Molecular detection of SARS-COV-2 in exhaled breath at the point-of-need.

The SARS-CoV-2 pandemic has highlighted the need for improved technologies to help control the spread of contagious pathogens. While rapid point-of-need testing plays a key role in strategies to rapidly identify and isolate infectious patients, current test approaches have significant shortcomings related to assay limitations and sample type. Direct quantification of viral shedding in exhaled particles may offer a better rapid testing approach, since SARS-CoV-2 is believed to spread mainly by aerosols. It assesses contagiousness directly, the sample is easy and comfortable to obtain, sampling can be standardized, and the limited sample volume lends itself to a fast and sensitive analysis. In view of these benefits, we developed and tested an approach where exhaled particles are efficiently sampled using inertial impaction in a micromachined silicon chip, followed by an RT-qPCR molecular assay to detect SARS-CoV-2 shedding. Our portable, silicon impactor allowed for the efficient capture (>85%) of respiratory particles down to 300 nm without the need for additional equipment. We demonstrate using both conventional off-chip and in-situ PCR directly on the silicon chip that sampling subjects' breath in less than a minute yields sufficient viral RNA to detect infections as early as standard sampling methods. A longitudinal study revealed clear differences in the temporal dynamics of viral load for nasopharyngeal swab, saliva, breath, and antigen tests. Overall, after an infection, the breath-based test remains positive during the first week but is the first to consistently report a negative result, putatively signalling the end of contagiousness and further emphasizing the potential of this tool to help manage the spread of airborne respiratory infections.

Exhaled breath SARS-CoV-2 shedding patterns across variants of concern.

OBJECTIVES: We performed exhaled breath (EB) and nasopharyngeal (NP) quantitative polymerase chain reaction (qPCR) and NP rapid antigen testing (NP RAT) of SARS-CoV-2 infections with different variants. METHODS: We included immuno-naïve alpha-infected (n = 11) and partly boosted omicron-infected patients (n = 8) as high-risk contacts. We compared peak NP and EB qPCR cycle time (ct) values between cohorts (Wilcoxon-Mann-Whitney test). Test positivity was compared for three infection phases using Cochran Q test. RESULTS: Peak median NP ct was 11.5 (interquartile range [IQR] 10.1-12.1) for alpha and 12.2 (IQR 11.1-15.3) for omicron infections. Peak median EB ct was 25.2 (IQR 24.5-26.9) and 28.3 (IQR 26.4-30.8) for alpha and omicron infections, respectively. Distributions did not differ between cohorts for NP (P = 0.19) or EB (P = 0.09). SARS-CoV-2 shedding peaked on day 1 in EB (confidence interval [CI] 0.0 - 4.5) and day 3 in NP (CI 1.5 - 6.0). EB qPCR positivity equaled NP qPCR positivity on D0-D1 (P = 0.44) and D2-D6 (P = 1.0). It superseded NP RAT positivity on D0-D1 (P = 0.003) and D2-D6 (P = 0.008). It was inferior to both on D7-D10 (P < 0.001). CONCLUSION: Peak EB and nasopharynx shedding were comparable across variants. EB qPCR positivity matched NP qPCR and superseded NP RAT in the first week of infection.

Sequence learning in Parkinson's disease: Focusing on action dynamics and the role of dopaminergic medication.

Previous studies on movement sequence learning in Parkinson's disease (PD) have produced mixed results. A possible explanation for the inconsistent findings is that some studies have taken dopaminergic medication into account while others have not. Additionally, in previous studies the response modalities did not allow for an investigation of the action dynamics of sequential movements as they unfold over time. In the current study we investigated sequence learning in PD by specifically considering the role of medication status in a sequence learning task where mouse movements were performed. The focus on mouse movements allowed us to examine the action dynamics of sequential movement in terms of initiation time, movement time, movement accuracy, and velocity. PD patients performed the sequence learning task once on their regular medication, and once after overnight withdrawal from their medication. Results showed that sequence learning as reflected in initiation times was impaired when PD patients performed the task ON medication compared to OFF medication. In contrast, sequence learning as reflected in the accuracy of movement trajectories was enhanced when performing the task ON compared to OFF medication. Our findings suggest that while medication enhances execution processes of movement sequence learning, it may at the same time impair planning processes that precede actual execution. Overall, the current study extends earlier findings on movement sequence learning in PD by differentiating between various components of performance, and further refines previous dopamine overdose effects in sequence learning.

