Virtual (Zoom) Interactions Alter Conversational Behavior and Interbrain Coherence.

A growing number of social interactions are taking place virtually on videoconferencing platforms. Here, we explore potential effects of virtual interactions on observed behavior, subjective experience, and neural "single-brain" and "interbrain" activity via functional near-infrared spectroscopy neuroimaging. We scanned a total of 36 human dyads (72 participants, 36 males, 36 females) who engaged in three naturalistic tasks (i.e., problem-solving, creative-innovation, socio-emotional task) in either an in-person or virtual (Zoom) condition. We also coded cooperative behavior from audio recordings. We observed reduced conversational turn-taking behavior during the virtual condition. Given that conversational turn-taking was associated with other metrics of positive social interaction (e.g., subjective cooperation and task performance), this measure may be an indicator of prosocial interaction. In addition, we observed altered patterns of averaged and dynamic interbrain coherence in virtual interactions. Interbrain coherence patterns that were characteristic of the virtual condition were associated with reduced conversational turn-taking. These insights can inform the design and engineering of the next generation of videoconferencing technology.SIGNIFICANCE STATEMENT Videoconferencing has become an integral part of our lives. Whether this technology impacts behavior and neurobiology is not well understood. We explored potential effects of virtual interaction on social behavior, brain activity, and interbrain coupling. We found that virtual interactions were characterized by patterns of interbrain coupling that were negatively implicated in cooperation. Our findings are consistent with the perspective that videoconferencing technology adversely affects individuals and dyads during social interaction. As virtual interactions become even more necessary, improving the design of videoconferencing technology will be crucial for supporting effective communication.

Large-scale proteomics in the first trimester of pregnancy predict psychopathology and temperament in preschool children: an exploratory study.

BACKGROUND: Understanding the prenatal origins of children's psychopathology is a fundamental goal in developmental and clinical science. Recent research suggests that inflammation during pregnancy can trigger a cascade of fetal programming changes that contribute to vulnerability for the emergence of psychopathology. Most studies, however, have focused on a handful of proinflammatory cytokines and have not explored a range of prenatal biological pathways that may be involved in increasing postnatal risk for emotional and behavioral difficulties. METHODS: Using extreme gradient boosted machine learning models, we explored large-scale proteomics, considering over 1,000 proteins from first trimester blood samples, to predict behavior in early childhood. Mothers reported on their 3- to 5-year-old children's (N = 89, 51% female) temperament (Child Behavior Questionnaire) and psychopathology (Child Behavior Checklist). RESULTS: We found that machine learning models of prenatal proteomics predict 5%-10% of the variance in children's sadness, perceptual sensitivity, attention problems, and emotional reactivity. Enrichment analyses identified immune function, nervous system development, and cell signaling pathways as being particularly important in predicting children's outcomes. CONCLUSIONS: Our findings, though exploratory, suggest processes in early pregnancy that are related to functioning in early childhood. Predictive features included far more proteins than have been considered in prior work. Specifically, proteins implicated in inflammation, in the development of the central nervous system, and in key cell-signaling pathways were enriched in relation to child temperament and psychopathology measures.

Expressing appreciation is linked to interpersonal closeness and inter-brain coherence, both in person and over Zoom.

Expressing appreciation is essential for establishing interpersonal closeness, but virtual interactions are increasingly common and create social distance. Little is known about the neural and inter-brain correlates of expressing appreciation and the potential effects of virtual videoconferencing on this kind of interaction. Here, we assess inter-brain coherence with functional near-infrared spectroscopy while dyads expressed appreciation to one another. We scanned 36 dyads (72 participants) who interacted in either an in-person or virtual (Zoom®) condition. Participants reported on their subjective experience of interpersonal closeness. As predicted, expressing appreciation increased interpersonal closeness between dyad partners. Relative to 3 other cooperation tasks (i.e. problem-solving task, creative-innovation task, socio-emotional task), we observed increased inter-brain coherence in socio-cognitive areas of the cortex (anterior frontopolar area, inferior frontal gyrus, premotor cortex, middle temporal gyrus, supramarginal gyrus, and visual association cortex) during the appreciation task. Increased inter-brain coherence in socio-cognitive areas during the appreciation task was associated with increased interpersonal closeness. These findings support the perspective that expressing appreciation, both in-person and virtually, increases subjective and neural metrics of interpersonal closeness.

