Youth Generalized Anxiety and Brain Activation States During Socioemotional Processing
Authors: M. Catalina Camacho, Rebecca F. Schwarzlose, Michael T. Perino, Alyssa K. Labonte, Sanju Koirala, Deanna M. Barch, Chad M. Sylvester
Journal: JAMA Psychiatry (2024)

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. To characterize brain activation states during socioemotional processing (movie stimuli) and assess associations between state characteristics and movie features and anxiety symptoms. 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. 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. 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. 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.