Developmental changes in brain function linked with addiction-like social media use two years later.

Addiction-like social media use (ASMU) is widely reported among adolescents and is associated with depression and other negative health outcomes. We aimed to identify developmental trajectories of neural social feedback processing that are linked to higher levels of ASMU in later adolescence. Within a longitudinal design, 103 adolescents completed a social incentive delay task during 1-3 fMRI scans (6-9th grade), and a 4th self-report assessment of ASMU and depressive symptoms ∼2 years later (10-11th grade). We assessed ASMU effects on brain responsivity to positive social feedback across puberty and relationships between brain responsivity development, ASMU symptoms, and depressive symptoms while considering gender effects. Findings demonstrate decreasing responsivity, across puberty, in the ventral media prefrontal cortex, medial prefrontal cortex, posterior cingulate cortex, and right inferior frontal gyrus associated with higher ASMU symptoms over 2 years later. Significant moderated mediation models suggest that these pubertal decreases in brain responsivity are associated with increased ASMU symptoms which, among adolescent girls (but not boys), is in turn associated with increased depressive symptoms. Results suggest initial hyperresponsivity to positive social feedback, before puberty onset, and decreases in this response across development, may be risk factors for ASMU in later adolescence.

Neurobiological sensitivity to popular peers moderates daily links between social media use and affect.

Social media behaviors increase during adolescence, and quantifiable feedback metrics (e.g., likes, followers) may amplify the value of social status for teens. Social media's impact on adolescents' daily affect may be exacerbated given the neurodevelopmental changes that increase youths' sensitivity to socio-emotional information. This study examines whether neurobiological sensitivity to popularity moderates daily links between social media use and affect. Adolescents (N = 91, Mage=13.6 years, SDage=0.6 years) completed an fMRI task in which they viewed faces of their high (>1 SD above the mean) and low (<1 SD below the mean) popular peers based on peer-nominated sociometric ratings from their school social networks. Two years later, adolescents reported their time spent on social media and affect daily for two weeks. Neural tracking of popularity in the ventromedial and dorsomedial prefrontal cortex moderated the association between time on social media and affect. Specifically, adolescents who tracked high popular peers in the vmPFC reported more positive affect on days when they used social media more. Adolescents who tracked low popular peers in the vmPFC and dmPFC reported more negative affect on days when they used social media more. Results suggest that links between social media and affect depend on individual differences in neural sensitivity to popularity.

Neural tracking of social hierarchies in adolescents' real-world social networks.

In the current study, we combined sociometric nominations and neuroimaging techniques to examine adolescents' neural tracking of peers from their real-world social network that varied in social preferences and popularity. Adolescent participants from an entire school district (N = 873) completed peer sociometric nominations of their grade at school, and a subset of participants (N = 117, Mage = 13.59 years) completed a neuroimaging task in which they viewed peer faces from their social networks. We revealed two neural processes by which adolescents track social preference: (1) the fusiform face area, an important region for early visual perception and social categorization, simultaneously represented both peers high in social preference and low in social preference; (2) the dorsolateral prefrontal cortex (DLPFC), which was differentially engaged in tracking peers high and low in social preference. No regions specifically tracked peers high in popularity and only the inferior parietal lobe, temporoparietal junction, midcingulate cortex and insula were involved in tracking unpopular peers. This is the first study to examine the neural circuits that support adolescents' perception of peer-based social networks. These findings identify the neural processes that allow youths to spontaneously keep track of peers' social value within their social network.

Adolescents' neural sensitivity to high and low popularity: Longitudinal links to risk-taking and prosocial behavior.

Adolescents are particularly attuned to popularity within peer groups, which impacts behaviors such as risk-taking and prosocial behavior. Neurodevelopmental changes orient adolescents toward salient social cues in their environment. We examined whether neural regions that track popularity are associated with longitudinal changes in risk-taking and prosocial behavior. During an fMRI scan, adolescents (n = 109, Mage=13.59, SD=0.59) viewed pictures of their popular and unpopular classmates based on sociometric nominations from their social networks. Neural tracking of high popularity in the dorsomedial prefrontal cortex was associated with increases in risk-taking behavior, whereas tracking of low popularity in the right insula was associated with increases in prosocial behavior. Results suggest that individual differences in neural tracking of popularity relate to longitudinal changes in adolescents' social behaviors.

Developmental Changes in Habenular and Striatal Social Reinforcement Responsivity Across Adolescence Linked With Substance Use.

