How negative emotions affect young and older adults' numerosity estimation performance.

In this study, we investigated the influence of negative emotions on numerosity estimation and whether this influence changes with aging during adulthood. Young and older adults were asked to estimate and compare the numerosity of collections of elements (cars or dots) with a two-digit number. Collections of elements were preceded by emotionally neutral (e.g., mushrooms) or emotionally negative (e.g., a corpse) pictures. Stimuli were easier (i.e., small-ratio) or harder (i.e., large-ratio) items. Young and older participants obtained similar numerosity estimation performance. Interestingly, participants were less accurate under negative emotions than under neutral emotions when they estimated numerosity of collections of abstract elements (i.e., dots). In contrast, participants improved their performance under negative emotions while estimating collections of non-abstract, daily-life elements (i.e., cars). These findings have important implications for furthering our understanding of the role of negative emotions in numerosity estimation and age-related differences therein.

Classification of Electrophysiological Signatures With Explainable Artificial Intelligence: The Case of Alarm Detection in Flight Simulator.

Relevant sounds such as alarms are sometimes involuntarily ignored, a phenomenon called inattentional deafness. This phenomenon occurs under specific conditions including high workload (i.e., multitasking) and/or cognitive fatigue. In the context of aviation, such an error can have drastic consequences on flight safety. This study uses an oddball paradigm in which participants had to detect rare sounds in an ecological context of simulated flight. Cognitive fatigue and cognitive load were manipulated to trigger inattentional deafness, and brain activity was recorded via electroencephalography (EEG). Our results showed that alarm omission and alarm detection can be classified based on time-frequency analysis of brain activity. We reached a maximum accuracy of 76.4% when the algorithm was trained on all participants and a maximum of 90.5%, on one participant, when the algorithm was trained individually. This method can benefit from explainable artificial intelligence to develop efficient and understandable passive brain-computer interfaces, improve flight safety by detecting such attentional failures in real time, and give appropriate feedback to pilots, according to our ambitious goal, providing them with reliable and rich human/machine interactions.

An Electromyographic Analysis of the Effects of Cognitive Fatigue on Online and Anticipatory Action Control.

Cognitive fatigue is a problem for the safety of critical systems (e.g., aircraft) as it can lead to accidents, especially during unexpected events. In order to determine the extent to which it disrupts adaptive capabilities, we evaluated its effect on online and anticipatory control. Despite numerous studies conducted to determine its effects, the exact mechanism(s) affected by fatigue remains to be clarified. In this study, we used distribution and electromyographic analysis to assess whether cognitive fatigue increases the capture of the incorrect automatic response or if it impairs its suppression (online control), and whether the conflict adaptation effect is reduced (anticipatory control). To this end, we evaluated the evolution of the performance over time during the Simon task, a classic conflict task that elicits incorrect automatic responses. To accentuate the presence of fatigue during the Simon task, two groups previously performed a dual-task with two different cognitive load levels to create two different levels of fatigue. The results revealed that time on task impaired online control by disrupting the capacity to suppress the incorrect response but leaving unaffected the expression of the automatic response. Furthermore, participants emphasized speed rather than accuracy with time on task, with in addition more fast guesses, suggesting that they opted for a less effortful response strategy. As the implementation of the suppression mechanism requires cognitive effort, the conjunction of these results suggests that the deficits observed may be due to disengagement of effort over time rather than reflecting an incapacity to make an effort.

How Emotions Modulate Arithmetic Performance.

The goal of the present study was to test whether and how emotions influence arithmetic performance. Participants had to verify arithmetic problems. True problems were either easier or harder problems. False problems were parity-match or parity-mismatch problems. The odd/even status of proposed and correct answers was the same in parity-match problems (e.g., 19 × 7 = 131) and different in parity-mismatch problems (e.g., 17 × 9 = 152). Before each problem, participants saw a positive (e.g., smiling baby), negative (e.g., mutilations), or neutral pictures (e.g., neutral face) selected from International Affective Picture System (IAPS). They had to decide whether each picture includes a person or not before verifying each arithmetic problem. Results showed different effects of emotion on true- and false problem verification. Participants' performance on true problems showed decreased problem-difficulty after processing negative pictures and increased difficulty effects after processing positive pictures. On false problems, we found smaller parity-violation effects after negative pictures (i.e., decreased performance on parity-mismatch problems), together with larger parity-violation effects after positive pictures (i.e., decreased performance on parity-match problems). These findings suggest that emotions influence arithmetic performance via which strategy is used and how each strategy is executed on each problem. They have important implications for understanding the role of emotions on arithmetic performance, and more generally on how emotions influence cognition.

HTS-compatible FRET-based conformational sensors clarify membrane receptor activation.

Cell surface receptors represent a vast majority of drug targets. Efforts have been conducted to develop biosensors reporting their conformational changes in live cells for pharmacological and functional studies. Although Förster resonance energy transfer (FRET) appears to be an ideal approach, its use is limited by the low signal-to-noise ratio. Here we report a toolbox composed of a combination of labeling technologies, specific fluorophores compatible with time-resolved FRET and a novel method to quantify signals. This approach enables the development of receptor biosensors with a large signal-to-noise ratio. We illustrate the usefulness of this toolbox through the development of biosensors for various G-protein-coupled receptors and receptor tyrosine kinases. These receptors include mGlu, GABAB, LH, PTH, EGF and insulin receptors among others. These biosensors can be used for high-throughput studies and also revealed new information on the activation process of these receptors in their cellular environment.

