Using second-person neuroscience to elucidate the mechanisms of social interaction.

Although a large proportion of our lives are spent participating in social interactions, the investigation of the neural mechanisms supporting these interactions has largely been restricted to situations of social observation - that is, situations in which an individual observes a social stimulus without opportunity for interaction. In recent years, efforts have been made to develop a truly social, or 'second-person', neuroscientific approach to these investigations in which neural processes are examined within the context of a real-time reciprocal social interaction. These developments have helped to elucidate the behavioural and neural mechanisms of social interactions; however, further theoretical and methodological innovations are still needed. Findings to date suggest that the neural mechanisms supporting social interaction differ from those involved in social observation and highlight a role of the so-called 'mentalizing network' as important in this distinction. Taking social interaction seriously may also be particularly important for the advancement of the neuroscientific study of different psychiatric conditions.

Neural sensitivity to social reward predicts links between social behavior and loneliness in youth during the COVID-19 pandemic.

Neural reward network sensitivity in youth is proposed to differentially impact the effects of social environments on social outcomes. The COVID-19 pandemic provided an opportunity to test this hypothesis within a context of diminished in-person social interaction. We examined whether neural sensitivity to interactive social reward moderates the relationship between a frequency of interactive or passive social activity and social satisfaction. Survey reports of frequency of interactions with friends, passive social media use, and loneliness and social satisfaction were gathered in 2020 during mandated precautions limiting in-person contact. A subset of participants (age = 10-17) previously participated in a functional magnetic resonance imaging (fMRI) study examining social-interactive reward during a simulated peer interaction (survey n = 76; survey + fMRI n = 40). We found evidence of differential response to social context, such that youth with higher neural reward sensitivity showed a negative association between a frequency of interactive connections with friends and a combined loneliness and social dissatisfaction component (LSDC) score, whereas those with lower sensitivity showed the opposite effect. Further, high reward sensitivity was associated with greater LSDC as passive social media use increased, whereas low reward sensitivity showed the opposite. This indicates that youth with greater sensitivity to social-interactive reward may be more susceptible to negative effects of infrequent contact than their low reward-sensitive counterparts, who instead maintain social well-being through passive viewing of social content. These differential outcomes could have implications for supporting youth during times of major social disruption as well as ensuring mental health and well-being more broadly.

Longitudinal Change in Adolescent Depression and Anxiety Symptoms from before to during the COVID-19 Pandemic.

This study aimed to examine changes in depression and anxiety symptoms from before to during the first 6 months of the COVID-19 pandemic in a sample of 1,339 adolescents (9-18 years old, 59% female) from three countries. We also examined if age, race/ethnicity, disease burden, or strictness of government restrictions moderated change in symptoms. Data from 12 longitudinal studies (10 U.S., 1 Netherlands, 1 Peru) were combined. Linear mixed effect models showed that depression, but not anxiety, symptoms increased significantly (median increase = 28%). The most negative mental health impacts were reported by multiracial adolescents and those under 'lockdown' restrictions. Policy makers need to consider these impacts by investing in ways to support adolescents' mental health during the pandemic.

Neural similarity between mentalizing and live social interaction during the transition to adolescence.

Social interactions are essential for human development, yet little neuroimaging research has examined their underlying neurocognitive mechanisms using socially interactive paradigms during childhood and adolescence. Recent neuroimaging research has revealed activity in the mentalizing network when children engage with a live social partner, even when mentalizing is not required. While this finding suggests that social-interactive contexts may spontaneously engage mentalizing, it is not a direct test of how similarly the brain responds to these two contexts. The current study used representational similarity analysis on data from 8- to 14-year-olds who made mental and nonmental judgments about an abstract character and a live interaction partner during fMRI. A within-subject, 2 (Mental/Nonmental) × 2 (Peer/Character) design enabled us to examine response pattern similarity between conditions, and estimate fit to three conceptual models of how the two contexts relate: (1) social interaction and mentalizing about an abstract character are represented similarly; (2) interactive peers and abstract characters are represented differently regardless of the evaluation type; and (3) mental and nonmental states are represented dissimilarly regardless of target. We found that the temporal poles represent mentalizing and peer interactions similarly (Model 1), suggesting a neurocognitive link between the two in these regions. Much of the rest of the social brain exhibits different representations of interactive peers and abstract characters (Model 2). Our findings highlight the importance of studying social-cognitive processes using interactive approaches, and the utility of pattern-based analyses for understanding how social-cognitive processes relate to each other.