Towards assessing subcortical "deep brain" biomarkers of PTSD with functional near-infrared spectroscopy.

Assessment of brain function with functional near-infrared spectroscopy (fNIRS) is limited to the outer regions of the cortex. Previously, we demonstrated the feasibility of inferring activity in subcortical "deep brain" regions using cortical functional magnetic resonance imaging (fMRI) and fNIRS activity in healthy adults. Access to subcortical regions subserving emotion and arousal using affordable and portable fNIRS is likely to be transformative for clinical diagnostic and treatment planning. Here, we validate the feasibility of inferring activity in subcortical regions that are central to the pathophysiology of posttraumatic stress disorder (PTSD; i.e. amygdala and hippocampus) using cortical fMRI and simulated fNIRS activity in a sample of adolescents diagnosed with PTSD (N = 20, mean age = 15.3 ± 1.9 years) and age-matched healthy controls (N = 20, mean age = 14.5 ± 2.0 years) as they performed a facial expression task. We tested different prediction models, including linear regression, a multilayer perceptron neural network, and a k-nearest neighbors model. Inference of subcortical fMRI activity with cortical fMRI showed high prediction performance for the amygdala (r > 0.91) and hippocampus (r > 0.95) in both groups. Using fNIRS simulated data, relatively high prediction performance for deep brain regions was maintained in healthy controls (r > 0.79), as well as in youths with PTSD (r > 0.75). The linear regression and neural network models provided the best predictions.

Early life stress predicts trajectories of emotional problems and hippocampal volume in adolescence.

Exposure to early life stress (ELS) has been consistently associated with adverse emotional and neural consequences in youth. The development of brain structures such as the hippocampus, which plays a significant role in stress and emotion regulation, may be particularly salient in the development of psychopathology. Prior work has documented smaller hippocampal volume (HCV) in relation to both ELS exposure and risk for psychopathology. We used longitudinal k-means clustering to identify simultaneous trajectories of HCV and emotional problems in 155 youth across three assessments conducted approximately two years apart (mean baseline age = 11.33 years, 57% female). We also examined depressive symptoms and resilience approximately two years after the third timepoint. We identified three clusters of participants: a cluster with high HCV and low emotional problems; a cluster with low HCV and high emotional problems; and a cluster with low HCV and low emotional problems. Importantly, severity of ELS was associated with greater likelihood of belonging to the low HCV/high symptom cluster than to the low HCV/low symptom cluster. Further, low HCV/high symptom participants had more depressive symptoms and lower resilience scores than did participants in the low HCV/low symptom, but not than in the high HCV/low symptom cluster. Our findings suggest that smaller HCV indexes biological sensitivity to stress. This adds to our understanding of the ways in which ELS can affect hippocampal and emotional development in young people and points to hippocampal volume as a marker of susceptibility to context.

Aberrant brain network and eye gaze patterns during natural social interaction predict multi-domain social-cognitive behaviors in girls with fragile X syndrome.

Girls with fragile X syndrome (FXS) often manifest significant symptoms of avoidance, anxiety, and arousal, particularly in the context of social interaction. However, little is currently known about the associations among neurobiological, biobehavioral such as eye gaze pattern, and social-cognitive dysfunction in real-world settings. In this study, we sought to characterize brain network properties and eye gaze patterns in girls with FXS during natural social interaction. Participants included 42 girls with FXS and 31 age- and verbal IQ-matched girls (control). Portable functional near-infrared spectroscopy (fNIRS) and an eye gaze tracker were used to investigate brain network alterations and eye gaze patterns associated with social-cognitive dysfunction in girls with FXS during a structured face-to-face conversation. Compared to controls, girls with FXS showed significantly increased inter-regional functional connectivity and greater excitability within the prefrontal cortex (PFC), frontal eye field (FEF) and superior temporal gyrus (STG) during the conversation. Girls with FXS showed significantly less eye contact with their conversational partner and more unregulated eye gaze behavior compared to the control group. We also demonstrated that a machine learning approach based on multimodal data, including brain network properties and eye gaze patterns, was predictive of multiple domains of social-cognitive behaviors in girls with FXS. Our findings expand current knowledge of neural mechanisms and eye gaze behaviors underlying naturalistic social interaction in girls with FXS. These results could be further evaluated and developed as intermediate phenotypic endpoints for treatment trial evaluation in girls with FXS.

