Disentangling the effects of early caregiving experience and heritable factors on brain white matter development in rhesus monkeys

• Type of Material: Article
• Authors: Brittany R. Howell, Emory University; Mihye Ahn, University of Nevada; Yundi Shi, University of North Carolina; Jodi R. Godfrey, Emory University; Hongtu Zhu, University of North Carolina; Xiaoping Hu, Emory University; Martin Styner, University of North Carolina; Maria Sanchez, Emory University
• Language: English
• Date: 2019-08-15
• Publisher: Elsevier Sience Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neuroimage.2019.04.013
• Title of Journal or Parent Work: NeuroImage
• Volume: 197
• Start Page: 625
• End Page: 642
• Grant/Funding Information: This research was supported by NIMH grants MH078105, MH086203, and MH015755, NICHD grant HD055255, NIGMS grant P20 GM103650, and Office of Research Infrastructure Programs/OD grant OD11132 (YNPRC Base grant, formerly RR000165).
• Keywords: Human corpus-callosum; Middle longitudinal fasciculus; Internal capsule; Diffusion tensor tractography; Nervous system myelination; Science & Technology; Maternal care; Radiology, Nuclear Medicine & Medical Imaging; Uncinate fasciculus; Childhood maltreatment; Nonhuman primate; Inferior longitudinal fasciculus; Neuroimaging; Neurosciences & Neurology; Early adverse experience; Temporal white matter; Early life stress; Life Sciences & Biomedicine; Sex-differences; Diffusion tensor imaging; Neurosciences; Infant maltreatment; Infant abuse
• Research Categories: Psychology, Psychobiology; Engineering, Biomedical; Biology, Biostatistics; Psychology, Behavioral

Abstract

Early social experiences, particularly maternal care, shape behavioral and physiological development in primates. Thus, it is not surprising that adverse caregiving, such as child maltreatment leads to a vast array of poor developmental outcomes, including increased risk for psychopathology across the lifespan. Studies of the underlying neurobiology of this risk have identified structural and functional alterations in cortico-limbic brain circuits that seem particularly sensitive to these early adverse experiences and are associated with anxiety and affective disorders. However, it is not understood how these neurobiological alterations unfold during development as it is very difficult to study these early phases in humans, where the effects of maltreatment experience cannot be disentangled from heritable traits. The current study examined the specific effects of experience (“nurture”)versus heritable factors (“nature”)on the development of brain white matter (WM)tracts with putative roles in socioemotional behavior in primates from birth through the juvenile period. For this we used a randomized crossfostering experimental design in a naturalistic rhesus monkey model of infant maltreatment, where infant monkeys were randomly assigned at birth to either a mother with a history of maltreating her infants, or a competent mother. Using a longitudinal diffusion tensor imaging (DTI)atlas-based tract-profile approach we identified widespread, but also specific, maturational changes on major brain tracts, as well as alterations in a measure of WM integrity (fractional anisotropy, FA)in the middle longitudinal fasciculus (MdLF)and the inferior longitudinal fasciculus (ILF), of maltreated animals, suggesting decreased structural integrity in these tracts due to early adverse experience. Exploratory voxelwise analyses confirmed the tract-based approach, finding additional effects of early adversity, biological mother, social dominance rank, and sex in other WM tracts. These results suggest tract-specific effects of postnatal maternal care experience versus heritable or biological factors on primate WM microstructural development. Further studies are needed to determine the specific behavioral outcomes and biological mechanisms associated with these alterations in WM integrity.