Effects of social and emotional context on neural activation and synchrony during movie viewing.

Sharing emotional experiences impacts how we perceive and interact with the world, but the neural mechanisms that support this sharing are not well characterized. In this study, participants (N = 52) watched videos in an MRI scanner in the presence of an unfamiliar peer. Videos varied in valence and social context (i.e., participants believed their partner was viewing the same (joint condition) or a different (solo condition) video). Reported togetherness increased during positive videos regardless of social condition, indicating that positive contexts may lessen the experience of being alone. Two analysis approaches were used to examine both sustained neural activity averaged over time and dynamic synchrony throughout the videos. Both approaches revealed clusters in the medial prefrontal cortex that were more responsive to the joint condition. We observed a time-averaged social-emotion interaction in the ventromedial prefrontal cortex, although this region did not demonstrate synchrony effects. Alternatively, social-emotion interactions in the amygdala and superior temporal sulcus showed greater neural synchrony in the joint compared to solo conditions during positive videos, but the opposite pattern for negative videos. These findings suggest that positive stimuli may be more salient when experienced together, suggesting a mechanism for forming social bonds.

Social cognition in context: A naturalistic imaging approach.

Social processing occurs within dynamic, complex, and multimodal contexts, but the study of social cognition typically involves static, artificial stimuli. Naturalistic approaches (e.g., movie viewing) can recapture the richness and complexity of real-world interactions. Novel analytic approaches allow for the investigation of functional brain organization in response to contextually embedded and extended events with a complex temporal structure during movie viewing or narrative processing. In addition to these within-brain measures, movies afford between-brain analyses such as inter-subject correlation, which allows for identification of stimulus-specific brain response through the correlation of brain activity between participants' brains. Research using these approaches offers both practical and theoretical advantages in understanding how we navigate our social world. Practically, movies are engaging stimuli that allow for more rapid presentation of multiple event types and improve compliance even in very young populations. Theoretically, studies have validated the use of these measures by demonstrating functional selectivity to contextually embedded stimuli. Naturalistic approaches also allow for novel insights. For example, regions associated with social cognition have longer temporal receptive windows, making them well suited to social-cognitive processes that require integration of information over longer timescales. Furthermore, the similarity in the temporal and spatial brain response between individuals during naturalistic viewing is related to age, predictive of friendships, and reduced in autism spectrum disorder. These findings offer first glimpses into the power of using these naturalistic, dynamic approaches to understand how we perceive, reason about, and interact with others.

Cortical temporal hierarchy is immature in middle childhood.

The development of successful social-cognitive abilities requires one to track, accumulate, and integrate knowledge of other people's mental states across time. Regions of the brain differ in their temporal scale (i.e., a cortical temporal hierarchy) and those receptive to long temporal windows may facilitate social-cognitive abilities; however, the cortical development of long timescale processing remains to be investigated. The current study utilized naturalistic viewing to examine cortical development of long timescale processing and its relation to social-cognitive abilities in middle childhood - a time of expanding social spheres and increasing social-cognitive abilities. We found that, compared to adults, children exhibited reduced low-frequency power in the temporo-parietal junction (TPJ) and reduced specialization for long timescale processing within the TPJ and other regions broadly implicated in the default mode network and higher-order visual processing. Further, specialization for long timescales within the right dorsal medial prefrontal cortex became more 'adult-like' as a function of children's comprehension of character mental states. These results suggest that cortical temporal hierarchy in middle childhood is immature and may be important for an accurate representation of complex naturalistic social stimuli during this age.