Conflict adaptation in schizophrenia: reviewing past and previewing future efforts.

INTRODUCTION: Cognitive control impairments have been suggested to be a critical component in the overall cognitive deficits observed in patients diagnosed with schizophrenia. Here, we zoom in on a specific function of cognitive control, conflict adaptation. Abnormal neural activity patterns have been observed for patients diagnosed with schizophrenia in core conflict adaptation areas such as anterior cingulate cortex and prefrontal cortex. On the one hand, this strongly indicates that conflict adaptation is affected. On the other hand, however, outcomes at the behavioural level are needed to create a window into a precise interpretation of this abnormal neural activity. METHODS: We present a narrative review of behavioural work within the context of conflict adaptation in schizophrenia, focusing on various major conflict adaptation markers: congruency sequence effects, proportion congruency effects, and post-error and post-conflict slowing. The review emphasises both methodological and theoretical aspects that are relevant to the understanding of conflict adaptation in schizophrenia. RESULTS: Based on the currently available set of behavioural studies on conflict adaptation, no clear-cut answer can be provided as to the precise conflict adaptation processes that are impaired (and to what extent) in schizophrenia populations. CONCLUSIONS: Future work is needed in state-of-the-art designs in order to reach better insight into the specifics of conflict adaptation impairments associated with schizophrenia.

Pupil size directly modulates the feedforward response in human primary visual cortex independently of attention.

Controversy revolves around the question of whether psychological factors like attention and emotion can influence the initial feedforward response in primary visual cortex (V1). Although traditionally, the electrophysiological correlate of this response in humans (the C1 component) has been found to be unaltered by psychological influences, a number of recent studies have described attentional and emotional modulations. Yet, research into psychological effects on the feedforward V1 response has neglected possible direct contributions of concomitant pupil-size modulations, which are known to also occur under various conditions of attentional load and emotional state. Here we tested the hypothesis that such pupil-size differences themselves directly affect the feedforward V1 response. We report data from two complementary experiments, in which we used procedures that modulate pupil size without differences in attentional load or emotion while simultaneously recording pupil-size and EEG data. Our results confirm that pupil size indeed directly influences the feedforward V1 response, showing an inverse relationship between pupil size and early V1 activity. While it is unclear in how far this effect represents a functionally-relevant adaptation, it identifies pupil-size differences as an important modulating factor of the feedforward response of V1 and could hence represent a confounding variable in research investigating the neural influence of psychological factors on early visual processing.

Sequential movement skill in Parkinson's disease: a state-of-the-art.

The present work reviews research on the learning and skilled performance of movement sequences in Parkinson's disease (PD). We focus specifically on the serial reaction time (SRT) task, and start by outlining behavioral studies on PD patients and healthy control participants. The literature is not unequivocal: Whereas the majority of studies indicate impaired sequencing skill in PD, still a considerable set of studies opposes this conclusion. We identify and discuss various determinants of sequence skill in PD that may contribute to the inconclusiveness of the literature. One major determinant is the role of dopaminergic medication. It has been hypothesized that while such medication restores dopamine levels in depleted parts of the brain, it may also overdose brain regions in which dopamine depletion is less pronounced. As sequence learning involves the contribution of both affected and unaffected brain areas, dopaminergic medication may enhance particular (motor-related) processes involved in sequence learning, but hinder other (cognition-related) processes that are still intact in PD. We discuss studies supporting this notion and finish with some recommendations for future research: systematically consider the impact of medication, build on models of sequence learning that include both cognitive and motor components, and include more elaborated motor skill to be able to better dissociate cognitive and motor-based problems and explore their interactions.

Generalizing attentional control across dimensions and tasks: evidence from transfer of proportion-congruent effects.

