Test-retest reliability and validity of the Importance of Olfaction Questionnaire in Denmark.

While measures to detect psychophysical olfactory ability are a crucial part of clinicians' assessment of potential olfactory loss, it gives no indication of how olfaction is experienced by the patient and these different aspects often deviate substantially. To ensure quality and reproducibility of subjectively reported olfactory experience and significance, the Importance of Olfaction Questionnaire (IO-Q) was introduced around a decade ago, and while initial validations have produced promising results, important aspects remain nearly unexamined. For example, the test-retest reliability has rarely been examined and the difference of online versus pen-and-paper administration remains unexplored. Here, we translated IO-Q to Danish and examined its validity, test-retest reliability and mode of administration. A cohort of 179 younger, Danish participants with a high level of English proficiency took the test twice with varying time in-between. The first test was taken digitally and in English, while the second was taken using pen-and-paper and in Danish. The distribution of scores and the relationship between the IO-Q and subscale scores were nearly identical between tests, indicating little to no influence of language/test modality in the sampled population. The internal consistency was comparable to previously published results. Likewise, an acceptable test-retest reliability was observed for the full IO-Q and slightly lower for subscales. No significant effect of time was found across several weeks. In conclusion, the IO-Q performed satisfactorily in all examinations and could therefore serve as a valuable clinical measure of subjective olfactory experience, and its Danish translation shows highly similar characteristics to the original, English version.

Shared parenting and father involvement after divorce in Denmark.

The Scandinavian countries make interesting samples for the study of shared parenting as they are characterized by some of the highest levels of father involvement and gender equality globally. Despite numerous studies, data from Denmark is noticeably absent in the international debate, partly due to a researcher preference for publishing in Danish. Here, I present an overview of the increase in father involvement in Denmark since the 1960s and on the increase in shared parenting across recent decades. I further examine Danish law, ministerial guidelines and guidelines from major Danish public and private institutions/organizations involved in deciding or advising on parenting practices post-divorce. I relate these to international research findings as well as to findings from Danish research. Overall, I find that Danish guidelines/practice have several reservations against shared parenting and substantial father involvement, which are not considered warranted by a substantial number of scientists and which are not supported by the majority of the available evidence. It thus appears that societal transition toward increased shared parenting has happened on a largely voluntary basis in spite of official law/practice. Updated law and/or ministerial guidelines are likely necessary if politicians desire that children experience the same high degree of father involvement post-divorce that they experience in society in general.

Continuous Theta Burst Stimulation to the left anterior medial prefrontal cortex influences metacognitive efficiency.

The contribution of the prefrontal areas to visual awareness is critical for the Global Neuronal Workspace Theory and higher-order theories of consciousness. The goal of the present study was to test the potential engagement of the anterior medial prefrontal cortex (aMPFC) in visual awareness judgements. We aimed to temporarily influence the neuronal dynamics of the left aMPFC via neuroplasticity-like mechanisms. We used different Theta Burst Stimulation (TBS) protocols in combination with a visual identification task and visual awareness ratings. Either continuous TBS (cTBS), intermittent TBS (iTBS), or sham TBS was applied prior to the experimental paradigm in a within-participant design. Compared with sham TBS, we observed an increase in participants' ability to judge their perception adequately (metacognitive efficiency) following cTBS but not iTBS. The effect was accompanied by lower visual awareness ratings in incorrect responses. No significant differences in the identification task performance were observed. We interpret these results as evidence of the involvement of PFC in the brain network that underlies metacognition. Further, we discuss whether the results of TMS studies on perceptual metacognition can be taken as evidence for PFC involvement in awareness itself.

The role of mindful acceptance and lucid dreaming in nightmare frequency and distress.