Functional near-infrared spectroscopy in toddlers: Neural differentiation of communicative cues and relation to future language abilities.

The toddler and preschool years are a time of significant development in both expressive and receptive communication abilities. However, little is known about the neurobiological underpinnings of language development during this period, likely due to difficulties acquiring functional neuroimaging data. Functional near-infrared spectroscopy (fNIRS) is a motion-tolerant neuroimaging technique that assesses cortical brain activity and can be used in very young children. Here, we use fNIRS during perception of communicative and noncommunicative speech and gestures in typically developing 2- and 3-year-olds (Study 1, n = 15, n = 12 respectively) and in a sample of 2-year-olds with both fNIRS data collected at age 2 and language outcome data at age 3 (Study 2, n = 18). In Study 1, 2- and 3-year-olds differentiated between communicative and noncommunicative stimuli as well as between speech and gestures in the left lateral frontal region. However, 2-year-olds showed different patterns of activation from 3-year-olds in right medial frontal regions. In Study 2, which included two toddlers identified with early language delays along with 16 typically developing toddlers, neural differentiation of communicative stimuli in the right medial frontal region at age 2 predicted receptive language at age 3. Specifically, after accounting for variance related to verbal ability at age 2, increased neural activation for communicative gestures (vs. both communicative speech and noncommunicative gestures) at age 2 predicted higher receptive language scores at age 3. These results are discussed in the context of the underlying mechanisms of toddler language development and use of fNIRS in prediction of language outcomes.

Interpersonal Synchrony in Autism.

PURPOSE OF REVIEW: We review evidence for the presence, quality, and correlates of interpersonal synchrony in autism spectrum disorder (ASD) across four domains: motor, conversational, physiological, and neural. We also propose cognitive and neural mechanisms for the disruption of interpersonal synchrony and investigate synchrony as a mechanism of intervention in ASD. RECENT FINDINGS: Across domains, synchrony is present but reduced or atypical in individuals with ASD during interactions with individuals with typical development (TD). Atypical synchrony may reflect the contribution of both intrapersonal mechanisms, such as atypical motor timing, and interpersonal mechanisms, such as atypical interindividual coupling. Research suggests evidence for synchrony interventions leading to improvements in some aspects of social behavior. Understanding synchrony in ASD has the potential to lead to biomarkers and interventions to support social functioning. However, further research should clarify mechanisms of atypical synchrony in ASD including taking features of the dyad into account.

A conceptual model of risk and protective factors associated with internalizing symptoms in autism spectrum disorder: A scoping review, synthesis, and call for more research.

This paper reviews and synthesizes key areas of research related to the etiology, development, and maintenance of internalizing symptoms in children, adolescents, and adults with autism spectrum disorder (ASD). In developing an integrated conceptual model, we draw from current conceptual models of internalizing symptoms in ASD and extend the model to include factors related to internalizing within other populations (e.g., children that have experienced early life stress, children with other neurodevelopmental conditions, typically developing children) that have not been systematically examined in ASD. Our review highlights the need for more research to understand the developmental course of internalizing symptoms, potential moderators, and the interplay between early risk and protective factors. Longitudinal studies incorporating multiple methods and both environmental and biological factors will be important in order to elucidate these mechanisms.

The influence of age and performance on hippocampal function and the encoding of contextual information in early childhood.

Studies in school-aged children and adults consistently implicate hippocampus, cortical regions, and their interaction as being critical for memory. However, few studies have examined this neural network in younger children (<8 years), despite the fact that behavioral studies consistently report substantial improvements in memory earlier in life. This study aimed to fill this gap by integrating task-based (i.e., memory encoding task) and task-free fMRI scans in 4- to 8-year-old children. Results showed that during memory encoding the hippocampus and several cortical regions (e.g., inferior frontal gyrus, IFG) were activated, consistent with findings in older individuals. Novel findings during memory encoding showed: 1) additional regions (i.e., orbital frontal gyrus, OFG) were recruited, 2) hippocampal activation varied due to age and performance, and 3) differentiation of connectivity between hippocampal subregions and IFG was greater in older versus younger participants, implying increased speicalization with age. Novel findings from task-free fMRI data suggested the extent of functional differentiation along the longitudinal axis of the hippocampus, particularly between hippocampus and OFG, was moderated by both age and performance. Our findings support and extend previous research, suggesting that maturation of hippocampal activity, connectivity, and differentiation may all contribute to development of memory during early childhood.

