Sometimes, perception fluctuates spontaneously between two distinct interpretations of a constant sensory input. These bistable perceptual phenomena provide a unique window into the neural mechanisms that create the contents of conscious perception. Models of bistable perception posit that mutual inhibition between stimulus-selective neural populations in visual cortex plays a key role in these spontaneous perceptual fluctuations. However, a direct link between neural inhibition and bistable perception has not yet been established experimentally. Here, we link perceptual dynamics in three distinct bistable visual illusions (binocular rivalry, motion-induced blindness, and structure from motion) to measurements of gamma-aminobutyric acid (GABA) concentrations in human visual cortex (as measured with magnetic resonance spectroscopy) and to pharmacological stimulation of the GABAA receptor by means of lorazepam. As predicted by a model of neural interactions underlying bistability, both higher GABA concentrations in visual cortex and lorazepam administration induced slower perceptual dynamics, as reflected in a reduced number of perceptual switches and a lengthening of percept durations. Thus, we show that GABA, the main inhibitory neurotransmitter, shapes the dynamics of bistable perception. These results pave the way for future studies into the competitive neural interactions across the visual cortical hierarchy that elicit conscious perception.

Changes in pupil size at constant light levels reflect the activity of neuromodulatory brainstem centers that control global brain state. These endogenously driven pupil dynamics can be synchronized with cognitive acts. For example, the pupil dilates during the spontaneous switches of perception of a constant sensory input in bistable perceptual illusions. It is unknown whether this pupil dilation only indicates the occurrence of perceptual switches, or also their content. Here, we measured pupil diameter in human subjects reporting the subjective disappearance and re-appearance of a physically constant visual target surrounded by a moving pattern ('motion-induced blindness' illusion). We show that the pupil dilates during the perceptual switches in the illusion and a stimulus-evoked 'replay' of that illusion. Critically, the switch-related pupil dilation encodes perceptual content, with larger amplitude for disappearance than re-appearance. This difference in pupil response amplitude enables prediction of the type of report (disappearance vs. re-appearance) on individual switches (receiver-operating characteristic: 61%). The amplitude difference is independent of the relative durations of target-visible and target-invisible intervals and subjects' overt behavioral report of the perceptual switches. Further, we show that pupil dilation during the replay also scales with the level of surprise about the timing of switches, but there is no evidence for an interaction between the effects of surprise and perceptual content on the pupil response. Taken together, our results suggest that pupil-linked brain systems track both the content of, and surprise about, perceptual events.

What are the limits of unconscious language processing? Can language circuits process simple grammatical constructions unconsciously and integrate the meaning of several unseen words? Using behavioural priming and electroencephalography (EEG), we studied a specific rule-based linguistic operation traditionally thought to require conscious cognitive control: the negation of valence. In a masked priming paradigm, two masked words were successively (Experiment 1) or simultaneously presented (Experiment 2), a modifier (‘not’/‘very’) and an adjective (e.g. ‘good’/‘bad’), followed by a visible target noun (e.g. ‘peace’/‘murder’). Subjects indicated whether the target noun had a positive or negative valence. The combination of these three words could either be contextually consistent (e.g. ‘very bad - murder’) or inconsistent (e.g. ‘not bad - murder’). EEG recordings revealed that grammatical negations could unfold partly unconsciously, as reflected in similar occipito-parietal N400 effects for conscious and unconscious three-word sequences forming inconsistent combinations. However, only conscious word sequences elicited P600 effects, later in time. Overall, these results suggest that multiple unconscious words can be rapidly integrated and that an unconscious negation can automatically ‘flip the sign’ of an unconscious adjective. These findings not only extend the limits of subliminal combinatorial language processes, but also highlight how consciousness modulates the grammatical integration of multiple words.

Emotional stimuli may prime the motor system and facilitate action readiness. Direct evidence for this effect has been shown by recent studies using transcranial magnetic stimulation (TMS). When administered over the primary motor cortex involved in responding, TMS pulses elicit motor-evoked potentials (MEPs) in the represented muscles. The amplitudes of these MEPs reflect the state of corticospinal excitability. Here, we investigated the dynamic effects of induced emotions on action readiness, as reflected by corticospinal excitability. Subjects performed a choice task while viewing task-irrelevant emotional and neutral pictures. The pattern of MEP amplitudes showed a typical increase as the TMS pulse was presented closer in time to the imminent response. This dynamic pattern was amplified by both pleasant and unpleasant emotional stimuli, but more so when unpleasant pictures were viewed. These patterns present novel evidence in support of the notion that emotional stimuli modulate action readiness.