A theoretical and empirical association between lucid dreaming and mindfulness, as well as lucid dreaming and nightmares has previously been observed; however, the relationship between nightmares and mindfulness has received surprisingly little attention. Here, we present the findings of two studies exploring the relation of nightmare frequency and distress with two components of mindfulness, termed presence and acceptance, as well as lucid dreaming. Study 1 (N = 338) consisted of a low percentage of frequent lucid dreamers whereas Study 2 (N = 187) consisted primarily of frequent lucid dreamers that used lucid dream induction training techniques and meditation. Across studies, nightmare-related variables showed a more robust association with mindful acceptance as opposed to mindful presence. Moreover, individuals with high levels of meditation expertise and practice of lucid dreaming induction techniques reported lower nightmare frequency. Finally, in Study 2, which consisted of frequent lucid dreamers, a positive correlation between lucid dreaming frequency and mindfulness was apparent. The present findings support the notion that wakeful mindfulness is associated with the quality of dreams and extend previous research by suggesting a disentangled role of the two facets of mindfulness in dream variation. This association remains open for experimental manipulation, the result of which could have clinical implications.

Task requirements affect the neural correlates of consciousness.

In the search for the neural correlates of consciousness, it is often assumed that there is a stable set within the relevant sensory modality. Within the visual modality, the debate has centred upon whether frontal or occipital activations are the best predictors of perceptual awareness. Although not accepted by all as definitive evidence, no-report and decoding studies have indicated that occipital activity is the most consistently correlated with perceptual awareness whereas frontal activity might be closely related to aspects of cognition typically related to reports. However, perception is rarely just passive perception of something, but more or less always perception for something. That is, the task at hand for the perceiver may influence what is being perceived. This suggests an alternative view: that consciousness is not one specific 'function' that can be localized consistently to one area or event-related component and that the specific attributes of the neural correlates of consciousness depend on the task at hand. To investigate whether and how tasks may influence the neural correlates of consciousness, we here contrasted two tasks, a perceptual task and a conceptual task, using identical stimuli in both tasks. Using magnetoencephalography, we found that the perceptual task recruited more occipital resources than the conceptual task. Furthermore, we found that between the two conditions, the amount of frontal resources recruited differed between different gradations of perceptual awareness partly in an unexpected manner. These findings support a view of task affecting the neural correlates of consciousness.

A window of subliminal perception.

Under labels such as unconscious processing and subliminal perception, identification of stimuli falling below the subjective threshold (whether truly unconscious or not) has been found remarkably accurate in some experiments while completely at chance in others. Here, we first identify that an apparent window of subliminal perception arises in humans under specific stimulus conditions using different experimental paradigms and analysis methods. We then show that the standard signal detection theory (SDT) model is unable to account for this window and extend it until it is. We finally compare a range of models on empirical data. The models performing best are notable for their absence of hierarchical levels, indicating that the window could be a base property of any phenomenally conscious system. The models explain previously incompatible findings in the literature, and they allow for estimations of peaks in subthreshold perception across the spectrum of stimulus saliency, which may be used in further studies of subliminal perception.

Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses.

Drugs targeting SARS-CoV-2 could have saved millions of lives during the COVID-19 pandemic, and it is now crucial to develop inhibitors of coronavirus replication in preparation for future outbreaks. We explored two virtual screening strategies to find inhibitors of the SARS-CoV-2 main protease in ultralarge chemical libraries. First, structure-based docking was used to screen a diverse library of 235 million virtual compounds against the active site. One hundred top-ranked compounds were tested in binding and enzymatic assays. Second, a fragment discovered by crystallographic screening was optimized guided by docking of millions of elaborated molecules and experimental testing of 93 compounds. Three inhibitors were identified in the first library screen, and five of the selected fragment elaborations showed inhibitory effects. Crystal structures of target-inhibitor complexes confirmed docking predictions and guided hit-to-lead optimization, resulting in a noncovalent main protease inhibitor with nanomolar affinity, a promising in vitro pharmacokinetic profile, and broad-spectrum antiviral effect in infected cells.

The Perceptual Awareness Scale-recent controversies and debates.

Accurate insight into subjective experience is crucial for the science of consciousness. The Perceptual Awareness Scale (PAS) was created in 2004 as a method for obtaining precise introspective reports for participants in research projects, and since then, the scale has become increasingly popular. This does not mean, of course, that no critiques have been voiced. Here, we briefly recapitulate our main thoughts on the intended PAS usage and the findings of the first decade, and we update this with the latest empirical and theoretical developments. We focus specifically on findings with relevance to whether consciousness is gradual or all-or-none phenomenon, to what should be considered conscious/unconscious, and to whether PAS is preferable to alternative measures of awareness. We respond in detail to some recent, selected articles.

