Aberrant Maturation of the Uncinate Fasciculus Follows Exposure to Unpredictable Patterns of Maternal Signals

Steven J. Granger, Laura M. Glynn, Curt A. Sandman, Steven L. Small, Andre Obenaus, David B. Keator, Tallie Z. Baram, Hal Stern, Michael A. Yassa, Elysia Poggi Davis

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother-child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key component of the medial temporal lobe-prefrontal cortex circuit. Infant exposure to unpredictable maternal sensory signals was assessed at 6 and 12 months. Using high angular resolution diffusion imaging, we quantified the integrity of the uncinate fasciculus using generalized fractional anisotropy (GFA). Higher maternal unpredictability during infancy presaged greater uncinate fasciculus GFA in children 9-11 years of age (n = 69, 29 female). In contrast to the uncinate, GFA of a second corticolimbic projection, the hippocampal cingulum, was not associated with maternal unpredictability. Addressing the overall functional significance of the uncinate and cingulum relationships, we found that the resulting imbalance of medial temporal lobe-prefrontal cortex connectivity partially mediated the association between unpredictable maternal sensory signals and impaired episodic memory function. These results suggest that unbalanced maturation of corticolimbic circuits is a mechanism by which early unpredictable sensory signals may impact cognition later in life.SIGNIFICANCE STATEMENT Our prior work across species demonstrated that unpredictable patterns of maternal care are associated with compromised memory function. However, the neurobiological mechanisms by which this occurs in humans remain unknown. Here, we identify an association of exposure to unpredictable patterns of maternal sensory signals with the integrity of corticolimbic circuits involved in emotion and cognition using state-of-the-art diffusion imaging techniques and analyses. We find that exposure to early unpredictability is associated with higher integrity of the uncinate fasciculus with no effect on a second corticolimbic pathway, the cingulum. The resulting imbalance of corticolimbic circuit development is a novel mediator of the association between unpredictable patterns of maternal care and poorer episodic memory.

Original languageEnglish (US)
Pages (from-to)1242-1250
Number of pages9
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Issue number6
StatePublished - Feb 10 2021
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Aberrant Maturation of the Uncinate Fasciculus Follows Exposure to Unpredictable Patterns of Maternal Signals'. Together they form a unique fingerprint.

Cite this