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Importance: The brain enters distinct activation states to support differential cognitive and emotional processes, but little is known about how brain activation states differ in youths with clinical anxiety., Objective: To characterize brain activation states during socioemotional processing (movie stimuli) and assess associations between state characteristics and movie features and anxiety symptoms., Design, Setting, and Participants: The Healthy Brain Network is an ongoing cross-sectional study of individuals aged 5 to 21 years experiencing difficulties in school, of whom approximately 45% met criteria for a lifetime anxiety disorder diagnosis. Data used in this study are from the first 9 releases (collected in a nonclinical research setting in the New York City metropolitan area from 2015 to 2020) and include 620 youths aged 5 to 15 years (53% of whom met criteria for a lifetime anxiety disorder diagnosis) who watched an emotional video during functional magnetic resonance imaging and completed questionnaires and clinical evaluation. Of those with functional magnetic resonance imaging data, 432 youths aged 7 to 15 years also self-reported on anxiety symptoms. Data were processed and analyzed between February 2020 and August 2024., Main Outcomes and Measures: A hidden Markov model was trained to identify brain activation states across participants during video watching. Time spent in each state and the moment-to-moment probability of being in each state were extracted. Videos were annotated for emotion-specific and nonspecific information using the EmoCodes system. Self-reported anxiety symptoms were assessed using the Screen for Child Anxiety Related Disorders. Time spent in each state across the video and during and outside of peaks in negative content correlated with generalized and social anxiety scores., Results: Among the 620 youths in the overall analysis, 369 were male and the mean (SD) age was 10.4 (2.8) years. In the anxiety symptom analysis, 263 of 432 youths were male and the mean (SD) age was 11.5 (2.2) years. Three brain activation states were identified: a high somatomotor activation state (state 1), a high cingulo-opercular network activation state (state 2), and a high ventral attention and default mode state (state 3). The probability of being in state 3 was correlated with video content that was more negative, quieter, and with less visual motion (ρ < 0.08; P < .001). Increased generalized anxiety was associated with greater time in state 3 (B, 0.10; 95% CI, 0.01 to 0.20; false discovery rate [FDR]-corrected P = .048) and less time in state 2 (B, -0.11; 95% CI, -0.21 to -0.02; FDR-corrected P = .048) when negative social cues were present., Conclusions and Relevance: Youths entered 3 distinct brain activation states during movie watching, and youths with anxiety spent more time in a state with high ventral attention and default activation during negative socioemotional processing. Youths high in generalized anxiety may be more engaged in deeply processing negative emotional content, which may influence self-regulation. Interventions that focus on changing physiological and psychological state during negative social interactions in youths with anxiety should be considered.

Importance: Adolescence is a neurodevelopmental period during which experience-dependent plasticity in brain circuitry may confer vulnerability to depression as well as resilience to disorder. Little is known, however, about the neural mechanisms that underlie resilience during this critical period of brain development., Objective: To examine neural functional connectivity correlates of resilience in adolescent females at high and low familial risk for depression who did and did not develop the disorder., Design, Setting, and Participants: A longitudinal study was conducted at Stanford University from October 1, 2003, to January 31, 2017. Sixty-five female adolescents participated in the study: 20 at high risk in whom depression did not develop (resilient), 20 at high risk in whom depression developed (converted), and 25 at low risk with no history of psychopathology (control)., Main Outcomes and Measures: We compared functional connectivity between resilient and converted, and between resilient and control, adolescent females using voxelwise 2-sided t tests to examine neural markers of resilience to depression as the main outcomes of interest. Specifically, we assessed differences in connectivity of the limbic (amygdala seed), salience (anterior insula seed), and executive control (dorsolateral prefrontal cortex seed) networks, implicated in emotion regulation. We also examined the association between functional connectivity and life events., Results: Of the 65 participants (mean [SD] age, 18.9 [2.5] years), adolescent females in the resilient group had greater connectivity between the amygdala and orbitofrontal cortex (z score = 0.23; P < .001) and between the dorsolateral prefrontal cortex and frontotemporal regions (z score = 0.24; P < .001) than did converted adolescent females. In adolescent females in the resilient group only, strength of amygdala-orbitofrontal cortex connectivity was correlated with positive life events (r18 = 0.48; P = .03). Resilient adolescent females had greater connectivity within frontal (z score = 0.07; P < .001) and limbic (z score = 0.21; P < .001) networks than did control individuals. Both high-risk groups had greater salience network connectivity: the converted group had greater intranetwork connectivity than did the resilient (z score = 0.13; P < .001) and control (z score = 0.10; P < .001) groups, and the adolescent females in the resilient group had greater salience network connectivity with the superior frontal gyrus than did the converted (z score = 0.24; P < .001) adolescent females., Conclusions and Relevance: Resilient adolescent females have compensatory functional connectivity patterns in emotion regulatory networks that correlate with positive life events, suggesting that experience-dependent plasticity within these networks may confer resilience to depression. Further studies are warranted concerning connectivity-associated targets for promoting resilience in high-risk individuals.