Population receptive fields of human primary visual cortex organised as DC-balanced bandpass filters.

The response to visual stimulation of population receptive fields (pRF) in the human visual cortex has been modelled with a Difference of Gaussians model, yet many aspects of their organisation remain poorly understood. Here, we examined the mathematical basis and signal-processing properties of this model and argue that the DC-balanced Difference of Gaussians (DoG) holds a number of advantages over a DC-biased DoG. Through functional magnetic resonance imaging (fMRI) pRF mapping, we compared performance of DC-balanced and DC-biased models in human primary visual cortex and found that when model complexity is taken into account, the DC-balanced model is preferred. Finally, we present evidence indicating that the BOLD signal DC offset contains information related to the processing of visual stimuli. Taken together, the results indicate that V1 pRFs are at least frequently organised in the exact constellation that allows them to function as bandpass filters, which makes the separation of stimulus contrast and luminance possible. We further speculate that if the DoG models stimulus contrast, the DC offset may reflect stimulus luminance. These findings suggest that it may be possible to separate contrast and luminance processing in fMRI experiments and this could lead to new insights on the haemodynamic response.

Comparing theories of consciousness: why it matters and how to do it.

The theoretical landscape of scientific studies of consciousness has flourished. Today, even multiple versions of the same theory are sometimes available. To advance the field, these theories should be directly compared to determine which are better at predicting and explaining empirical data. Systematic inquiries of this sort are seen in many subfields in cognitive psychology and neuroscience, e.g. in working memory. Nonetheless, when we surveyed publications on consciousness research, we found that most focused on a single theory. When 'comparisons' happened, they were often verbal and non-systematic. This fact in itself could be a contributing reason for the lack of convergence between theories in consciousness research. In this paper, we focus on how to compare theories of consciousness to ensure that the comparisons are meaningful, e.g. whether their predictions are parallel or contrasting. We evaluate how theories are typically compared in consciousness research and related subdisciplines in cognitive psychology and neuroscience, and we provide an example of our approach. We then examine the different reasons why direct comparisons between theories are rarely seen. One possible explanation is the unique nature of the consciousness phenomenon. We conclude that the field should embrace this uniqueness, and we set out the features that a theory of consciousness should account for.

Transcranial Magnetic Stimulation-Induced Motor Cortex Activity Influences Visual Awareness Judgments.

The influence of non-visual information on visual awareness judgments has recently gained substantial interest. Using single-pulse transcranial magnetic stimulation (TMS), we investigate the potential contribution of evidence from the motor system to judgment of visual awareness. We hypothesized that TMS-induced activity in the primary motor cortex (M1) would increase reported visual awareness as compared to the control condition. Additionally, we investigated whether TMS-induced motor-evoked potential (MEP) could measure accumulated evidence for stimulus perception. Following stimulus presentation and TMS, participants first rated their visual awareness verbally using the Perceptual Awareness Scale (PAS), after which they responded manually to a Gabor orientation identification task. Delivering TMS to M1 resulted in higher average awareness ratings as compared to the control condition, in both correct and incorrect identification task response trials, when the hand with which participants responded was contralateral to the stimulated hemisphere (TMS-response-congruent trials). This effect was accompanied by longer PAS response times (RTs), irrespective of the congruence between TMS and identification response. Moreover, longer identification RTs were observed in TMS-response-congruent trials in the M1 condition as compared to the control condition. Additionally, the amplitudes of MEPs were related to the awareness ratings when response congruence was taken into account. We argue that MEP can serve as an indirect measure of evidence accumulated for stimulus perception and that longer PAS RTs and higher amplitudes of MEPs in the M1 condition reflect integration of additional evidence with visual awareness judgment. In conclusion, we advocate that motor activity influences perceptual awareness judgments.

Comparing theories of consciousness: Object position, not probe modality, reliably influences experience and accuracy in object recognition tasks.

