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. Yet, it is challenging to administer and score these assessments alongside high-quality infant neuroimaging data. The current study aims to identify infant resting state functional connectivity (rsFC) associated with both parent-report and observed behavioral estimates of infant novelty-evoked distress. Methods Using data from the Origins of Infant Temperament (OIT) 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 MRI sample was a “synthetic cohort”, harmonizing data from two fMRI studies of 4-month-old infants (OIT and Baby Connectome Project [BCP]; n=101) both of which included 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 three network pairs: Dorsal Attention–Salience/Ventral Attention, Dorsal Attention-Default, 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). Conclusion 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.