Three experiments investigated transfer of list-wide proportion congruent (LWPC) effects from a set of congruent and incongruent items with different frequency (inducer task) to a set of congruent and incongruent items with equal frequency (diagnostic task). Experiments 1 and 2 mixed items from horizontal and vertical Simon tasks. Tasks always involved different stimuli that varied on the same dimension (colour) in Experiment 1 and on different dimensions (colour, shape) in Experiment 2. Experiment 3 mixed trials from a manual Simon task with trials from a vocal Stroop task, with colour being the relevant stimulus in both tasks. There were two major results. First, we observed transfer of LWPC effects in Experiments 1 and 3, when tasks shared the relevant dimension, but not in Experiment 2. Second, sequential modulations of congruency effects transferred in Experiment 1 only. Hence, the different transfer patterns suggest that LWPC effects and sequential modulations arise from different mechanisms. Moreover, the observation of transfer supports an account of LWPC effects in terms of list-wide cognitive control, while being at odds with accounts in terms of stimulus-response (contingency) learning and item-specific control.

What determines the specificity of conflict adaptation? A review, critical analysis, and proposed synthesis.

Over the past decade, many cognitive control researchers have studied to what extent adaptations to conflict are domain-general or rather specific, mostly by testing whether or not the congruency sequence effect (CSE) transfers across different conditions (e.g., conflict type, task sets, contexts, et cetera). The CSE refers to the observation that congruency effects in conflict tasks tend to be reduced following incongruent relative to following congruent trials, and is considered a prime measure of cognitive control. By investigating the transfer of this CSE across different conflict types, tasks, or contexts, researchers made several inferences about the scope of cognitive control. This method gained popularity during the last few years, spawning an interesting, yet seemingly inconsistent set of results. Consequently, these observations gave rise to a number of equally divergent theories about the determinants and scope of conflict adaptation. In this review, we offer a systematic overview of these past studies, as well as an evaluation of the theories that have been put forward to account for the results. Finally, we propose an integration of these various theoretical views in a unifying framework that centers on the role of context (dis)similarity. This framework allows us to generate new predictions about the relation between task or context similarity and the scope of cognitive control. Specifically, while most theories imply that increasing contextual differences will result in reduced transfer of the CSE, we propose that context similarity and across-context control follow a U-shaped function instead.

The congruency sequence effect 3.0: a critical test of conflict adaptation.

Over the last two decades, the congruency sequence effect (CSE) -the finding of a reduced congruency effect following incongruent trials in conflict tasks- has played a central role in advancing research on cognitive control. According to the influential conflict-monitoring account, the CSE reflects adjustments in selective attention that enhance task focus when needed, often termed conflict adaptation. However, this dominant interpretation of the CSE has been called into question by several alternative accounts that stress the role of episodic memory processes: feature binding and (stimulus-response) contingency learning. To evaluate the notion of conflict adaptation in accounting for the CSE, we construed versions of three widely used experimental paradigms (the colour-word Stroop, picture-word Stroop and flanker task) that effectively control for feature binding and contingency learning. Results revealed that a CSE can emerge in all three tasks. This strongly suggests a contribution of attentional control to the CSE and highlights the potential of these unprecedentedly clean paradigms for further examining cognitive control.

The heterogeneous world of congruency sequence effects: an update.

Congruency sequence effects (CSEs) refer to the observation that congruency effects in conflict tasks are typically smaller following incongruent compared to following congruent trials. This measure has long been thought to provide a unique window into top-down attentional adjustments and their underlying brain mechanisms. According to the renowned conflict monitoring theory, CSEs reflect enhanced selective attention following conflict detection. Still, alternative accounts suggested that bottom-up associative learning suffices to explain the pattern of reaction times and error rates. A couple of years ago, a review by Egner (2007) pitted these two rivalry accounts against each other, concluding that both conflict adaptation and feature integration contribute to the CSE. Since then, a wealth of studies has further debated this issue, and two additional accounts have been proposed, offering intriguing alternative explanations. Contingency learning accounts put forward that predictive relationships between stimuli and responses drive the CSE, whereas the repetition expectancy hypothesis suggests that top-down, expectancy-driven control adjustments affect the CSE. In the present paper, we build further on the previous review (Egner, 2007) by summarizing and integrating recent behavioral and neurophysiological studies on the CSE. In doing so, we evaluate the relative contribution and theoretical value of the different attentional and memory-based accounts. Moreover, we review how all of these influences can be experimentally isolated, and discuss designs and procedures that can critically judge between them.