Neural correlates of developing theory of mind competence in early childhood.

Theory of mind (ToM) encompasses a range of abilities that show different developmental time courses. However, relatively little work has examined the neural correlates of ToM during early childhood. In this study, we investigated the neural correlates of ToM in typically developing children aged 4-8 years using resting-state functional magnetic resonance imaging. We calculated whole-brain functional connectivity with the right temporo-parietal junction (RTPJ), a core region involved in ToM, and examined its relation to children's early, basic, and advanced components of ToM competence assessed by a parent-report measure. Total ToM and both basic and advanced ToM components, but not early, consistently showed a positive correlation with connectivity between RTPJ and posterior cingulate cortex/precuneus; advanced ToM was also correlated with RTPJ to left TPJ connectivity. However, early and advanced ToM components showed negative correlation with the right inferior/superior parietal lobe, suggesting that RTPJ network differentiation is also related to ToM abilities. We confirmed and extended these results using a Bayesian modeling approach demonstrating significant relations between multiple nodes of the mentalizing network and ToM abilities, with no evidence for differences in relations between ToM components. Our data provide new insights into the neural correlates of multiple aspects of ToM in early childhood and may have implications for both typical and atypical development of ToM.

Social interaction recruits mentalizing and reward systems in middle childhood.

Social cognition develops in the context of reciprocal social interaction. However, most neuroimaging studies of mentalizing have used noninteractive tasks that may fail to capture important aspects of real-world mentalizing. In adults, social-interactive context modulates activity in regions linked to social cognition and reward, but few interactive studies have been done with children. The current fMRI study examines children aged 8-12 using a novel paradigm in which children believed they were interacting online with a peer. We compared mental and non-mental state reasoning about a live partner (Peer) versus a story character (Character), testing the effects of mentalizing and social interaction in a 2 × 2 design. Mental versus Non-Mental reasoning engaged regions identified in prior mentalizing studies, including the temporoparietal junction, superior temporal sulcus, and dorsomedial prefrontal cortex. Moreover, peer interaction, even in conditions without explicit mentalizing demands, activated many of the same mentalizing regions. Peer interaction also activated areas outside the traditional mentalizing network, including the reward system. Our results demonstrate that social interaction engages multiple neural systems during middle childhood and contribute further evidence that social-interactive paradigms are needed to fully capture how the brain supports social processing in the real world.

Let's chat: developmental neural bases of social motivation during real-time peer interaction.

Humans are motivated to interact with each other, but the neural bases of social motivation have been predominantly examined in non-interactive contexts. Understanding real-world social motivation is of special importance during middle childhood (ages 8-12), a period when social skills improve, social networks grow, and social brain networks specialize. To assess interactive social motivation, the current study used a novel fMRI paradigm in which children believed they were chatting with a peer. The design targeted two phases of interaction: (1) Initiation, in which children engaged in a social bid via sharing a like or hobby, and (2) Reply, in which children received either an engaged ("Me too") or non-engaged ("I'm away") reply from the peer. On control trials, children were told that their answers were not shared and that they would receive either engaged ("Matched") or non-engaged ("Disconnected") replies from the computer. Results indicated that during Initiation and Reply, key components of reward circuitry (e.g., ventral striatum) were more active for the peer than the computer trials. In addition, during Reply, social cognitive regions were more activated by the peer, and this social cognitive specialization increased with age. Finally, the effect of engagement type on reward circuitry activation was larger for social than non-social trials, indicating developmental sensitivity to social contingency. These findings demonstrate that both reward and social cognitive brain systems support real-time social interaction in middle childhood. An interactive approach to understanding social reward has implications for clinical disorders, where social motivation is more affected in real-world contexts.

