Predictions concerning development, interrelations, and possible independence of working memory, inhibition, and cognitive flexibility were tested in 325 participants (roughly 30 per age from 4 to 13 years and young adults; 50% female). All were tested on the same computerized battery, designed to manipulate memory and inhibition independently and together, in steady state (single-task blocks) and during task-switching, and to be appropriate over the lifespan and for neuroimaging (fMRI). This is one of the first studies, in children or adults, to explore: (a) how memory requirements interact with spatial compatibility and (b) spatial incompatibility effects both with stimulus-specific rules (Simon task) and with higher-level, conceptual rules. Even the youngest children could hold information in mind, inhibit a dominant response, and combine those as long as the inhibition required was steady-state and the rules remained constant. Cognitive flexibility (switching between rules), even with memory demands minimized, showed a longer developmental progression, with 13-yearolds still not at adult levels. Effects elicited only in Mixed blocks with adults were found in young children even in single-task blocks; while young children could exercise inhibition in steady state it exacted a cost not seen in adults, who (unlike young children) seemed to re-set their default response when inhibition of the same tendency was required throughout a block. The costs associated with manipulations of inhibition were greater in young children while the costs associated with increasing memory demands were greater in adults. Effects seen only in RT in adults were seen primarily in accuracy in young children. Adults slowed down on difficult trials to preserve accuracy; but the youngest children were impulsive; their RT remained more constant but at an accuracy cost on difficult trials. Contrary to our predictions of independence between memory and inhibition, when matched for difficulty RT correlations between these were as high as 0.8, although accuracy correlations were less than half that. Spatial incompatibility effects and global and local switch costs were evident in children and adults, differing only in size. Other effects (e.g., asymmetric switch costs and the interaction of switching rules and switching response-sites) differed fundamentally over age. Mature cognition is characterized by abilities that include being able: (a) to hold information in mind, including complicated representational structures, to mentally manipulate that information, and to act on the basis of it, (b) to act on the basis of choice rather than impulse, exercising self-control (or self-regulation) by resisting inappropriate behaviors and responding appropriately, and (c) to quickly and flexibly adapt behavior to changing situations. These abilities are referred to respectively as working memory, inhibition, and cognitive flexibility. Together they are key components of both "cognitive control" and "executive functions" and have been studied i...

Mouse models are useful for studying genes involved in behavior, but whether they are relevant for human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat, and in the efficacy of treatments that rely on extinction mechanisms such as exposure therapy.Genetically modified mice provide useful model systems for testing the role of candidate genes in behavior. The extent to which such genetic manipulations in the mouse and the resulting phenotype can be translated across species, from mouse to human, is less clear. In this report we focused on identifying biologically valid phenotypes across species. We utilized a common single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene that leads to a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met). In an inbred genetic knock-in mouse strain that expresses the variant BDNF allele to recapitulate the specific phenotypic properties of the human polymorphism in vivo, we found the BDNF Val66Met genotype was associated with treatment resistant forms of anxiety-like behavior (1). The objective of this study was to test if the Val66Met genotype could impact extinction learning in our mouse model, and if such findings could be generalized to human populations.BDNF mediates synaptic plasticity associated with learning and memory (2,3) specifically in fear learning and extinction (4,5). BDNF-dependent forms of fear learning have known biological substrates, and lie at the core of a number of clinical disorders (6,7) associated with the variant BDNF (8-10). Fear learning paradigms require the ability to recognize and +To whom correspondence should be addressed. fas2002@med.cornell.edu or bjc2002@med.cornell.edu. remember cues that signal safety or threat and to extinguish these associations when they no longer exist. These abilities are impaired in anxiety disorders such as posttraumatic stress disorder and phobias (11,12). Behavioral treatments for these disorders such as exposure therapy rely on basic principles of extinction learning (13) in which an individual is repeatedly exposed to an event that was previously associated with aversive consequences. Understanding the effect of the BDNF Met allele on these forms of learning can provide insight into the mechanism of risk for anxiety disorders, refine existing treatments, and may lead to genotypebased personalized medicine. NIH Public AccessWe examined the impact of the variant BDNF on classic fear...

The day-night task requires saying "night" to a picture of the sun and "day" to a picture of the moon. In this investigation of why young children fail at this task, systematic variations of the task were administered to 96 children, half 4 years old and half 4 1/2 years old. Training children on the strategy of chunking the 2 rules into I ("say the opposite"), thus reducing memory load, did not help their performance. What helped was reducing the inhibitory demand by instructing them to say "dog" and "pig" (not "night" and "day") even though memory of 2 rules and inhibiting saying what the pictures represented were still required. Here the response to be activated and the response to be inhibited were unrelated. When the correct response was semantically related to, and the direct opposite of, the to-be-inhibited response, children performed poorly. Inserting a delay between stimulus and response helped even though that delay was filled with distraction. Young children apparently need several seconds to compute the answer on this task. Often they do not take the needed time; when forced to do so, they do well.

Visual attention functions as a filter to select environmental information for learning and memory, making it the first step in the eventual cascade of thought and action systems. Here, we review studies of typical and atypical visual attention development and explain how they offer insights into the mechanisms of adult visual attention. We detail interactions between visual processing and visual attention, as well as the contribution of visual attention to memory. Finally, we discuss genetic mechanisms underlying attention disorders and how attention may be modified by training.

Concepts of objects as enduring and complete across space and time have been documented in infants within several months after birth, but little is known about how such concepts arise during development. Current theories that stress innate knowledge may neglect the potential contributions of experience to guide acquisition of object concepts. To examine whether learning plays an important role in early development of object representations, we used an eye-tracking paradigm with 4-and 6-month-old infants who were provided with an initial period of experience viewing an unoccluded trajectory, or no experience with this particular stimulus. After exposure to the unoccluded trajectory for only 2 min, there was a reliable increase in 4-month-old infants' anticipatory eye movement when the infants subsequently viewed occludedtrajectory displays, relative to 4-month-old infants who did not receive this experience. This effect of training in 4-month-old infants was found to generalize to another category of trajectory orientation. Older infants received no additional benefit from training, most likely because they enter the task capable of forming robust object representations under these conditions. This finding provides compelling evidence that very brief training facilitated formation of object representations, and suggests more generally that infants learn such representations from real-world experience viewing objects undergoing occlusion and disocclusion.

IMPORTANCEAssociations between in utero exposure to maternal SARS-CoV-2 infection and neurodevelopment are speculated, but currently unknown.OBJECTIVE To examine the associations between maternal SARS-CoV-2 infection during pregnancy, being born during the COVID-19 pandemic regardless of maternal SARS-CoV-2 status, and neurodevelopment at age 6 months. DESIGN, SETTING, AND PARTICIPANTSA cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls was enrolled in the COVID-19 Mother Baby Outcomes Initiative at Columbia University Irving Medical Center in New York City. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were approached. Women with unexposed infants were approached based on similar gestational age at birth, date of birth, sex, and mode of delivery. Neurodevelopment was assessed using the Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at age 6 months. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 were included in secondary analyses.EXPOSURES Maternal SARS-CoV-2 infection during pregnancy and birth during the COVID-19 pandemic. MAIN OUTCOMES AND MEASURESOutcomes were scores on the 5 ASQ-3 subdomains, with the hypothesis that maternal SARS-CoV-2 infection during pregnancy would be associated with decrements in social and motor development at age 6 months. RESULTSOf 1706 women approached, 596 enrolled; 385 women were invited to a 6-month assessment, of whom 272 (70.6%) completed the ASQ-3. Data were available for 255 infants enrolled in the COVID-19 Mother Baby Outcomes Initiative (114 in utero exposed, 141 unexposed to SARS-CoV-2; median maternal age at delivery, 32.0 [IQR, 19.0-45.0] years). Data were also available from a historical cohort of 62 infants born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences on any ASQ-3 subdomain, regardless of infection timing or severity. However, compared with the historical cohort, infants born during the pandemic had significantly lower scores on gross motor

The authors examined how visual selection mechanisms may relate to developing cognitive functions in infancy. Twenty-two 3-month-old infants were tested in 2 tasks on the same day: perceptual completion and visual search. In the perceptual completion task, infants were habituated to a partly occluded moving rod and subsequently presented with unoccluded broken and complete rod test stimuli. In the visual search task, infants viewed displays in which single targets of varying levels of salience were cast among homogeneous static vertical distractors. Infants whose posthabituation preference indicated unity perception in the completion task provided evidence of a functional visual selective attention mechanism in the search task. The authors discuss the implications of the efficiency of attentional mechanisms for information processing and learning.

Newborn babies look preferentially at faces and face-like displays; yet over the course of their first year, much changes about both the way infants process visual stimuli and how they allocate their attention to the social world. Despite this initial preference for faces in restricted contexts, the amount that infants look at faces increases considerably in the first year. Is this development related to changes in attentional orienting abilities? We explored this possibility by showing 3-, 6-, and 9-month-olds engaging animated and live-action videos of social stimuli and additionally measuring their visual search performance with both moving and static search displays. Replicating previous findings, looking at faces increased with age; in addition, the amount of looking at faces was strongly related to the youngest infants’ performance in visual search. These results suggest that infants’ attentional abilities may be an important factor facilitating their social attention early in development.