Reward determines the context-sensitivity of cognitive control.

Reward is thought to enhance cognitive control processes in various ways, but the impact of reward on the context-sensitivity of cognitive control remains unclear. Evidence from perception and attention studies suggests that a good outcome, in contrast to a suboptimal outcome, acts to increase saliency and attentional capture for attended visual features that led to this outcome. As a consequence, such features gain a competitive advantage in future perception. In the present article, we investigate the possibility that this interplay between reward and contextual visual features can impact the scope of higher cognitive control processes, specifically conflict monitoring. To this end, we ran 2 experiments. First, by combining a visual search paradigm with a letter flanker task, we demonstrate how the congruency sequence effect can be observed when salient task irrelevant features repeat, but disappears when those features alternate. These findings are in line with earlier observations on the context-sensitivity of cognitive control. In a second experiment, we added a reward manipulation, demonstrating that this context-sensitivity is promoted following high reward but disappears following low reward. The results suggest a role for reward in modulating the context-sensitivity and scope of cognitive control.

Punishment sensitivity predicts the impact of punishment on cognitive control.

Cognitive control theories predict enhanced conflict adaptation after punishment. However, no such effect was found in previous work. In the present study, we demonstrate in a flanker task how behavioural adjustments following punishment signals are highly dependent on punishment sensitivity (as measured by the Behavioural Inhibition System (BIS) scale): Whereas low punishment-sensitive participants do show increased conflict adaptation after punishment, high punishment-sensitive participants show no such modulation. Interestingly, participants with a high punishment-sensitivity showed an overall reaction time increase after punishments. Our results stress the role of individual differences in explaining motivational modulations of cognitive control.

Dopaminergic medication counteracts conflict adaptation in patients with Parkinson's disease.

OBJECTIVE: We tested the role of dopamine in conflict-induced behavioral adjustments by evaluating the effect of dopaminergic medication on conflict adaptation in Parkinson's disease (PD) patients. METHOD: Nine PD patients performed a vocal Stroop task on two separate testing occasions: once on their regular medication and once after overnight withdrawal. RESULTS: In line with previous studies (e.g., Bonnin, Houeto, Gil, & Bouquet, 2010), patients displayed no conflict adaptation when tested on medication. However, the same patients tested off of their medication did display a conflict adaptation effect in that the size of the interference effect was reduced after incongruent trials compared with after congruent trials. CONCLUSIONS: This difference is discussed in terms of an inverted U-shaped relation between dopamine and performance, according to which dopaminergic medication has detrimental effects on PD patients' performance by overdosing brain regions that are relatively spared in the initial stage of the disease, including the ventral striatum and prefrontal cortex.

Attention modulation by proportion congruency: the asymmetrical list shifting effect.

Proportion congruency effects represent hallmark phenomena in current theorizing about cognitive control. This is based on the notion that proportion congruency determines the relative levels of attention to relevant and irrelevant information in conflict tasks. However, little empirical evidence exists that uniquely supports such an attention modulation account; moreover, a rivaling account was recently proposed that attributes the effect of proportion congruency to mere contingency learning. In the present study, the influences of shifts in list-wide (Experiment 1) or item-specific (Experiment 2) proportion congruency were investigated. As predicted by attention modulation but not by contingency learning, strong asymmetries were observed in such shifting: An increase in the proportion of congruent trials had only limited impact on the size of the congruency effect when participants were initially trained with a mostly incongruent list, but the impact was substantial for an equivalent increase of incongruent trials when participants were initially trained with a mostly congruent list. This asymmetrical list shifting effect directly supports attention modulation by proportion congruency manipulations and as such provides a novel tool for exploring cognitive control. Implications of our findings for existing theories of cognitive control are discussed.

The hot-hand fallacy in cognitive control: repetition expectancy modulates the congruency sequence effect.