Adaptive behavior requires the separation of current from future goals in working memory. We used fMRI of object-selective cortex to determine the representational (dis)similarities of memory representations serving current and prospective perceptual tasks. Participants remembered an object drawn from three possible categories as the target for one of two consecutive visual search tasks. A cue indicated whether the target object should be looked for first (currently relevant), second (prospectively relevant), or if it could be forgotten (irrelevant). Prior to the first search, representations of current, prospective and irrelevant objects were similar, with strongest decoding for current representations compared to prospective (Experiment 1) and irrelevant (Experiment 2). Remarkably, during the first search, prospective representations could also be decoded, but revealed anti-correlated voxel patterns compared to currently relevant representations of the same category. We propose that the brain separates current from prospective memories within the same neuronal ensembles through opposite representational patterns.

Perceptual decisions seem to be made automatically and almost instantly. Constructing a unitary subjective conscious experience takes more time. For example, when trying to avoid a collision with a car on a foggy road you brake or steer away in a reflex, before realizing you were in a near accident. This subjective aspect of object recognition has been given little attention. We used metacognition (assessed with confidence ratings) to measure subjective experience during object detection and object categorization for degraded and masked objects, while objective performance was matched. Metacognition was equal for degraded and masked objects, but categorization led to higher metacognition than did detection. This effect turned out to be driven by a difference in metacognition for correct rejection trials, which seemed to be caused by an asymmetry of the distractor stimulus: It does not contain object-related information in the detection task, whereas it does contain such information in the categorization task. Strikingly, this asymmetry selectively impacted metacognitive ability when objective performance was matched. This finding reveals a fundamental difference in how humans reflect versus act on information: When matching the amount of information required to perform two tasks at some objective level of accuracy (acting), metacognitive ability (reflecting) is still better in tasks that rely on positive evidence (categorization) than in tasks that rely more strongly on an absence of evidence (detection).

Objectives To describe symptomatology, mortality and risk factors for mortality in a large group of Dutch nursing home (NH) residents with clinically-suspected COVID-19 who were tested with a Reverse Transcription Polymerase Chain Reaction (RT-PCR) test. Design Prospective cohort study. Setting and participants Residents of Dutch NHs with clinically-suspected COVID-19 and who received RT-PCR test. Methods We collected data of NH residents with clinically-suspected COVID-19, via electronic health records between March 18 th and May 13 th , 2020. Registration was performed on diagnostic status (confirmed (COVID-19+)/ruled out (COVID-19-)) and symptomatology (typical and atypical symptoms). Information on mortality and risk factors for mortality were extracted from usual care data. Results In our sample of residents with clinically-suspected COVID-19 (N=4007), COVID-19 was confirmed in 1538 residents (38%). Although, symptomatology overlapped between residents with COVID-19+ and COVID-19-, those with COVID-19+ were three times more likely to die within 30 days (hazard ratio (HR), 3·1; 95% CI, 2·7 to 3·6). Within this group, mortality was higher for men than for women (HR, 1·8; 95%, 1·5-2·2) and we observed a higher mortality for residents with dementia, reduced kidney function, and Parkinson’s Disease, even when corrected for age, gender, and comorbidities. Conclusions and implications About 40% of the residents with clinically-suspected COVID-19 actually had COVID-19, based on the RT-PCR test. Despite an overlap in symptomatology, mortality rate was three times higher for residents with COVID-19+. This emphasizes the importance of using low-threshold testing in NH residents which is an essential prerequisite to using limited personal protective equipment and isolation measures efficiently.

It is a well-established fact that top-down processes influence neural representations in lower-level visual areas. Electrophysiological recordings in monkeys as well as theoretical models suggest that these top-down processes depend on NMDA receptor functioning. However, this underlying neural mechanism has not been tested in humans. We used fMRI multivoxel pattern analysis to compare the neural representations of ambiguous Mooney images before and after they were recognized with their unambiguous grayscale version. Additionally, we administered ketamine, an NMDA receptor antagonist, to interfere with this process. Our results demonstrate that after recognition, the pattern of brain activation elicited by a Mooney image is more similar to that of its easily recognizable grayscale version than to the pattern evoked by the identical Mooney image before recognition. Moreover, recognition of Mooney images decreased mean response; however, neural representations of separate images became more dissimilar. So from the neural perspective, unrecognizable Mooney images all "look the same", whereas recognized Mooneys look different. We observed these effects in posterior fusiform part of lateral occipital cortex and in early visual cortex. Ketamine distorted these effects of recognition, but in early visual cortex only. This suggests that top-down processes from higher- to lower-level visual areas might operate via an NMDA pathway.