People often claim seeing images completely despite performing poorly. This highlights an issue with conscious representations. We introduce an experimental manipulation aiming to disentangle two prevalent positions: Rich views posit that people virtually represent the external world with unlimited capacity; Sparse views state that representations are reconstructed from expectations and information. In two experiments using the object recognition task, we tested two probe types: Images, which should aid reconstruction more, and Words, which should aid it less. From a sparse view, one should expect that Images lead to greater accuracy and reported experience. We found no reliable differences in accuracy and reported experience across probe types; however, we observed that the object positions influenced both accuracy and reported experience, which is surprising from a Rich view as it seemingly requires assumptions of different access across the visual field. Both theoretical positions thus currently need further development to explain our results.

Causal Inferences in Repetitive Transcranial Magnetic Stimulation Research: Challenges and Perspectives.

Transcranial magnetic stimulation (TMS) is used to make inferences about relationships between brain areas and their functions because, in contrast to neuroimaging tools, it modulates neuronal activity. The central aim of this article is to critically evaluate to what extent it is possible to draw causal inferences from repetitive TMS (rTMS) data. To that end, we describe the logical limitations of inferences based on rTMS experiments. The presented analysis suggests that rTMS alone does not provide the sort of premises that are sufficient to warrant strong inferences about the direct causal properties of targeted brain structures. Overcoming these limitations demands a close look at the designs of rTMS studies, especially the methodological and theoretical conditions which are necessary for the functional decomposition of the relations between brain areas and cognitive functions. The main points of this article are that TMS-based inferences are limited in that stimulation-related causal effects are not equivalent to structure-related causal effects due to TMS side effects, the electric field distribution, and the sensitivity of neuroimaging and behavioral methods in detecting structure-related effects and disentangling them from confounds. Moreover, the postulated causal effects can be based on indirect (network) effects. A few suggestions on how to manage some of these limitations are presented. We discuss the benefits of combining rTMS with neuroimaging in experimental reasoning and we address the restrictions and requirements of rTMS control conditions. The use of neuroimaging and control conditions allows stronger inferences to be gained, but the strength of the inferences that can be drawn depends on the individual experiment's designs. Moreover, in some cases, TMS might not be an appropriate method of answering causality-related questions or the hypotheses have to account for the limitations of this technique. We hope this summary and formalization of the reasoning behind rTMS research can be of use not only for scientists and clinicians who intend to interpret rTMS results causally but also for philosophers interested in causal inferences based on brain stimulation research.

Spatiotemporal dynamics of brightness coding in human visual cortex revealed by the temporal context effect.

Human visual perception is modulated by both temporal and spatial contexts. One type of modulation is apparent in the temporal context effect (TCE): In the presence of a constant luminance patch (a long flash), the perceived brightness of a short flash increases monotonically with onset asynchrony. The aim of the current study was to delineate the neural correlates of this illusory effect, particularly focusing on its dynamic neural representation among visual cortical areas. We reconstructed sources of magnetoencephalographic (MEG) data recorded from observers (6 male and 9 female human adults) experiencing the TCE. Together with retinotopic mapping, signals from different occipital lobe areas were extracted to investigate whether different visual areas have differential representation of the onset vs. offset synchronized short flashes. From the data, TCE related responses were observed in LO and V4 in the time window of 200-250 m s, while neuronal responses to physical luminances were observed in the early time window at around 100 m s across early visual cortex, such as V1 and V2, also in V4 and VO. Based on these findings, we suggest that two distinct processes might be involved in brightness coding: one bottom-up process which is stimulus energy driven and responds fast, and another process which may be broadly characterized as top-down or lateral, is context driven, and responds slower. For both processes, we found that V4 might play a critical role in dynamically integrating luminances into brightness perception, a finding that is consistent with the view of V4 as a bottom-up and top-down integration complex.

Binocular rivalry and emotion: Implications for neural correlates of consciousness and emotional biases in conscious perception.