In this study, the role of expectancies in cognitive control was tested. On the basis of the original interpretation of the congruency sequence effect (Gratton, Coles, & Donchin, Journal of Experimental Psychology: General 121:480-506, 1992), we sought evidence for a repetition bias steering attentional control. In a series of four Stroop experiments, we investigated how participants' explicit predictions about the upcoming (in)congruency proactively influenced subsequent Stroop performance. Similar to the fallacious "hot-hand" belief in gambling, repeating stimulus events were overpredicted, as participants consistently expected more repetitions of the congruency level than the actual presented number of congruency-level repetitions (50 %). Moreover, behavioral adjustments (i.e., a congruency sequence effect) were only found when participants anticipated a congruency-level repetition, whereas no modulation of the Stroop effect was found following alternation predictions. We propose that proactive control processes in general, and repetition expectancy in particular, should be given more attention in current theorizing and modeling of cognitive control, which is characterized by an emphasis on reactive, conflict-induced control adjustments.

The effect of alcohol and placebo on post-error adjustments.

Several studies have shown detrimental effects of alcohol on post-error adjustments. In contrast to previous studies, which focused on only one aspect of post-error adaptive behavior, we compared the effect of alcohol and placebo on post-error slowing (PES), post-error reduction of interference (PERI) and post-error improvement of accuracy (PIA). Moreover, we used a between-subjects design (N = 45) comparing a control condition to both an alcohol and an alcohol-placebo condition as to disentangle physiological and expectancy effects of alcohol. In a standard Stroop congruency task, we found that intoxicated participants as well as participants with the incorrect belief of being intoxicated showed significant decreased PES compared to a control group. Furthermore, we found evidence for a condition-independent post-error increase of interference and post-error decrease of accuracy. The underlying mechanisms of the post-error adaptation effects are discussed in terms of the orienting account (Notebaert et al., 2009).

When predictions take control: the effect of task predictions on task switching performance.

In this paper, we aimed to investigate the role of self-generated predictions in the flexible control of behavior. Therefore, we ran a task switching experiment in which participants were asked to try to predict the upcoming task in three conditions varying in switch rate (30, 50, and 70%). Irrespective of their predictions, the color of the target indicated which task participants had to perform. In line with previous studies (Mayr, 2006; Monsell and Mizon, 2006), the switch cost was attenuated as the switch rate increased. Importantly, a clear task repetition bias was found in all conditions, yet the task repetition prediction rate dropped from 78 over 66 to 49% with increasing switch probability in the three conditions. Irrespective of condition, the switch cost was strongly reduced in expectation of a task alternation compared to the cost of an unexpected task alternation following repetition predictions. Hence, our data suggest that the reduction in the switch cost with increasing switch probability is caused by a diminished expectancy for the task to repeat. Taken together, this paper highlights the importance of predictions in the flexible control of behavior, and suggests a crucial role for task repetition expectancy in the context-sensitive adjusting of task switching performance.

Conflict adaptation: it is not what you expect.

In two studies, a vocal Stroop task with eight different colours was employed in order to put two core assumptions of the original interpretation of the Gratton effect to the test. We verified whether top-down control processes can elicit conflict adaptation when episodic memory effects are controlled for and to what extent proactive adjustments driven by the subjects' expectancy for congruency level repetition contribute to this effect. Therefore, we presented Stroop stimuli without feature repetitions and investigated whether the induced expectancy manipulation of raising the amount of either congruency level repetitions or alternations in a training phase transferred to an unmanipulated test phase. Over the two experiments, a sequential modulation of the Stroop effect was found in the absence of stimulus feature repetitions, strongly confirming a share for top-down control processes in bringing about the Gratton effect. In the condition where congruency level repetitions were raised, a strong Gratton effect was found. When congruency level alternations outnumbered repetitions, the Gratton effect disappeared completely. However, this difference seemed mainly due to cumulative effects of local, dynamic, trial-to-trial control adjustments rather than expectancy-induced attentional shifting. Once the transition probability changed back to 50% in the test phase of each experiment, a similar Gratton effect was found in both conditions. Taken together, these results are best explained in terms of dynamic reactive control.