Immunogenicity of an AS01-adjuvanted respiratory syncytial virus prefusion F (RSVPreF3) vaccine in animal models.

Respiratory syncytial virus (RSV) causes a high disease burden in older adults. An effective vaccine for this RSV-primed population may need to boost/elicit robust RSV-neutralizing antibody responses and recall/induce RSV-specific T cell responses. To inform the selection of the vaccine formulation for older adults, RSVPreF3 (RSV fusion glycoprotein engineered to maintain the prefusion conformation) with/without AS01 adjuvant was evaluated in mice and bovine RSV infection-primed cattle. In mice, RSVPreF3/AS01 elicited robust RSV-A/B-specific neutralization titers and RSV F-specific polyfunctional CD4+ T cell responses exceeding those induced by non-adjuvanted RSVPreF3. In primed bovines, RSVPreF3/AS01 tended to induce higher pre-/post-vaccination fold-increases in RSV-A/B-specific neutralization titers relative to non-adjuvanted and Alum-adjuvanted RSVPreF3 formulations, and elicited higher RSV F-specific CD4+ T cell frequencies relative to the non-adjuvanted vaccine. Though AS01 adjuvanticity varied by animal species and priming status, RSVPreF3/AS01 elicited/boosted RSV-A/B-specific neutralization titers and RSV F-specific CD4+ T cell responses in both animal models, which supported its further clinical evaluation as prophylactic candidate vaccine for older adults.

The RSVPreF3-AS01 vaccine elicits broad neutralization of contemporary and antigenically distant respiratory syncytial virus strains.

The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization responses against historical RSV strains and to be efficacious in preventing RSV-associated lower respiratory tract diseases in older adults. Although RSV F is highly conserved, variation does exist between strains. Here, we characterized variations in the major viral antigenic sites among contemporary RSV sequences when compared with RSVPreF3 and showed that, in older adults, RSVPreF3-AS01 broadly boosts neutralization responses against currently dominant and antigenically distant RSV strains. RSV-neutralizing responses are thought to play a central role in preventing RSV infection. Therefore, the breadth of RSVPreF3-AS01-elicited neutralization responses may contribute to vaccine efficacy against contemporary RSV strains and those that may emerge in the future.

Cognitive Fatigue, Sleep and Cortical Activity in Multiple Sclerosis Disease. A Behavioral, Polysomnographic and Functional Near-Infrared Spectroscopy Investigation.

Patients with multiple sclerosis (MS) disease frequently experience fatigue as their most debilitating symptom. Fatigue in MS partially refers to a cognitive component, cognitive fatigue (CF), characterized by a faster and stronger than usual development of the subjective feeling of exhaustion that follows sustained cognitive demands. The feeling of CF might result from supplementary task-related brain activity following MS-related demyelination and neurodegeneration. Besides, CF in MS disease might also stem from disrupted sleep. The present study investigated the association between the triggering of CF, task-related brain activity and sleep features. In a counterbalance mixed design, 10 patients with MS and 11 healthy controls were exposed twice for 16 min to a CF-inducing dual working memory updating task (TloadDback) under low or high cognitive demands conditions, counterbalanced. Considering known inter-individual differences and potential cognitive deficits in MS, the maximal cognitive load of the task was individually adapted to each participant's own upper limits. During the experimental sessions, cortical brain activity was measured using near-infrared spectroscopy (NIRS) during the CF-induction task, and in a resting state immediately before and after. Ambulatory polysomnography recordings were obtained on the nights preceding experimental sessions. When cognitive load was individually adapted to their processing capabilities, patients with MS exhibited similar than healthy controls levels of subjectively perceived CF, evolution of performance during the task, and brain activity patterns. Linear mixed models indicate a negative association between oxygenation level changes in the dorsolateral prefrontal cortex (DLPFC) and the triggering of subjective CF in patients with MS only. Longer total sleep time was also associated with higher CF in MS patients. These results suggest that controlling for cognitive load between individuals with and without MS results in a similar task-related development of subjective CF. Besides comparable performance and cortical brain activity between groups, mixed model analyses suggest a possible association between CF, DLPFC activity and sleep duration in MS disease.

Lack of frequency-tagged magnetic responses suggests statistical regularities remain undetected during NREM sleep.