Fine Particulate Air Pollution, Early Life Stress, and Their Interactive Effects on Adolescent Structural Brain Development: A Longitudinal Tensor-Based Morphometry Study.

Air pollution is a major environmental threat to public health; we know little, however, about its effects on adolescent brain development. Exposure to air pollution co-occurs, and may interact, with social factors that also affect brain development, such as early life stress (ELS). Here, we show that severity of ELS and fine particulate air pollution (PM2.5) are associated with volumetric changes in distinct brain regions, but also uncover regions in which ELS moderates the effects of PM2.5. We interviewed adolescents about ELS events, used satellite-derived estimates of ambient PM2.5 concentrations, and conducted longitudinal tensor-based morphometry to assess regional changes in brain volume over an approximately 2-year period (N = 115, ages 9-13 years at Time 1). For adolescents who had experienced less severe ELS, PM2.5 was associated with volumetric changes across several gray and white matter regions. Fewer effects of PM2.5 were observed for adolescents who had experienced more severe ELS, although occasionally they were in the opposite direction. This pattern of results suggests that for many brain regions, moderate to severe ELS largely constrains the effects of PM2.5 on structural development. Further theory and research is needed on the joint effects of ELS and air pollution on the brain.

Neuroanatomical Profile of Young Females with Fragile X Syndrome: A Voxel-Based Morphometry Analysis.

Fragile X syndrome is a genetic condition associated with alterations in brain and subsequent cognitive development. However, due to a milder phenotype relative to males, females with fragile X syndrome are underrepresented in research studies. In the current study, we investigate neuroanatomical differences in young females (age range: 6.03-16.32 years) with fragile X syndrome (N = 46) as compared to age-, sex-, and verbal abilities-matched participants (comparison group; N = 35). Between-group analyses of whole-brain and regional brain volumes were assessed using voxel-based morphometry. Results demonstrate significantly larger total gray and white matter volumes in girls with fragile X syndrome compared to a matched comparison group (Ps < 0.001). In addition, the fragile X group showed significantly larger gray matter volume in a bilateral parieto-occipital cluster and a right parieto-occipital cluster (Ps < 0.001). Conversely, the fragile X group showed significantly smaller gray matter volume in the bilateral gyrus rectus (P < 0.03). Associations between these regional brain volumes and key socio-emotional variables provide insight into gene-brain-behavior relationships underlying the fragile X syndrome phenotype in females. These findings represent the first characterization of a neuroanatomical phenotype in a large sample of girls with fragile X syndrome and expand our knowledge about potential neurodevelopmental mechanisms underlying cognitive-behavioral outcomes in this condition.

Vagal flexibility to negative emotions moderates the relations between environmental risk and adjustment problems in childhood.

Neurobiological and social-contextual influences shape children's adjustment, yet limited biopsychosocial studies have integrated temporal features when modeling physiological regulation of emotion. This study explored whether a common underlying pattern of non-linear change in respiratory sinus arrhythmia (RSA) across emotional scenarios characterized 4-6 year-old children's parasympathetic reactivity (N = 180). Additionally, we tested whether dynamic RSA reactivity was an index of neurobiological susceptibility or a diathesis in the association between socioeconomic status, authoritarian parenting, and the development of externalizing problems (EP) and internalizing problems over two years. There was a shared RSA pattern across all emotions, characterized by more initial RSA suppression and a subsequent return toward baseline, which we call vagal flexibility (VF). VF interacted with parenting to predict EP. More authoritarian parenting predicted increased EP two years later only when VF was low; conversely, when VF was very high, authoritarian mothers reported that their children had fewer EP. Altogether, children's patterns of dynamic RSA change to negative emotions can be characterized by a higher order factor, and the nature by which VF contributes to EP depends on maternal socialization practices, with low VF augmenting and high VF buffering children against the effects of authoritarian parenting.

Social gaze behavior and hyperarousal in young females with fragile X syndrome: A within-person approach.