Studies of the neural correlates of consciousness (NCCs) combining MEG/EEG with behavioral data have described two main time ranges relating to conscious perception: 130-320 (the visual awareness negativity; VAN) and 300-500 (P3a) ms after stimulus onset. At the same time, two event-related potential (ERP) peaks have shown an emotional modulation of endogenous attention: the early posterior negativity (EPN; peaking around 250 msec) and the late positive potential (LPP, peaking around 600 msec). Furthermore, an emotional bias on conscious perception has been reported in Binocular Rivalry (BR) studies. Here, we combined an intermittent BR paradigm with neutral and emotional stimuli while recording the behavioral subjective perception and ERPs with two aims: i) to explore the NCCs of emotional content in the time ranges previously described, and ii) to study the emotional bias in conscious perception as first percept when neutral and emotional images rival against each other. First, results revealed a specific ERP emotional modulation (emotional content awareness modulation; ECAM) at the VAN time range. This was the first time window sensitive to the emotional information and showing the strongest modulation in conscious emotional content. Second, results revealed an emotional bias in conscious perception towards the positive valence. This work shows how conscious perception pertaining to emotional content relates to perceptual areas at the VAN latency, which supports the claim of the 130-320 msec time window as the earliest NCC and extends the claim to apply to more than visual perceptual features. Additionally, our findings show that positive and negative content modulates the conscious perception differently.

Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci.

Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential. Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping. Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity. Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

Human Occipital and Parietal GABA Selectively Influence Visual Perception of Orientation and Size.

GABA is the primary inhibitory neurotransmitter in human brain. The level of GABA varies substantially across individuals, and this variability is associated with interindividual differences in visual perception. However, it remains unclear whether the association between GABA level and visual perception reflects a general influence of visual inhibition or whether the GABA levels of different cortical regions selectively influence perception of different visual features. To address this, we studied how the GABA levels of parietal and occipital cortices related to interindividual differences in size, orientation, and brightness perception. We used visual contextual illusion as a perceptual assay since the illusion dissociates perceptual content from stimulus content and the magnitude of the illusion reflects the effect of visual inhibition. Across individuals, we observed selective correlations between the level of GABA and the magnitude of contextual illusion. Specifically, parietal GABA level correlated with size illusion magnitude but not with orientation or brightness illusion magnitude; in contrast, occipital GABA level correlated with orientation illusion magnitude but not with size or brightness illusion magnitude. Our findings reveal a region- and feature-dependent influence of GABA level on human visual perception. Parietal and occipital cortices contain, respectively, topographic maps of size and orientation preference in which neural responses to stimulus sizes and stimulus orientations are modulated by intraregional lateral connections. We propose that these lateral connections may underlie the selective influence of GABA on visual perception.SIGNIFICANCE STATEMENT GABA, the primary inhibitory neurotransmitter in human visual system, varies substantially across individuals. This interindividual variability in GABA level is linked to interindividual differences in many aspects of visual perception. However, the widespread influence of GABA raises the question of whether interindividual variability in GABA reflects an overall variability in visual inhibition and has a general influence on visual perception or whether the GABA levels of different cortical regions have selective influence on perception of different visual features. Here we report a region- and feature-dependent influence of GABA level on human visual perception. Our findings suggest that GABA level of a cortical region selectively influences perception of visual features that are topographically mapped in this region through intraregional lateral connections.

Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab.

The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants.

Weak experiences sufficient for creating illusory figures that influence perception of actual lines.

The question of whether conscious experience is best viewed as graded or dichotomous has received much scientific attention in recent years as the answer is relevant not only to models of consciousness, but also to the examination of neural markers of consciousness in patients and infants. Although some studies have found evidence of graded perception, it is unclear whether such perception is simply composed of individual stimulus features perceived in an all-or-none manner. Here, we examined whether the Kanizsa triangle (an illusory figure that is supposedly only perceived when all its parts are visible) has an impact on line length discrimination across four degrees of subjective visibility. We found that the presence of the Kanizsa triangle biases line length judgments (a phenomenon called the Ponzo illusion) when participants reported any experience (even a weak glimpse) of the stimulus. The results support the view that consciousness is a graded phenomenon. The strength of this support depends on the assumption that all parts of the illusory figure must be perceived for the illusion to work but this assumption is not resolved in the present literature. Currently, evidence can be found both for and against this notion.