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Many researchers in the behavioral sciences depend on research software that presents stimuli, and records response times, with sub-millisecond precision. There are a large number of software packages with which to conduct these behavioral experiments and measure response times and performance of participants. Very little information is available, however, on what timing performance they achieve in practice. Here we report a wide-ranging study looking at the precision and accuracy of visual and auditory stimulus timing and response times, measured with a Black Box Toolkit. We compared a range of popular packages: PsychoPy, E-Prime®, NBS Presentation®, Psychophysics Toolbox, OpenSesame, Expyriment, Gorilla, jsPsych, Lab.js and Testable. Where possible, the packages were tested on Windows, macOS, and Ubuntu, and in a range of browsers for the online studies, to try to identify common patterns in performance. Among the lab-based experiments , Psychtoolbox, PsychoPy, Presentation and E-Prime provided the best timing, all with mean precision under 1 millisecond across the visual, audio and response measures. OpenSesame had slightly less precision across the board, but most notably in audio stimuli and Expyriment had rather poor precision. Across operating systems , the pattern was that precision was generally very slightly better under Ubuntu than Windows, and that macOS was the worst, at least for visual stimuli, for all packages. Online studies did not deliver the same level of precision as lab-based systems, with slightly more variability in all measurements. That said, PsychoPy and Gorilla, broadly the best performers, were achieving very close to millisecond precision on several browser/operating system combinations. For response times (measured using a high-performance button box), most of the packages achieved precision at least under 10 ms in all browsers, with PsychoPy achieving a precision under 3.5 ms in all. There was considerable variability between OS/browser combinations, especially in audio-visual synchrony which is the least precise aspect of the browser-based experiments. Nonetheless, the data indicate that online methods can be suitable for a wide range of studies, with due thought about the sources of variability that result. The results, from over 110,000 trials, highlight the wide range of timing qualities that can occur even in these dedicated software packages for the task. We stress the importance of scientists making their own timing validation measurements for their own stimuli and computer configuration.

When animals are previously exposed to two different visual stimuli simultaneously, their learning performance at discriminating those stimuli delays: such a phenomenon is known as \"classifying-together\" or \"Bateson effect\". However, the consistency of this phenomenon has not been wholly endorsed, especially considering the evidence collected in several vertebrates. The current study addressed whether a teleost fish, Xenotoca eiseni, was liable to the Bateson effect. Three experiments were designed, by handling the visual stimuli (i.e., a full red disk, an amputated red disk, a red cross) and the presence of an exposure phase, before performing a discriminative learning task (Exp. 1: full red disk vs. amputated red disk; Exp. 2: full red disk vs. red cross). In the exposure phase, three conditions per pairs of training stimuli were arranged: \"congruence\", where fish were exposed and trained to choose the same stimulus; \"wide-incongruence\", where fish were exposed to one stimulus and trained to choose the other one; \"narrow-incongruence\", where fish were exposed to both the stimuli and trained to choose one of them. In the absence of exposure (Exp. 3), the discrimination learning task was carried out to establish a baseline performance as regards the full red disk vs. amputated red disk, and the full red disk vs. red cross. Results showed that fish ran into retardation effects at learning when trained to choose a novel stimulus with respect to the one experienced during the exposure-phase (wide-incongruence condition), as well as after being simultaneously exposed to both stimuli (narrow-incongruence condition). Furthermore, there were no facilitation effects due to the congruence compared with the baseline: in such a case, familiar stimuli did not ease the performance at learning. The study provides the first evidence about the consistency of the classifying-together effect in a fish species, further highlighting the impact of visual similarities on discrimination processes.

Key Points The immunology of pregnancy has been considered as a host–graft response characterized by immune suppression and consequently a period of increased risk of bacterial and viral infection. However, accumulating evidence suggests that pregnancy is a more complex immunological condition, and thus a reassessment of many the immunological processes evaluated during pregnancy is required. Whereas a successful organ transplant requires constant immunosuppression, a successful pregnancy requires a robust, dynamic and responsive immune system. Embryo implantation and trophoblast invasion require a local inflammatory environment that promotes cell clearance, angiogenesis, cell growth and tolerance. Pregnancy complications, such as preterm birth, are often polymicrobial in nature and can involve viral infections that sensitize the pregnant mother to subsequent bacterial infections. Interferon-β is a crucial immune modulator during pregnancy; it protects the fetus against viral infections and contributes to the process of immune regulation at the maternal–fetal interface. The immune response associated with placental viral infections can affect maternal and fetal survival. Maternal inflammation due to viral or bacterial infections has detrimental consequences for fetal development. Although healthy pregnancies were traditionally considered to require an anti-inflammatory state, emerging evidence suggests that inflammation is important for a healthy pregnancy. Here, the authors discuss how the immune response varies throughout the main stages of pregnancy, and they consider how bacterial and viral infections can affect immune responses at the maternal–fetal interface. The comparison of the immunological state of pregnancy to an immunosuppressed host–graft model continues to lead research and clinical practice to ill-defined approaches. This Review discusses recent evidence that supports the idea that immunological responses at the receptive maternal–fetal interface are not simply suppressed but are instead highly dynamic. We discuss the crucial role of trophoblast cells in shaping not only the way in which immune cells respond to the invading blastocyst but also how they collectively react to external stimuli. We also discuss the role of the microbiota in promoting a tolerogenic maternal immune system and highlight how subclinical viral infections can disrupt this status quo, leading to pregnancy complications.

