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Tuesday, November 8, 2022

Fetal frontolimbic connectivity prospectively associates with aggression in toddlers

Hendrix, C. L., Ji, L.,  et al. (2022).
Biological Psychiatry Global Open Science. 

Aggression is a major public health concern that emerges early in development and lacks optimized treatment, highlighting need for improved mechanistic understanding of aggression etiology. The present study leverages fetal resting-state functional MRI (rsfMRI) to identify candidate neurocircuitry for the onset of aggressive behaviors, prior to symptom emergence.

Pregnant mothers were recruited during the third trimester of pregnancy to complete a fetal rsfMRI scan. Mothers subsequently completed the Child Behavior Checklist to assess child aggression at 3 years postpartum (N=79). Independent component analysis was used to define frontal and limbic regions of interest.

Child aggression was not related to within network connectivity of subcortical limbic regions or within medial prefrontal network connectivity in fetuses. However, weaker functional coupling between the subcortical limbic network and medial prefrontal network in fetuses was prospectively associated with greater maternal-rated child aggression at 3 years of age even after controlling for maternal emotion dysregulation and toddler language ability. We observed similar, but weaker, associations between fetal frontolimbic FC and toddler internalizing symptoms.

Neural correlates of aggressive behavior may be detectable in utero, well before the onset of aggression symptomatology. These preliminary results highlight frontolimbic connections as potential candidate neurocircuitry that should be further investigated in relation to the unfolding of child behavior and psychiatric risk.


In a prospective study of 79 mother-child dyads, we found that lower intrinsic functional coupling between medial prefrontal and limbic regions prior to birth was associated with greater maternal report of aggressive behavior when children reached 3 years of age. This association was specific to between network coactivation, as neither within-network connectivity of the mPFC nor within-network connectivity of the limbic network was associated with subsequent child aggression. Our results are consistent with extant fMRI studies showing links between aggressive behavior and altered frontolimbic circuitry in childhood, adolescence, and adulthood, and extend these findings to demonstrate prospective associations with frontolimbic connections measured prior to the onset of symptomatology and prior to birth.

Not quite Minority Report, but stunning nonetheless.