Developmental relations between amygdala volume and anxiety traits: Effects of informant, sex, and age.

Although substantial human and animal evidence suggests a role for the amygdala in anxiety, literature linking amygdala volume to anxiety symptomatology is inconclusive, with studies finding positive, negative, and null results. Clarifying this brain-behavior relation in middle to late childhood is especially important, as this is a time both of amygdala structural maturation and the emergence of many anxiety disorders. The goal of the current study was to clarify inconsistent findings in previous literature by identifying factors moderating the relation between amygdala volume and anxiety traits in a large sample of typically developing children aged 6-13 years (N = 72). In particular, we investigated the moderating effects of informant (parent vs. child), age, and sex. We found that children's reports (i.e., self-reports) were related to amygdala volume; children who reported higher anxiety levels had smaller amygdalae. This negative relation between amygdala volume and anxiety weakened with age. There was also an independent effect of sex, such that relations were stronger in males than in females. These results indicate the importance of considering sample and informant characteristics when charting the neurobiological mechanisms underlying developmental anxiety.

Development of hippocampal functional connectivity during childhood.

The hippocampus is a medial temporal lobe structure involved in memory, spatial navigation, and regulation of stress responses, making it a structure critical to daily functioning. However, little is known about the functional development of the hippocampus during childhood due to methodological challenges of acquiring neuroimaging data in young participants. This is a critical gap given evidence that hippocampally-mediated behaviors (e.g., episodic memory) undergo rapid and important changes during childhood. To address this gap, the present investigation collected resting-state fMRI scans in 97, 4- to 10-year-old children. Whole brain seed-based analyses of anterior, posterior, and whole hippocampal connectivity were performed to identify regions demonstrating stable (i.e., age-controlled) connectivity profiles as well as age-related differences in connectivity. Results reveal that the hippocampus is a highly connected structure of the brain and that most of the major components of the adult network are evident during childhood, including both unique and overlapping connectivity between anterior and posterior regions. Despite widespread age-controlled connectivity, the strength of hippocampal connectivity with regions of lateral temporal lobes and the anterior cingulate increased throughout the studied age range. These findings have implications for future investigations of the development of hippocampally-mediated behaviors and methodological applications for the appropriateness of whole versus segmented hippocampal seeds in connectivity analyses. Hum Brain Mapp 38:182-201, 2017. © 2016 Wiley Periodicals, Inc.

Communicative Signals Promote Object Recognition Memory and Modulate the Right Posterior STS.

Detection of communicative signals is thought to facilitate knowledge acquisition early in life, but less is known about the role these signals play in adult learning or about the brain systems supporting sensitivity to communicative intent. The current study examined how ostensive gaze cues and communicative actions affect adult recognition memory and modulate neural activity as measured by fMRI. For both the behavioral and fMRI experiments, participants viewed a series of videos of an actress acting on one of two objects in front of her. Communicative context in the videos was manipulated in a 2 × 2 design in which the actress either had direct gaze (Gaze) or wore a visor (NoGaze) and either pointed at (Point) or reached for (Reach) one of the objects (target) in front of her. Participants then completed a recognition memory task with old (target and nontarget) objects and novel objects. Recognition memory for target objects in the Gaze conditions was greater than NoGaze, but no effects of gesture type were seen. Similarly, the fMRI video-viewing task revealed a significant effect of Gaze within right posterior STS (pSTS), but no significant effects of Gesture. Furthermore, pSTS sensitivity to Gaze conditions was related to greater memory for objects viewed in Gaze, as compared with NoGaze, conditions. Taken together, these results demonstrate that the ostensive, communicative signal of direct gaze preceding an object-directed action enhances recognition memory for attended items and modulates the pSTS response to object-directed actions. Thus, establishment of a communicative context through ostensive signals remains an important component of learning and memory into adulthood, and the pSTS may play a role in facilitating this type of social learning.