Children with fragile X syndrome (FXS) often avoid eye contact, a behavior that is potentially related to hyperarousal. Prior studies, however, have focused on between-person associations rather than coupling of within-person changes in gaze behaviors and arousal. In addition, there is debate about whether prompts to maintain eye contact are beneficial for individuals with FXS. In a study of young females (ages 6-16), we used eye tracking to assess gaze behavior and pupil dilation during social interactions in a group with FXS (n = 32) and a developmentally similar comparison group (n = 23). Participants engaged in semi-structured conversations with a female examiner during blocks with and without verbal prompts to maintain eye contact. We identified a social-behavioral and psychophysiological profile that is specific to females with FXS; this group exhibited lower mean levels of eye contact, significantly increased mean pupil dilation during conversations that included prompts to maintain eye contact, and showed stronger positive coupling between eye contact and pupil dilation. Our findings strengthen support for the perspective that gaze aversion in FXS reflects negative reinforcement of social avoidance behavior. We also found that behavioral skills training may improve eye contact, but maintaining eye contact appears to be physiologically taxing for females with FXS.

A meta-analysis of mother-child synchrony in respiratory sinus arrhythmia and contextual risk.

Biobehavioral frameworks of attachment posit that mother-child dyads engage in physiological synchrony that is uniquely formative for children's neurobiological, social, and emotional development. Much of the work on mother-child physiological synchrony has focused on respiratory sinus arrhythmia (RSA). However, the strength of the existing evidence for mother-child RSA synchrony during interaction is unclear. Using meta-analysis, we summarized results from 12 eligible studies comprising 14 samples and 1201 children ranging from infancy to adolescence (Mage  = 5.68 years, SD = 4.13, range = 0.4-17 years) and their mothers. We found that there was a statistically significant, albeit modest, positive within-dyad association between mother and child fluctuations in RSA. There also was evidence for significant heterogeneity across studies. Less mother-child RSA synchrony was observed in high-risk samples characterized by clinical difficulties, history of maltreatment, or socioeconomic disadvantage. We did not find that mother-child RSA synchrony significantly differed by task context, mean child age, or by epoch length for computing RSA. Collectively, these findings suggest that mother-child dyads show correspondence in their fluctuations in RSA, and that RSA synchrony is disrupted in high-risk contexts. Future directions and implications for the study of parent-child physiological synchrony are discussed.

Prefrontal activation in preschool children is associated with maternal adversity and child temperament: A preliminary fNIRS study of inhibitory control.

Exposure to adversity is a well-documented risk factor for cognitive, behavioral, and mental health problems. In fact, the consequences of adversity may be intergenerational. A growing body of research suggests that maternal exposures to adversity, including those prior to childbirth, are associated with offspring biobehavioral development. In a sample of 36 mothers and their preschool-age children (mean child age = 4.21 ± 0.92 years), we used functional near-infrared spectroscopy to replicate and extend this work to include brain activation during inhibitory control in young children. We found that measures of maternal exposure to adversity, including cumulative, childhood, and preconception exposures, were significantly and positively associated with activation in the right frontopolar prefrontal cortex (PFC) and in the left temporal and parietal clusters during inhibitory control. In addition, and consistent with previous findings, children's increased negative affect and decreased effortful control were associated with increased right PFC activation during inhibitory control. These findings provide preliminary evidence that maternal and dispositional risk factors are linked to alterations in PFC functioning during the preschool years. Children of mothers with a history of exposure to adversity, as well as children who are less temperamentally regulated, may require increased neural resources to meet the cognitive demands of inhibitory control.

Updates in Butterfly Graft Technique.

Nasal obstruction is a significant challenge greatly affecting individual quality of life. It is one of the most common presentations in the otolaryngology clinic, often persisting despite medical and, at times, surgical intervention. The butterfly graft has proven to be a veritable option addressing nasal valve collapse. Herein, we describe our most recent operative technique, highlight its application in ethnic rhinoplasty and revision cases, and discuss incorporation of dorsal preservation techniques in functional rhinoplasty.

COVID-19 Pandemic: Mental Health in Girls With and Without Fragile X Syndrome.

