Understanding the neural underpinnings of mental health disorders has become a pivotal area of research in precision psychiatry. Large-scale brain networks, specifically the default mode network (DMN), the frontoparietal network (FPN), and the salience network (SN) – which together constitute the triple network model (Menon, 2011) - are increasingly recognized for their critical role in the development, maintenance, and exacerbation of psychological conditions including mood disorders, schizophrenia, neurodegenerative disease, and other pathologies (Beckmann et al., 2024; Dong et al., 2018; Jiang et al., 2017; Menon, 2019; Seeley et al., 2009; Wang et al., 2020; Weng et al., 2019; Xi et al., 2021). These networks are composed of spatially distributed regions with coordinated activity and are essential for cognitive flexibility (Cai et al., 2021; Menon and D'Esposito, 2022), attentional processes (Schimmelpfennig et al., 2023), emotional regulation (Li et al., 2021), and learning and adaptive planning (Dohmatob et al., 2020; Vriend et al., 2020). These processes serve as transdiagnostic mechanisms that underlie a broad spectrum of mental health disorders, highlighting the utility of integrative models, such as the triple network, to investigate the neural underpinning of clinical phenotypes, an example of which is social anxiety (Insel et al., 2010; Kapur et al., 2012).

Adolescence represents a critical time period for both social-emotional and brain development (Blakemore, 2008). Neurodevelopmental processes such as synaptic pruning (Germann et al., 2021; Selemon, 2013), increased myelination particularly in the prefrontal cortex (Corrigan et al., 2021; Vanes et al., 2020), and increased functional network connectivity (FNC; i.e., synchronized activity) between brain regions (Burnett and Blakemore, 2009; López-Vicente et al., 2021) coincide with social-emotional processes such as identity development, emotional regulation development, and increased importance on social connections and peer groups. During this time of substantial brain maturation, particularly within regions associated with self-regulation, social cognition, and emotional processing (Blakemore and Mills, 2014; Casey, 2015), FNC between large-scale brain networks (i.e., triple network model) are also changing (Baker et al., 2015; Power et al., 2010). Understanding FNC in the context of concurrent neurodevelopmental and social-emotional development is essential for identifying mechanisms that underlie the onset of social anxiety and informing targeted early interventions.

Building on these developmental considerations, the default mode network (DMN) emerges as a central network associated with self-referential thought and social-cognitive processes, thereby positioning it at the forefront of inquiries into adolescent social anxiety. The DMN, which shares significant overlap with the “social brain” (Frith, 2007; Mars et al., 2012), underpins processes of creating, reinforcing, and monitoring one's internal world (Andrews-Hanna et al., 2010; Menon, 2011). Variations in DMN activation during resting-state functional magnetic resonance imaging (rs-fMRI) have been associated with socially oriented and observable features (i.e., eye contact and body movements) across diagnoses of attention deficit hyperactivity disorder (Tang et al., 2018), autism spectrum disorder (Hickson et al., 2024), and social anxiety (Mizzi et al., 2022; Yu et al., 2021) during adolescence. The FPN, underpinning task-oriented processes (i.e., cognitive control/regulation, decision-making, task switching; Kim et al., 2012; Murray et al., 2017; Zanto and Gazzaley, 2013) has also been implicated in the development of social anxiety during adolescence (Arnold Anteraper et al., 2014; Zhang et al., 2023). Furthermore, the SN, which subserves the allocation of attention and switching between the DMN and the FPN, has been implicated in attentional avoidance, a key characteristic of social anxiety (Pannekoek et al., 2013; Schimmelpfennig et al., 2023). Together, the DMN, the FPN, and the SN are critical networks in understanding the development of social anxiety during adolescence; therefore, investigating FNC within these networks and their connections to other brain networks is crucial for identifying early biomarkers for social anxiety.

The triple network model has emerged as a promising framework for studying the interplay between large-scale brain networks and their role in social anxiety. Furthermore, adolescence is a critical period of brain plasticity where changes in FNC between large-scale networks coincide with the development of self-identity and social identity (Blakemore, 2008). In this study, we aimed to understand if resting-state differences in brain activity and FNC between large-scale networks, specifically within the triple network, are related to symptoms of anxiety. We examined rs-fMRI FNC between the DMN, the FPN, and the SN among themselves and among nine other large-scale brain networks as their internetwork connectivity relates to symptoms of social anxiety during early adolescence. Accordingly, we hypothesized that alterations in FNC between the DMN and the FPN (i.e., DMN-FPN), DMN-SN, and FPN-SN connectivity would be associated with greater symptoms of social anxiety in adolescence.