Neural Responsivity to Unexpected Stimuli Moderates a Developmental Pathway to Anxiety: A Community-Sample Replication in Early Infancy and Childhood

Background: Temperamental risk, including negative reactivity (NR) and behavioral inhibition (BI), represents a robust early pathway to anxiety. Neural responsivity to unexpected sensory stimuli, indexed by the mismatch response (MMR), has been shown to moderate associations linking early temperament to later anxiety. This study extends prior work by testing whether MMR measured as early as 4 months, in a community sample, moderate the developmental pathways from NR to BI and from BI to childhood anxiety. Methods: Participants included 147 infants from the Origins of Infant Temperament study. NR and EEG were assessed at 4 months, with EEG recorded during an auditory oddball paradigm. BI was observationally measured at 14 months, and anxiety symptoms were assessed at 30 months and 4 to 6 years using the Child Behavior Checklist. Structural equation modeling with full-information maximum likelihood tested moderation effects of MMR on NR to BI and BI to anxiety pathways. Results: MMR significantly moderated both pathways. More negative MMR at 4 months were associated with the risk pathways from high NR to high BI and from high BI to high anxiety at 30 months. No significant associations were observed at more positive MMR levels. Anxiety symptoms were stable from 30 months to 4 to 6 years. Conclusions: Neural responsivity to unexpected stimuli in early infancy moderates developmental pathways from temperamental risk to childhood anxiety. Findings replicate and extend prior work to an earlier developmental window and a community sample, highlighting infancy as a critical period for identifying neurobiological markers of anxiety risk. Key words: mismatch response; negative reactivity; behavioral inhibition; infancy; anxiety Abbreviations: BI, behavioral inhibition; EEG, electroencephalography; MMR, mismatch response; NR, negative reactivity.