OBJECTIVE: Children and adolescents, who have less developed coping skills, are affected by natural disasters and other traumatic events differently than adults. Emotional and behavioral effects are particularly pronounced during a pandemic-related disaster, when support networks that typically promote healthy coping, such as friends, teachers, and family members, may be less available. Children and adolescents with fragile X syndrome (FXS), who are at increased risk for developing anxiety and depression, may be particularly vulnerable to behavioral or emotional difficulties during a pandemic. This study examined the mental health outcomes of school-aged girls with FXS during the COVID-19 pandemic and associated stay-at-home orders. METHODS: Participants included 47 school-aged girls with FXS and 33 age- and developmentally matched comparison girls. Associations between COVID-19 behavioral and emotional outcomes and prior academic, adaptive, behavioral, and emotional functioning as well as prior maternal mental health and characteristics of the mother-child relationship were examined. Qualitative data from the parental report of emotional and behavioral responses to the pandemic were also obtained. RESULTS: Results indicate that school-aged girls with FXS demonstrate a distinct profile of COVID-19 related associations compared to the comparison group, such that pandemic-related worries and emotional impact of pandemic restrictions were predicted by prior mental health factors for the comparison group but by prior social, behavioral, and relational factors for the FXS group. CONCLUSIONS: Findings provide insight into factors that may confer risk or resilience for youth with special needs, suggesting potential therapeutic targets and informing public health initiatives in response to the pandemic.

Maternal-prenatal stress and depression predict infant temperament during the COVID-19 pandemic.

Researchers have begun to examine the psychological toll of the ongoing global COVID-19 pandemic. Data are now emerging indicating that there may be long-term adverse effects of the pandemic on new mothers and on children born during this period. In a longitudinal study of maternal mental health and child emotional development during the pandemic, we conducted online assessments of a cohort of women at two time points: when they were pregnant at the beginning of the surge of the pandemic in the United States (baseline, N = 725), and approximately 1 year postpartum (follow-up, N = 296), examining prenatal and postnatal maternal mental health, prenatal pandemic-related stress, and infant temperament. Pandemic-related stress at baseline was associated with concurrent depressive symptoms and infant negative affect at follow-up. Baseline maternal depressive symptoms were associated with follow-up depressive symptoms, which in turn were also associated with infant negative affect. Pandemic-related stress during pregnancy may have enduring effects on infant temperament. These findings have important implications for our understanding of the emotional development of children who were in utero during the COVID-19 pandemic.

An exploration of dimensions of early adversity and the development of functional brain network connectivity during adolescence: Implications for trajectories of internalizing symptoms.

Different dimensions of adversity may affect mental health through distinct neurobiological mechanisms, though current supporting evidence consists largely of cross-sectional associations between threat or deprivation and fronto-limbic circuitry. In this exploratory three-wave longitudinal study spanning ages 9-19 years, we examined the associations between experiences of unpredictability, threat, and deprivation with the development of functional connectivity within and between three brain networks implicated in psychopathology: the salience (SAL), default mode (DMN), and fronto-parietal (FPN) networks, and tested whether network trajectories moderated associations between adversity and changes in internalizing symptoms. Connectivity decreased with age on average; these changes differed by dimension of adversity. Whereas family-level deprivation was associated with lower initial levels and more stability across most networks, unpredictability was associated with stability only in SAL connectivity, and threat was associated with stability in FPN and DMN-SAL connectivity. In youth exposed to higher levels of any adversity, lower initial levels and more stability in connectivity were related to smaller increases in internalizing symptoms. Our findings suggest that whereas deprivation is associated with widespread neurodevelopmental differences in cognitive and emotion processing networks, unpredictability is related selectively to salience detection circuitry. Studies with wider developmental windows should examine whether these neurodevelopmental alterations are adaptive or serve to maintain internalizing symptoms.

Negative caregiving and stress reactivity moderate the relation between early life stress and externalizing in adolescence.