BACKGROUND: Habenula (HB) function is implicated in substance use disorders and is involved in inhibiting dopamine release in the ventral striatum (VS). While blunted VS reward responsivity is implicated in risk for later substance use, links between HB reinforcement processing and progression of use have not, to our knowledge, been examined among adolescents. In the present study, we longitudinally assessed HB and VS responsivity to social rewards and punishments across adolescence and examined associations with substance use. METHODS: Within a longitudinal design, 170 adolescents (53.5% female) completed 1 to 3 functional magnetic resonance imaging scans across 6th to 9th grade and reported yearly substance use across 6th to 11th grade. We examined VS and HB responsivity to social reinforcement during a social incentive delay task in which adolescents received social rewards (smiling faces) and punishments (scowling faces). RESULTS: We observed increased VS responsivity to social rewards (vs. reward omissions) and increased VS, but decreased HB, responsivity to social punishment avoidance versus receipt. However, contrary to hypotheses, the HB displayed increased responsivity to social rewards (vs. reward omissions). Further, adolescents reporting regular substance use displayed longitudinally declining HB responsivity to social rewards (vs. reward omissions), whereas adolescents reporting no substance use displayed longitudinally increasing HB responsivity. In contrast, whereas VS responsivity to punishment avoidance versus receipt increased longitudinally among regular substance users, it stayed relatively stable among nonusers. CONCLUSIONS: These results suggest that differential HB and VS social reinforcement processing trajectories across adolescence are associated with substance use.

Neighborhood disadvantage, race/ethnicity and neural sensitivity to social threat and reward among adolescents.

Experiences within one's social environment shape neural sensitivity to threatening and rewarding social cues. However, in racialized societies like the USA, youth from minoritized racial/ethnic backgrounds can have different experiences and perceptions within neighborhoods that share similar characteristics. The current study examined how neighborhood disadvantage intersects with racial/ethnic background in relation to neural sensitivity to social cues. A racially diverse (59 Hispanic/Latine, 48 White, 37 Black/African American, 15 multi-racial and 6 other) and primarily low to middle socioeconomic status sample of 165 adolescents (88 female; Mage = 12.89) completed a social incentive delay task while undergoing functional magnetic resonance imaging (fMRI) scanning. We tested for differences in the association between neighborhood disadvantage and neural responses to social threat and reward cues across racial/ethnic groups. For threat processing, compared to White youth, neighborhood disadvantage was related to greater neural activation in regions involved in salience detection (e.g. anterior cingulate cortex) for Black youth and regions involved in mentalizing (e.g. temporoparietal junction) for Latine youth. For reward processing, neighborhood disadvantage was related to greater brain activation in reward, salience and mentalizing regions for Black youth only. This study offers a novel exploration of diversity within adolescent neural development and important insights into our understanding of how social environments may 'get under the skull' differentially across racial/ethnic groups.

Neural Reactivity to Social Punishment Predicts Future Engagement in Nonsuicidal Self-injury Among Peer-Rejected Adolescents.

BACKGROUND: Rates of nonsuicidal self-injury (NSSI) increase dramatically in adolescence. Affective reactivity and adverse social experiences have been linked to NSSI, but less is known about whether these factors may separately or interactively predict NSSI, especially longitudinally. This study combined functional magnetic resonance imaging and a sociometric measure to test whether a combination of neural (e.g., amygdala) reactivity to social punishment and peer-nominated peer acceptance/rejection predicts NSSI longitudinally in adolescence. Amygdala reactivity was examined as a potential neural marker of affective reactivity to social punishment, which may heighten NSSI risk in contexts of social adversity. METHODS: One hundred twenty-five adolescents (63 female) completed a social incentive delay task during neuroimaging and school-based peer nominations to measure peer acceptance/rejection. NSSI engagement was assessed at baseline and 1-year follow-up. RESULTS: Greater amygdala reactivity to social punishment predicted greater NSSI engagement 1 year later among adolescents with high peer rejection. This effect for the amygdala was specific to social punishment (vs. reward) and held when controlling for biological sex and pubertal development. Exploratory analyses found that ventral striatum reactivity to social reward and punishment similarly interacted with peer rejection to predict NSSI but that amygdala connectivity with salience network regions did not. CONCLUSIONS: Amygdala reactivity to social punishment, in combination with high peer rejection, may increase NSSI risk in adolescence, possibly via heightened affective reactivity to adverse social experiences. Objective measures of neurobiological and social risk factors may improve prediction of NSSI, while therapeutic approaches that target affective reactivity and increase prosocial skills may protect against NSSI in adolescence.