The base sequences of DNA are endowed with the rich structural and functional information and are available for the precise construction of the 2D and 3D macro products. The hydrogels formed by DNA are biocompatible, stable, tunable and biologically versatile, thus, these have a wide range of promising applications in bioanalysis and biomedicine. In particular, the stimuli-responsive DNA hydrogels (smart DNA hydrogels), which exhibit a reversible and switchable hydrogel to sol transition under different triggers, have emerged as smart materials for sensing. Thus far, the combination of the stimuli-responsive DNA hydrogels and multiple sensing platforms is considered as biocompatible and is useful as the flexible recognition components. A review of the stimuli-responsive DNA hydrogels and their biosensing applications has been presented in this study. The synthesis methods to prepare the DNA hydrogels have been introduced. Subsequently, the current status of the stimuli-responsive DNA hydrogels in biosensing has been described. The analytical mechanisms are further elaborated by the combination of the stimuli-responsive DNA hydrogels with the optical, electrochemical, point-of-care testing (POCT) and other detection platforms. In addition, the prospects of the application of the stimuli-responsive DNA hydrogels in biosensing are presented. Graphical abstract

The ability to categorize sensory stimuli is crucial for an animal’s survival in a complex environment. Memorizing categories instead of individual exemplars enables greater behavioural flexibility and is computationally advantageous. Neurons that show category selectivity have been found in several areas of the mammalian neocortex 1 – 4 , but the prefrontal cortex seems to have a prominent role 4 , 5 in this context. Specifically, in primates that are extensively trained on a categorization task, neurons in the prefrontal cortex rapidly and flexibly represent learned categories 6 , 7 . However, how these representations first emerge in naive animals remains unexplored, leaving it unclear whether flexible representations are gradually built up as part of semantic memory or assigned more or less instantly during task execution 8 , 9 . Here we investigate the formation of a neuronal category representation throughout the entire learning process by repeatedly imaging individual cells in the mouse medial prefrontal cortex. We show that mice readily learn rule-based categorization and generalize to novel stimuli. Over the course of learning, neurons in the prefrontal cortex display distinct dynamics in acquiring category selectivity and are differentially engaged during a later switch in rules. A subset of neurons selectively and uniquely respond to categories and reflect generalization behaviour. Thus, a category representation in the mouse prefrontal cortex is gradually acquired during learning rather than recruited ad hoc. This gradual process suggests that neurons in the medial prefrontal cortex are part of a specific semantic memory for visual categories. Neurons in the mouse medial prefrontal cortex acquire category-selective responses with learning.

In natural behaviour, animals actively interrogate their environments using endogenously generated ‘question-and-answer’ strategies. However, in laboratory settings participants typically engage with externally imposed stimuli and tasks, and the mechanisms of active sampling remain poorly understood. We review a nascent neuroscientific literature that examines active-sampling policies and their relation to attention and curiosity. We distinguish between information sampling, in which organisms reduce uncertainty relevant to a familiar task, and information search, in which they investigate in an open-ended fashion to discover new tasks. We review evidence that both sampling and search depend on individual preferences over cognitive states, including attitudes towards uncertainty, learning progress and types of information. We propose that, although these preferences are non-instrumental and can on occasion interfere with external goals, they are important heuristics that allow organisms to cope with the high complexity of both sampling and search, and generate curiosity-driven investigations in large, open environments in which rewards are sparse and ex ante unknown.