Hypnopedia, or the capacity to learn during sleep, is debatable. De novo acquisition of reflex stimulus-response associations was shown possible both in man and animal. Whether sleep allows more sophisticated forms of learning remains unclear. We recorded during diurnal Non-Rapid Eye Movement (NREM) sleep auditory magnetoencephalographic (MEG) frequency-tagged responses mirroring ongoing statistical learning. While in NREM sleep, participants were exposed at non-awakenings thresholds to fast auditory streams of pure tones, either randomly organized or structured in such a way that the stream statistically segmented in sets of 3 elements (tritones). During NREM sleep, only tone-related frequency-tagged MEG responses were observed, evidencing successful perception of individual tones. No participant showed tritone-related frequency-tagged responses, suggesting lack of segmentation. In the ensuing wake period however, all participants exhibited robust tritone-related responses during exposure to statistical (but not random) streams. Our data suggest that associations embedded in statistical regularities remain undetected during NREM sleep, although implicitly learned during subsequent wakefulness. These results suggest intrinsic limitations in de novo learning during NREM sleep that might confine the NREM sleeping brain's learning capabilities to simple, elementary associations. It remains to be ascertained whether it similarly applies to REM sleep.

Objectifying the subjective: Building blocks of metacognitive experiences in conflict tasks.

Metacognitive appraisals are essential for optimizing our information processing. In conflict tasks, metacognitive appraisals can result from different interrelated features (e.g., motor activity, visual awareness, response speed). Thanks to an original approach combining behavioral and electromyographic measures, the current study objectified the contribution of three features (reaction time [RT], motor hesitation with and without response competition, and visual congruency) to the subjective experience of urge-to-err in a priming conflict task. Both RT and motor hesitation with response competition were major determinants of metacognitive appraisals. Importantly, motor hesitation in absence of response competition and visual congruency had limited effect. Because science aims to rely on objectivity, subjective experiences are often discarded from scientific inquiry. The current study shows that subjectivity can be objectified. (PsycINFO Database Record

Dissociating perception from action during conscious and unconscious conflict adaptation.

The detection of a conflict between relevant and irrelevant information on a given trial typically results in a smaller conflict effect on the next trial. This sequential effect has been interpreted as an expression of cognitive control implemented to resolve conflict. In this context, 2 different but related issues have received increasing attention in the literature. The first issue is whether the detection of motor conflict is necessary to induce cognitive control or, alternatively, whether the detection of perceptual conflict is sufficient. The second issue concerns whether awareness of the conflict is necessary to induce cognitive control. Here, we address both issues in a single design. Our reaction-time (RT) results indicate that conflict-driven control is domain-specific. The detection of perceptual conflict on the previous trial selectively reduces perceptual conflict on the next trial. Similarly, the detection of motor conflict on the previous trial selectively reduces motor conflict on the next trial. For errors, adaptive control seemed to be more general: The detection of perceptual or motor conflict on the previous trial reduced the frequency of errors on response-conflict trials. Furthermore, unconsciously triggered conflict adaptation was observed, but not systematically. Results on errors provide some evidence that sensitivity to an unconscious conflict on the previous trial reduces the frequency of errors on the current trial. For RT analyses however, unconscious conflict appeared not to be sufficient to induce cognitive control. This pattern of results is in line with previous studies examining the role of consciousness in conflict adaptation. (PsycINFO Database Record

The temporal dynamic of automatic inhibition of irrelevant actions.

Motor inhibition can occur even without conscious perception and any voluntary effort. Although it is now clear that such an inhibitory process needs time to unfold, its exact temporal dynamic remains to be elucidated. Therefore, the present study aims to examine the impact of various temporal factors on automatic motor inhibition using the masked priming task. Results show that this process can be modulated by any factor that introduces time between the mask onset and the execution of target response, whether it stems from a purely external origin (mask-target stimulus-onset asynchrony [SOA]), a purely internal origin (spontaneous reaction time [RT] fluctuations), or a mix of both (RT fluctuations from the target sequence). Moreover, when the external temporal factor could not determine the direction of prime influence, the RT fluctuations had the strongest impact on the priming effect. These RT fluctuations are plausibly the result of spontaneous trial-to-trial changes from more impulsive and error-prone decisions to more cautious and accurate decisions to the target. Indeed, both accuracy and speed were equally required during the task, but both requirements are impossible to achieve perfectly in every trial. This suggests that fluctuations in the level of caution in voluntary decisions can modulate unconscious and involuntary motor inhibition.

