Development of social-visual engagement in infant rhesus monkeys (Macaca mulatta) translation missing: es.hyrax.visibility.files_restricted.text

Wang, Arick (Summer 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/9z903106j?locale=es
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Abstract

Autism Spectrum Disorder (ASD) consists of a range of pervasive developmental disorders, including impairments of social interaction and communication (DSM-V). Despite high degree of heterogeneity in ASD symptoms, reliable deviations in social-visual engagement occur in infancy. Yet, the neural mechanisms supporting these early developing social skills (and the lack thereof) remain unclear. Given technical and ethical limitations in performing longitudinal neuroimaging studies in human infants, a nonhuman primate (NHP) model was used to delineate the neural changes linked to the emergence of these social skills. The first study traced social- visual engagement skills in infant rhesus macaques from 2 to 24 weeks (≈ 2 to 24 months in human infants), using methodologies paralleling human infant studies. The changes in interest to facial cues in infant macaques closely parallel those reported in human infants, with a few species-specific differences due to differing ethological constraints. The second study followed the development of gaze following, a more elaborate form of social-visual engagement in the same animals. Gaze following skills emerged later in monkeys than in humans, though there were important changes in mutual eye gaze and saccade velocities, two critical behaviors associated with gaze following. Finally, the neural underpinning of these early developing social skills was assessed using longitudinal neuroimaging tool (Diffusion Tensor Imaging, DTI) on infants of Studies 1 and 2. Prolonged development of white matter tracts were found within the three cortical visual pathways supporting visual perception, motion, and attention throughout infancy. These changes in white-matter properties showed moderate to strong correlations with the behavioral changes reported above. Collectively, the NHP brain-behavior findings suggest that the period between 2-24 weeks represents a critical period for the refinement of social skills that parallels the fine-tuning of neural connections in social visual pathways. The early-emerging and highly-conserved quantitative phenotypes between the two species indicate that infant NHP provide a critical model to study genetic variations, molecular, or experimental manipulations altering the normative development of social-visual attention. Such studies will further our knowledge of the brain-behavior pathogenesis of ASD and will ultimately help validate efficacy of potential therapeutic treatments for attenuating social deficits in ASD.

Table of Contents

General Introduction....................................................................................1

Social-visual engagement in humans...........................................................4

Social-visual engagement in nonhuman primates.......................................7

Neural substrates of social-visual engagement.........................................10

Summary....................................................................................................24

Figures and Tables.....................................................................................27

References.................................................................................................30

Chapter 1: EARLY DEVELOPMENTAL CHANGES IN VISUAL SOCIAL

ENGAGEMENT IN INFANT RHESUS MACAQUES......................................41

Abstract......................................................................................................42

Methods.....................................................................................................46

Subjects.....................................................................................................46

Data Analysis.............................................................................................49

Results.......................................................................................................50

Discussion..................................................................................................52

Figures and Tables.....................................................................................61

References.................................................................................................68

Chapter 2: THE DEVELOPMENT OF GAZE FOLLOWING SKILLS IN

INFANT RHESUS MACAQUES.....................................................................73

Abstract......................................................................................................74

Methods.....................................................................................................80

Data Analysis.............................................................................................83

Results.......................................................................................................84

Discussion..................................................................................................86

Figures and Tables.....................................................................................95

References...............................................................................................104

Chapter 3: DEVELOPMENTAL TRAJECTORIES OF WHITE MATTER

MICROSTRUCTURE ALONG THE VISUAL PATHWAYS OF INFANT

RHESUS MACAQUES.................................................................................109

Abstract....................................................................................................110

Methods...................................................................................................114

Data Analysis...........................................................................................118

Results.....................................................................................................119

Discussion................................................................................................132

Figures and Tables...................................................................................141

References...............................................................................................152

General Discussion...................................................................................157

Summary of the findings..........................................................................158

Clinical and behavioral relevance / Future Directions..............................166

References...............................................................................................170

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