Development of mother-infant co-regulation: The role of infant vagal tone and temperament at 6, 9, and 12 months of age.

Using Porges' (2011) Polyvagal Theory as a backdrop, this study examined whether changes in parasympathetic functioning, as indexed by baseline measures of cardiac vagal tone at 6, 9, and 12 months of age, were linked to changes in infants' (N = 101) dyadic co-regulation over these same time points. Mothers and infants were observed at each time point during a 15-minute unstructured free-play and co-regulated patterns of interactions were coded using the Revised Relational Coding System (Fogel et al., 2003). Analyses were carried out using multi-process growth curve modeling to examine baseline measurements (intercepts) and changes (slopes) in vagal tone, co-regulation as well as mothers' report of infant temperament. Findings demonstrate links between infants' vagal tone and changes in mother-infant co-regulation. Specifically, increasing levels of cardiac vagal tone was related to increases in symmetrical but decreases in unilateral patterns of co-regulation over time. These findings suggest that changes in the autonomic nervous system likely undergird infants' improving capacity to engage in more mutually sustained patterns of co-regulation.

Toddler-mother attachment moderates adolescents' behavioral and neural evaluation of trustworthiness.

This longitudinal study examined the prospective association between toddler-mother attachment to adolescents' (n = 52; 34 boys; Mage = 13.22 years; 90% White) behavioral and neural responses during the evaluation of trustworthiness from unfamiliar, emotionally neutral faces. At 33 months, toddler-mother attachment status (secure vs insecure classification) was assessed using a modified Strange Situation procedure. Results revealed that attachment moderated the processing of trustworthiness facial cues. As faces became less trustworthy, adolescents with a secure (vs insecure) attachment history rated the faces as correspondingly less trustworthy and showed increasing (vs overall blunted) activation in brain regions involved in trustworthiness perception (i.e. bilateral amygdala, bilateral fusiform, right anterior insula and right posterior superior temporal sulcus). Findings suggest that a secure compared with insecure child-mother attachment in toddlerhood may be associated with greater capacity for, or openness to, processing potentially negative social information at both the behavioral and neural levels during adolescence.

Social neural sensitivity as a susceptibility marker to family context in predicting adolescent externalizing behavior.

Adolescence represents a period of risk for developing patterns of risk-taking and conduct problems, and the quality of the family environment is one robust predictor of such externalizing behavior. However, family factors may not affect all youth uniformly, and individual differences in neurobiological susceptibility to the family context may moderate its influence. The current study investigated brain-based individual differences in social motivational processing as a susceptibility marker to family conflict in predicting externalizing behavior in early adolescent youth. 163 adolescents (Mage = 12.87 years) completed an fMRI scan during which they anticipated social rewards and social punishments. For adolescents with heightened ventral striatum and amygdala blood oxygen-level dependent (BOLD) response during the anticipation of social rewards and heightened ventral striatum BOLD response during the anticipation of social punishments, higher levels of family conflict were associated with greater externalizing behavior. BOLD response when anticipating both social rewards and punishments suggested increased susceptibility to maladaptive family contexts, highlighting the importance of considering adolescent social motivation in positive and negatively valenced contexts.

Neurobiological Sensitivity to Social Rewards and Punishments Moderates Link Between Peer Norms and Adolescent Risk Taking.

Although peer influence is a strong predictor of adolescents' risk-taking behaviors, not all adolescents are susceptible to their peer group. One hundred and thirty-six adolescents (Mage  = 12.79 years) completed an fMRI scan, measures of perceived peer group norms, and engagement in risky behavior. Ventral striatum (VS) sensitivity when anticipating social rewards and avoiding social punishments significantly moderated the association between perceived peer norms and adolescents' own risk behaviors. Perceptions of more deviant peer norms were associated with increased risky behavior, but only for adolescents with high VS sensitivity; adolescents with low VS sensitivity were resilient to deviant peer norms, showing low risk taking regardless of peer context. Findings provide a novel contribution to the study of peer influence susceptibility.

A Call for Greater Attention to Culture in the Study of Brain and Development.

