Calmodulin binds the N-terminus of the functional amyloid Orb2A inhibiting fibril formation

The cytoplasmic polyadenylation element-binding protein Orb2 is a key regulator of long-term memory (LTM) in Drosophila. The N-terminus of the Orb2 isoform A is required for LTM and forms cross-β fibrils on its own. However, this N-terminus is not part of the core found in ex vivo fibrils. We previously showed that besides forming cross-β fibrils, the N-terminus of Orb2A binds anionic lipid membranes as an amphipathic helix. Here, we show that the Orb2A N-terminus can similarly interact with calcium activated calmodulin (CaM) and that this interaction prevents fibril formation. Because CaM is a known regulator of LTM, this interaction could potentially explain the regulatory role of Orb2A in LTM.

Refined Analysis of Chronic White Matter Changes after Traumatic Brain Injury and Repeated Sports-Related Concussions: Of Use in Targeted Rehabilitative Approaches?

Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC. Six patients with moderate/severe TBI, and 12 athletes with rSRC were included ≥6 months post-injury, and 10 (age-matched) healthy controls (HC) were analyzed. The Repeatable Battery for the Assessment of Neuropsychological Status was performed at the time of DTI. Major white matter pathways were tracked using q-space diffeomorphic reconstruction and analyzed for global and regional changes with a controlled false discovery rate. TBI patients displayed multiple classic white matter injuries compared with HC (p < 0.01). At the regional white matter analysis, the left frontal aslant tract, anterior thalamic radiation, and the genu of the corpus callosum displayed focal changes in both groups compared with HC but with different trends. Both TBI and rSRC displayed worse memory performance compared with HC (p < 0.05). While global analysis of DTI-based parameters did not reveal common abnormalities in TBI and rSRC, abnormalities to the fronto-thalamic network were observed in both groups using regional analysis of the white matter pathways. These results may be valuable to tailor individualized rehabilitative approaches for post-injury cognitive impairment in both TBI and rSRC patients.

Similar Profile and Magnitude of Cognitive Impairments in Focal and Generalized Epilepsy: A Pilot Study

Introduction: Cognitive impairments in epilepsy are not well-understood. In addition, long-term emotional, interpersonal, and social consequences of the underlying disturbances are important to evaluate.Purpose: To compare cognitive function including language in young adults with focal or generalized epilepsy. In addition, quality of life and self-esteem were investigated.Patients and Methods: Young adults with no primary intellectual disability, 17 with focal epilepsy and 11 with generalized epilepsy participated and were compared to 28 healthy controls. Groups were matched on age (mean = 26 years), sex, and education. Participants were administered a battery of neuropsychological tasks and carried out self-ratings of quality of life, self-esteem, and psychological problems.Results: Similar impairments regarding cognitive function were noted in focal and generalized epilepsy. The cognitive domains tested were episodic long-term memory, executive functions, attention, working memory, visuospatial functions, and language. Both epilepsy groups had lower results compared to controls (effect sizes 0.24–1.07). The total number of convulsive seizures was predictive of episodic long-term memory function. Participants with focal epilepsy reported lower quality of life than participants with generalized epilepsy. Lowered self-esteem values were seen in both epilepsy groups and particularly in those with focal epilepsy. Along with measures of cognitive speed and depression, the total number of seizures explained more than 50% of variation in quality of life.Conclusion: Interestingly, similarities rather than differences characterized the widespread cognitive deficits that were seen in focal and generalized epilepsy, ranging from mild to moderate. These similarities were modified by quality of life and self-esteem. This study confirms the notion that epilepsy is a network disorder.

Recruitment of a long-term memory supporting neural network during repeated maintenance of a multi-item abstract visual image in working memory

Humans can flexibly transfer information between different memory systems. Information in visual working memory (VWM) can for instance be stored in long-term memory (LTM). Conversely, information can be retrieved from LTM and temporarily held in WM when needed. It has previously been suggested that a neural transition from parietal- to midfrontal activity during repeated visual search reflects transfer of information from WM to LTM. Whether this neural transition indeed reflects consolidation and is also observed when memorizing a rich visual scene (rather than responding to a single target), is not known. To investigate this, we employed an EEG paradigm, in which abstract six-item colour-arrays were repeatedly memorized and explicitly visualized, or merely attended to. Importantly, we tested the functional significance of a potential neural shift for longer-term consolidation in a subsequent recognition task. Our results show a gradually enhanced- and sustained modulation of the midfrontal P170 component and a decline in parietal CDA, during repeated WM maintenance. Improved recollection/visualization of memoranda upon WM-cueing, was associated with contralateral parietal- and right temporal activity. Importantly, only colour-arrays previously held in WM, induced a greater midfrontal P170-response, together with left temporal- and late centro-parietal activity, upon re-exposure. These findings provide evidence for recruitment of an LTM-supporting neural network which facilitates visual WM maintenance.

Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors

T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide–MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

A change in taste: The role of MicroRNAs in altering hedonic value

The mechanisms associated with neophobia, and anhedonia remain largely unknown. Neuropsychological disorders such as depression and schizophrenia are associated with excessive fear and anhedonia and have been linked to microRNA 137. We hypothesized that microRNAs (miRNAs) in the snail Lymnaea stagnalis are important for regulating feeding behaviour through either preventing neophobia or establishing hedonic value. To test these hypotheses, we used an injection of Poly-L-Lysine (PLL) to inhibit miRNA biogenesis and observed its effects on feeding behaviour. We repeated these experiments with pre-exposure to novel stimuli capable of eliciting neophobia to disentangle the processes predicted to regulate feeding behaviour. Next, we exposed snails to food stimuli of high hedonic value after PLL injection to reset their hedonic value for that food. Finally, we consolidated our results with previous research by examining the effect of PLL injection on a one trial appetitive classical conditioning procedure (1TT) to induce long term memory (LTM). We found that miRNAs are likely not required for preventing neophobia. Moreover, we discovered that snails experienced anhedonia in response to inhibition of miRNA biogenesis, resulting in diminished feeding behaviour for food stimuli with a previously high hedonic value. Snails showed diminished feeding behaviour for multiple food stimuli of high hedonic value post 1TT with PLL injection. This finding suggested that PLL causes anhedonia rather than an impairment of LTM formation following the 1TT procedure. This is the first evidence suggesting that inhibiting the biogenesis of miRNAs contributes to anhedonia in Lymnaea.

A cognitive neuroscience perspective on insight as a memory process: encoding the solution

This is one of two chapters on "A cognitive neuroscience perspective on insight as a memory process" to be published in the "Routledge International Handbook of Creative Cognition" by L. J. Ball &amp; F. Valleé-Tourangeau (Eds.). While the previous chapter discussed the role of long-term memory for solving problems by insight [https://psyarxiv.com/zv4dk], the current chapter focuses on the role of insight problem solving for long-term memory formation. Insight in problem solving has long been assumed to facilitate memory formation for the problem and its solution. Here, we discuss cognitive, affective, and neurocognitive candidate mechanisms that may underlie learning in insight problem solving. We conclude that insight appears to combine several beneficial effects that each on their own have been found to facilitate long-term memory formation: the generation effect, subjective importance of the discovery of the solution, intrinsic reward, schema congruence, and level-of-processing. A distributed set of brain regions is identified that is associated with these processes. On the one hand, the more affective response related to pleasure, surprise, and novelty detection is linked to amygdala, ventral striatum, and dopaminergic midbrain activity, supporting an important role of reward learning. On the other hand, insight as completing a schema is associated with prior knowledge dependent and medial prefrontal cortex mediated memory formation. Thus, learning by insight may reflect a fast route to cortical memory representations. However, many open questions remain, which we explicitly point out during this review.

Examination of distributed learning on recent and remote memory using in-person and online experimental paradigms

Learning is crucial in everyday life. However, how much information we retain depends on the type and schedule of training. It has been widely acknowledged that spaced learning holds a distinct advantage over massed learning for cognitively healthy adults and should be considered an educational standard, particularly when consolidating long-term memory. Given that many experiments have been required to be conducted online as a result of social distancing regulations during the Covid-19 pandemic, we examined whether the spacing advantage could be replicated in an online setup. Two experiments were conducted to examine the effects of spacing across recent (24 hours) and remote (one-month) retention intervals using the Face-Name Pairs task either in-person (Experiment 1) or online (Experiment 2). The results of Experiment 1 suggest that the beneficial memory effects of spaced training are particularly observed with remote memory. The results of Experiment 2 suggest that although participants learn and recall better in an online setup compared to in-person, the spacing effects were not as robust and did not confer any real advantage. These results are discussed in terms of advantages and disadvantages of the two procedures and the implications for online studies.

A cognitive neuroscience perspective on insight as a memory process: Searching for the solution.

What are the cognitive and brain processes that lead to an insight? This is one of two chapters on "A cognitive neuroscience perspective on insight as a memory process" to be published in the "Routledge International Handbook of Creative Cognition" by L. J. Ball &amp; F. Valleé-Tourangeau (Eds.). In this chapter, we will describe the insight solution process from a neurocognitive perspective. Inspired by cognitive theories, we translate some of insight's main cognitive subprocesses (problem representation, search, representational change, solution) into related neurocognitive ones and summarize them in a descriptive framework. Those described processes focus primarily on verbal insight and are explained using the remote associates task. In this task, the solver is provided with several problem elements (e.g. drop, coat, summer) and needs to find the (remotely related) target that matches those cues (e.g., rain). In a nutshell, insight is the consequence of a problem-solving process where the target is encoded in long-term memory but cannot be retrieved at first because the relationship between the problem elements and the target is unknown, precluding a simple memory search. Upon problem display, the problem elements and a whole network of associated concepts are automatically activated in long-term memory in distinct areas of the brain representing those concepts (=problem representation). Insight is assumed to occur when automatic processes suddenly activate the target after control processes associated with inferior frontal gyrus and anterior cingulate cortex activation manage to overcome prior knowledge and/or perceptual constraints by revising the current activation pattern (=representational change). The next chapter (https://psyarxiv.com/bevjm) will focus on the role of insight problem solving for long-term memory formation.

The role of cognitive functions in the dynamics of work accidents

This paper brings to the fore the need to study the causality of work accidents starting from the hypothesis that the causes must be identified immediately, respectively the dysfunctions of the work system, which contribute to their occurrence. So, in the causal chain of the work accident, the last link is the “meeting” between the victim and the material agent who injures her, and often the factors of the work system, which are potential causes of injury, are specific to the worker and represent an error inappropriate behaviour in terms of occupational safety, in the form of wrongdoing or omissions. In this regard, cognitive ergonomics is still an untapped area, although it can make significant contributions to improving work performance and creating safe and healthy working environments in industry. Cognitive functions are relevant when we talk about 4 essential skills of the worker, respectively: sensation and perception, attention, short and long term memory. The paper brings more information for the scientific community because the analysis highlights the link between the cognitive functions of workers and the errors generated by them in the dynamics of a work accident, and can also be a starting point for new research.