The reversal of perceptual and motor compatibility effects differs qualitatively between metacontrast and random-line masks.

In masked priming tasks, participants typically respond faster to compatible than to incompatible primes, an effect that has been dubbed as the positive compatibility effect (PCE). However, when the interval between the prime and the mask is relatively long, responses are faster to incompatible than to compatible primes. This inversion is called the negative compatibility effect (NCE). Two main origins of the NCE have been proposed. The object-updating theory holds that when the masks share stimulus features with the primes, both perceptual and motor processes generate an NCE. As an example, for masks composed of overlaid left and right prime arrows, the NCE is thought to be positive priming induced by the arrow of the mask pointing in the opposite direction of the prime. In contrast, the motor inhibition theories hold that the origin of the NCE is purely motor and can be demonstrated when masks do not share features with primes. To test both hypotheses, the present study aims at delineating the respective contributions of perceptual and motor components of the NCE in the context of different types of masks. Consistent with the object-updating hypothesis, we found both perceptual and motor NCEs at the long SOA with metacontrast masks (with internal contours corresponding to left and right overlaid arrows). Consistent with the motor inhibition hypothesis, we found motor NCE but no perceptual NCE at the long SOA with random-line masks (containing no prime features). The study thus suggests that the origin of the NCE depends on the type of mask.

The graded and dichotomous nature of visual awareness.

Is our visual experience of the world graded or dichotomous? Opposite pre-theoretical intuitions apply in different cases. For instance, when looking at a scene, one has a distinct sense that our experience has a graded character: one cannot say that there is no experience of contents that fall outside the focus of attention, but one cannot say that there is full awareness of such contents either. By contrast, when performing a visual detection task, our sense of having perceived the stimulus or not exhibits a more dichotomous character. Such issues have recently been the object of intense debate because different theoretical frameworks make different predictions about the graded versus dichotomous character of consciousness. Here, we review both relevant empirical findings as well as the associated theories (i.e. local recurrent processing versus global neural workspace theory). Next, we attempt to reconcile such contradictory theories by suggesting that level of processing is an often-ignored but highly relevant dimension through which we can cast a novel look at existing empirical findings. Thus, using a range of different stimuli, tasks and subjective scales, we show that processing low-level, non-semantic content results in graded visual experience, whereas processing high-level semantic content is experienced in a more dichotomous manner. We close by comparing our perspective with existing proposals, focusing in particular on the partial awareness hypothesis.

Nonconscious learning from crowded sequences.

Can people learn complex information without conscious awareness? Implicit learning-learning without awareness of what has been learned-has been the focus of intense investigation over the last 50 years. However, it remains controversial whether complex knowledge can be learned implicitly. In the research reported here, we addressed this challenge by asking participants to differentiate between sequences of symbols they could not perceive consciously. Using an operant-conditioning task, we showed that participants learned to associate distinct sequences of crowded (nondiscriminable) symbols with their respective monetary outcomes (reward or punishment). Overall, our study demonstrates that sensitivity to sequential regularities can arise through the nonconscious temporal integration of perceptual information.

Repeating a strongly masked stimulus increases priming and awareness.

Previous studies [Marcel, A. J. (1983). Conscious and unconscious perception: Experiments on visual masking and word recognition. Cognitive Psychology, 15(2), 197-237; Wentura, D., & Frings, C. (2005). Repeated masked category primes interfere with related exemplars: New evidence for negative semantic priming. Journal of Experimental Psychology: Learning, Memory, and Cognition, 31(1), 108-120] suggested that repeatedly presenting a masked stimulus improves priming without increasing perceptual awareness. However, neural theories of consciousness predict the opposite: Increasing bottom-up strength in such a paradigm should also result in increasing availability to awareness. Here, we tested this prediction by manipulating the number of repetitions of a strongly masked digit. Our results do not replicate the dissociation observed in previous studies and are instead suggestive that repeating an unconscious and attended masked stimulus enables the progressive emergence of perceptual awareness.