Monozygotic twins show high concordance in eye- and mouth-looking, and this behaviour is markedly reduced in toddlers with autism spectrum disorder. An infant's view of the social scene An early and critical aspect of infant development is visual exploration of socially relevant stimuli such as faces and biological motion. Warren Jones and colleagues present an eye-tracking study of both typically developing children and those with autism to show that several aspects of visual social engagement, including propensity to look at facial features, as well as spatial and temporal dynamics of gaze, are highly heritable. Some measures of social visual engagement that are most highly heritable, such as attention to faces, are also those that most clearly distinguish typically developing children from those with autism. The authors propose social visual engagement as a neurodevelopmental endophenotype that is not just relevant for autism, but also broader population-wide variation. Long before infants reach, crawl or walk, they explore the world by looking: they look to learn and to engage 1 , giving preferential attention to social stimuli, including faces 2 , face-like stimuli 3 and biological motion 4 . This capacity—social visual engagement—shapes typical infant development from birth 5 and is pathognomonically impaired in children affected by autism 6 . Here we show that variation in viewing of social scenes, including levels of preferential attention and the timing, direction and targeting of individual eye movements, is strongly influenced by genetic factors, with effects directly traceable to the active seeking of social information 7 . In a series of eye-tracking experiments conducted with 338 toddlers, including 166 epidemiologically ascertained twins (enrolled by representative sampling from the general population), 88 non-twins with autism and 84 singleton controls, we find high monozygotic twin–twin concordance (0.91) and relatively low dizygotic concordance (0.35). Moreover, the characteristics that are the most highly heritable, preferential attention to eye and mouth regions of the face, are also those that are differentially decreased in children with autism ( χ 2  = 64.03, P  < 0.0001). These results implicate social visual engagement as a neurodevelopmental endophenotype not only for autism, but also for population-wide variation in social-information seeking 8 . In addition, these results reveal a means of human biological niche construction, with phenotypic differences emerging from the interaction of individual genotypes with early life experience 7 .

Key Points Newly developed technologies enable us to gain novel insights into how the brain generates fear and anxiety states, based on the identification and manipulation of neuronal circuits within and among individual brain regions. Fear is mediated by a brain-wide distributed network involving long-range projection pathways and local connectivity. The disinhibitory microcircuit is a common motif in the basolateral amygdala (BLA), central amygdala and the prelimbic region of the medial prefrontal cortex, and is instrumental in fear acquisition and expression. Encoding of fear extinction involves many of the same brain areas that are involved in fear acquisition and expression; however, different circuits within the amygdala and prefrontal cortex are involved. Indeed, fear extinction circuits may in fact inhibit fear circuits to dampen fearful responding. As with fear and fear extinction, a brain-wide neuronal network underlies anxiety, with identified local microcircuits within the bed nucleus of the stria terminalis, the lateral septum, the ventral tegmental area (VTA) and the BLA. Importantly, there is potential overlap between fear and anxiety circuits. There is overlap of neuronal circuits that mediate negative and positive valence in areas such as the VTA. Understanding the interplay between these circuits is of vital importance for understanding adaptive behavioural states. Recent methodological progress has greatly facilitated the determination of the connectivity and functional characterization of complex neural circuits. In this Review, Tovote, Fadok and Lüthi examine studies that have adopted circuit-based approaches to gain insight into how the brain governs fear and anxiety. Decades of research has identified the brain areas that are involved in fear, fear extinction, anxiety and related defensive behaviours. Newly developed genetic and viral tools, optogenetics and advanced in vivo imaging techniques have now made it possible to characterize the activity, connectivity and function of specific cell types within complex neuronal circuits. Recent findings that have been made using these tools and techniques have provided mechanistic insights into the exquisite organization of the circuitry underlying internal defensive states. This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.

Humans are highly adept at categorizing visual stimuli, but studies of human categorization are typically validated by verbal reports. This makes it difficult to perform comparative studies of categorization using non-human animals. Interpretation of comparative studies is further complicated by the possibility that animal performance may merely reflect reinforcement learning, whereby discrete features act as discriminative cues for categorization. To assess and compare how humans and monkeys classified visual stimuli, we trained 7 rhesus macaques and 41 human volunteers to respond, in a specific order, to four simultaneously presented stimuli at a time, each belonging to a different perceptual category. These exemplars were drawn at random from large banks of images, such that the stimuli presented changed on every trial. Subjects nevertheless identified and ordered these changing stimuli correctly. Three monkeys learned to order naturalistic photographs; four others, close-up sections of paintings with distinctive styles. Humans learned to order both types of stimuli. All subjects classified stimuli at levels substantially greater than that predicted by chance or by feature-driven learning alone, even when stimuli changed on every trial. However, humans more closely resembled monkeys when classifying the more abstract painting stimuli than the photographic stimuli. This points to a common classification strategy in both species, one that humans can rely on in the absence of linguistic labels for categories.

Social animals detect the affective states of conspecifics and utilize this information to orchestrate social interactions. In a social affective preference text in which experimental adult male rats could interact with either naive or stressed conspecifics, the experimental rats either approached or avoided the stressed conspecific, depending upon the age of the conspecific. Specifically, experimental rats approached stressed juveniles but avoided stressed adults. Inhibition of insular cortex, which is implicated in social cognition, and blockade of insular oxytocin receptors disrupted the social affective behaviors. Oxytocin application increased intrinsic excitability and synaptic efficacy in acute insular cortex slices, and insular oxytocin administration recapitulated the behaviors observed toward stressed conspecifics. Network analysis of c-Fos immunoreactivity in 29 regions identified functional connectivity between insular cortex, prefrontal cortex, amygdala and the social decision-making network. These results implicate insular cortex as a key component in the circuit underlying age-dependent social responses to stressed conspecifics.