The Effect of Self-Reported REM Behavior Disorder Symptomology on Intrusive Memories in Post-Traumatic Stress Disorder

Background: PTSD is characterised by severe sleep disturbances, which is increasingly recognised to in many cases consist of similar symptomology to sleep disorders such as REM Behaviour Disorder (RBD). The present study aimed to investigate whether different aspects of sleep quality influence intrusive memory development and whether PTSD status moderates this relationship.Participants and Methods: 34 PTSD, 52 trauma-exposed (TE) and 42 non-trauma exposed (NTE) participants completed an emotional memory task, where they viewed 60 images (20 positive, 20 negative and 20 neutral) and, two days later, reported how many intrusive memories they had of each valence category. Participants also completed three measures of sleep quality: the Pittsburgh Sleep Quality Index, the REM Behaviour Disorder Screening Questionnaire and total hours slept before each session.Results: The PTSD group reported poorer sleep quality than both TE and NTE groups on all three measures, and significantly more negative intrusive memories than the NTE group. Mediation analyses revealed that self-reported RBD symptomology before the second session mediated the relationship between PTSD status and intrusive memories. Follow-up moderation analyses revealed that self-reported RBD symptomology before the second session was only a significant predictor of intrusion in the PTSD group, though with a small effect size.Conclusions: These findings suggest that RBD symptomology is an indicator of consolidation of intrusive memories in PTSD but not trauma-exposed or healthy participants, which supports the relevance of characterising RBD in PTSD

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage

Sex differences in intrusive memories following trauma

<div><p>Background</p><p>A key mechanism thought to underlie Posttraumatic Stress Disorder (PTSD) is enhanced emotional memory consolidation. Recent evidence in healthy controls revealed that women have greater negative memory consolidation following stress relative to men. This study examined emotional memory consolidation in women and men with PTSD, and in trauma-exposed and non-trauma controls to test the hypothesis that emotionally negative memory consolidation would be greater in women with PTSD.</p><p>Method</p><p>One hundred and forty-seven men and women (47 with PTSD, 49 trauma-exposed controls, and 51 non-trauma controls) completed an emotional memory task where they looked at negative, neutral and positive images from the International Affective Picture System (IAPS). Delayed recall and an intrusive memory diary were completed two days later.</p><p>Results</p><p>Women displayed greater recall, and reported more negative intrusive memories than men. A gender x group interaction effect showed that both women with PTSD and trauma-exposed women reported more intrusive memories than women without trauma exposure or men.</p><p>Conclusion</p><p>This study provided preliminary evidence of sex differences in intrusive memories in those with PTSD as well as those with a history of trauma exposure. Future research should include measures of sex hormones to further examine sex differences on memory consolidation in the context of trauma exposure and PTSD.</p></div

Single Neurons in M1 and Premotor Cortex Directly Reflect Behavioral Interference

Some motor tasks, if learned together, interfere with each other's consolidation and subsequent retention, whereas other tasks do not. Interfering tasks are said to employ the same internal model whereas noninterfering tasks use different models. The division of function among internal models, as well as their possible neural substrates, are not well understood. To investigate these questions, we compared responses of single cells in the primary motor cortex and premotor cortex of primates to interfering and noninterfering tasks. The interfering tasks were visuomotor rotation followed by opposing visuomotor rotation. The noninterfering tasks were visuomotor rotation followed by an arbitrary association task. Learning two noninterfering tasks led to the simultaneous formation of neural activity typical of both tasks, at the level of single neurons. In contrast, and in accordance with behavioral results, after learning two interfering tasks, only the second task was successfully reflected in motor cortical single cell activity. These results support the hypothesis that the representational capacity of motor cortical cells is the basis of behavioral interference and division between internal models

RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy

<p>Abstract</p> <p>Background</p> <p>To study the dynamics of wild-type and drug-resistant HIV-1 RT variants, we developed a methodology that follows the fates of individual genomes over time within the viral quasispecies. Single genome sequences were obtained from 3 pigtail macaques infected with a recombinant simian immunodeficiency virus containing the RT coding region from HIV-1 (RT-SHIV) and treated with short-course efavirenz monotherapy 13 weeks post-infection followed by daily combination antiretroviral therapy (ART) beginning at week 17. Bioinformatics tools were constructed to trace individual genomes from the beginning of infection to the end of the treatment.</p> <p>Results</p> <p>A well characterized challenge RT-SHIV inoculum was used to infect three monkeys. The RT-SHIV inoculum had 9 variant subpopulations and the dominant subpopulation accounted for 80% of the total genomes. In two of the three monkeys, the inoculated wild-type virus was rapidly replaced by new wild type variants. By week 13, the original dominant subpopulation in the inoculum was replaced by new dominant subpopulations, followed by emergence of variants carrying known NNRTI resistance mutations. However, during ART, virus subpopulations containing resistance mutations did not outgrow the wide-type subpopulations until a minor subpopulation carrying linked drug resistance mutations (K103N/M184I) emerged. We observed that persistent viremia during ART is primarily made up of wild type subpopulations. We also found that subpopulations carrying the V75L mutation, not known to be associated with NNRTI resistance, emerged initially in week 13 in two macaques. Eventually, all subpopulations from these two macaques carried the V75L mutation.</p> <p>Conclusion</p> <p>This study quantitatively describes virus evolution and population dynamics patterns in an animal model. The fact that wild type subpopulations remained as dominant subpopulations during ART treatment suggests that the presence or absence of at least some known drug resistant mutations may not greatly affect virus replication capacity <it>in vivo</it>. Additionally, the emergence and prevalence of V75L indicates that this mutation may provide the virus a selective advantage, perhaps escaping the host immure system surveillance. Our new method to quantitatively analyze viral population dynamics enabled us to observe the relative competitiveness and adaption of different viral variants and provided a valuable tool for studying HIV subpopulation emergence, persistence, and decline during ART.</p

An Animal Model of Emotional Blunting in Schizophrenia

Schizophrenia is often associated with emotional blunting—the diminished ability to respond to emotionally salient stimuli—particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed

A Symbiotic Brain-Machine Interface through Value-Based Decision Making

BACKGROUND: In the development of Brain Machine Interfaces (BMIs), there is a great need to enable users to interact with changing environments during the activities of daily life. It is expected that the number and scope of the learning tasks encountered during interaction with the environment as well as the pattern of brain activity will vary over time. These conditions, in addition to neural reorganization, pose a challenge to decoding neural commands for BMIs. We have developed a new BMI framework in which a computational agent symbiotically decoded users' intended actions by utilizing both motor commands and goal information directly from the brain through a continuous Perception-Action-Reward Cycle (PARC). METHODOLOGY: The control architecture designed was based on Actor-Critic learning, which is a PARC-based reinforcement learning method. Our neurophysiology studies in rat models suggested that Nucleus Accumbens (NAcc) contained a rich representation of goal information in terms of predicting the probability of earning reward and it could be translated into an evaluative feedback for adaptation of the decoder with high precision. Simulated neural control experiments showed that the system was able to maintain high performance in decoding neural motor commands during novel tasks or in the presence of reorganization in the neural input. We then implanted a dual micro-wire array in the primary motor cortex (M1) and the NAcc of rat brain and implemented a full closed-loop system in which robot actions were decoded from the single unit activity in M1 based on an evaluative feedback that was estimated from NAcc. CONCLUSIONS: Our results suggest that adapting the BMI decoder with an evaluative feedback that is directly extracted from the brain is a possible solution to the problem of operating BMIs in changing environments with dynamic neural signals. During closed-loop control, the agent was able to solve a reaching task by capturing the action and reward interdependency in the brain

TCR cross-reactivity and allorecognition: new insights into the immunogenetics of allorecognition

Alloreactive T cells are core mediators of graft rejection and are a potent barrier to transplantation tolerance. It was previously unclear how T cells educated in the recipient thymus could recognize allogeneic HLA molecules. Recently it was shown that both naïve and memory CD4+ and CD8+ T cells are frequently cross-reactive against allogeneic HLA molecules and that this allorecognition exhibits exquisite peptide and HLA specificity and is dependent on both public and private specificities of the T cell receptor. In this review we highlight new insights gained into the immunogenetics of allorecognition, with particular emphasis on how viral infection and vaccination may specifically activate allo-HLA reactive T cells. We also briefly discuss the potential for virus-specific T cell infusions to produce GvHD. The progress made in understanding the molecular basis of allograft rejection will hopefully be translated into improved allograft function and/or survival, and eventually tolerance induction

Psycho-social factors associated with mental resilience in the Corona lockdown

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics