Longitudinal effects of prenatal alcohol exposure on visual neurodevelopment over infancy.

Prenatal alcohol exposure (PAE) affects neurodevelopment in over 59 million individuals globally. Prior studies using dichotomous categorization of alcohol use and comorbid substance exposures provide limited knowledge of how prenatal alcohol specifically impacts early human neurodevelopment. In this longitudinal cohort study from Cape Town, South Africa, PAE is measured continuously-characterizing timing, dose, and drinking patterns (i.e., binge drinking). High-density electroencephalography (EEG) during a visual-evoked potential (VEP) task was collected from infants aged 8 to 52 weeks with prenatal exposure exclusively to alcohol and matched on sociodemographic factors to infants with no substance exposure in utero. First trimester alcohol exposure related to altered timing of the P1 VEP component over the first 6 months postnatally, and first trimester binge drinking exposure altered timing of the P1 VEP components such that increased exposure was associated with longer VEP latencies while increasing age was related to shorter VEP latencies (n = 108). These results suggest alcohol exposure in the first trimester may alter visual neurodevelopmental timing in early infancy. Exploratory individual-difference analysis across infants with and without PAE tested the relation between VEP latencies and myelination for a subsample of infants with usable magnetic resonance imaging (MRI) T1w and T2w scans collected at the same time point as EEG (n = 47). Decreased MRI T1w/T2w ratios (an indicator of myelin) in the primary visual cortex (n = 47) were linked to longer P1 VEP latencies. Results from these two sets of analyses suggest that prenatal alcohol and postnatal myelination may both separately impact VEP latency over infancy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Visual and cognitive processes contribute to age-related improvements in visual selective attention.

Children (N = 103, 4-9 years, 59 females, 84% White, c. 2019) completed visual processing, visual feature integration (color, luminance, motion), and visual search tasks. Contrast sensitivity and feature search improved with age similarly for luminance and color-defined targets. Incidental feature integration improved more with age for color-motion than luminance-motion. Individual differences in feature search ( ß = .11) and incidental feature integration ( ß = .06) mediated age-related changes in conjunction visual search, an index of visual selective attention. These findings suggest that visual selective attention is best conceptualized as a series of developmental trajectories, within an individual, that vary by an object's defining features. These data have implications for design of educational and interventional strategies intended to maximize attention for learning and memory.

The Ecological Resilience Framework: The Justice Ambassadors Youth Council as a model for community-based resilience.

We present an 'Ecological Resilience Framework' (ERF) to demonstrate how resilience is created through the Justice Ambassadors Youth Council (JAYC) program. JAYC is a platform in which New York government representatives collaboratively learn and develop policy solutions alongside emerging adults who are criminal legal system impacted and reside in predominantly Black and Hispanic communities characterized by chronically high levels of poverty, violence, and incarceration. We focus our work on the process of developing resilience in the context of structural social inequity and injustice. We argue that resilience can best be understood in the context of the adversity to which it is a response, not as an isolated individual quality. Therefore, resilience science is at its best when it incorporates a multi-disciplinary scientific perspective, one that addresses a continuum from individual- to community- to society-level physical, cognitive, relationship, and mental health variables. To demonstrate how our ERF incorporates this approach, we outline how JAYC not only supports young adult participants in understanding their individual life trajectories and narrative identity, but also actively connects them within a diverse social network of mentors and to various opportunities that support a healthy transition to adult resilience.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy.

Importance: Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. Objective: To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. Design, Setting, and Participants: This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Results: Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. Conclusions and Relevance: In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

Infants use contextual memory to attend and learn in naturalistic scenes.

Infants encounter new objects and learn about object features in relation to a rich and detailed visuospatial context. Using a contextual cueing task, recent work showed that 6- and 10-month-old infants search more efficiently for target objects in repeated rather than novel visuospatial contexts (i.e., arrays of shapes on a blank background). Here, we investigate whether infants' sensitivity to visuospatial context scales up to more complex and potentially more distracting, naturalistic scenes. In an eye-tracking task, 8-month-olds searched for a novel target object in colorful photographs of everyday environments (e.g., bedrooms and kitchens). Repeated ("Old") contexts co-varied with target locations, such that the target object appeared in exactly the same location on the same scene, while varying ("New") contexts contained target objects placed in different counterbalanced locations across a variety of scenes. Infants exhibited faster search times, more anticipation of target animation, and longer looking at targets that appeared in Old relative to New contexts. In a subsequent memory test, infants showed better recognition of label-object pairings for target objects that had appeared in Old, rather than New, contexts. These results indicate that infants can use visuospatial contextual information in complex naturalistic scenes to facilitate memory-guided attention and learning of object-paired labels.

Pandemic beyond the virus: maternal COVID-related postnatal stress is associated with infant temperament.

BACKGROUND: Studies have shown that infant temperament varies with maternal psychosocial factors, in utero illness, and environmental stressors. We predicted that the pandemic would shape infant temperament through maternal SARS-CoV-2 infection during pregnancy and/or maternal postnatal stress. To test this, we examined associations among infant temperament, maternal prenatal SARS-CoV-2 infection, maternal postnatal stress, and postnatal COVID-related life disruptions. METHODS: We tested 63 mother-infant dyads with prenatal maternal SARS-CoV-2 infections and a comparable group of 110 dyads without infections. To assess postnatal maternal stress, mothers completed the Perceived Stress Scale 4 months postpartum and an evaluation of COVID-related stress and life disruptions 6 months postpartum. Mothers reported on infant temperament when infants were 6-months-old using the Infant Behavior Questionnaire-Revised (IBQ-R) Very Short Form. RESULTS: Maternal SARS-CoV-2 infection during pregnancy was not associated with infant temperament or maternal postnatal stress. Mothers with higher self-reported postnatal stress rated their infants lower on the Positive Affectivity/Surgency and Orienting/Regulation IBQ-R subscales. Mothers who reported greater COVID-related life disruptions rated their infants higher on the Negative Emotionality IBQ-R subscale. CONCLUSIONS: Despite no effect of prenatal maternal SARS-CoV-2 infection, stress and life disruptions incurred by the COVID-19 pandemic were associated with infant temperament at 6-months. IMPACT: SARS-CoV-2 infection during pregnancy is not associated with postnatal ratings of COVID-related life disruptions, maternal stress, or infant temperament. Postnatal ratings of maternal stress during the COVID-19 pandemic are associated with normative variation in maternal report of infant temperament at 6 months of age. Higher postnatal ratings of maternal stress are associated with lower scores on infant Positive Affectivity/Surgency and Orienting/Regulation at 6 months of age. Higher postnatal ratings of COVID-related life disruptions are associated with higher scores on infant Negative Emotionality at 6 months of age.

Attention along the cortical hierarchy: Development matters.

We build on the existing biased competition view to argue that attention is an emergent property of neural computations within and across hierarchically embedded and structurally connected cortical pathways. Critically then, one must ask, what is attention emergent from? Within this framework, developmental changes in the quality of sensory input and feedforward-feedback information flow shape the emergence and efficiency of attention. Several gradients of developing structural and functional cortical architecture across the caudal-to-rostral axis provide the substrate for attention to emerge. Neural activity within visual areas depends on neuronal density, receptive field size, tuning properties of neurons, and the location of and competition between features and objects in the visual field. These visual cortical properties highlight the information processing bottleneck attention needs to resolve. Recurrent feedforward and feedback connections convey sensory information through a series of steps at each level of the cortical hierarchy, integrating sensory information across the entire extent of the cortical hierarchy and linking sensory processing to higher-order brain regions. Higher-order regions concurrently provide input conveying behavioral context and goals. Thus, attention reflects the output of a series of complex biased competition neural computations that occur within and across hierarchically embedded cortical regions. Cortical development proceeds along the caudal-to-rostral axis, mirroring the flow in sensory information from caudal to rostral regions, and visual processing continues to develop into childhood. Examining both typical and atypical development will offer critical mechanistic insight not otherwise available in the adult stable state. This article is categorized under: Psychology > Attention.

Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection.

Importance: Associations 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 Participants: A 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 Measures: Outcomes 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. Results: Of 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 (mean difference, -5.63; 95% CI, -8.75 to -2.51; F1,267 = 12.63; P<.005), fine motor (mean difference, -6.61; 95% CI, -10.00 to -3.21; F1,267 = 14.71; P < .005), and personal-social (mean difference, -3.71; 95% CI, -6.61 to -0.82; F1,267 = 6.37; P<.05) subdomains in fully adjusted models. Conclusions and Relevance: In this study, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, was associated with differences in neurodevelopment at age 6 months. These early findings support the need for long-term monitoring of children born during the COVID-19 pandemic.

Context and attention control determine whether attending to competing information helps or hinders learning in school-aged children.

Attention control regulates efficient processing of goal-relevant information by suppressing interference from irrelevant competing inputs while also flexibly allocating attention across relevant inputs according to task demands. Research has established that developing attention control skills promote effective learning by minimizing distractions from task-irrelevant competing information. Additional research also suggests that competing contextual information can provide meaningful input for learning and should not always be ignored. Instead, attending to competing information that is relevant to task goals can facilitate and broaden the scope of children's learning. We review this past research examining effects of attending to task-relevant and task-irrelevant competing information on learning outcomes, focusing on relations between visual attention and learning in childhood. We then present a synthesis argument that complex interactions across learning goals, the contexts of learning environments and tasks, and developing attention control mechanisms will determine whether attending to competing information helps or hinders learning. This article is categorized under: Psychology > Attention Psychology > Learning Psychology > Development and Aging.

Pre-symptomatic intervention for autism spectrum disorder (ASD): defining a research agenda.

Autism spectrum disorder (ASD) impacts an individual's ability to socialize, communicate, and interact with, and adapt to, the environment. Over the last two decades, research has focused on early identification of ASD with significant progress being made in understanding the early behavioral and biological markers that precede a diagnosis, providing a catalyst for pre-symptomatic identification and intervention. Evidence from preclinical trials suggest that intervention prior to the onset of ASD symptoms may yield more improved developmental outcomes, and clinical studies suggest that the earlier intervention is administered, the better the outcomes. This article brings together a multidisciplinary group of experts to develop a conceptual framework for behavioral intervention, during the pre-symptomatic period prior to the consolidation of symptoms into diagnosis, in infants at very-high-likelihood for developing ASD (VHL-ASD). The overarching goals of this paper are to promote the development of new intervention approaches, empirical research, and policy efforts aimed at VHL-ASD infants during the pre-symptomatic period (i.e., prior to the consolidation of the defining features of ASD).

Towards a more inclusive and equitable developmental cognitive neuroscience.

Brain and cognitive development is a burgeoning area of scientific inquiry, with tremendous potential to better the lives of children. Large scale longitudinal neuroimaging studies offer opportunities for significant scientific advances in our understanding of developing brain structure and function. The proposed manuscript will focus on the scientific potential of the HEALthy Brain and Cognitive Development (HBCD) Study, highlighting what questions these data can and what they cannot answer about child development. Specifically, we caution against the misuse of these data for advancing de-contextualized and scientifically questionable narratives about the development of children from marginalized communities. We will focus on building and organizing a framework for interpreting HBCD data through the lens of sampling, cultural context, measurement, and developmental science theory. Our goal is to thoughtfully offer the scientific community opportunities to use the large scale and collaborative nature of HBCD to collectively revise practices in developmental science that to-date have not carefully considered their own role in perpetuating narratives that support systemic injustice.

All contexts are not created equal: Social stimuli win the competition for organizing reinforcement learning in 9-month-old infants.

Previous work has shown that infants as young as 8 months of age can use certain features of the environment, such as the shape or color of visual stimuli, as cues to organize simple inputs into hierarchical rule structures, a robust form of reinforcement learning that supports generalization of prior learning to new contexts. However, especially in cluttered naturalistic environments, there are an abundance of potential cues that can be used to structure learning into hierarchical rule structures. It is unclear how infants determine what features constitute a higher-order context to organize inputs into hierarchical rule structures. Here, we examine whether 9-month-old infants are biased to use social stimuli, relative to non-social stimuli, as a higher-order context to organize learning of simple visuospatial inputs into hierarchical rule sets. Infants were presented with four face/color-target location pairings, which could be learned most simply as individual associations. Alternatively, infants could use the faces or colorful backgrounds as a higher-order context to organize the inputs into simpler color-location or face-location rules, respectively. Infants were then given a generalization test designed to probe how they learned the initial pairings. The results indicated that infants appeared to use the faces as a higher-order context to organize simpler color-location rules, which then supported generalization of learning to new face contexts. These findings provide new evidence that infants are biased to organize reinforcement learning around social stimuli.

The value of proactive goal setting and choice in 3- to 7-year-olds' use of working memory gating strategies in a naturalistic task.

Rule-guided behavior depends on the ability to strategically update and act on content held in working memory. Proactive and reactive control strategies were contrasted across two experiments using an adapted input/output gating paradigm (Neuron, 81, 2014 and 930). Behavioral accuracies of 3-, 5-, and 7-year-olds were higher when a contextual cue appeared at the beginning of the task (input gating) rather than at the end (output gating). This finding supports prior work in older children, suggesting that children are better when input gating but rely on the more effortful output gating strategy for goal-oriented action selection (Cognition, 155, 2016 and 8). A manipulation was added to investigate whether children's use of working memory strategies becomes more flexible when task goals are specified internally rather than externally provided by the experimenter. A shift toward more proactive control was observed when children chose the task goal among two alternatives. Scan path analyses of saccadic eye movement indicated that giving children agency and choice over the task goal resulted in less use of a reactive strategy than when the goal was determined by the experimenter.

The Ontogeny of Hippocampus-Dependent Memories.

The formation of memories that contain information about the specific time and place of acquisition, which are commonly referred to as "autobiographical" or "episodic" memories, critically relies on the hippocampus and on a series of interconnected structures located in the medial temporal lobe of the mammalian brain. The observation that adults retain very few of these memories from the first years of their life has fueled a long-standing debate on whether infants can make the types of memories that in adults are processed by the hippocampus-dependent memory system, and whether the hippocampus is involved in learning and memory processes early in life. Recent evidence shows that, even at a time when its circuitry is not yet mature, the infant hippocampus is able to produce long-lasting memories. However, the ability to acquire and store such memories relies on molecular pathways and network-based activity dynamics different from the adult system, which mature with age. The mechanisms underlying the formation of hippocampus-dependent memories during infancy, and the role that experience exerts in promoting the maturation of the hippocampus-dependent memory system, remain to be understood. In this review, we discuss recent advances in our understanding of the ontogeny and the biological correlates of hippocampus-dependent memories.

Principles for Guiding the Selection of Early Childhood Neurodevelopmental Risk and Resilience Measures: HEALthy Brain and Child Development Study as an Exemplar.

The vast individual differences in the developmental origins of risk and resilience pathways combined with sophisticated capabilities of big data science increasingly point to the imperative of large, neurodevelopmental consortia to capture population heterogeneity and key variations in developmental trajectories. At the same time, such large-scale population-based designs involving multiple independent sites also must weigh competing demands. For example, the need for efficient, scalable assessment strategies must be balanced with the need for nuanced, developmentally sensitive phenotyping optimized for linkage to neural mechanisms and specification of common and distinct exposure pathways. Standardized epidemiologic batteries designed for this purpose such as PhenX (consensus measures for Phenotypes and eXposures) and the National Institutes of Health (NIH) Toolbox provide excellent "off the shelf" assessment tools that are well-validated and enable cross-study comparability. However, these standardized toolkits can also constrain ability to leverage advances in neurodevelopmental measurement over time, at times disproportionately advantaging established measures. In addition, individual consortia often expend exhaustive effort "reinventing the wheel," which is inefficient and fails to fully maximize potential synergies with other like initiatives. To address these issues, this paper lays forth an early childhood neurodevelopmental assessment strategy, guided by a set of principles synthesizing developmental and pragmatic considerations generated by the Neurodevelopmental Workgroup of the HEALthy Brain and Child Development (HBCD) Planning Consortium. These principles emphasize characterization of both risk- and resilience-promoting processes. Specific measurement recommendations to HBCD are provided to illustrate application. However, principles are intended as a guiding framework to transcend any particular initiative as a broad neurodevelopmentally informed, early childhood assessment strategy for large-scale consortia science.

