma. Our study revealed that platelet number is elevated prior to cachexia development in ApcMin/+ mice and can become activated during its progression. We also observed increased expression of TGFß2, TGFß3, and SMAD3 in the skeletal muscle of pre-cachectic ApcMin/+ mice. In severely cachectic mice, we observed an increase in Ly6g, CD206, and IL-10 mRNA. Meanwhile, IL-1ß gene expression was elevated in the pre-cachectic stage. Our behavioral and metabolic phenotyping results indicate that pre-cachectic ApcMin/+ mice exhibit decreased physical activity. Additionally, we found an increase in anemia at pre-cachectic and severely cachectic stages. These findings highlight the altered platelet status during early and late stages of cachexia and provide a basis for further investigation of platelets in the field of cancer cachexia.

Visuospatial computer game play after memory reminder delivered three days after a traumatic film reduces the number of intrusive memories of the experimental trauma.

OBJECTIVE: The experience of intrusive memories is a core clinical symptom of posttraumatic stress disorder (PTSD), and can be distressing in its own right. Notions of dual task interference and reconsolidation-update mechanisms suggest novel approaches to target intrusive memories. This study tested the hypothesis that a single-session cognitive intervention (memory reminder task plus Tetris gameplay) would reduce the occurrence of experimental trauma memories even when delivered 3 days post-trauma. Critically, this study tested effects against two control groups: Reminder-only, and reminder plus another computer game (a form of Quiz). METHODS: 86 healthy volunteers (59% female, age M = 24.35, SD = 4.59 years) watched a trauma film and then recorded their intrusive memories in a diary for 3 days (pre-intervention). They then returned to the lab. After presentation of visual reminder cues for the film plus a 10 min wait period (memory reminder task), participants were randomized into one of three task conditions (Tetris game play, Quiz game play, vs. reminder-only). They then kept the diary for a further 3 days (post-intervention). RESULTS: As predicted, after the experimental manipulation, the reminder + Tetris group experienced significantly fewer intrusions than the reminder-only group (d = 1.37). Further, the reminder + Tetris group also experienced significantly fewer intrusions than the reminder + Quiz (d = 0.65) group. Contrary to predictions, the reminder + Quiz group experienced significantly fewer intrusions than the reminder-only group (d = 0.69). Prior to the experimental manipulation, there was no significant difference between groups in number of intrusions. Recognition memory test scores for facts of the trauma film after 6 days were comparable between groups. CONCLUSIONS: We demonstrated that 3 days after experimental trauma (i.e. after memory consolidation) an intervention comprising a reminder task prior to a 15 min cognitive interference task (one of two computer games) led to a reduction in intrusion occurrence compared to reminder only. We interpret and discuss our findings within the framework of supposed reconsolidation-update mechanisms and competition for limited (visuospatial) working memory resources. Should these effects hold true in clinical populations, this type of simple intervention approach could help contribute to reducing intrusive memories of trauma.

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.

'I Can't Concentrate': A Feasibility Study with Young Refugees in Sweden on Developing Science-Driven Interventions for Intrusive Memories Related to Trauma.

BACKGROUND: The number of refugees is the highest ever worldwide. Many have experienced trauma in home countries or on their escape which has mental health sequelae. Intrusive memories comprise distressing scenes of trauma which spring to mind unbidden. Development of novel scalable psychological interventions is needed urgently. AIMS: We propose that brief cognitive science-driven interventions should be developed which pinpoint a focal symptom alongside a means to monitor it using behavioural techniques. The aim of the current study was to assess the feasibility and acceptability of the methodology required to develop such an intervention. METHOD: In this study we recruited 22 refugees (16-25 years), predominantly from Syria and residing in Sweden. Participants were asked to monitor the frequency of intrusive memories of trauma using a daily diary; rate intrusions and concentration; and complete a 1-session behavioural intervention involving Tetris game-play via smartphone. RESULTS: Frequency of intrusive memories was high, and associated with high levels of distress and impaired concentration. Levels of engagement with study procedures were highly promising. CONCLUSIONS: The current work opens the way for developing novel cognitive behavioural approaches for traumatized refugees that are mechanistically derived, freely available and internationally scalable.

Playing the computer game Tetris prior to viewing traumatic film material and subsequent intrusive memories: Examining proactive interference.

BACKGROUND AND OBJECTIVES: Visuospatial working memory (WM) tasks performed concurrently or after an experimental trauma (traumatic film viewing) have been shown to reduce subsequent intrusive memories (concurrent or retroactive interference, respectively). This effect is thought to arise because, during the time window of memory consolidation, the film memory is labile and vulnerable to interference by the WM task. However, it is not known whether tasks before an experimental trauma (i.e. proactive interference) would also be effective. Therefore, we tested if a visuospatial WM task given before a traumatic film reduced intrusions. Findings are relevant to the development of preventative strategies to reduce intrusive memories of trauma for groups who are routinely exposed to trauma (e.g. emergency services personnel) and for whom tasks prior to trauma exposure might be beneficial. METHODS: Participants were randomly assigned to 1 of 2 conditions. In the Tetris condition (n = 28), participants engaged in the computer game for 11 min immediately before viewing a 12-min traumatic film, whereas those in the Control condition (n = 28) had no task during this period. Intrusive memory frequency was assessed using an intrusion diary over 1-week and an Intrusion Provocation Task at 1-week follow-up. Recognition memory for the film was also assessed at 1-week. RESULTS: Compared to the Control condition, participants in the Tetris condition did not report statistically significant difference in intrusive memories of the trauma film on either measure. There was also no statistically significant difference in recognition memory scores between conditions. LIMITATIONS: The study used an experimental trauma paradigm and findings may not be generalizable to a clinical population. CONCLUSIONS: Compared to control, playing Tetris before viewing a trauma film did not lead to a statistically significant reduction in the frequency of later intrusive memories of the film. It is unlikely that proactive interference, at least with this task, effectively influences intrusive memory development. WM tasks administered during or after trauma stimuli, rather than proactively, may be a better focus for intrusive memory amelioration.

