Brains systems undergo unique and specific dynamic changes at the cellular, circuit, and systems level that underlie the transition to adult-level cognitive control. We integrate literature from these different levels of analyses to propose a novel model of the brain basis of the development of cognitive control. The ability to consistently exert cognitive control improves into adulthood as the flexible integration of component processes, including inhibitory control, performance monitoring, and working memory, increases. Unique maturational changes in brain structure, supported by interactions between dopaminergic and GABAergic systems, contribute to enhanced network synchronization and an improved signal-to-noise ratio. In turn, these factors facilitate the specialization and strengthening of connectivity in networks supporting the transition to adult levels of cognitive control. This model provides a novel understanding of the adolescent period as an adaptive period of heightened experience-seeking necessary for the specialization of brain systems supporting cognitive control.

Background Early pubertal maturation has been posited to be a biopsychosocial risk factor for the onset of internalizing psychopathology in adolescence; further, early-maturing youth exhibit heightened reactivity to stressful events. School closures and enforced social distancing, as well as health and financial uncertainties, during the COVID-19 pandemic are expected to adversely affect mental health in youth, particularly adolescents who are already at risk for experiencing emotional difficulties. The executive control network (ECN) supports cognitive processes required to successfully navigate novel challenges and regulate emotions in stressful contexts. Methods : We examined whether functional coherence of the ECN, measured using resting-state fMRI five years before the pandemic (at T1), is a neurobiological marker of resilience to increases in the severity of internalizing symptoms during COVID-19 in adolescents who were in more advanced stages of puberty at T1 relative to their same-age peers (N=85; 49 F). Results On average, participants reported an increase in symptoms from the three months prior to pandemic to the two most recent weeks during the pandemic. We found that early-maturing youth exhibited greater increases in internalizing symptoms during the pandemic if their ECN coherence was low; in contrast, relative pubertal stage was not associated with changes in internalizing symptoms in adolescents with higher ECN coherence at T1. Conclusions These findings highlight the role of the functional architecture of the brain that supports executive functioning in protecting against risk factors that may exacerbate symptoms of internalizing psychopathology during periods of stress and uncertainty.

BackgroundExposure to early life stress (ELS) is alarmingly prevalent and has been linked to the high rates of depression documented in adolescence. Researchers have theorized that ELS may increase adolescents’ vulnerability or reactivity to the effects of subsequent stressors, placing them at higher risk for developing symptoms of depression.MethodsWe tested this formulation in a longitudinal study by assessing levels of stress and depression during the COVID-19 pandemic in a sample of adolescents from the San Francisco Bay Area (N = 109; 43 male; ages 13–20 years) who had been characterized 3–7 years earlier (M = 5.06, SD = 0.86 years) with respect to exposure to ELS and symptoms of depression.ResultsAs expected, severity of ELS predicted levels of depressive symptoms during the pandemic [r(107) = 0.26, p = 0.006], which were higher in females than in males [t(107) = −3.56, p < 0.001]. Importantly, the association between ELS and depression was mediated by adolescents’ reported levels of stress, even after controlling for demographic variables.ConclusionsThese findings underscore the importance of monitoring the mental health of vulnerable children and adolescents during this pandemic and targeting perceived stress in high-risk youth.

Background: Exposure to early life stress (ELS) is alarmingly prevalent, and has been linked to the high rates of depression documented in adolescence. Researchers have theorized that ELS may increase adolescents’ vulnerability or reactivity to the effects of subsequent stressors, placing them at higher risk for developing symptoms of depression. Methods: We tested this formulation in a longitudinal study by assessing levels of stress and depression during the COVID-19 pandemic in a sample of adolescents from the San Francisco Bay Area (N=100; 43 male; ages 13-20 years) who had been characterized 4-7 years earlier (M=5.27, SD=0.75 years) with respect to exposure to ELS and symptoms of depression. Results: As expected, severity of ELS predicted levels of depressive symptoms during the pandemic (r(98)=0.25, p=.012), which were higher in females than in males (t(98)=-3.36, p=.001). Importantly, the association between ELS and depression was mediated by adolescents’ reported levels of stress, even after controlling for demographic and other COVID-19-related variables. Conclusions: These findings underscore the importance of monitoring the mental health of vulnerable children and adolescents during this pandemic and targeting perceived stress and isolation in high-risk youth.