Adaptive rule learning of event sequences during the A-not-B task in 9-month-old infants.

Prior work indicates that infants can use social information to organize simple audiovisual inputs into predictable rules by 8 months of age. However, it is unclear whether infants can use social information to organize more complex events into predictable rules that can be used to guide motor action. To examine these issues, we tested 9-month-old infants using a modified version of an A-not-B task, in which hiding event sequences were paired with different experimenters, who could be used to organize the events into rules that guide action. We predicted that infants' reaching accuracy would be better when the experimenter changes when the toy's hiding location changes, relative to when the experimenter stays the same, as this should cue a novel rule used to guide action. Experiments 1 and 2 validated this prediction. Experiment 3 showed that reaching accuracy was better when the toy's hiding location switched but was consistent with the rule associated with the experimenter, relative to when the toy's hiding location repeated but was inconsistent with the rule associated with the experimenter. These data suggest that infants can use the identities of experimenters to organize events into predictable rules that guide action in the A-not-B task.

What underlies visual selective attention development? Evidence that age-related improvements in visual feature integration influence visual selective attention performance.

Visual selective attention (VSA) improves across childhood. Conjunction search tasks require integrating multiple visual features in order to find a target among distractors and are often used to measure VSA. Motivated by the visual system's architecture and developmental changes in neural connectivity, we predicted that feature integration across separate visual pathways (e.g., color and motion) should develop later than feature integration within the same visual pathways (e.g., luminance and motion). A total of 89 4- to 10-year-old children completed a visual search task that manipulated whether feature integration was between separate parallel visual pathways or within the same visual pathway. We first examined whether color-motion integration was associated with a performance cost relative to luminance-motion integration across childhood. We found that color-motion integration was worse than luminance-motion integration in early childhood but that this difference decreased with age. We also examined whether luminance-motion and color-motion visual search performance developed differently across childhood. Reaction time (RT) visual search slopes for the luminance-motion condition were both stable across childhood and steeper overall than those for the color-motion condition. In contrast, RT search slopes for the color-motion condition became steeperincrease across childhood. Finally, we found that age-related improvements in color-motion integration, relative to luminance-motion integration, were associated with longer color-motion search rates across childhood. These data suggest that age-related improvements in color-motion feature integration may increase competition between color-motion targets and distractors, thereby increasing the amount of time needed to process distractors as nontargets during the selection process.

The role of the visual association cortex in scaffolding prefrontal cortex development: A novel mechanism linking socioeconomic status and executive function.

Socioeconomic status (SES) is associated with executive function (EF) and prefrontal cortex (PFC) development. However, understanding of the specific aspects of SES that influence development of EF and the PFC remains limited. We briefly review existing literature on proposed mechanisms linking SES with EF. Then, we present a novel conceptual model arguing that early cognitive stimulation shapes EF and PFC development. We propose that cognitive stimulation drives lower-level sensory and perceptual processes that may impact EF and PFC development through reciprocal connections between the ventral visual stream and PFC. We argue that caregivers guide attention and associative learning, which provides children the opportunity to regulate attention and gain semantic knowledge. This experience in turn allows for opportunities to train the PFC to resolve conflict between stimuli with overlapping features and engage in increasingly complex computations as visual processing systems develop; this may lay the groundwork for development of EF. We review existing evidence for this model and end by highlighting how this conceptual model could launch future research questions.