Neural Correlates of Novelty-Evoked Distress in 4-Month-Old Infants: A Synthetic Cohort Study

Background: Observational assessments of infant temperament have provided unparalleled insight into prediction of risk for social anxiety. However, it is challenging to administer and score these assessments alongside high-quality infant neuroimaging data. In the current study, we aimed to identify infant resting-state functional connectivity associated with both parent report and observed behavioral estimates of infant novelty-evoked distress. Methods: Using data from the OIT (Origins of Infant Temperament) study, which includes deep phenotyping of infant temperament, we identified parent-report measures that were associated with observed novelty-evoked distress. These parent-report measures were then summarized into a composite score used for imaging analysis. Our infant magnetic resonance imaging sample was a synthetic cohort, harmonizing data from 2 functional magnetic resonance imaging studies of 4-month-old infants (OIT and BCP [Baby Connectome Project]; n = 101), both of which included measures of parent-reported temperament. Brain-behavior associations were evaluated using enrichment, a statistical approach that quantifies the clustering of brain-behavior associations within network pairs. Results: Results demonstrated that parent-report composites of novelty-evoked distress were significantly associated with 3 network pairs: dorsal attention–salience/ventral attention, dorsal attention–default mode, and dorsal attention–control. These network pairs demonstrated negative associations with novelty-evoked distress, indicating that less connectivity between these network pairs was associated with greater novelty-evoked distress. Additional analyses demonstrated that dorsal attention–control network connectivity was associated with observed novelty-evoked distress in the OIT sample (n = 38). Conclusions: Overall, this work is broadly consistent with existing work and implicates dorsal attention network connectivity in novelty-evoked distress. This study provides novel data on the neural basis of infant novelty-evoked distress.