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.

Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms.

Memory of a traumatic event becomes consolidated within hours. Intrusive memories can then flash back repeatedly into the mind's eye and cause distress. We investigated whether reconsolidation-the process during which memories become malleable when recalled-can be blocked using a cognitive task and whether such an approach can reduce these unbidden intrusions. We predicted that reconsolidation of a reactivated visual memory of experimental trauma could be disrupted by engaging in a visuospatial task that would compete for visual working memory resources. We showed that intrusive memories were virtually abolished by playing the computer game Tetris following a memory-reactivation task 24 hr after initial exposure to experimental trauma. Furthermore, both memory reactivation and playing Tetris were required to reduce subsequent intrusions (Experiment 2), consistent with reconsolidation-update mechanisms. A simple, noninvasive cognitive-task procedure administered after emotional memory has already consolidated (i.e., > 24 hours after exposure to experimental trauma) may prevent the recurrence of intrusive memories of those emotional events.

Key steps in developing a cognitive vaccine against traumatic flashbacks: visuospatial Tetris versus verbal Pub Quiz.

BACKGROUND: Flashbacks (intrusive memories of a traumatic event) are the hallmark feature of Post Traumatic Stress Disorder, however preventative interventions are lacking. Tetris may offer a 'cognitive vaccine' [1] against flashback development after trauma exposure. We previously reported that playing the computer game Tetris soon after viewing traumatic material reduced flashbacks compared to no-task [1]. However, two criticisms need to be addressed for clinical translation: (1) Would all games have this effect via distraction/enjoyment, or might some games even be harmful? (2) Would effects be found if administered several hours post-trauma? Accordingly, we tested Tetris versus an alternative computer game--Pub Quiz--which we hypothesized not to be helpful (Experiments 1 and 2), and extended the intervention interval to 4 hours (Experiment 2). METHODOLOGY/PRINCIPAL FINDINGS: The trauma film paradigm was used as an experimental analog for flashback development in healthy volunteers. In both experiments, participants viewed traumatic film footage of death and injury before completing one of the following: (1) no-task control condition (2) Tetris or (3) Pub Quiz. Flashbacks were monitored for 1 week. Experiment 1: 30 min after the traumatic film, playing Tetris led to a significant reduction in flashbacks compared to no-task control, whereas Pub Quiz led to a significant increase in flashbacks. Experiment 2: 4 hours post-film, playing Tetris led to a significant reduction in flashbacks compared to no-task control, whereas Pub Quiz did not. CONCLUSIONS/SIGNIFICANCE: First, computer games can have differential effects post-trauma, as predicted by a cognitive science formulation of trauma memory. In both Experiments, playing Tetris post-trauma film reduced flashbacks. Pub Quiz did not have this effect, even increasing flashbacks in Experiment 1. Thus not all computer games are beneficial or merely distracting post-trauma - some may be harmful. Second, the beneficial effects of Tetris are retained at 4 hours post-trauma. Clinically, this delivers a feasible time-window to administer a post-trauma "cognitive vaccine".

Can playing the computer game "Tetris" reduce the build-up of flashbacks for trauma? A proposal from cognitive science.

BACKGROUND: Flashbacks are the hallmark symptom of Posttraumatic Stress Disorder (PTSD). Although we have successful treatments for full-blown PTSD, early interventions are lacking. We propose the utility of developing a 'cognitive vaccine' to prevent PTSD flashback development following exposure to trauma. Our theory is based on two key findings: 1) Cognitive science suggests that the brain has selective resources with limited capacity; 2) The neurobiology of memory suggests a 6-hr window to disrupt memory consolidation. The rationale for a 'cognitive vaccine' approach is as follows: Trauma flashbacks are sensory-perceptual, visuospatial mental images. Visuospatial cognitive tasks selectively compete for resources required to generate mental images. Thus, a visuospatial computer game (e.g. "Tetris") will interfere with flashbacks. Visuospatial tasks post-trauma, performed within the time window for memory consolidation, will reduce subsequent flashbacks. We predicted that playing "Tetris" half an hour after viewing trauma would reduce flashback frequency over 1-week. METHODOLOGY/PRINCIPAL FINDINGS: The Trauma Film paradigm was used as a well-established experimental analog for Post-traumatic Stress. All participants viewed a traumatic film consisting of scenes of real injury and death followed by a 30-min structured break. Participants were then randomly allocated to either a no-task or visuospatial ("Tetris") condition which they undertook for 10-min. Flashbacks were monitored for 1-week. Results indicated that compared to the no-task condition, the "Tetris" condition produced a significant reduction in flashback frequency over 1-week. Convergent results were found on a clinical measure of PTSD symptomatology at 1-week. Recognition memory between groups did not differ significantly. CONCLUSIONS/SIGNIFICANCE: Playing "Tetris" after viewing traumatic material reduces unwanted, involuntary memory flashbacks to that traumatic film, leaving deliberate memory recall of the event intact. Pathological aspects of human memory in the aftermath of trauma may be malleable using non-invasive, cognitive interventions. This has implications for a novel avenue of preventative treatment development, much-needed as a crisis intervention for the aftermath of traumatic events.