Background Adolescence is a period of high risk for the onset of depression, characterized by variability in symptoms, severity, and course. During adolescence, the neurocircuitry implicated in depression continues to mature, suggesting that it is an important period for intervention. Reflecting the recent emergence of ‘precision mental health’ – a person‐centered approach to identifying, preventing, and treating psychopathology – researchers have begun to document associations between heterogeneity in features of depression and individual differences in brain circuitry, most frequently in resting‐state functional connectivity (RSFC). Methods In this review, we present emerging work examining pre‐ and post‐treatment measures of network connectivity in depressed adolescents; these studies reveal potential intervention‐specific neural markers of treatment efficacy. We also review findings from studies examining associations between network connectivity and both types of depressive symptoms and response to treatment in adults, and indicate how this work can be extended to depressed adolescents. Finally, we offer recommendations for research that we believe will advance the science of precision mental health of adolescence. Results Nascent studies suggest that linking RSFC‐based pathophysiological variation with effects of different types of treatment and changes in mood following specific interventions will strengthen predictions of prognosis and treatment response. Studies with larger sample sizes and direct comparisons of treatments are required to determine whether RSFC patterns are reliable neuromarkers of treatment response for depressed adolescents. Although we are not yet at the point of using RSFC to guide clinical decision‐making, findings from research examining the stability and reliability of RSFC point to a favorable future for network‐based clinical phenotyping. Conclusions Delineating the correspondence between specific clinical characteristics of depression (e.g., symptoms, severity, and treatment response) and patterns of network‐based connectivity will facilitate the development of more tailored and effective approaches to the assessment, prevention, and treatment of depression in adolescents.

Sensation seeking is a personality construct associated with an increased propensity for engaging in risk-taking. Associations with deleterious outcomes ranging from mental health impairments to increased mortality rates highlight important public health concerns related to this construct. Although some have suggested that increased neural responsivity to reward within the ventral striatum (e.g., nucleus accumbens) may drive sensation seeking behaviors, few studies have examined the neural mechanisms associated with stable individual differences in sensation seeking across development. To address this issue, the current study used functional magnetic resonance imaging to examine the association between neural responding to reward and stable patterns of sensation seeking across a three-year follow-up period among healthy adolescents and young adults (N = 139). Results indicated that during early adolescence (~ages 10–12), increased reactivity to reward within the nucleus accumbens (NAcc) was associated with lower levels of sensation seeking across a three-year follow-up. In middle adolescence (~ages 12–16), there was no evidence of a relationship between NAcc reactivity and sensation seeking. However, during the transition from late adolescence into adulthood (~ages 17–25), heightened reward-related reactivity in the NAcc was linked to increased sensation seeking. Findings suggest that the neural mechanisms underlying individual differences in trait-like levels of sensation seeking change from early to late adolescence.

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.

Patterns of pubertal maturation have been linked to vulnerability for emotion dysregulation disorders in girls, as well as white matter (WM) development, suggestive of a potential mechanism between pubertal maturation and emotional health. Because pubertal processes begin at varying ages (i.e., status, timing) and proceed at varying rates (i.e., tempo), identifying individual differences in the pubertal course associated with subsequent WM microstructure development may reveal clues about neurobiological mechanisms of girls' emotional well-being. In a prospective cohort study of 107 girls, we examined associations between pubertal status at age 9, pubertal timing and tempo from ages 9-15, and WM microstructure at age 19. Tract-based spatial statistics revealed that girls with more advanced pubertal status at age 9, specific to gonadal-related physical changes, had higher fractional anisotropy, and lower mean diffusivity (MD) and radial diffusivity in tracts relevant to cognitive control and emotion regulation (e.g., the superior longitudinal fasciculus, external capsule, and uncinate fasciculus). Additionally, girls with earlier pubertal timing showed lower MD in the left anterior cingulum bundle. Tempo was unrelated to WM measures. These findings implicate specific aspects of pubertal maturation in subsequent neural signatures, suggesting possible neuroendocrine mechanisms relevant to emotional development. Future work incorporating longitudinal neuroimaging in parallel with pubertal measures may contribute to the understanding of individual variation in pubertal course and WM development.