Fine tuning of sub-millisecond conformational dynamics controls metabotropic glutamate receptors agonist efficacy.

Efficient cell-to-cell communication relies on the accurate signalling of cell surface receptors. Understanding the molecular bases of their activation requires the characterization of the dynamic equilibrium between active and resting states. Here, we monitor, using single-molecule Förster resonance energy transfer, the kinetics of the reorientation of the extracellular ligand-binding domain of the metabotropic glutamate receptor (mGluR), a class C G-protein-coupled receptor. We demonstrate that most receptors oscillate between a resting- and an active-conformation on a sub-millisecond timescale. Interestingly, we demonstrate that differences in agonist efficacies stem from differing abilities to shift the conformational equilibrium towards the fully active state, rather than from the stabilization of alternative static conformations, which further highlights the dynamic nature of mGluRs and revises our understanding of receptor activation and allosteric modulation.

Illuminating the activation mechanisms and allosteric properties of metabotropic glutamate receptors.

In multimeric cell-surface receptors, the conformational changes of the extracellular ligand-binding domains (ECDs) associated with receptor activation remain largely unknown. This is the case for the dimeric metabotropic glutamate receptors even though a number of ECD structures have been solved. Here, using an innovative approach based on cell-surface labeling and FRET, we demonstrate that a reorientation of the ECDs is associated with receptor and G-protein activation. Our approach helps identify partial agonists and highlights allosteric interactions between the effector and binding domains. Any approach expected to stabilize the active conformation of the effector domain increased the agonist potency in stabilizing the active ECDs conformation. These data provide key information on the structural dynamics and drug action at metabotropic glutamate receptors and validate an approach for tackling such analysis on other receptors.

PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity.

Kallmann syndrome (KS) combines hypogonadism due to gonadotropin-releasing hormone deficiency, and anosmia or hyposmia, related to defective olfactory bulb morphogenesis. In a large series of KS patients, ten different missense mutations (p.R85C, p.R85H, p.R164Q, p.L173R, p.W178S, p.Q210R, p.R268C, p.P290S, p.M323I, p.V331M) have been identified in the gene encoding the G protein-coupled receptor prokineticin receptor-2 (PROKR2), most often in the heterozygous state. Many of these mutations were, however, also found in clinically unaffected individuals, thus raising the question of their actual implication in the KS phenotype. We reproduced each of the ten mutations in a recombinant murine Prokr2, and tested their effects on the signalling activity in transfected HEK-293 cells, by measuring intracellular calcium release upon ligand-activation of the receptor. We found that all mutated receptors except one (M323I) had decreased signalling activities. These could be explained by different defective mechanisms. Three mutations (L173R, W178S, P290S) impaired cell surface-targeting of the receptor. One mutation (Q210R) abolished ligand-binding. Finally, five mutations (R85C, R85H, R164Q, R268C, V331M) presumably impaired G protein-coupling of the receptor. In addition, when wild-type and mutant receptors were coexpressed in HEK-293 cells, none of the mutant receptors that were retained within the cells did affect cell surface-targeting of the wild-type receptor, and none of the mutant receptors properly addressed at the plasma membrane did affect wild-type receptor signalling activity. This argues against a dominant negative effect of the mutations in vivo.

Attentional modulation of masked repetition and categorical priming in young and older adults.

Three experiments examined the effects of temporal attention and aging on masked repetition and categorical priming for numbers and words. Participants' temporal attention was manipulated by varying the stimulus onset asynchrony (i.e., constant or variable SOA). In Experiment 1, participants performed a parity judgment task and a lexical decision task in which categorical priming and repetition priming were, respectively, tested. Experiment 2 used a semantic categorization task testing categorical priming. In Experiment 3, repetition and categorical priming were tested in the same semantic categorization task with the same stimuli. The results of the three experiments showed that masked repetition priming is insensitive to manipulations of temporal attention whereas categorical priming is. Furthermore, no differences were found between young and older adults in repetition priming effects, again contrasting with the categorical priming results for which older adults were more sensitive to attentional manipulations than young adults.

Age-related differences in automatic stimulus-response associations: insights from young and older adults' parity judgments.

Young and older adults completed a parity judgment task (i.e., judging whether a target digit was odd or even) in which target numbers were preceded by masked prime numbers presented for 43 msec. Targets were either congruent (i.e., they had the same parity status as their primes) or incongruent (i.e., odd primes were paired with even targets, and even primes were paired with odd targets). Response times, percent errors, and event-related potentials (ERPs) were recorded for all items to compare automatic stimulus-response association (ASRA) and congruence effects (i.e., better performance on congruent than on incongruent trials) across age groups. Two important original sets of findings were obtained in this sample of participants. First, both age groups showed ASRA effects in behavioral measures. Second, age-related differences were observed in amplitude, timing, and scalp distributions for each congruent and incongruent ERP. These findings have implications for furthering the understanding of ASRA effects and of general characteristics of cognitive processes affected (or not affected) by aging.