Effects of Maternal Care on Prefrontal Cortex, Hippocampal and Amygdalar Development in Rhesus Monkeys 公开

Abstract

Childhood maltreatment is a major public health concern because it can lead to psychiatric illnesses and disorders, as well as neurobiological alterations. Childhood maltreatment is a phenomenon prevalent in both human and nonhuman primates. Due to the difficulty of studying childhood maltreatment in humans, this study used a rhesus monkey model to examine the developmental effects of child maltreatment on brain structure. Rhesus macaques in particular are an ideal model because of their similarities to humans in that they are highly social complex primates, and mother-infant bonds are critical for their development, making them a translational model for human infant development. The goal of this study was to further our knowledge on the effects of infant maltreatment on brain development by focusing on the impact on structural development of the hippocampus, amygdala, and prefrontal cortex (PFC), due to their critical role in stress and emotion regulation and their vulnerability to early life stress (ELS). In addition, this study examined whether exposure to elevated prenatal or postnatal cortisol levels, as well as rates of abuse and rejection experienced during infancy predicted structural changes in those cortico-limbic regions. This study used a powerful cross-fostering design with a random assignment of infants to either maltreating or competent mother at birth. The purpose of the design was to minimize the potential of confounding effects of heritability. Structural MRI techniques were used at 3, 6 and 12 months to examine the developmental effects of maltreatment from infancy to early juvenile period. This study found reduced total brain, PFC grey matter and hippocampal volumes in the maltreated group in comparison to controls, but the differences emerged with increasing age. Lateralized group effects were found in the amygdala. These findings suggest that the ELS experience had a negative impact on neurodevelopment, but that the effects are region-specific and emerge with age.

Table of Contents

Introduction ……………………………………………………………...………………………1

Methods …………………………………………………………………………………………..7

Subjects and Housing……………………………………………………………………….……..7

Cross-fostering design and Collection of Maternal Care Data…………………………7

Structural MRI Image Acquisition…………………………………………………………….…...9

MRI Data Processing, Analysis and Region of Interest (ROI) Volume Computation……10

Neuroanatomical definition of Regions of Interest (ROI) in the atlas……………………..12

Hair Cortisol Samples……………………………………...………………………….…………13

Statistical Analysis………………………………………………………………….……………14

Results…………………………………………………………….……………………………..15

Intracranial volume (ICV) ……………………………………………………………….………15

Total WM, GM, and CSF volume…………………………………………………………....……15

Hippocampal volume……………………………………………………………….……………16

Hippocampus (ICV-Corrected …………………………………………………………..………17

Amygdala volume…………………………………………………………………...……………18

Amygdala (ICV-Corrected) ……………………………………………………………...………18

PFC volume (WM, GM, CSF) ……………………………………………………………....……19

PFC volume (WM, GM, CSF– ICV Corrected)...……………………………………………....…19

PFC volume (Total) ……………………………………………………………………...………20

PFC (ICV-Corrected) …………………………………………………………………….…...…21

Negative control cortical regions………………………………………………………....…...…21

Frontal Lobe volume……………………………………………………………………..…...…21

Frontal Lobe (ICV-Corrected) ………………………………………………..……………...…22

Correlations between brain volumetric, cortisol, and maternal care measures. ………22

Figures and Tables………………………………..……………….……………………………23

Discussion…………………………………………………………………………….…………43

Literature Cited………………………………………………………………………………...52

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
关键词	rhesus monkey early life stress maltreatment limbic system
Committee Chair / Thesis Advisor	Sanchez, Mar, Emory University
Committee Members	Treadway, Michael, Emory University Wallen, Kim, Emory University Dilks, Daniel, Emory University

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