Exposure to early life stress (ELS) is common and has been implicated in the development of psychopathology; importantly, however, many individuals who experience ELS do not develop emotional or behavioral difficulties. Prior research implicates stress exposure, negative caregiving behaviors, and patterns of physiological reactivity in predicting psychological well-being; however, the precise factors that contribute to resilience versus vulnerability to the adverse effects of stress exposures are not well understood. In a longitudinal study of adolescents (N = 120) assessed at three timepoints approximately every 2 years beginning at the ages of 913 years, we examined the roles of autonomic reactivity to social stress (assessed through skin conductance during the Trier Social Stress Task) and negative caregiving behaviors as moderators of the association between exposure to ELS and internalizing and externalizing symptoms. We found that the relation between ELS and externalizing symptoms was moderated by both negative caregiving and autonomic reactivity, such that the relation between ELS and externalizing was positive at low levels of negative caregiving and at high levels of autonomic reactivity; interactions predicting internalizing symptoms were not statistically significant. These findings highlight the importance of considering physiological and environmental variables that might contribute to susceptibility or resilience to symptoms of psychopathology following exposure to ELS.

Empathy for others versus for one's child: Associations with mothers' brain activation during a social cognitive task and with their toddlers' functioning.

Caregivers who are higher in dispositional empathy tend to have children with better developmental outcomes; however, few studies have considered the role of child-directed (i.e., "parental") empathy, which may be relevant for the caregiver-child relationship. We hypothesized that mothers' parental empathy during their child's infancy will be a stronger predictor of their child's social-emotional functioning as a toddler than will mothers' dispositional empathy. We further explored whether parental and dispositional empathy have shared or distinct patterns of neural activation during a social-cognitive movie-watching task. In 118 mother-infant dyads, greater parental empathy assessed when infants were 6 months old was associated with more social-emotional competencies and fewer problems in the children 1 year later, even after adjusting for dispositional empathy. In contrast, dispositional empathy was not associated with child functioning when controlling for parental empathy. In a subset of 20 mothers, insula activation was positively associated with specific facets of both dispositional and parental empathy, whereas right temporoparietal junction activation was associated only with parental empathy. Thus, dispositional and parental empathy appear to be dissociable by both brain and behavioral metrics. Parental empathy may be a viable target for interventions, especially for toddlers at risk for developing social-emotional difficulties.

Hippocampal volume indexes neurobiological sensitivity to the effect of pollution burden on telomere length in adolescents.

Exposure to environmental pollutants has been associated with cellular aging in children and adolescents. Individuals may vary, however, in their sensitivity or vulnerability to the effects of environmental pollutants. Larger hippocampal volume has emerged as a potential index of increased sensitivity to social contexts. In exploratory analyses (N = 214), we extend work in this area by providing evidence that larger hippocampal volume in early adolescence reflects increased sensitivity to the effect of neighborhood pollution burden on telomere length (standardized ß = -0.40, 95% CI[-0.65, -0.15]). In contrast, smaller hippocampal volume appears to buffer this association (standardized ß = 0.02). In youth with larger hippocampal volume, pollution burden was indirectly associated with shorter telomere length approximately 2 years later through shorter telomere length at baseline (indirect standardized ß = -0.25, 95% CI[-0.40, 0.10]). For these youth, living in high or low pollution-burdened neighborhoods may predispose them to develop shorter or longer telomeres, respectively, later in adolescence.

Early Life Stress, Frontoamygdala Connectivity, and Biological Aging in Adolescence: A Longitudinal Investigation.

Early life stress (ELS) may accelerate frontoamygdala development related to socioemotional processing, serving as a potential source of resilience. Whether this circuit is associated with other proposed measures of accelerated development is unknown. In a sample of young adolescents, we examined the relations among ELS, frontoamygdala circuitry during viewing of emotional faces, cellular aging as measured by telomere shortening, and pubertal tempo. We found that greater cumulative severity of ELS was associated with stronger negative coupling between bilateral centromedial amygdala and the ventromedial prefrontal cortex, a pattern that may reflect more mature connectivity. More negative frontoamygdala coupling (for distinct amygdala subdivisions) was associated with slower telomere shortening and pubertal tempo over 2 years. These potentially protective associations of negative frontoamygdala connectivity were most pronounced in adolescents who had been exposed to higher ELS. Our findings provide support for the formulation that ELS accelerates maturation of frontoamygdala connectivity and provide novel evidence that this neural circuitry confers protection against accelerated biological aging, particularly for adolescents who have experienced higher ELS. Although negative frontoamygdala connectivity may be an adaptation to ELS, frontoamygdala connectivity, cellular aging, and pubertal tempo do not appear to be measures of the same developmental process.