Interaction matters: A perceived social partner alters the neural processing of human speech.

Mounting evidence suggests that social interaction changes how communicative behaviors (e.g., spoken language, gaze) are processed, but the precise neural bases by which social-interactive context may alter communication remain unknown. Various perspectives suggest that live interactions are more rewarding, more attention-grabbing, or require increased mentalizing-thinking about the thoughts of others. Dissociating between these possibilities is difficult because most extant neuroimaging paradigms examining social interaction have not directly compared live paradigms to conventional "offline" (or recorded) paradigms. We developed a novel fMRI paradigm to assess whether and how an interactive context changes the processing of speech matched in content and vocal characteristics. Participants listened to short vignettes--which contained no reference to people or mental states--believing that some vignettes were prerecorded and that others were presented over a real-time audio-feed by a live social partner. In actuality, all speech was prerecorded. Simply believing that speech was live increased activation in each participant's own mentalizing regions, defined using a functional localizer. Contrasting live to recorded speech did not reveal significant differences in attention or reward regions. Further, higher levels of autistic-like traits were associated with altered neural specialization for live interaction. These results suggest that humans engage in ongoing mentalizing about social partners, even when such mentalizing is not explicitly required, illustrating how social context shapes social cognition. Understanding communication in social context has important implications for typical and atypical social processing, especially for disorders like autism where social difficulties are more acute in live interaction.

Perceived communicative intent in gesture and language modulates the superior temporal sulcus.

Behavioral evidence and theory suggest gesture and language processing may be part of a shared cognitive system for communication. While much research demonstrates both gesture and language recruit regions along perisylvian cortex, relatively less work has tested functional segregation within these regions on an individual level. Additionally, while most work has focused on a shared semantic network, less has examined shared regions for processing communicative intent. To address these questions, functional and structural MRI data were collected from 24 adult participants while viewing videos of an experimenter producing communicative, Participant-Directed Gestures (PDG) (e.g., "Hello, come here"), noncommunicative Self-adaptor Gestures (SG) (e.g., smoothing hair), and three written text conditions: (1) Participant-Directed Sentences (PDS), matched in content to PDG, (2) Third-person Sentences (3PS), describing a character's actions from a third-person perspective, and (3) meaningless sentences, Jabberwocky (JW). Surface-based conjunction and individual functional region of interest analyses identified shared neural activation between gesture (PDGvsSG) and language processing using two different language contrasts. Conjunction analyses of gesture (PDGvsSG) and Third-person Sentences versus Jabberwocky revealed overlap within left anterior and posterior superior temporal sulcus (STS). Conjunction analyses of gesture and Participant-Directed Sentences to Third-person Sentences revealed regions sensitive to communicative intent, including the left middle and posterior STS and left inferior frontal gyrus. Further, parametric modulation using participants' ratings of stimuli revealed sensitivity of left posterior STS to individual perceptions of communicative intent in gesture. These data highlight an important role of the STS in processing participant-directed communicative intent through gesture and language. Hum Brain Mapp 37:3444-3461, 2016. © 2016 Wiley Periodicals, Inc.

Reprint of "Biological motion perception links diverse facets of theory of mind during middle childhood".

Two cornerstones of social development-social perception and theory of mind-undergo brain and behavioral changes during middle childhood, but the link between these developing domains is unclear. One theoretical perspective argues that these skills represent domain-specific areas of social development, whereas other perspectives suggest that both skills may reflect a more integrated social system. Given recent evidence from adults that these superficially different domains may be related, the current study examined the developmental relation between these social processes in 52 children aged 7 to 12years. Controlling for age and IQ, social perception (perception of biological motion in noise) was significantly correlated with two measures of theory of mind: one in which children made mental state inferences based on photographs of the eye region of the face and another in which children made mental state inferences based on stories. Social perception, however, was not correlated with children's ability to make physical inferences from stories about people. Furthermore, the mental state inference tasks were not correlated with each other, suggesting a role for social perception in linking various facets of theory of mind.