Despite growing research on neurobiological development, little attention has been paid to cultural and ethnic variation in neurodevelopmental processes. We present an overview of the current state of developmental cognitive neuroscience with respect to its attention to cultural issues. Analyses based on 80 publications represented in five recent meta-analyses related to adolescent developmental neuroscience show that 99% of the publications used samples in Western countries. Only 22% of studies provided a detailed description of participants' racial/ethnic background, and only 18% provided for socioeconomic status. Results reveal a trend in developmental cognitive neuroscience research: The body of research is derived not only mostly from Western samples but also from participants whose race/ethnicity is unknown. To achieve a holistic perspective on brain development in different cultural contexts, we propose and highlight an emerging interdisciplinary approach-developmental cultural neuroscience-the intersection of developmental psychology, cultural psychology, and cognitive neuroscience. Developmental cultural neuroscience aims to elucidate cultural similarities and differences in neural processing across the life span. We call attention to the importance of incorporating culture into the empirical investigation of neurodevelopment.

The WD40 domain is required for LRRK2 neurotoxicity.

BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson disease (PD). LRRK2 contains an "enzymatic core" composed of GTPase and kinase domains that is flanked by leucine-rich repeat (LRR) and WD40 protein-protein interaction domains. While kinase activity and GTP-binding have both been implicated in LRRK2 neurotoxicity, the potential role of other LRRK2 domains has not been as extensively explored. PRINCIPAL FINDINGS: We demonstrate that LRRK2 normally exists in a dimeric complex, and that removing the WD40 domain prevents complex formation and autophosphorylation. Moreover, loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD mutations. CONCLUSION: These findings suggest that LRRK2 dimerization and autophosphorylation may be required for the neurotoxicity of LRRK2 PD mutations and highlight a potential role for the WD40 domain in the mechanism of LRRK2-mediated cell death.

Phosphorylation of ATXN1 at Ser776 in the cerebellum.

Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited neurodegenerative disorders caused by a mutant protein with an expanded polyglutamine tract. Phosphorylation of ataxin-1 (ATXN1) at serine 776 is implicated in SCA1 pathogenesis. Previous studies, utilizing transfected cell lines and a Drosophila photoreceptor model of SCA1, suggest that phosphorylating ATXN1 at S776 renders it less susceptible to degradation. This work also indicated that oncogene from AKR mouse thymoma (Akt) promotes the phosphorylation of ATXN1 at S776 and severity of neurodegeneration. Here, we examined the phosphorylation of ATXN1 at S776 in cerebellar Purkinje cells, a prominent site of pathology in SCA1. We found that while phosphorylation of S776 is associated with a stabilization of ATXN1 in Purkinje cells, inhibition of Akt either in vivo or in a cerebellar extract-based phosphorylation assay did not decrease the phosphorylation of ATXN1-S776. In contrast, immunodepletion and inhibition of cyclic AMP-dependent protein kinase decreased phosphorylation of ATXN1-S776. These results argue against Akt as the in vivo kinase that phosphorylates S776 of ATXN1 and suggest that cyclic AMP-dependent protein kinase is the active ATXN1-S776 kinase in the cerebellum.

Hsp70/Hsc70 regulates the effect phosphorylation has on stabilizing ataxin-1.

Spinocerebellar ataxia type 1 (SCA1) is an inherited neurodegenerative disorder. The mutation causing SCA1 is an expansion in the polyglutamine tract of the ATXN1 protein. Previous work demonstrated that phosphorylation of mutant ATXN1 at serine 776 (S776), a putative Akt phosphorylation site, is critical for pathogenesis. To examine this pathway further, we utilized a cell-transfection system that allowed the targeting of Akt to either the cytoplasm or the nucleus. In contrast to HeLa cells, we found that Akt targeted to the cytoplasm increased the degradation of ATXN1 in Chinese hamster ovary cells. However, Akt targeted to the cytoplasm failed to destabilize ATXN1 if Hsp70/Hsc70 was present. Thus, Hsp70/Hsc70 can regulate ATXN1 levels in concert with phosphorylation of ATXN1 at S776.

RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.

Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited, typically adult onset, polyglutamine neurodegenerative diseases. To examine whether development impacts SCA1, we used a conditional transgenic mouse model of SCA1 to delay the postnatal expression of mutant ATXN1 until after completion of cerebellar development. Delayed postnatal expression of mutant ATXN1 led to a substantial reduction in severity of disease in adults in comparison with early postnatal gene expression. This was linked to a destabilization of RORalpha, a transcription factor critical for cerebellar development. In SCA1 mice, there was a depletion of RORalpha and a reduction in expression of genes controlled by RORalpha. Partial loss of RORalpha enhanced mutant ATXN1 pathogenicity. Additionally, evidence points to the existence of a complex containing ATXN1, RORalpha, and the RORalpha coactivator Tip60. These studies indicate RORalpha and Tip60 have a role in SCA1 and suggest a mechanism by which compromising cerebellar development contributes to severity of neurodegeneration in an adult.